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THE GENETICS REVDLUTIDN HISTDRY, FEARS, A N D FUTURE D F A LIFE-ALTERING S C I E N C E
RDSE
M.
MDRGAN
Greenwood Press Westport, Connecticut • London
Library of Congress Cataloging4n-Publication Data Morgan, Rose M., 1935— T h e genetics revolution : history, fears, and future of a life-altering science / Rose M . Morgan, p. cm. Includes bibliographical references and index. ISBN 0 - 3 1 3 - 3 3 6 7 2 - 5 (alk. paper) 1. Medical genetics—Research—Moral and ethical aspects. 2. Genetic engineering—Moral and ethical aspects. 3. H u m a n cloning—Moral and ethical aspects. I. Title. [ D N L M : 1. Genetics, Medical—ethics. 2. Genetics, Medical—trends. 3. Ethics, Medical. 4. Genetic Techniques—ethics. 5. Genetic Techniques— trends. 6. G e n o m e , H u m a n . 7. Stem Cells. Q Z 50 M849g 2006] RB155.M673 2006 174.2'8—dc22 2005019205 British Library Cataloguing in Publication Data is available. Copyright © 2006 by Rose M . Morgan All rights reserved. N o p o r t i o n of this b o o k may be reproduced, by any process or technique, without the express written consent of the publisher. Library of Congress Catalog Card N u m b e r : 2005019205 ISBN: 0 - 3 1 3 - 3 3 6 7 2 - 5 First published in 2006 G r e e n w o o d Press, 88 Post Road West, W e s t p o r t , C T 06881 A n imprint of G r e e n w o o d Publishing Group, Inc. www.greenwood.com Printed in the United States of America
The paper used in this b o o k complies with the Permanent Paper Standard issued by the National Information Standards Organization (Z39.48-1984). 10
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Every reasonable effort has been made to trace the owners of copyright materials in this b o o k , b u t in some instances this has proven impossible. T h e author and publisher will be glad to receive information leading to more complete acknowledgments in subsequent printings of the b o o k and in the meantime extend their apologies for any omissions.
CDNTENTS Preface Part I. On the Brink of Altering Life 1. Recombining D N A Molecules 2. Splicing Life: Technological Revolution or Pandora's Box? 3. The Book of Life: The Human Genome Project Part II. Beauty and the Beast 4. Laboratory Babies: New Biology, Old Morality 5. The Warnock Report Part III. Fighting to Save a Gene Pool 6. The Human Genome Diversity Project 7. The HGDP Debate Part IV. Threading an Ethical Needle 8. Stem-cell Research 9. A Major Decision Part V. To Clone or Not to Clone: That Is the Question 10. Reproductive Cloning 11. Cloning a Human
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Notes
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Bibliography
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Index
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PREFACE The discovery of the structure of DNA by Crick and Watson, with all its biological implications, has been one of the major scientific events of the 20th century Sir Lawrence Bragg, Nobel Prize recipient and director of the Cavendish Laboratory at Cambridge University, in the foreword to Watson's book, The Double Helix Humanity has much to learn from history In this context we are reminded that the rise of modern-day DNA technology owes its origin to the many scientific events that occurred over a relatively long period of time. Despite past successes of the various DNA technologies, however, the public has always been uneasy as to what scientists should and can do. Today, as in past, the world struggles with an ability to thread its way through an ethical minefield surrounding various genetic issues. The scientific method had its beginnings in the fifteenth and sixteenth centuries. However, systematic experimentation in the laboratory was not carried out until the seventeenth century. Even in the early nineteenth century science and technology were not included in the mainstream of major achievements. Rather, it was a time when questions were posed about evolution, the purpose of advancement, and the nature of human beings. It was a different story from the mid-nineteenth century to end of the twentieth century, when there were decades of enormous development in scientific knowledge. In 1865, Gregor Mendel, an Austrian monk, was credited as the first to lay the mathematical foundation of the science of genetics. Later he became
PREFACE known as the "Father of Genetics." Charles Darwin's revolutionary ideas on evolution were finally recognized during this period in time and there followed a dazzling burst of genetic information. In 1931 it took Aldous Huxley, the brilliant English author, only four months to write his most famous novel, Brave New World, Huxley used Brave New World as a warning against the misuse of science and about the consequences of a soulless technology. During this time there were significant political, philosophical, and economic changes taking place in the United States and Europe. It was a time when Adolf Hitler and the Nazi party came into power in Germany, but before Joseph Stalin's Bolshevik Revolution in the Soviet Union and before Benito Mussolini led an authoritarian, fascist Italy. In April 1953, two young scientists, James Watson and Francis Crick, elucidated the double-helical, spiral-staircase structure of DNA that became the key to the technology of life. The dividends that resulted from Watson and Crick's discovery are too numerous to count, and today in laboratories worldwide scientists use the information from that scientific milestone. By 1970 Watson and Crick's discovery had been known for seventeen years and a new term, recombinant DNA technology (also known as gene splicing and genetic engineering), was introduced into our vocabularies. What it meant for society was a second mobilization of biology. It permitted the transfer of genetic material not only across species lines but out of the animal kingdom—for example, transferring a human's insulin gene into bacteria. However, the new DNA technology had important consequences because for the first time it gave humans control over various possibilities for curing diseases. The first child ever conceived outside a mother's body under controlled conditions, Louise Brown, was born on July 25, 1978, in Oldham, England. Drs. Robert Edwards and Patrick Steptoe, English physicians who performed the IVF procedure, had taken it as their duty to satisfy the natural desire of every couple to have a child, by natural or artificial means. However, behind the beauty of Louise Brown's unique creation there lurked a beast in the form of nightmares and concerns voiced by ethicists, philosophers, theologians, lawyers, and physicians. These individuals, on both sides of the Atlantic, warned that the medical miracle of IVF indicated the arrival of unorthodox medicine as forecast in Brave New World. In response to the heated controversy over IVF, the British government commissioned Dame Mary Warnock, of Girton College, Cambridge University, to form a committee to study recent and potential developments in medicine and science related to human fertilization and embryology. Warnock's Committee of Inquiry into Human Fertilization and Embryology eventually issued sixty-four recommendations. Progress in elucidating the molecular basis of disease at the genetic level continued to progress at a rapid rate. This was due largely to the Human Genome Project (HGP), the largest and most expensive scientific study conducted since the Apollo project and the race to send a human to the moon. For the first time, there was tangible hope for the control of most genetic diseases and even some degenerative ones. In June 2001 the HGP was completed, ahead of the April 23, 2003, deadline that marked the fiftieth anniversary of Watson and Crick's discovery.
VII
PREFACE In 1991 a group of prominent Bay Area human geneticists and molecular biologists proposed to the scientific community that a five-year international study, known as the Human Genome Diversity Project (HGDP), be undertaken to determine variation in the human genome. The well-intended study was to be an effort to collect and preserve DNA samples from a part of the world's 4,000-8,000 endangered populations and was designed to give insights into the origins of ancient populations. However, from its beginnings, indigenous groups voiced concerns about patenting human genes, diversion of funds, the potential for biological warfare, violation of human rights, informed consent, and biopiracy. Almost from the beginning, various indigenous groups called for a halt of the HGDP. The first authentic reproductive cloning made news on July 5, 1996, when the cloned lamb named "Dolly" (after the entertainer Dolly Parton) was born near the Roslin Institute in Edinburgh, Scotland. Essentially her mother's physical twin, Dolly was in all appearances a normal sheep, the first-ever cloned animal from a specialized (differentiated) adult cell. On January 6, 1998, Chicago physicist Richard Seed shocked the world by announcing plans to clone a human, setting off an emotionally charged national debate. As a result, U.S. president Bill Clinton immediately renewed efforts for federal legislation to outlaw both public and private attempts to clone a human. Several bills were introduced to outlaw cloning of any kind, opponents arguing that humankind would be reduced to genes. Supporters countered that therapeutic cloning/stem-cell research had the potential to cure many major illnesses. On August 9, 2002, in a prime-time speech to the nation, President George W. Bush gave the go-ahead for limited federal funding on existing embryonic stem-cell research. Attempting to thread an ethical needle, the president's decision was a definite compromise that allowed him to address concerns about the willful destruction of potential human life, while giving hope to those suffering from horrible diseases that might be cured by embryonic stem-cell research. Like the arts, DNA science and thought have experienced substantial political pressures. The Qenetics Revolution: History, Tears, and Future of a Life-Altering Science is a book that will confront you, the reader, with alternative points of view on complex and sensitive genetic issues. However, we are reminded that moral and ethical genetic issues are continually changing and what may not be moral and ethical today could well be acceptable in the near future. This may become more pronounced as the skills and expertise of scientists and physicians become more advanced. As you read the book you will have a deeper understanding of some of the genetic issues that surround us today, as well as those of yesterday. In the twentyfirst century, the success of the new DNA technologies will transform the course of society's thought and activity, bringing a heightened degree of social awareness and compassion. The Chinese have a pertinent saying: "May you live in interesting times." That we do!
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PART I On the Brink of Altering Life By 1970 the double-helix structure of DNA had been known for seventeen years. In the early 1970s the ability to recombine DNA molecules became the single most important biological tool developed. The Human Genome Project became a worldwide effort to analyze the structure of DNA and to determine the location of the genes. Ethical and legal issues were discussed in almost every church in the United States and throughout the entire world. As a result, the 1970s represented a decade of intense scientific controversy.
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1 RECDMBINING MDLECULES
DNA
You can stop splitting the atom; you can stop visiting the moon; you can stop using aerosols; you may even decide not to kill entire populations by the use of a few bombs. But you cannot recall a new form of life. Erwin Chargaff, biochemistry professor at Columbia University, in a 1976 letter to the editor of Science Late one winter day in 1953, two excited young men, James D. Watson, twentyfour, and Francis Crick, thirty-six, ran out of Cambridge University's Cavendish Laboratory and into the Eagle, a pub traditionally frequented by Cambridge scientists. As the two talked intensely over drinks, friends stopped to learn the reason for the excitement. At the time, Crick burst out exultantly, "We have discovered the secret of life."1 On that day, Watson and Crick, until then unknown outside the Cavendish Laboratory, had finally worked out the now famous double-helical, spiral-staircase structure of DNA. Their discovery was based in part on the sharp X-ray diffraction photographs of DNA provided by Maurice Wilkins and Rosalind Franklin, coworkers at King's College, London. 2 On April 25, 1953, Watson and Crick announced in the prestigious British journal Nature their spectacular discovery of the double helical structure of DNA, considered the most important biological work of the twentieth century and the key to the technology of life. The discovery stimulated dramatic new research and changed forever understanding of the gene, inheritance, and natural selection. 3
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Since the discovery by Watson and Crick the study of DNA has become the focal point of research examining normal and abnormal biological processes. Today, more than 5,000 human genetic diseases are known to exist and a major effort of modern molecular biology is to identify the defects in DNA that result in pathologic states.
Recombining DNA Molecules By 1970 Watson and Crick's double-helix structure of DNA had been known for seventeen years. In the early 1970s, a new term was introduced to our vocabularies— recombinant D N A (rDNA), also called genetic engineering or gene splicing. This was a unique technology that allowed a new and more precise kind of gene manipulation. What was not known at that time, but was discovered shortly thereafter, was that segments of the DNA genetic code could be spliced together precisely from virtually any source to recode a cell's genetic information. Recombinant DNA technology permitted the transfer of genetic material not only across species lines but out of the animal kingdom—for example, a human's insulin gene into bacteria. The perfected rDNA technique made it possible to isolate genes, changes in the genes and how they were expressed and, together with other techniques, to insert the genes into the whole organism. Recombinant DNA technology was followed by the isolation of bacterial enzymes called "restriction endonucleases" ("restriction enzymes") that could splice together D N A from different species. This ability to recombine the D N A molecule to create novel life forms was the single most important new biological tool developed in the 1970s. As a result of rDNA technology, the 1970s took its place as a discrete historical epoch in the United States, much like the Great Depression or the Roaring Twenties. 4
A Decade of Intense Science Controversy Controversy is nothing new to scientists. It is absolutely counter to scientists to take anything on faith, so it was not unusual that when scientists were developing rDNA techniques that a vicious controversy erupted. The debate within the community of biological and social scientists became one of the largest controversies in recent scientific history. The rDNA controversy actually got into full swing in 1971 when scientists postulated, devised, and began to refine a unique technique to splice and recombine segments of DNA between cells from different species of living things, regardless of the sexual compatibility of the organisms or the distance of their evolutionary relationship. 5,6 The debate over rDNA was passionate and with ongoing power struggles erupting on all sides, the scientific community became more aggressive and highly competitive, taking control and manipulating genes through rDNA. Subsequently, this led to the diagnosis, treatment, prevention, and potential cure of thousands of different diseases. Quite literally, it marked a watershed for those who were concerned with rDNA. 7
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As the debate intensified and extended among those not only in science but in politics and technology as well, many professional relationships were hurt beyond repair. On one side, rDNA technology presented itself as a new and innovative technology. On the other hand, it presented itself as an evil Frankenstein monster, frightening and terrifying even to those who believed in it. Clearly, at the center of the rDNA controversy were potential biohazards and risk. Many worried about the hazards of novel genetically-engineered organisms, adequate safety precautions, and what was being done to safeguard the populus. As a result, fear and hostility toward rDNA technology became rampant in the United States. There were numerous issues relevant to genetic manipulation—for example, the possibility of some ecological disruption; the ethics of human genetic intervention; the argument over regulatory policy; and the possibility of using rDNA technology for biological warfare.8 It was not until 1977 that the U.S. government really became involved with safety issues. Opponents argued that the production of rDNA was a new evolutionary event, one that would violate natural barriers and result in the production of new species.9 Some opposed rDNA technology for religious beliefs, ethical concerns, and conflicting ideology. Others had specific fears of nuclear wastes, chemical and biological pollution of the earth and its atmosphere, and evil, self-serving scientists and physicians much like those depicted in Aldous Huxley's Brave New World. Opponents of rDNA technology repeatedly referred to the period of nuclear arms to emphasize their fears. History has shown rDNA technology to be neither good nor bad. Whereas there has been no definitive evidence to show that rDNA is a biohazard, neither has there been any evidence to show that it has not been a biohazard. Many thousands of rDNA experiments, in thousands of laboratories over three decades, have not produced hazards. Even the original experiments, which took apart a D N A molecule and put segments of it back together again, have not appeared hazardous. 10 Yet, despite decades of safety, there are still those who believe strongly that the technology should have been stopped—or at least slowed down. As new and increasingly more sophisticated rDNA technology surfaced, the rDNA controversy gradually came to a head. Government-sponsored groups, federal and local, played key roles in settling the rDNA debate, as well as the complex sociological, political, and psychological factors that impinged upon science. Discussions centered mostly around positions of strong public health and safety standards, as well as the future of genetically-engineered weapons, some in the hands of foreign dictators. In 1970 a team of Harvard scientists succeeded in isolating a DNA fragment. However, two of the scientists on the team felt so strongly that genetic research would be used for evil purposes that they quit the Harvard team. Dr. James Shapiro, one of the scientists who quit, gave three major reasons for doing so. First, he felt that his research would be put to evil uses by government and large corporations that controlled science.11,12 He also believed that the research would lead to political oppression and the creation of so-called inferior subclasses of beings based on genetic classification.13
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Second, Shapiro said he wouldn't work where he didn't have a say in what scientists do. Third, he felt that the U.S. problems needed political solutions more urgently than they did scientific ones. Shapiro, who was twenty-six years old at the time, said he felt compelled to quit genetic engineering research to try a career in politics; his political ideology was "having all of society decide what work scientists will do." 1 4 The other researcher who decided to quit was Dr. Jonathan Beckwith, age thirty-three. Seeking opportunities in other areas of genetics, he later became a leader of a group called Science for the People, a radical congregation that believed genetics would "diminish awareness of the social and political causes of health problems" and would allow genetics to be used as a tool of social control against "the people." In effect, both Shapiro and Beckwith reportedly quit because they wanted the genetic research they were involved in to be stopped. Interestingly, their quitting had little effect on further research by other investigators; nor did it make any significant impression on public opinion. Many of the strongest opponents of rDNA research, who included Beckwith, Shapiro, and Nobel Prize winner and Harvard scientist George Wald, along with others from the Science for the People organization, were already firmly established on the intellectual American left. Science for the People argued against permitting rDNA research in the United States on the grounds that it was intrinsically dangerous to humans and nature and that scientists were only concerned with their immediate, personal advantage. 15 Emphasis on technological solutions to health problems, Science for the People declared, would result in diversion or distraction from other goals that were essential for real social progress. 16 In 1971 Robert Pollack at the Cold Spring Harbor Laboratory Tumor Virus Workshop began to raise safety issues associated with rDNA technology. That same year, Paul Berg, a professor at Stanford University who later won a Nobel Prize for his role in developing rDNA, and Janet Mertz (a graduate student in Berg's lab), attempted to produce a hybrid by using two different viruses, a mammalian tumor virus called SV40 (simian virus 40) and lambda (a virus of E. coli bacteria, the common bacteria of the human intestinal tract). However, while working on the project, Berg and his team became concerned that the experiment might possibly produce an organism that could carry cancer genes (oncogenes), with the potential ability to spread epidemics of cancer. During the summer of 1971, Mertz described the experiment to the Cold Springs Harbor Seminar. In her talk, Mertz acknowledged that even though E. coli flourished in the human intestine and was relatively harmless, SV40 posed serious problems since it was a suspected carcinogen. Seminar participants posed the question to Mertz: If this kind of genetically-engineered organism were to escape from the lab, could it infect people and increase their chances of developing cancer? At the time, scientists believed that there were both known and unknown risks in genetic research. Later, however, it was shown that the specific experiment Mertz described would have interrupted the reproduction genes of lambda and the products would have constituted no danger. However, this was not known at the time and, as a result, the concerns of conference participants were taken very seriously.
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Asilomar I Conference The worries of Berg, Mertz, and others resulted in an assembly of great scientists at the Conference on Biohazards in Biological Research (designated the Asilomar 1 Conference), held at the Asilomar Conference Center in Pacific Grove, California, on January 22-24, 1973. Conference attendees held important discussions over safety issues of rDNA and eventually came to substantial agreement as to what could and should be done. However, before the results of the conference could lead to action, late in 1973 Stanley Cohen of Stanford University and Herbert Boyer of the University of California at San Francisco chemically cut a gene out of a cell from Xenopus laevis (the common toad) and spliced the gene into the microbe E. coli.11 Cohen and Boyer succeeded in getting the microbe to express the toad gene exactly, as if it were one of its own, and in so doing they were given credit for discovering recombinant DNA (rDNA). Some hailed the discovery as a huge step for molecular genetics; others feared it had opened Pandora's box. Because of the potential dangers of rDNA research, members of the Conference placed a moratorium on two phases of rDNA research. First, they stopped the introduction of antibiotic-resistant genes or bacterial toxin genes into bacteria. Second, they stopped the introduction of DNA from tumor viruses or any other animal viruses into reproducing DNA organisms. 18
Gordon Research Conference on Nucleic Acids The Asilomar I Conference was followed on June 11-15, 1973, by the Gordon Research Conference on Nucleic Acids, a gathering of some of the world's greatest scientists at New Hampton, New Hampshire. Many still consider this gathering the birth of the rDNA controversy. The goal of Gordon Conferences has always been to stimulate research in universities, research foundations, and industrial laboratories. Chaired by Paul Berg and sponsored by the prestigious National Academy of Science, the informal Gordon Conference was designed to place a great deal of emphasis on informal discussions for the exchange of new, as well as published, scientific rDNA information. Two kinds of scientific concerns were expressed at the meeting—specific fears of identifiable risks associated with specific experiments, and general fears of cataclysmic dangers if the rDNA research were pursued. Scientists at the conference expressed concerns that parts of DNA from disparate organisms could be hooked together in a test tube (in vitro) and then reinserted into a host organism. 19 Not surprisingly, definite political lines were drawn among the 143 attendees at the conference. Younger scientists were more aggressive, raising broad socially oriented questions, with the exception of those scientists actively involved in rDNA research. In contrast, conservative older scientists generally favored restricting rDNA research. One participant at the Gordon Conference was Edward Ziff, a respected scientist who called for discussion of rDNA biohazards. Ziff had two specific concerns.
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The first concern was with the production of DNA hybrids that were synthesized by recombining parts of DNA. His second concern was that large-scale production and isolation of potential cancer-causing viruses could become a reality and that laboratory personnel might contract cancer from the tumor viruses with which they were working. Because of these concerns, Ziff called for the establishment of better containment facilities for rDNA research. Other scientists attending the Gordon Conference drew parallels between rDNA research and the early years when biological weapons and atomic energy were used and the secrecy that had surrounded the buildup of nuclear arms. Regardless of their stand on the rDNA issue, however, conference attendees overwhelmingly voted to send a letter stating their concerns to the National Academy of Sciences, with a request that the letter be openly published in the journal Science. Paul Berg was elected to head the Assembly of Life Sciences of the National Research Council, composed of distinguished scientists in the field. Concern at the meeting also centered around publicizing the issue. A moratorium was proposed on the introduction of new antibiotic resistance or bacterial toxin genes into bacteria that did not normally carry these genes, and on the introduction of D N A from tumor viruses of other animal viruses into autonomously reproducing DNA elements. 20 Members of the Gordon Conference proposed a number of recommendations, and on September 21, 1973, a letter, carefully worded and comprehensible to scientists in the field, was published in full in Science. The letter, coauthored by Maxine Singer and Dieter Soil, cochairs of the 1973 Gordon Conference, expressed sentiments of Conference participants on the potential hazards of rDNA techniques and recommended to laboratory scientists a few specific types of experiments. 21 As a result of the Gordon letter, molecular biology became more widely known. On April 17, 1974, the first meeting of a free-standing committee convened. Attended by highly regarded scientists including Nobel laureate David Baltimore, the conference was directed to assess the current status of rDNA technology Committee members agreed on two items that should be accomplished. First, it would determine what kind of experiments (if any) should be deferred. Second, it would determine the kinds of experiments that would be allowed in which animal D N A fragments were inserted into bacteria. At the meeting, some scientists favored a moratorium. However, most attendees agreed that scientific inquiry was needed and that constraints of any kind were a transgression of that inalienable right. After considerable discussion, the following conclusions were reached: First, major efforts would be taken to keep decision making within the professional boundaries of the scientific community. Second, little effort would be made to outline the long-term impacts of rDNA techniques in the industrial sector. Third, it would be decided as to who should have monopoly on rDNA procedures. In June 1974 David Baltimore read a draft of a letter to members at the Cold Spring Tumor Virus meeting where he announced that parts of DNA from disparate organisms could be hooked together in the test tube and then reinserted into a host organism. 22
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The Berg Letter On July 26, 1974, a letter, composed by Berg and ten other internationally famous molecular scientists, laid out concerns about the possible creation of new types of infectious rDNA elements and stressed the potential biohazards of rDNA molecules. The full text of the letter was published in the July 1974 journal Science and was carefully worded and comprehensible to scientists in the field. Signers of the letter were representatives of several organizations, including the Committee on Recombinant DNA Molecules, Assembly of Life Sciences, National Research Council, and the National Academy of Sciences. In the famous "Berg letter," scientists requested that the National Academy of Sciences give attention to matters relating to rDNA research. In particular, scientists were concerned about elements that could prove biologically hazardous— that is, those capable of exchanging genetic information with other types of bacteria, some of which were pathogenic to humans. They concluded that scientists have social responsibilities that are a result of their work. 23 Berg and colleagues offered the following proposals: First, until the potential hazards of such rDNA molecules were better evaluated, scientists throughout the world should place a moratorium on rDNA research. Second, plans to link fragments of animal DNA to bacterial plasmid DNA should be carefully weighed since many animal cell DNAs contained sequences common to RNA tumor viruses. Third, the National Institutes of Health (NIH) should establish an advisory committee charged with overseeing and developing procedures and devising guidelines for rDNA experiments. Finally, an international meeting of involved scientists should be convened to review progress and discuss appropriate ways to deal with rDNA molecules. 24 The NIH took the lead in regulating rDNA research and on October 7, 1974, established the Recombinant DNA Molecule Program Advisory Committee (RAC) to study potential rDNA biohazards. After much discussion, the following conclusions were reached by members present at the meeting: First, major efforts must be taken to keep decision making within the professional boundaries of the scientific community; second, little effort should be made to outline the long-term impacts of rDNA techniques in the industrial sector; and, third, top-level scientists expressed concern as to who should have monopoly on rDNA research. Because of these conclusions, a temporary moratorium was initiated.
Asilomar Conference II O n February 24-27, 1975, the International Conference on Recombinant DNA Molecule Research (Asilomar Conference II) was held at the Asilomar Conference Center, Pacific Grove, California. The conference was organized for several reasons: first, to discuss concerns for the possible unfortunate consequences of indiscriminate application of rDNA technology; second, to review scientific progress in this area; and third, to propose appropriate ways to deal with potential rDNA hazards. Although the primary goal was to devise tight safeguards, there was also
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concern that if scientists did not set standards for DNA research, it would be possible for outside groups to intervene. Stanley Cohen of Stanford University stated that "if the collected wisdom of this group doesn't result in recommendations, the recommendations may come from other groups less qualified." 25 One hundred fifty representatives from fifteen countries attended the conference. Most attendees were generally pleased with the results of the conference, and members of the press gave the meeting wide and immediate coverage. Nicholas Wade, a journalist for Science, praised Paul Berg, chair of the Asilomar II Conference, for his work, saying: "Probably few other people could have asked for a moratorium, got it to stick worldwide, and then handled the issue with the openness and disinterest that disarmed resentment and led the world's scientific community to a notable and generally harmonious consensus." 26 Attempting to move ahead, conference attendees discussed the possibility of dispensing with the voluntary moratorium on rDNA experiments. Aware that if they did not end it, others outside the scientific community might, they voted to end the voluntary moratorium. Dr. Robert Sinsheimer, an active participant at the conference, felt that the U.S. government should stop all genetic research, primarily because of DNA's possible evolutionary and social dangers. 27 Sinsheimer argued that a governmental authority should take responsibility for and restrain this "great and terrible power." 28 Eventually, Sinsheimer favored a permanent moratorium on D N A experiments. However, no permanent moratorium was ever enacted after the initial, temporary 1974-75 moratorium. In addition to lifting the moratorium, conference attendees set up safety guidelines for future rDNA research. 29 The two guiding principles were: first, containment of the experiments within specially constructed laboratories, based on the established practices of scientists working with contagious diseases and tumor viruses; and second, containment of the use of enfeebled vectors (carrier organisms) for the rDNA molecules. The vectors consisted of mutated strains of the intestinal bacteria E. coli, which, even if they should escape the experiment and enter a human intestinal tract, could survive only a short time. 30 Two important items came out of the conference: first, the proposed NIH Quidelines for Research Involving Recombinant DNA Molecules; and second, the concepts for physical and biological containment. The NIH later used the Quidelines as their model for safety in the United States and defined the types of containment. Physical containment meant limiting the spread of potentially dangerous microorganisms by using specially designed labs, whereas biological containment involved the use of microorganisms that were attenuated in some way so they could not live outside lab culture conditions. 31 O n April 22, 1975, the Senate Subcommittee on Health, Committee on Labor and Public Welfare met to discuss rDNA technology. Senator Edward Kennedy was chosen to chair the Senate Subcommittee. On May 12-13, the RAC met to frame guidelines for research with rDNA molecules. An RAC subcommittee meeting was held on July 18-19 to draft provisional guidelines (Woods Hole Guidelines). In November 1975 the NIH Advisory Committee asked for public comments and then published its own proposed safety guidelines. Doubts, fears, and marked
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apprehension of scientists and the public were expressed to the committee. Although the guidelines followed the Asilomar principles, they were much stricter about the levels of safety protection required for particular types of experiments. During that time a legislative aide to a congressional subcommittee on Health and the Environment, expecting legislative regulation to prevail, described the scientists' response to proposed legislation in this way: Nevertheless, the greatest fear response exhibited by any group came from the scientists as soon as legislation was proposed. It was particularly frustrating for me to deal with a barrage of protests so fraught with a nearly total lack of understanding of administrative law, often a lack of knowledge of the content of particular bills and a failure to distinguish between the various House and Senate bills. The extent to which bills were misunderstood, misinterpreted and false conclusions drawn from them was unbelievable. . . . The most offensive features of this reaction of scientists was not their initial ignorance and naivity—that can be forgiven—but their subsequent refusal to learn. Numerous briefings were held and memoranda written to explain in detail how each section of the House bill should be interpreted, but a significant segment of the scientific establishment held steadfast to their misconceptions and false conclusions. This was something worse than hubris and basically unforgivable. . . . . . . one must conclude that this was purely an instinctive, emotional and defensive response to fear. . . . But fear of what? How could the mere extension of safety standards by law pose such a threat? Clearly, if the purpose and content of legislation had been understood in the first place, it wouldn't have been perceived as a threat at all. But since it was somehow regarded as control of the content of scientific research, where scientists were sent to jail for forgetting to plug a pipette, no wonder such a frozen state of emotional intransigence resulted.32 Erwin Chargaff, biochemistry professor at Columbia University, expressed his personal fears in a letter to Science magazine. In the article, Chargaff's main concern was for future generations and the possible evil results of introducing new forms of life into the biosphere: A bizarre problem is posed by recent attempts to make so-called genetic engineering palatable to the public . . . what seems to have been disregarded completely is that we are dealing here much more with an ethical problem than with one in public health, and that the principal question to be answered is whether we have the right to put an additional fearful load on generations that are not yet born. I use the adjective "additional" in view of the unresolved and equally fearful problem of the disposal of nuclear waste. Our time is cursed with the necessity for feeble men, masquerading as experts, to make enormously far-reaching decisions. Is there anything more far-reaching than the creation of new forms of life? . . . But beyond all this, there arises
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a general problem of the greatest significance, namely, the awesome irreversibility of what is being contemplated. You can stop splitting the atom; you can stop visiting the moon; you can stop using aerosols; you may even decide not to kill entire populations by the use of a few bombs. But you cannot recall a new form of life. . . . An irreversible attack on the biosphere is something so unheard of, so unthinkable to previous generations, that I could only wish that mine had not been guilty of it. The hybridization of Prometheus with Herostratus is bound to give evil results. 33 Chargaff claimed that the ultimate goal of research on gene manipulation was the correction of genetic abnormalities—the replacement of defective genes by good ones. Chargaff, at the time, had a great mistrust of those he called "biological do-gooders," believing that some of the greatest atrocities had been committed under the pretext of helping suffering humanity.
Academic Involvement As the war in Southeast Asia began to infiltrate deeply onto college campuses, scientists and ethicists became deeply involved in the increasing turmoil. At research institutions of higher learning, such as the Massachusetts Institute of Technology (MIT), students eagerly helped to prepare technological tools that would help in the war effort. In campus laboratories all over the United States, events were taking place that appeared to be almost schizophrenic in nature. On one hand, rDNA research meant making life easier and more humane for many. O n the other hand, it meant designing means which might effectively provide for destruction of human life. Debra Peattie spent a time of the rDNA revolution, 1975-80, as a doctoral student in the Harvard Biological Laboratories (which she fondly recalls as the "Bio Labs"). Later, she recalled: Genetic engineering was an emotional—often vitriolic—topic for scientists in the mid 70's. The summer of 1977 was your typical hot and muggy Boston summer, whipped to frothing by continuous debates between individual scientists, groups of scientists, public interest groups, interested public groups, then Mayor Alfred Vellucci and the Cambridge City Council. In the mid 70's, genetic engineering was not viewed with the sanguine eye it is today. Indeed, there were many people who believed it quite likely that inserting foreign DNA into bacteria (the "essence" of genetic engineering if you will) could lead to "killer" bacteria that could escape from the laboratory and run amuck in the City of Cambridge. How could these killer bacteria escape? One theory postulated that bacteria would be carried out on the legs of the big South American cockroaches that infested the bio Labs due to the ongoing research on them there. I kid you not. The more salient question might actually
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have been, "Could these bacteria withstand some of the other things running amuck in the City of Cambridge in the 70's?" But that's another story. The fact that a child care center operated (and still operates) behind the Bio Labs raised concerns to a fever pitch: scientists risking their lives by cloning foreign genes into bacteria were one thing, but innocent children threatened by the recombinant bacteria wafting out of air vents or windows was another thing. So much for thesis work being boring, as I used to tell my parents on the phone. I was working in the laboratory of Walter Gilbert, a man who was racing to clone the human insulin gene and who was in the midst of performing his Nobel Prize winning research, so life was far from dull for those of us in the lab at the time. Gilbert's scientific stature and progenetic engineering stance turned the summer of 1977 into an ongoing exchange between the lab and the news media, the public, other labs, other universities, other scientists, you name it. Incoming telephone calls about genetic engineering got so numerous that some of us just took the lab phone off the hook in order to get our work done; others took to answering the phone with a terse "No comment." A couple of us from the lab lugged a six-foot-tall DNA molecule by car down to the then-bare fields of Kendall square for a Harvard-MIT "teach-in" about recombinant DNA and genetic engineering for the public that summer, and others of us went before the Cambridge City Council to testify at a hearing about the safety of the revolutionary new technology. After receiving obscene telephone calls at home due to my defense of genetic engineering in front of the Cambridge City Council, I emulated our lab practice and took the phone off the hook, too. The Cambridge City Council decided it needed time to digest the information it had gathered about genetic engineering, and the City declared a moratorium on recombinant DNA research. The Department of Biochemistry and Molecular Biology lost a newly hired professor to Cal Tech because he would have been unable to perform his research in moratorium-bound Cambridge. Students and post-docs were thrown into a frenzy because they suddenly could not do the experiments they needed for their theses and research fellowships. Luckily, Harvard Medical School was in Boston and unfettered by the moratorium, so work could continue there—albeit on tenterhooks while the public and scientific community were still fractured by debate. So what happened to the controversy? The moratorium eventually ended, the City of Cambridge was threatened more by its everyday eccentricities rather than by killer recombinant bacteria, the Cal Tech professor moved to Harvard as he had originally intended and the practice of gene cloning evolved from a closely monitored novelty to the immensely powerful science that produced Humulin®, the genetically engineered insulin that Eli Lilly licensed from Genentech and that got me started on all of this in the first place. Funny, it all seems like just yesterday instead of eighteen years ago. Forget those killer bacteria— that's the really scary part! 34
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NIH Guidelines An enormous amount of time, thought, and labor went into producing the guidelines for rDNA technology. In November 1975 the NIH Advisory Committee published its own proposed NIH Quidelines. Designed primarily to diffuse the rDNA controversy, the Quidelines represented a negotiated settlement. At its December 4-5, 1975, meeting the RAC adopted proposed guidelines for rDNA research that were carried out with NIH funding. The meeting included many noted scientific and public representatives, and as a result many useful comments and suggestions were received. In February 1976, Maxine Singer made a presentation before the NIH Director's Advisory Committee (DAC), citing four principles: 35 • First, in light of current information, certain experiments may be judged to present sufficiently serious potential hazards so that they should not be attempted at this time; • Second, the group of experiments that pose either lesser or no potential hazards could be performed provided (a) the information to be obtained or the practical benefits anticipated could not be obtained by conventional methods, and (b) appropriate safeguards for containment are incorporated into the design; • Third, the more potentially hazardous the experiment, the more stringent should be the safeguards against escape of the agents; • Finally, that there should be an annual review of the Quidelines. On June 9-12, 1976, the Ten Miles International Symposium on Recombinant D N A Molecules: Impact on Science and Society meeting was held at the Massachusetts Institute of Technology in Cambridge, Massachusetts. Essentially, this was an RAC working group on safer hosts and vectors. Shortly thereafter, on June 23, 1976, the RAC issued the Quidelines for rDNA research. The Quidelines required rDNA research proposals to first be reviewed by the home institution's biosafety committee (IBC) and then by the RAC. It was determined that because of federal regulations on research involving human subjects, rDNA research must be reviewed by the local IBC. The Quidelines applied to all federally funded institutions performing rDNA research, regardless of the source of funding for the specific project or where the research took place. The Quidelines specified that there must be levels of physical and biological containment which were dependent on the kinds of experiments conducted. The four levels of physical containment were PI, P2, P3, and P4. PI corresponded to microbiology diagnostic laboratories in all hospitals; P2 referred to biological safety cabinets used in most operations; P3 designated inward air flow in all laboratories, much like a giant hood, as well as overall special practices for each laboratory; and P4 designated that all experiments must be confined to air-tight biological safety cabinets and that scientists must perform their work through glove ports. In addition, the Quidelines discussed roles and responsibilities of all scientists conducting rDNA research, his or her university affiliation, members of the uni-
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versity's biosafety committee, and the NIH. After their promulgation in 1976, the NIH Quidelines were accepted by other federal agencies including the National Science Foundation (NSF) and the U.S. Department of Agriculture. Some of these views found support in Washington, D C . In July 1976 Senators Jacob Javits and Edward Kennedy wrote to President Gerald Ford, urging that "every possible measure be explored for assuring that the NIH Quidelines were adhered to in all sectors of the research community." 36 Senators Javits and Kennedy also wrote that they were "gravely concerned that these relatively stringent (NIH) guidelines may not be implemented in all sectors of the domestic and international research communities and that the public will therefore be subjected to undue risk. . . . We urge you to implement these [NIH] Quidelines immediately whenever possible by executive directive and/or rule making, and to explore every possible mechanism to assure compliance." 37 Earlier, Senator Kennedy had been critical of scientists who made public policy in private. Favoring more public participation in science, he drafted a bill that would have established an independent national regulatory commission specifically for rDNA research. Composed primarily of nonscientists, the commission would control all rDNA research (except that local communities could set more severe restrictions, or ban the research altogether). Later, at a risk assessment workshop in Falmouth, Massachusetts, on June 20-21, 1977, it was concluded that Escherichia coli K-12 was a harmless organism and could not be converted into a pathogen by insertion of rDNA. President Gerald Ford created the Federal Interagency Advisory Committee on Recombinant DNA Research and in 1977, the committee recommended new legislature to extend the NIH Quidelines to private industry. Based on approximately 170 responses from persons who had expressed concerns over rDNA, revision of the NIH Quidelines was issued in December 1978. The revised Quidelines contained many steps and some major changes. First, experiments in general were assigned lower levels of required containment. Second, certain classes of experiments deemed of the lowest potential hazard were exempted entirely from the guidelines. Third, increased representation was mandated on local institutional biosafety committees that monitored rDNA research at individual institutions and on the RAC. Finally, procedures were built into the guidelines for changing them in the future. This was considered a major change where any person wishing to suggest a revision of the Quidelines could submit them to NIH. The Quidelines were published by the Federal Register at least thirty days before a regular meeting of the RAC, for public comment. Members of the public were encouraged to speak on the subject. 38 In 1981 the NIH took the first steps toward removing mandatory controls on the conduct of rDNA research. Meeting in Bethesda, Maryland, the RAC set up a subcommittee to look into the future of the Quidelines and to discuss whether then-current Quidelines, which all federally sponsored scientists had to observe, should be turned into a voluntary code of practice. The committee considered two proposals, both of which would relax current mandatory guidelines. The first proposal, offered by Dr. Allan Campbell of Stanford University and Dr. David Baltimore of M.I.T., suggested that the NIH
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Quidelines should be voluntary, thus eliminating the formal need for review by bodies such as local institutional biosafety committees. Baltimore suggested that the RAC continue to monitor rDNA research, to make decisions about experiments that would present certain dangers, and to help evaluate significant ethical issues. In addition, Campbell and Baltimore suggested that specifics should be reviewed by the NIH director in order to monitor large-scale experiments that might have unsuspected results. They also suggested that there should be major reductions in the containment levels recommended for various types of rDNA experiments. However, other members, particularly those from the public interest community, were cautiously opposed to reducing the containment conditions too quickly. The other proposal was a mandatory plan that loosened present experimental restrictions, but not to the extent of the RAC's September proposal. The proposal was offered by Susan Gottesman, a senior investigator in molecular biology at the National Cancer Institute and a former RAC member. Her proposal retained Institutional Biosafety Committees, which the RAC proposal eliminated. However, the proposal by Gottesman did not lower containment levels as much as the RAC proposal. Gottesman's proposal passed sixteen to five. Elena Nightingale of the Institute of Medicine stated: "We should keep in mind that the probability of something going wrong is small, but . . . [if something goes wrong] the consequences are large. A powerful technology has powerful consequences." 39 However, many committee members were uncomfortable with the prospect that the public might react negatively if the NIH Quidelines were made voluntary. Urging a careful relaxation of the rules, William N. Lipscomb, chair of Harvard's Biosafety Committee, in a letter to the committee warned that public concern and subsequent actions "should not be underestimated." Some committee members thought it possible that various kinds of state and local regulations might spring up across the country if the NIH abandoned the mandatory guidelines. Baltimore argued that the RAC proposal "tries to reflect the judgment of a vast majority of scientists who believe that rDNA research is no more hazardous than the mainstream of research. Those who do not agree with me represent, at best, a small fraction of the scientific community." 40 Given the commendable track record of most scientists, committee members agreed that the risks of hazards in rDNA research were small. As a result, controversy over rDNA research intensified and charges of conflict of interest were fired against Baltimore. At the time, he served as a board member and chair of a scientific advisory committee at a biotechnology company called Collaborative Research while at the same time he retained his faculty post at Harvard. The NIH committee chose to keep the rules mandatory for two principal reasons. First, some members were clearly worried about public backlash and the possibility that the removal of federal regulation would invite local and state legislators to enact their own laws to restrict rDNA research. Second, some members had lingering concerns about the safety of some experiments regulated by guidelines. Several RAC members pointed out that there was still considerable public fear about rDNA research and suggested that rDNA research be regulated in a
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responsible manner. In 1981, the RAC recommended that virtually all the remaining "requirements" be converted to "recommendations," since federal controls no longer seemed necessary. Acting on behalf of, and with the endorsement of, the Assembly of Life Sciences of the National Research Council, the RAC proposed a number of recommendations. The first recommendation involved two types of DNA recombination. Type 1 described construction of new, autonomously replicating bacterial plasmids that might result in the introduction of genetic determinants for antibiotic resistance or bacterial toxin formation into bacterial strains that did not at the present time carry such determinants; or construction of new bacterial plasmids containing combinations of resistance to clinically useful antibiotics unless plasmids containing such combinations of antibiotic resistance determinants already existed in nature. Type 2 discussed linkage of all or segments of the DNAs from oncogenic or other animal viruses to autonomously replicating DNA elements such as bacterial plasmids or other viral DNAs. They reasoned that rDNA molecules might be more easily disseminated to bacterial populations in humans and other species, and thus possibly increase the incidence of cancer or other diseases. The second recommendation discussed plans to link fragments of animal DNAs to bacterial plasmid DNA or bacteriophage DNA. It expressed concern that this should be carefully weighed in light of the fact that many types of animal cell DNAs contained sequences common to RNA tumor viruses. Since joining of any foreign DNA to a DNA replication system created new recombinant DNA molecules whose biological properties could not be predicted with certainty, the committee reasoned that such experiments should not be taken lightly. The committee's third recommendation was that the director of the National Institutes of Health be requested to give immediate consideration to establishing an advisory committee charged with (a) overseeing an experimental program to evaluate the potential biological and ecological hazards of the above types of recombinant DNA molecules, (b) developing procedures that would minimize the spread of such molecules within human and other populations and, (c) devising guidelines to be followed by investigators working with potentially hazardous recombinant DNA molecules. It was suggested that these standards would be enforced through the NIH and other government agencies that disburse government research grants. The fourth recommendation advocated an international meeting of involved scientists from all over the world to be convened early in the coming year to review scientific progress in this area and to further discuss appropriate ways to deal with the potential biohazards of rDNA molecules and recombination techniques. In February 1982 a National Institutes of Health Advisory Panel voted to relax somewhat the regulations that governed federally funded rDNA research. At the same time they approved keeping the Quidelines compulsory and in so doing, the RAC continued steering a conservative course on rDNA research. The panel strongly rejected another proposal that would have made the Quidelines completely voluntary because most committee members were not ready to forgo all the restrictions and oversight that the NIH had exercised over rDNA research since 1976.
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Not surprisingly, the United States was not the only country that had trouble in setting up rDNA research guidelines. In 1990 Germany passed a gene technology law that was very similar to the NIH's safety Quidelines outlined at the Asilomar Conference. However, German scientists were very unhappy with the strictness and enforcement policies of the new law. In addition, the German people were very fearful of the words "genetic engineering" because they feared that the German people might be used for eugenic purposes as proposed during Hitler's regime or that German scientists might deceive them about the safety of the rDNA experiments.
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2 S P L I C I N G LIFE Technological Revolution or Pandora's Box? At this point in the development of genetic engineering no reasons have been found for abandoning the entire enterprise— indeed, it would probably be naive to assume that it could be. Given the great scientific, medical, and commercial interest in this technology, it is doubtful that efforts to foreclose important lines of investigation would succeed. If, for example, the United States were to attempt such a step, researchers and investment capital would probably shift to other countries where such prohibitions did not exist. To expect humanity to turn its back on what may be one of the greatest technological revolutions may itself betray a failure to recognize the limits of individual and social restraint. Morris B. Abram, chair of the President's Commission for the Study of Ethical Problems in Medicine and Biomedical Research Current concerns about biological, chemical, and nuclear-weapons terrorism remind us of how well-intentioned scientific advances, such as recombinant D N A (rDNA) technology, provide human beings with vast powers that may endanger our fundamental social and political values. Yet, the spector of such power has haunted the development of rDNA technology since its beginnings in the 1970s. Whereas some claim the scientific development of rDNA technology to be a huge success, others fear it may have opened a Pandora's box.
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Social and Political Actions Initial public debate over the rDNA issue created a storm of social and political action, with government agencies scrambling to acquire new regulatory territory. Overall, there was an increased public mistrust of rDNA technology, and the fundamental question raised was, what shall be regulated and by whom? because the NIH Quidelines didn't apply to private individuals there was fear that profit might overshadow scientific integrity. As a result of the general mistrust about rDNA technology, rapid commercialization became a real possibility. Erwin Chargaff once again expressed concerns about rDNA technology, stating that he had five main objections to the new technology. First, he objected to using E. coli as the host in rDNA experiments, believing that a more extensive search would have resulted in a better choice of a host; second, he felt that society would not be safe from anything that needed to be contained; third, he felt that too much money would be wasted on rDNA research and that other kinds of research would be ignored because of it; fourth, he felt that industrial research and production would be dangerous because they were outside government relations; and, finally, he believed that the uncertainty of rDNA research might result in one mistake changing the biosphere irreversibly.1 Scientists became engaged in political debate over the new technology, and legislative and administrative regulation seemed a compelling necessity. However, from the scientists' viewpoint, as well as the public interest, legislative regulation would be the worst thing that could happen, largely because enactment of legislation would have been a triumph for the leftist political ideology. However, some legislators and their aides saw it in a different light.2 During 1977 and the beginning of 1978 many scientists agreed that the risks of rDNA research were, at worst, more minimal than they had previously estimated— perhaps even nonexistent. This consensus grew after S. Chang and S. N Cohen wrote a scientific paper that announced that rDNA was also produced in nature. 3 Chang and Cohen's paper was considered the scientific turning point in the debate over whether rDNA research should be stopped because it demonstrated that rDNA production was not an unprecedented tampering with the balance of nature. As a result, Chang and Cohen, as well as other scientists, gained the attention of several senators including senators Edward Kennedy and Adlai Stevenson. In September 1977 Stevenson called on the Senate to put off legislation on rDNA technology and Senator Kennedy withdrew support for his sponsored Senate bill, joining with those who viewed the hazards of rDNA as questionable.
Interest/Action Groups During the middle and late 1970s interest and action groups met to discuss the rDNA issue. One of the leading centers concerned with the rDNA technology issue was the Hastings Center, located in Hastings-on-Hudson, New York. The Hastings Center enjoyed a sterling reputation and played a key role in international risk assessments, participating in some Gordon Conferences. Started in 1969 by Daniel Callahan, the Hastings Center was originally designed to sponsor
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workshops, publish teaching materials, and promote interdisciplinary research groups. The center also issued a bimonthly journal that contained essays on legal and ethical issues in science and medicine. Other interest/action groups entered the picture at about this same time, including the Federation of American Scientists (FAS), the oldest, largest, and strongest of the politically moderate groups. The FAS believed that it was their responsibility to inform the public on matters dealing with the technical and scientific importance of rDNA research. Also appearing on the scene was the Society for Social Responsibility in Science (SSRS), first conceived in 1949 and designed to push for "constructive alternatives to militarism." The SSRS, like the FAS, stressed the need to create an informed public opinion on rDNA technology issues. In 1976 Jeremy Rifkin, president of the Foundation on Emerging Technologies (an organization based in Washington, DC.) made public his organization's opposition to rDNA technology. Considered by many as one of the most prominent opponents of rDNA technology, Rifkin sponsored numerous lawsuits against genetic engineering experiments and organized public protests against biotechnology. Rifkin had written several books including Declaration of a Heretic and Algeny, in which he depicted genetic engineering as having the potential to redesign the human race. Rifkin worried that the future of mankind might be redesigned to change racial or socially undesirable traits, considered by some as a form of eugenics.4 Worried that genetic information might be widely used to discriminate against individuals attempting to obtain employment, education, or insurance, Rifkin predicted a genetic rights movement as potent and as powerful as the civil rights movement of the 1960's.5'6 Rifkin introduced a bill before the Government Operations Committee that was designed to regulate the collection, maintenance, use, and dissemination of genetic information gathered from individuals by the federal government and its contractors and grantees. The bill prohibited agencies from releasing genetic information without the individual's written consent, except in the case of a medical emergency or a criminal investigation where probable cause of reasonable suspicion had been shown. In addition, the bill gave individuals the right to file a lawsuit or an injunction against an agency that had released, or was intending to release, information without permission. It also provided criminal penalties for unauthorized release.7 Rifkin requested a voluntary moratorium and public debate on all human gene therapy research, and he asked that all gene therapy experiments cease until the NIH was able to set up a committee to evaluate the ethical and social issues of human gene research. Rifkin filed a lawsuit in federal court to stop gene therapy experiments on the grounds that the NIH's review of the experiments was flawed. He charged the NIH's RAC of ignoring the ethical issues of human gene therapy, referring to them as an elite group of NIH scientists with handpicked ethical consultants. Rifkin formed his own committee, the Human Eugenics Advisory Committee, composed of people in the fields of civil liberties, the rights of disabled workers, and insurance and consumer rights. The newly-formed committee provided advice on the ethical, social, economic, and eugenic implications and impacts of human genetic therapy.8 However, some RAC members felt that Rifkin was more interested in setting up a public debate than in stopping gene research. As a result,
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RAC members voted to "respectfully decline" Rifkin's proposal for a public debate. His request for a moratorium was denied and no national debate was held. 9 In March 1977 the National Academy of Sciences organized an Academy Forum on rDNA Research. The Hastings Center, led by Daniel Callahan and colleagues, was instrumental in getting scientists, philosophers, and legal experts together to discuss rDNA and its implications. In the spring of 1978, Sydney Brenner, a participant at the Asilomar Conferences and a distinguished scientist at the Medical Research Council's Laboratory of Molecular Biology in Cambridge, England, produced a substantive paper for the Genetic Manipulation Advisory Group (GMAG), the British counterpart to RAC. In the paper, Brenner suggested a generalized framework to estimate the potential biohazards of different classes of experiments. 10 In the late 1970s Nobel laureate James D Watson came to the forefront of the rDNA debate. Speaking in opposition to radical groups wanting to shut down rDNA research, he wrote in the Washington Post: "Such groups thrive on bad news, and the more the public worries about the environment, the more likely we are to keep providing them with the funds that they need to keep their organizations going. So if they do not watch themselves, they will always opt for the worst possible scenario." 11 In January 1979 Health, Education, and Welfare Secretary Joseph Califano of the Recombinant DNA Advisory Board invited members from several radical organizations and environmental groups to participate in discussions. Only the most activist environmental groups expressed opposition to rDNA research, and even they were under severe internal criticism from scientists who were prominent trustees of groups such as Friends of the Earth and the Natural Resources Defense Council.
The 95th Congress and Recombinant DNA Technology In the late 1970s the U.S. government had become moderately concerned over the possible risks involved in rDNA technology. As a result, during most of 1977 there was a scramble among government agencies to acquire new regulatory territory. The Ninety-fifth Congress, which lasted through all of 1977 to January of 1978, saw fifteen different bills on rDNA technology introduced. In general, there was substantial disagreement among the legislators and a lack of interest in controlling rDNA research. Subsequently, none of the bills ever reached the floor of the full House or Senate.
Patenting Life Forms Opponents of rDNA technology expressed substantial fear that profit from rDNA research and technology might supersede scientific integrity. The fear was enhanced when patents were issued by the U.S. Patent Office in June 1980 to Dr. Ananda Chakrabarty for a specially created Pseudomonas aeruginosa bacterium that could break down oil slicks, and to Cohen and Boyer in December 1980 to
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cover the basic process involved in generating rDNA molecules. 12 At the time, the idea that a newly created life form could be patented was unique. History recorded the landmark 1980 Supreme Court case of Diamond vs. Chakrabarty as the pivotal case of biotechnology. 13 What frightened most people at the time was the process of recombining DNA molecules and the capability to alter genetic properties of organisms by design. 14 There was also the fear that competition in patenting life forms might lead to a stifling of communication between scientists.
Churches1 Concerns During this same time, ethical and moral issues concerning rDNA technology were discussed in many churches throughout the United States and the world. In the United States the National Council of Churches commissioned a Task Force on Human Life and the New Genetics, which concluded: Possibilities such as cloning, mass genetic screening, and gene therapy challenge our understanding of the nature of personal identity, the meaning of human community, the inviolability of the body, the structure of human parenthood, and the limits on human intervention into natural processes. There is reason to ask of any specific genetic practice whether or not it is a rash act with unpredictable consequences. There is reason to ask also, as in any human exercise of power, whether or not it is an instrument for a strong elite to impose its prejudices on the less powerful. Such questions may lead to an ethical judgment that some genetic possibilities should not be exploited, now or ever. But that judgment, if made, is a specific judgment, not a universal rejection of genetic activity. Theologically understood, God may work as truly through intentionally human genetic acts as through the human unintended genetic processes that have made humanity genetically what it is now. The task force's report offered a sense of balance, neither condemning the new technology nor applauding it. The report was not designed to set forth any policy but was prepared to help people think for themselves and find their own convictions. 15 On July 20, 1980, the following letter was sent to U.S. president Jimmy Carter by the General Secretariats of the three main religious councils in America: Dr. Claire Randall, General Secretary of the National Council of Churches; Rabbi Bernard Mandelbaum, General Secretary of the Synagogue Council of America; and Bishop Thomas Kelly, General Secretary of the U.S. Catholic Conference. Dear President Carter: We are rapidly moving into a new era of fundamental danger triggered by the rapid growth of genetic engineering. Albeit, there may be opportunity for doing good; the very term suggests the danger. W h o
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shall determine how human good is best served when new life forms are being engineered? W h o shall control genetic experimentation and its results which could have untold implications for human survival? W h o will benefit and who will bear any adverse consequences, directly or indirectly? These are not ordinary questions. These are moral, ethical, and religious questions. They deal with the fundamental nature of human life and the dignity and worth of the individual human being. With the Supreme Court decision allowing patents on new forms of life—a purpose that could not have been imagined when patent laws were written—it is obvious that these laws must be reexamined. But the issue goes far beyond patents. New life forms may have dramatic potential for improving human life, whether by curing diseases, correcting genetic deficiencies or swallowing oil slicks. They may also, however, have unforeseen ramifications, and at this time the cure may be worse than the original problem. New chemicals that ultimately prove to be lethal may be tightly controlled or banned, but we may not be able to "recall" a new life form. For unlike D D T or DES, both of which were in wide use before their tragic side effects were discovered, life forms reproduce and grow on their own and thus would be infinitely harder to contain. Control of such life forms by an individual or group poses a potential threat to all of humanity. History has shown us that there will always be those who believe it is appropriate to "correct" our mental and social structures by genetic means, so as to fit their vision of humanity. This becomes more dangerous when the basic tools to do so are finally at hand. Those who would play God will be tempted as never before. We also know from experience that it would be naive and unfair to ask private corporations to suddenly abandon the profit motive when it comes to genetic engineering. Private corporations develop and sell new products to make money, whether those products are automobiles or new forms of life. Yet when the products are new life forms, with all the risks entailed, shouldn't there be broader criteria than profit for determining their use and distribution? Given all the responsibility to God and to our fellow human beings, do we have the right to let experimentation and ownership of new life forms move ahead without public regulation? These issues must be explored, and they must be explored now. It is not enough for the commercial, scientific, or medical communities alone to examine them; they must be examined by individuals and groups who represent the broader public interest. In the long-term interest of all humanity, our government must launch a thorough examination of the entire spectrum of issues involved in genetic engineering to determine before it is too late what oversight and controls are necessary. We believe, after careful investigation that no government agency or committee is currently exercising adequate oversight or control,
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not addressing the fundamental ethical questions in a major way. Therefore, we intend to request that President Carter provide a way for representatives of a broad spectrum of our society to consider these matters and advise the government on its necessary role. We also intend to ask the appropriate Congressional Committees to begin immediately a process of revising our patent laws looking to revisions that are necessary to deal with the new questions related to patenting life forms. In addition, we will ask our government to collaborate with other governments with the appropriate international bodies, such as the U N . , to evolve international guidelines related to genetic engineering. Finally, we pledge our own efforts to examine the religious and ethical issues involved in genetic engineering. The religious community must and will address these fundamental questions in a more urgent and organized way.16
President Carter's Commission Aware of the potential dangers of rDNA technology and at the prompting of various church and synagogue councils, President Jimmy Carter set up the Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. The commission later issued its published report, Splicing Life: The Social and Ethical Issues of Qenetic Engineering with Human Beings. In its report, the Carter Commission strongly defended the continuation of rDNA research and suggested that the RAC broaden its view and include the ethical and social implications of gene therapy. In effect, the commission's report denied the claim that rDNA was immoral because it had the potential to grant humans God-like powers, but rather concluded that rDNA technology was like any number of creative activities of God. Ultimately, the use of the new technology was not claimed to be wrong as such but wrong because of its potential consequences. 17 The Carter Commission examined many potentially dangerous consequences of rDNA technology, including whether rDNA would interfere harmfully with evolution, destroy parents' rights and sense of responsibility to their children, change peoples' sense of being human beings and the way they thought of themselves, and promote misuses between commercial interests and academic research projects. In considering the risk of destroying parental responsibility, the Carter Commission noted that if rDNA technology made use of reproductive techniques such as in vitro fertilization and artificial insemination, strains on traditional views of family and kinship would be exacerbated. In discussing potential effects of rDNA technology on personal identity, the commission reported that the "manipulation of genes that contribute significantly to personality or intelligence—if it ever becomes possible—could have considerable impact on the way people think of themselves. The Commission is intent on using a utilitarian calculus of benefits and risks." 18
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In its final arguments on social and ethical issues, the commission concluded that genetic engineering and research should not be halted: At this point in the development of genetic engineering no reasons have been found for abandoning the entire enterprise—indeed, it would probably be naive to assume that it could be. Given the great scientific, medical, and commercial interest in this technology, it is doubtful that efforts to foreclose important lines of investigation would succeed. If, for example, the United States were to attempt such a step, researchers and investment capital would probably shift to other countries where such prohibitions did not exist. To expect humanity to turn its back on what may be one of the greatest technological revolutions may itself betray a failure to recognize the limits of individual and social restraint. 19 O n November 16, 1982, Morris B. Abram, Chair of the President's Commission for the Study of Ethical Problems in Medicine and Biomedical Research, wrote the following letter to President Ronald Reagan: Dear Mr. President: On behalf of the President's Commission for the Study of Ethical Problems in Medicine and Biomedical Research, I am pleased to transmit Splicing Life, our report on the social and ethical issues of genetic engineering with human beings. This study, which was not within the Commission's legislative mandate, was prompted by a letter to your predecessor in July, 1980 from Jewish, Catholic, and Protestant church associations. We embarked upon it, pursuant to 1802(a)(2) of our statute, at the urging of the President's Science Advisor. Some people have suggested that developing the capability to splice human genes opens a Pandora's box, releasing mischief and harm far greater than the benefits for biomedical science. The Commission has not found this to be the case. The laboratory risks in this field have received careful attention from the scientific community and governmental bodies. The therapeutic applications now being planned are analogous to other forms of novel therapy and can be judged by general ethical standards and procedures, informed by an awareness of the particular risks and benefits that accompany each attempt at gene splicing. Other, still hypothetical uses of gene splicing in human beings hold the potential for great benefit, such as heretofore impossible forms of treatment, as well as raising fundamental new ethical concerns. The Commission believes that it would be wise to have engaged in careful prior thought about steps such as treatments that can lead to heritable changes in human beings or those intended to enhance human abilities rather than simply correct deficiencies caused by welldefined genetic disorders. In light of a detailed analysis of the ethical
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and social issues of this subject—issues beyond the purview of existing mechanisms for Federal oversight—the Commission suggests several possible means, in the private as well as the public sector, through which these important matters can receive the necessary advance consideration. The Commission is pleased to have had an opportunity to participate in the consideration of this issue of public concern and importance. Respectfully, Morris B. Abram, Chairman 20
Continuing Debate Originally, three main arguments were proposed and publicly debated with regard to rDNA technology. The first argument, titled the "free inquiry principle," stated that rDNA research should not be controlled or restricted—that scientists should have full and unqualified freedom to conduct rDNA research as they saw fit. The second argument, termed the "doomsday scenario," stated that there should be a total ban on rDNA research and it should be halted. Opponents of rDNA technology believed that even with low-risk DNA experimentation there was potential to produce long-term dangers and consequences or even eliminate our entire species and society. The third argument advocated a moratorium. New organisms of any kind or for any purpose would not be created, even if there were no dangerous side effects. In defending rDNA technology, scientists gave three reasons why they believed that the risks of rDNA technology were low. First, genetic engineering techniques allowed the DNA being inserted to be confined precisely to the gene(s) of interest and their controlling elements. Because the chemical sequence of the DNA could be determined before insertion, undesirable traits would not be introduced. Second, virulence in microorganisms requires the operation of many genes. The insertion of a limited number of defined genes would be highly unlikely to cause such a major change to the host organism and the likelihood that a nonpathogenic organism would be converted to a pathogenic one. Third, evolution itself results from the selection of successful mutations that occur randomly in nature. The new rDNA techniques simply increase the rate and precision of such changes, with minimal risk. Proponents of rDNA technology, however, stressed strict care and monitoring each time a new product was released into the environment or a new procedure was conducted. 21
Rifkin on the March In June 1983 activist Jeremy Rifkin and his organization, The Foundation on Economic Trends, issued a resolution on theological issues in genetic engineering
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research. Signed by sixty-three religious leaders and scientists, the basic premise of the resolution was that efforts to engineer genetic traits into the germ line of the human species should not be attempted. Rifkin and his supporters felt that there would be an ecological price to pay if genes were eliminated from the gene pool. Signers of the resolution said they were concerned about the price that would be paid in attempting to perfect the human species.22 Rifkin continued his attempt to stop rDNA experiments and in 1984 he succeeded in temporarily stopping rDNA experiments on potato plants in California. The potatoes were to be sprayed with a bacterium, Pseudomonas syringae, which had been genetically altered to protect the plants from frost. Rifkin and his followers claimed that the "altered bacteria" would cause some plants and insects to grow unpredictably at the expense of others. Launching a lawsuit, Rifkin claimed that the RAC did not have unbiased personnel because all members were molecular biologists except for one terrestrial biologist who had joined the RAC after it had already approved field tests. The lawsuit ended in Rifkin's favor when Judge John Sirica ordered the spraying stopped.
Other Groups Surface In 1984 the RAC created a new group called the Working Group on Human Gene Therapy, later called the Human Gene Therapy Subcommittee (HGTS). The purpose of the organization was to review gene therapy proposals. The first act of the Working Group was to produce the document Points to Consider for Protocols for the Transfer of Recombinant DNA into the Qenome of Human Subjects, a guide for those applying for RAC approval of gene therapy protocols. The group received public comments and by late 1985 the RAC subcommittee had revised the Points to Consider document and was ready to revise gene therapy protocols.
The Sharpies vs. Davis Debate In 1987 Science printed a debate between Frances E. Sharpies and Bernard D Davis, members of the RAC. The debate was over the safety of using genetically engineered organisms in the environment. In the debate, Sharpies advocated regulation of genetically engineered products and stressed evaluation and regulations of both genetic and ecological properties. Sharpies argued that environmental concerns over genetically engineered products were different from the laboratory uses of these products. In making her point, Sharpies stressed that it was necessary to take into consideration all of the human and nonhuman species in an ecological setting that might be exposed to the released organism. In the Science article, Sharpies pointed out that adding new organisms could influence the structure and also the energy of an ecological community. She pointed out that the degree of control was far different between experiments contained in a laboratory and those that involved the release of organisms in the field. Sharpies also emphasized that differences in scale were a factor to consider with "new" releases into the environment. Field testing, she said, was on a considerably
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smaller scale than that on which products are marketed and made available for public use. Sharpies advocated environmental regulations to safeguard against possible environmental problems. 23 Davis, on the other hand, felt that environmental regulations, set by the Environmental Protection Agency (EPA), were "too restrictive and elaborate." He also felt that environmental activists were too influential in setting the agenda of genetic field testing, and he advocated that the scientific community help society distinguish reasonable probabilities from remote fantasies.24
Gene Therapy Protocols On January 19, 1989, the U.S. government signed off on the first approved introduction of a foreign gene into humans—a research protocol that had undergone exhaustive review.25 An experiment to insert genes into humans prompted Jeremy Rifkin and the Foundation on Economic Trends to initiate a lawsuit. As a result, under the terms of the settlement, the NIH agreed to alter the charter of the RAC to make the approval process for gene transfer protocols more openly explicit.26 RAC approval was deemed necessary for gene therapy protocols supported by federal funds. In addition, approval by the U.S. Food and Drug Administration (FDA) was also necessary. It was further decided that approval by the RAC and the FDA could be obtained simultaneously or sequentially, in either order. The FDA focused on the safety of the manufacturing process, the safety and efficacy of the genetically altered products, and on control of the final product. In 1991, the FDA published its revised Points to Consider in Human Somatic Cell Therapy and Qene Therapy. It revised the document again in 1993. In December 1992 Dr. Bernadine Healy, then Director of NIH, approved a "compassionate use exemption" from the regular review process, allowing a critically ill patient to receive gene therapy. The compassionate use exemption, rather than the regular approval process, proved to be very controversial and, as a result, additional meetings were required to create RAC procedures for dealing with expedited review of single patient protocols.
President Clinton's National Bioethics Advisory Commission In October 1995 President Clinton issued an executive order that established the National Bioethics Advisory Commission (NBAC). The purpose of the eighteenmember commission was to make recommendations to the National Science and Technology Council and other government entities on bioethical and behavioral research. The NBAC focused its efforts on protecting the rights and welfare of human research subjects. In addition, it managed information, genetic privacy and confidentiality, and gene patenting. In February 1997 President Clinton requested that the NBAC thoroughly review the legal and ethical issues associated with the development of techniques to clone sheep, and in May of 1997 the President extended the NBAC's charter until 1999.
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Social Implications of rDNA Technology Social implications erupted when rDNA technology was in its infancy In a relatively short time, rDNA technology had a major impact on the knowledge of the structure and function of genes. Today, rDNA technology and the rest of the biotechnology industry are where the petrochemical and nuclear industries were over half a century ago. The experiences in those fields have been extremely valuable. The recent contribution of rDNA technology to the health of people worldwide cannot be questioned. Potential uses of rDNA technology in virtually every area of medicine, biology, and agriculture seem even more promising now than before. It is difficult for this author to envision a disease or ailment that could not be treated or cured by rDNA technology. In addition, rDNA technology has provided a way to isolate large quantities of specific segments of DNA in pure form. With that knowledge, rDNA techniques have provided understanding of antibiotics, vitamins, and hormones, as well as medically and industrially useful chemicals. A newly approved genetic test may soon eliminate the guesswork in prescribing many drugs. The AmpliChip CYP450 has been cleared for use by the U.S. Food and Drug Administration and will be used in June 2005. It is the first test to allow doctors to tailor medication doses to a patient's genetic makeup. The matchbox-size device was developed by Roche Molecular Systems, a division of Swiss pharmaceutical giant F. Hoffmann-LaRoche. Instead of circuits, the chip contains millions of DNA molecules to analyze genetic material from a patient's blood. DNA is extracted from the patient's blood and applied to the chip. A computer scans the chip and generates a detailed report. The AmpliChip CYP450 zeros in on two genes, 2D6 and 2C19, which regulate the enzymes that the liver produces to metabolize certain drugs, including the breast cancer drug tamoxifen, antidepressants, beta blockers used for hypertension, anti seizure medications, and others. In addition, the test can identify the rate at which drugs are cleared from a person's body. The test has the potential to determine how well a person will do on a specific drug. At one time, there was a charge that DNA technology would lead to genetic stigmatization and that rDNA technology would divert funds and attention from much-needed health needs. One example shows that this is not true is sickle-cell anemia, found mainly among black people, and which can be diagnosed in utero only by D N A technology. Overall, few, if any, have raised the issue of "stigmatization" with regard to sickle-cell anemia or other genetic diseases diagnosed by rDNA technology As rDNA technology grew, the U.S. government had to decide whether it should take control of the technology, particularly since public funds supported the basic research that had originally spawned rDNA technology. As a result, it became increasingly necessary to see that social priorities were set up so that the public would gain the advantages of rDNA technology. This was particularly necessary because if social priorities were not set, the public would lose some important applications of rDNA technology, simply because private companies found them unprofitable. During this time, many questioned whether and why
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the free market should decide which genetically altered organisms were produced. Several important questions surfaced, including but not limited to: • Would new genetically altered agricultural products be priced so that small farmers could take advantage of them? • Would society be protected from inadvertent secondary impacts of new products and processes, an ever-increasing reliance on drugs, or changes in the dependency on chemicals for agriculture? • What ethical considerations would be applied when considering the treatment of disease or in conjunction with reproductive experimentation? The U.S. government determined that social responsibility for developing rDNA technology also involved the Third World. Most scientists agreed that the United States should share with those countries the benefits of the new technology, aware that neglecting the needs of Third World economic systems and starting a cycle of negative feedback would leave those countries even more dependent on developed nations for aid. However, U.S. scientists were also concerned that cultural norms of Third World countries not be hurt or destroyed nor their capacity for self-determination inhibited.
Biological Warfare As the United States and the Coalition continue to wage aggressive action against world terrorism, many ask: What assurances do we have that rDNA technology will not be used in the development of weapons for biological warfare? The biological, chemical, and nuclear weapons scenario reminds us once again of how well-intentioned scientific advances, such as rDNA technology, may grant human beings such vast powers that they endanger our fundamental political and social values. Such power has haunted the development of rDNA research since its inception in the 1970s. Recent completion of the Human Genome Project (HGP) has made it possible to determine microbial gene sequences and to discover information we never before thought possible. Whereas some have hailed rDNA technology as a huge step for molecular genetics responsible for creating insulin, interferon, and other medications, others fear it has opened a Pandora's box. Some question whether rDNA technology is a rash act with unpredictable consequences and an instrument that the strong may impose on the less powerful. Opponents demand assurances that the technology will not be used for biological warfare or for sinister abuses of biopharmaceutics by evil dictators. We can look back and evaluate the 1975 Asilomar Conference that began as a scientist's strategy conference and evolved into a public-policy process involving not only 150 scientists but also a small group of lawyers and journalists. One of the most consequential criticisms of Asilomar was that it was public decision making without appropriate public access—a power play by special interest groups.
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Yet, in retrospect the primary motive for the conference was biohazard (risk). Perhaps the greatest potential for biohazard was related to possible military applications. At that time, panel members suggested an international treaty to prevent their construction. 27 Others wondered if the NIH Quidelines were strong enough to hold the military establishment accountable. After considerable discussion, it was concluded that unless nations were willing to forgo some of their rights of sovereign immunity, it was doubtful that adequate verification would be possible under even the best of guidelines. The major controversy over rDNA technology centered around unforeseen risks—for example, whether microorganisms that were genetically modified in a lab might escape and become dangerous to the general population. Other concerns were raised; however, organizers decided to concentrate entirely on the risk of escape. The problem was exacerbated because scientists not only were unable to quantify the odds of harm occurring; they could not predict the type of harm that might occur. At the time, the possible release into the environment of designer microorganisms was known to be very real, creating an important debate over safety. In 1987 a statement was issued by the Scientific Committee on Problems of the Environment and the Committee on Genetic Experimentation: "The environmental introduction of any organism should be undertaken within a framework that maintains appropriate safeguards for the protection of the environment and human health while not discouraging innovation." 28 We know well the possibilities of such an undertaking in the hands of dictators such as Iraq's past leader, Saddam Hussein. Genetically designed microorganisms can be made even more efficient than natural diseases at killing and disabling the enemy. In the past, Saddam Hussein and others have used ethnic weapons (pathogenic microorganisms that have been genetically modified) to infect and kill racial and ethnic groups. Recent advances in rDNA research and terrorism worldwide have made possible genetically transformed organisms ("designer bugs") packed with genes that simultaneously signal millions of human cells to commit suicide or wipe out the human immune system. Microorganisms that cause smallpox, botulism, tularemia, cholera, Q fever, and brucellosis are long-standing lethal favorites of bioweaponeers such as Dr. Hudah Ammash of Iraq, trained as a microbiologist in the United States and a prominent member of Saddam Hussein's inner cabinet. In effect, scientists such as Dr. Ammash are able to modify ordinary microbes, turning them into extra-virulent, drug-resistant superbugs. Such modifications of microbes make them harder to detect, diagnose, and treat, but they are also more useful militarily. Various other countries have been successful in creating "designer bugs." For example, Russian researchers in 1987 created a new form of anthrax. Funded by six federal agencies on the heels of the Human Genome Project, the new altered form of anthrax was developed at the State Research Center for Applied Microbiology in Obolensk, Russia. The research was formally published in December 1997 in the British scientific journal Vaccine. It is unclear why the Russian researchers developed the new organism—whether it was for offensive or defensive purposes. At the time, the Russian Federation was
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a signatory to the 1972 Biological Weapons Convention banning the development, production, and stockpiling of biological and toxin weapons. The Convention had no provisions for enforcement; however, the U N Secretary-General possessed the authority to investigate complaints of violations. Development of a new strain such as the Russian anthrax through rDNA technology is something that biological warfare experts around the world have feared since the advent of rDNA technology. Currently, a dozen or more countries are believed to have the capacity to load weapons with dry, powdered anthrax, a disease that can cause severe illness and death in humans and animals who inhale the spores in large doses. In assessing the risks of rDNA technology, society must decide whether the burden of proof will be on those who demand evidence of safety, or on those who demand evidence of hazard. The former countries will halt experiments until they are proven safe, whereas the latter countries will continue until they are proven harmful. Unless certain nations are willing to forgo some of their rights of sovereign immunity, it is doubtful that adequate verification would be possible under even the best of guidelines. As public and private individuals, most people strive to better their lives materially, biologically, intellectually, and emotionally. As a society, humans with knowledge of rDNA can, with various resources, promote their perception of a common good. Even more so, we can strive to make the world a better place for all societies.
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3 T H E B D D K D F LIFE The Human Genome Project None of us so privileged few who first saw the double helix in the spring of 1953 ever contemplated that we might in our lifetime see it completely decoded. James Watson, Nobel laureate and codiscoverer of the DNA double helix
In April 2003 the Human Genome Project (HGP), also known as the "Book of Life" and the "Human Genome Initiative" was completed to an accuracy of 99.9 percent, coinciding with the fiftieth anniversary of Watson and Crick's elucidation of DNA. A rough draft of the human genome was partially completed in the year 2000, but that draft included thousands of gaps in the long sequence of DNA base pairs. With the April 2003 completion, only 400 gaps remained open, down from 250,000. The human genome (the total amount of genetic material in a cell) is composed of about three billion pairs of DNA chemicals. The genes that control the body's growth, development, functions, and aging are made of specific sequences of these chemical or base pairs. Even a small change in one or more of these sequences may cause disease.
Spectacular Project The HGP was a multinational project aimed at obtaining a detailed map and a complete sequence of the human genome. The human DNA used for the HGP was almost exclusively from people of Europe or North America because those
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were the places where most HGP researchers lived. When the preliminary completion of the HGP was announced it was viewed as a spectacular event, one that exceeded expectations. "The newly completed sequence of the human genome is now on parade for the whole world to see. However, it may be as striking for what we don't see as what we do." 1 The HGP was hailed as the largest and most expensive study of biology conducted since the Apollo project and the race to send a human to the moon. Not only the U.S. government but governments around the world raced to map the location of what was then estimated to be 100,000 genes on chromosomes. Billions of dollars were devoted to the project. Inclusion of the word "human" in the name Human Genome Project does not accurately reflect the initiative, however, because the HGP was not exclusively a study of humans. The first genome project completed was that of the bacterium Haemophilus influenzae. Since then, the genomes of several other well-known organisms have been examined along with those of humans, including the common intestinal bacterium (Escherichia coli); yeast (Saccharomyces cerevesiae), the first eucaryotic genome completed in 1996; the fruit fly (Drosophila melanogaster); the roundworm (Caenorhabditis elegans); and the laboratory mouse. In particular, the mouse genome has provided an excellent approach to interpreting human genomic information, because many genes were conserved between the two species, as was gene order along some chromosomes. The mouse genome is about the same size and 85 percent identical to the human genome. Such information was deemed useful because it aided in the identification, characterization, and understanding of genes that directly and indirectly lead to human disease. The International Mouse Mutagenesis Consortium has created approximately 5,000 mutant mouse strains carrying genes for diseases resembling human diseases such as sickle-cell anemia and colorectal cancer.
A Solid Foundation Watson and Crick's discovery of the helical structure of DNA in April 1953 and the explosive development of cytogenetics from 1959 and somatic cell genetics from 1964 provided a solid foundation on which progress toward a human gene map could be made. These scientific discoveries, followed by the advent of rDNA technology in the early 1970s, made it possible to think of isolating individual genes. Those breakthroughs, combined with powerful DNA sequencing techniques developed by Allan Maxam and Walter Gilbert at Harvard University and Frederick Sanger at the United Kingdom's Medical Research Council (MRC), provided the technological basis for the HGP. In 1980 David Botstein of the Massachusetts Institute of Technology, Ronald Davis of Stanford University, and Mark Skolnick and Ray White of the University of Utah, proposed a method to map the entire human genome. Recombinant DNA (rDNA) technology enabled the cloning of DNA fragments. By 1985 the technology scientists were able to extract individual X and Y chromosomes. In 1986 the phenomenon of gene shuffling ("genes that jump") was announced by Dr. Barbara McClintock, proving that the genome was unstable. In 1960
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McClintock had come across a paper, coauthored by Francois Jacob and Jacques Monad, published in a French journal. Jacob and Monad had proposed a system called the "operon" that was composed of a structural gene and a regulator gene.2 McClintock won the Nobel Prize for her work—the first woman to win it alone for medicine. Detailed human genetic mapping and family pedigree analysis, a very important tool for the analysis and diagnosis of human genetic diseases, was initiated in 1986, allowing genes to be identified quite rapidly. The same year, Duchenne and Becker's muscular dystrophy genes were identified, entering a new era of medical treatment and diagnosis. About the same time, construction of an E. coli clone library was begun in order to analyze the E. coli genome. This included the construction of artificial chromosomes that replicated in yeast, allowing large fragmentation of genes.3 Small groups throughout the world worked to find chromosome markers for linkage analysis. Two groups, under the direction of Ray White at the University of Utah's Howard Hughes Medical Institute and Helen Donis-Keller at Collaborative Research outside Boston, began large-scale efforts. In 1987, the DonisKeller group published a linkage map of the human genome. 4 In 1988, the DNA polymerase chain reaction (PCR) was introduced, allowing rapid amplification of short regions of DNA with great ease.5
A Short History of the HGP The HGP was widely discussed within the scientific community and public press during the last half of the 1980s. When Robert Sinsheimer, then chancellor of the University of California at Santa Cruz, first got the idea to determine the complete nucleotide sequence of the human genome in 1985, he decided to invite some of the world's best scientists to the Santa Cruz campus. Among those invited to the May meeting were genetic mapper David Botstein of the Massachusetts Institute of Technology (MIT); Robert Waterston of Washington University in St. Louis; John Sulston of Cambridge University; Bart Barrell, head of the sequencing unit at the MRC; Helen Donis-Keller of Collaborative Research, Inc.; sequencing experts George Church and Walter Gilbert of Harvard University; and Leroy Hood of the California Institute of Technology in Pasadena. There were some skeptics among the outstanding scientists at the Santa Cruz meeting. One of the skeptics was Hood, who thought the proposed HGP seemed to be a huge science project with minimal value to the science community. Nobel laureate David Baltimore, then director of MIT's Whitehead Institute, and Botstein were among others who expressed doubts about the project. They feared that such an extensive project would have the same impact on science that the shuttle had on the space program—taking away significant amounts of money and scientific talent from smaller, yet vital, projects. Others questioned the value of undertaking a complete sequencing of the genome, especially given the high proportion of noneugenic sequences. The HGP evoked various questions, which included invasion of privacy, abortions, discrimination of the unfit, the right to know, and eugenics.6
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Despite some skepticism at the initial meeting to discuss the HGP, participants gave strong support to proceeding with the complete sequencing of the human model-organism DNA. Not surprisingly, a major concern was financing. Even so, most participants felt that there was technology enough to complete the HGP in reasonable time and at a reasonable cost. Overall, participants at the meeting felt that the proposed research was critical, that genomic sequence for most model organisms was cost effective, and that the proposed overall HGP goals were attainable. Dr. James Watson, Nobel laureate and codiscoverer of the double-helical structure of DNA, was singled out as the movement's most distinguished and creditable advocate. Participants at the initial meeting felt that the Department of Energy (DOE) and the National Institutes of Health (NIH) should be the main research agencies within the U.S. government responsible for developing and planning the HGP. The NIH had a long history of supporting research in genetics and molecular biology, as well as having the integral mission of improving the health of all Americans. However, the possibility of a highly visible health-related program operated by the DOE proved both irritating and stimulating to some individuals at the NIH. In addition to genome research programs at NIH and DOE, other U.S. groups were involved in the HGP project from early on: the Howard Hughes Medical Institute (HHMI), the National Science Foundation (NSF), and the Department of Agriculture. HHMI had a particularly strong interest in genetics and employed some of the best human genetics investigators in the United States. The DOE had earned a reputation as a credible player in genome work on chromosome sorting, computer-based DNA sequence informatics, and mouse genetics. Yet, despite their long-standing program of genetic research directed at improving the ability to assess the effects of radiation and energy-related chemicals on human health, many questioned why was the DOE was involved in the HGP. Some pointed out that the problem of detecting inherited mutations in humans had worried the DOE since the Manhattan Project and the U.S. use of atomic bombs against Japan at Hiroshima and Nagasaki in August of 1945. A meeting had been held in Alta, Utah, in December 1984 to assess how direct analysis of DNA might be useful in detecting mutations among atomic bomb survivors.7'8 As part of the planning process for the DOE program, Los Alamos National Laboratory organized a workshop in Santa Fe, New Mexico, in March 1986 to discuss plans to sequence the human genome. Workshop participants were enthused about the proposed DOE Human Genome Initiative and endorsed the HGP. The first published proposal for the HGP was an independent editorial by Renato Dulbecco, President of the Salk Institute at San Diego, in which he suggested that the fundamental problem of cancer could be studied by first determining the sequence of the entire human genome. Dulbecco's proposal was published the same week in March 1986 as the Santa Fe meeting. 9 In June 1986 at the Cold Spring Harbor symposium on the Molecular Biology of Homo sapiens, Walter Gilbert and Paul Berg cochaired a session on the HGP. Both Berg and Gilbert voiced substantial enthusiasm for a genome project growing out of the Santa Cruz and Santa Fe meetings. However, once again there was a great deal of skepticism voiced as to whether the DOE was the appropriate agency to direct such an effort. Others questioned whether a sequencing research
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project made technical sense. Because of its acrimonious tone, the meeting and its participants received widespread scientific press attention. As a result of intense interest, the National Research Council (NRC) of the National Academy of Sciences commenced a study in late September 1986. Soon after the Cold Spring Harbor meeting, several other meetings were scheduled near Washington, D.C., to discuss the HGP. Two of these were large international meetings attended by invited participants. The first was convened in August by the HHMI and was intended to discuss whether and how HHMI might contribute to a large international genome project. 10 Another meeting was held by the NIH in October to discuss the HGP's primary role. 11 The NRC met several times during 1987 and issued a report in February 1988 that argued strongly for a broader HGP. Bruce Alberts, the committee chair, had in 1985 written an editorial highly critical of big science in biology.12 The committee included several members who were very skeptical of genome proposals. Nonetheless, they were convinced of the merits of the HGP and forged a consensus by embracing work on nonhuman organisms and genetic linkage mapping. After deliberations, committee members recommended a new, dedicated genome research budget of $200 million per year for fifteen years. In the spring of 1987, a Report on the Human Qenome Initiative was prepared by the Health and Environmental Research and Advisory Committee (HERAC) of the DOE. By 1988, the DOE and NIH were working together in a fairly harmonious relationship that resulted in the publication of two widely circulated, influential reports. The House Committee on Energy and Commerce commissioned a report by the Office of Technology Assessment (OTA). Released in April 1988, the OTA report presented a comprehensive and detailed analysis of the scientific developments that had led to mapping and sequencing the human genome. The OTA report noted that the debate over the HGP was not about whether the research should go forward, but how it should be managed and who should coordinate it. The publication presented a number of options as to how the United States might pursue such a project. 13 The second publication, the National Research Council Report, recommended that the United States support the human genome research effort. The report outlined a multiphase research plan for sequencing human DNA over two decades. A report to the director of the NIH by the Ad Hoc Advisory Committee on Complex Genomes, also prepared in 1988, concurred with the NRC report. At the time the NRC and OTA reports were written, the scientific community believed that the art technology was sufficient to develop detailed genetic maps, but only limited physical maps of the HGP, because the genome was so large and complex. The scientific community continued to have concerns that there was not technology available for DNA sequencing the estimated three billion base pairs of human DNA. Because of this, the NRC committee and others recommended a multiphase program. Charles DeLisi of the DOE was very enthused about the HGP and conceived of a three-pronged research program that advocated advanced DNA sequencing technology, computer analysis, and methods to order DNA fragments cloned from the human genome. In 1987, DeLisi began a research program focused on these objectives and called the DOE Human Genome
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Initiative. This was the first government program on genome research, and it successfully catalyzed a vigorous debate in the United States and other nations. 14 By 1988, the DOE and NIH were making substantial scientific progress. Their solid relationship was formalized by the signing of a Memorandum of Understanding to "coordinate research and technical activities related to the human genome." 15 That same year, the U.S. Congress appropriated funds to both the D O E and the NIH for research efforts to determine the structure of complex genomes. In addition, the U.S. Congress also requested the NIH to prepare, by early 1990, a report on the optimal strategy for the conduct of the HGP; and the FY 1990 House Appropriations Committee Report asked the NIH for a comprehensive spending plan which was to be completed in time for the FY 1991 appropriation hearings. 16 In March 1988, NIH director James Wyngaarden, at a meeting held in Reston, Virginia, announced the creation of a special office for genome research. This was followed in June 1988 by the first annual genome meeting at Cold Spring Harbor Laboratory. In September 1988 the NIH established the National Center for Human Genome Research and appointed Nobel laureate James D. Watson as its head. Watson announced that 3 percent of the genome budget would be devoted to studies of social and ethical issues and that the primary goal of the first stage of the project would be to build maps of the human chromosomes. Watson declared that the project would be completed in five years. With his appointment and substantial leadership, the NIH moved ahead of the DOE. In October 1988, prior to the actual start of the HGP, a Workshop on International Cooperation for the Human Genome Project was held in Valencia, Spain. Fearing hazards that might lead to "Nazi-like atrocities," French researcher Jean Dausett asked for a moratorium on genetic manipulation of germ cells and on gene transfer experiments in embryos. However, Norton Zinder of Rockefeller University argued that the workshop had no actual authority to make the moratorium stick. As a result of Zinder's arguments, workshop participants drafted a resolution that called for international cooperation for the project. 17 At the meeting, participants supported Director-General Frederico Mayo's initiative and agreed that the United Nations Education, Scientific, and Cultural Organization (UNESCO) could help facilitate international cooperation. Following the workshop, Dr. Mayo assembled an advisory group of scientists to consider the role that UNESCO might play in the advancement of the HGP. 18 In January 1989 Zinder chaired the first program advisory committee meeting of the HGP. At that time, scientists quickly moved ahead by initiating the $3 billion HGP project, with the ultimate goal of detailing the entire genome. In addition, the U.S. Congress in 1989 approved $53 million following Watson's plea for financial support for the HGP. In October the NIH office was elevated to the National Center for Human Genome Research (NCHGR), with grant-awarding authority. A month later, the first NCHGR meeting was held in Paris. Overall, the DOE and NIH developed a well-integrated plan for carrying out the HGP initiative. During that time, the two agencies established joint working groups on mapping, informatics (dealing with databases and computational analysis), and social, ethical, and legal implications of genome research. The two agencies also agreed to
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notify one another about funding decisions regarding grant proposals reviewed by both agencies. In 1990-91 a program on the HGP was subsequently approved by the participants at the Twenty-fifth General Conference. Dr. Frederico Mayo set up a Scientific Coordinating Committee (SCC) to help plan and implement the program as proposed in the Moscow recommendations. The first meeting of the SCC was held at UNESCO headquarters in Paris, France, on February 1, 1990. A second consultative meeting was held in Moscow the following June in parallel with the Human Genome Organization (HUGO). At that meeting a number of conclusions were reached: first, full knowledge of the human genome was of vital importance and the medical, technological, scientific, and ethical implications of the program were inseparable; second, establishment of the program should be supported by governments; third, the influence of international organizations such as UNESCO and H U G O was recognized; and finally, it was acknowledged that UNESCO was in a unique position to promote interest in the HGP in developing countries. In April 1990 NIH and DOE together submitted a publication of a five-year joint research plan—an unprecedented accomplishment. 19 In August 1990 the NIH began large-scale sequencing trials on four model organisms, and the two agencies declared October 1 to be the official beginning of the HGP. Meanwhile, scientists were making substantial progress in their genome studies. By 1990, Sulston and his Cambridge University team were nearing completion of the physical map of the worm, and Maynard Olson and his team at the University of Washington-Seattle, were making progress on mapping yeast genes. In June 1991 Craig Venter, who ran a sequencing lab at the National Institute for Neurological Disorders and Stroke, announced that he and his colleague Mark Adams had developed a new technique (expressed sequence tags) that enabled them to quickly find genes. Venter and his colleagues also announced plans to patent the genes that they had found. However, at a congressional hearing, Watson called Venter's proposed patent "sheer lunacy" and a fight erupted. As a result of the disagreement, the NIH eventually withdrew its patent application. Venter left his position at the NIH in 1991 and with his second wife—Claire Fraser, a prominent molecular biologist—formed The Institute for Genomic Research (TIGR), a nonprofit company in Rockville, Maryland. They obtained long-term funding of $70 million from biotech entrepreneur Wallace Steinberg, with the understanding that any genes the company decoded would go to Human Genome Sciences, a company led by former AIDS researcher William Haseltine. Meanwhile, at the NIH, Watson was fighting with his boss, Dr. Bernadine Healy. As a result of that dispute, Watson left his job and returned to the Cold Spring Harbor Laboratory in April 1992. On May 12-15, 1992, the First South-North Genome Conference was held in Caxambu, Brazil. Approximately 200 participants from 22 countries assembled to design strategies that would enable developing nations to participate in the HGP. Main conference sponsors were UNESCO and the Brazilian Society of Biochemistry and Molecular Biology. Sergio Pena of the Federal University of Minas Gerais chaired the organizing committee. A number of international and Brazilian agencies provided financial support.
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In October 1992 U.S. and French scientific teams completed the first physical maps of chromosomes. David Page and his colleagues at the Whitehead Institute mapped the Y chromosome, and Daniel Cohen and his colleagues of the Centre d'Etude du Polymorphisme Humain (CEPH) and Genethon mapped chromosome 21. In April 1993 Francis Collins of the University of Michigan-Ann Arbor was named director of NCHGR. Recognized as a very successful scientist, Collins had discovered the genes for cystic fibrosis, Huntington's disease, neurofibromatosis, and a form of inherited breast cancer. O n April 23-24, 1993, the NIH NCHGR held a meeting in Hunt Valley, Maryland. At that time, participants decided on a number of topics: first, to appraise project accomplishments that were likely to be achieved by the end of the initial five-year phase; second, to generate creative and novel ideas for building on this progress to meet long-range goals; and third, to consider ways in which the project could most effectively and broadly benefit present and future research in biology and medicine. In October 1993 the NIH and DOE published a five-year revised plan (1993-98) that included completing the human genome by 2005. That same month the GenBank database officially moved from Los Alamos to the National Center for Biotechnical Information (NCBI), ending the NIH's and DOE's battle over control. In September 1994 Jeffrey Murray of the University of Iowa and Cohen and his colleagues at Genethon published a complete linkage map of the human genome. The year 1995 proved to be very productive for the HGP. Sequencing dyes were developed in mid-1995, and in August thermostable polymerase was developed. In July 1995, Craig Venter, Claire Fraser, and Rob Fleischmann of TIGR, along with Hamilton Smith at Johns Hopkins University, published the first sequence of a free-living bacterium, Haemophilus influenzae. The accomplishment, they reported, was done in twelve months using a bold new approach, whole-genome shotgun sequencing—a procedure that previously had been rejected by the NIH. In October 1995 Patrick Brown and his team at Stanford University published their first paper describing a printed glass microarray of complementary DNA (cDNA) probes. In December Eric Lander and Thomas Hudson published a physical map of 15,000 markers in the human genome, and by the end of 1995 the Japanese government had funded several sequencing groups at the University of Tokyo, Keio University, and Tokai University. In February 1996, at a conference in Bermuda funded by the Wellcome Trust, it was agreed that sequence data would be released into public databases. This was followed in April of that same year with funding of six groups by the NIH for large-scale sequencing of the human genome. The DOE also initiated six pilot projects, funded at a total of $5 million. In October 1996 an international consortium publicly released the complete genome sequence of the yeast Saccharomyces cerevisiae, and in November Yoshide Hayashizaki's group in Japan completed the first set of full-length muscle cDNAs. January 1997 saw the N C H G R promoted to the National Human Genome Research Institute, 20 and the DOE created the Joint Genome Institute. In September of that year, the DNA sequence of the bacterium E. coli was completed by Guy Plunkee and Fred Blattner at the University of Wisconsin at Madison. In
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February 1998 representatives of the United States, Japan, the European Union, China, and South Korea established guidelines for an international collaboration to sequence the rice genome.
An Intense Feud In May 1998, just days before the annual meeting of genome scientists at Cold Spring Harbor Laboratory, an intense scientific feud erupted between Francis Collins, director of the NIH's National Human Research Institute (NHGRI) and the HGP's official head, and J. Craig Venter, CEO of Celera Genomics, an independent genome-sequencing company. Venter announced that his newly formed company, Celera Genomics, planned to sequence the human genome within three years, at a price approaching $300 million. This was possible, he said, because Celera had teamed with Perkin-Elmer Corporation, which had designed the whole genome shotgun fragmentation method. The HGP team, on the other hand, was more conservative, saying that it planned to use landmark maps. At about the same time, the Wellcome Trust announced that it was doubling its financial support for the HGP to $330 million, amounting to about one-third of the sequencing. Venter and Collins were both deeply involved in sequencing DNA. Their main differences centered around who should get credit from the scientific community for the DNA sequencing. Venter had made a number of enemies—in addition to his feuding with Collins, he had angered James D Watson. Addressing a Senate hearing panel, Watson referred to Venter's work as sloppy and nonscientific, and implied that the new instrumentation made possible by Celera "could be run by monkeys." (Later, however, Watson recanted his statement.) Others, including William Haseltine, CEO of Human Genome Sciences and a partner of Venter's until 1997, accused Venter of egotistical motives in decoding the human genome. In September 1998 Collins, on behalf of the NIH and DOE, announced they were moving the completion date of the HGP draft from 2005 to 2003; and in December John Sulston of the Sanger Centre and Robert Waterston of Washington University completed the genomic sequence of the organism Caenorhabditis elegans. With no visible signs of the feud ending, in July 1999 Eric Lander of the Whitehead Institute offered to mediate a truce between Collins and Venter. In December 1999 they met at Celera headquarters; however, a truce could not be affected. Another attempt at a truce was planned. In March 2000, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, and Richard Klausner, director of the National Cancer Institute, met with Collins and Venter in Bethesda, Maryland. Once again, an agreement could not be reached. The NIH launched a project in September 1999 to sequence the mouse genome, devoting $130 million over three years. In December U.S., British, and Japanese researchers completed the first sequence of chromosome number 22. The NIH again moved the rough draft to spring 2000, and by March 2000 Celera and its collaborators had sequenced the genome of the fruit fly, Drosophila melanogaster—the largest genome yet sequenced. This was highly significant
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because D. melanogaster is an organism whose genes have many counterparts in humans. Wanting to show off his shotgun method of sequencing, Venter teamed with Gerald Rubin and his team at University of California at Berkeley. The feud continued to intensify with no signs of resolvement until on April 7, 2000, President Clinton issued a proclamation for the feud to end. On April 10, Aristides (Ari) Patrinos, a mediator at HGP's DOE, requested a meeting between Collins and Venter in neutral territory. On May 7, 2000, Collins and Venter met at Patrinos's town house, but still they could not come to an agreement. A second meeting at Patrinos's home ended in an informal agreement that Venter and Collins would coordinate their announcements. However, they did not agree to face the press together. Venter and Collins met again, once on May 30, 2000, and again on June 21, 2000, at Patrinos's home. At this time, Collins and Venter finally came to a workable agreement that each would get credit for sequencing and deciphering all 3.1 billion biochemical "letters" or base pairs of human DNA. In addition, they agreed to publish their work simultaneously in a major journal. (Eventually, however, each published in different journals, Venter in Science and Collins and HGP in Nature.) They also agreed to stop criticizing each other publicly.
Goals of the HGP The original HGP plan consisted of a set of specific goals for the first five years of the research project that focused the efforts of the research community on the most important initial objects. 21 Overall project goals were to: • identify all the estimated 100,000 genes in human DNA • determine the sequences of the 3.1 billion base pairs of nucleotides that made up the twenty-three human chromosomes that comprised the human genome • store the information in databases, develop tools for data analysis, and • address the ethical, legal, and social issues that might arise from the project. Four subgoals were also determined. The first subgoal was a comprehensive genetic map based on pedigree analysis. The second subgoal was a physical map of the distances between genes. (This was measured using the tendency of a gene to link to those around it.) The third subgoal was a transcript map of the location of genes in the human genome. The fourth subgoal was the gene sequence—a list of base pairs that made up a specific gene. When the initial goals were adopted in 1990, it was understood that achieving them would require a significant degree of improvement in technology and methodology in both molecular genetics and instrumentation. This would require improvements in storage, retrieval, and analysis of mapping and sequence information (informatics) to make data usefully available as required. By September 1990 the sequences of over 5,000 human genes had been realized, as well as the location of 1,900 genes to areas of specific chromosomes. 22
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The 1990 plan was updated in 1993 by extending the initial goals of genome research through September 1998. Designed to address both long-and short-term needs, the updated plan extended research goals in established categories. It also added specific new goals for developing technology for gene identification and mapping. This included mapping and sequencing the human genome; mapping and sequencing the genomes of model organisms; data collection and distribution; ethical, legal, and social considerations; research training; and technology development and transfer.23
Funding the HGP In the late 1980s, Congress appropriated funds to the NIH and DOE to establish the HGP and map genetic information. A portion of the funding was directed to establish the Ethical, Legal, and Social Issues (ELSI) program, a working group to address the legal, ethical, and social ramifications associated with the HGP. As a result, the HGP made a commitment to devote approximately 5 percent of its budget to research aimed at anticipating and resolving the ethical, legal, and social issues that might arise from the genome research. The United States took the lead with goals of as much as $200 annually adjusted for inflation.24'25 Although this amount was assumed when the initial goals were developed and implemented, appropriations never reached that level. Total funding rose from about $47 million in 1987 to around $182 million in 1995.
U.S. Genome Centers and Programs Large-scale sequencing of the HGP became concentrated in a small number of genome centers and programs in the United States. In 1989 the National Center for Human Genome Research (NCHGR) was one of twenty-four institutes, centers, or divisions established by the NIH. The NCHGR had several administrative units in its organization—the Office of the Director, the Division of Extramural Research (DER), and the Division of Intramural Research (DIR).26'27 The NCHGR Division of Intramural Research also sponsored a number of student training programs, including summer internships, post-baccalaureate trainee ships and a graduate program in genetics at George Washington University. The NCHGR supported numerous grants aimed at cultivating minority participation in genome research, such as the minority travel awards and the minority research supplements. These programs impacted a wide range of participants, since they were aimed at both students and faculty members. By disseminating information about the HGP and its technologies across the country, NCHGR hoped to foster minority student interest and participation in genetic research. The Ethical, Legal, and Social Implications (ELSI) Branch was responsible for research to analyze the legal, ethical, and social issues that arose from human genome research and to ensure that the information was used responsibly. In addition, ELSI fostered research and programs to improve public and professional education with regard to ethical, legal, and social issues.
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The Mammalian Genomics Branch was responsible for research directed to the construction of complete genetic and physical maps of individual mammalian chromosomes and genomes. In addition, it was responsible for accurate sequencing of large (megabase) regions of mammalian DNA. This branch was also responsible for the administration and support of research in genome informatics, including database research, development and maintenance of databases of genome information, and research into techniques for genomic analysis. The Mammalian Genomics Branch also supported policy development for the Genome Science and Technology Centers (GESTEC) program. The Mapping Technology Branch was responsible for the development of technology to improve the resolution, information content, and utility of genomic maps, including both genetic maps and physical maps. Specific areas of interest included new or improved methods for the construction and annotation of genetic and physical maps, and techniques and strategies for efficient identification of genes, coding regions, and other functional elements on a high-throughput, genome-wide basis. The Branch was also responsible for extramural training, career development, and special programs. Accordingly, the branch planned and administered programs of individual pre- and post-doctoral fellowships, institutional training grants, career awards, minority programs, international programs, short courses, and scientific meetings. The Sequencing Technology Branch was responsible for research to develop new methods, technologies, and instruments for fully integrated, innovative approaches to rapid low-cost determination of DNA sequence. Areas of interest included both refinement and full automation of current methods of DNA sequencing and novel approaches to achieve order-of-magnitude improvements in sequencing capability. The Sequencing Technology Branch also supported research to develop maps and genomic DNA sequence of non-mammalian organisms. This branch was also responsible for technology transfer activities, and promoted collaborative, multidisciplinary programs that closely integrated research projects at academic and industrial laboratories. The Diagnostic Development Branch focused on the molecular characterization of human development disorders. This branch was specifically interested in the mechanisms and consequences of chromosomal abnormalities that produced specific mental retardation syndromes due to gene dosage imbalance and genomic imprinting effects. It used positional cloning strategies and genome technologies to clone and characterize specific chromosomal regions and genes responsible for the disease phenotype. The Human Genome Education Program (HGEP) operated within the Stanford University Human Genome Center. It was a collaborative effort among HGEP, Genome Center scientists, collaborating staff from other education programs, experienced high-school teachers, and an advisory panel in the fields of science, education, social science, assessment, and ethics. The primary objectives for HGEP were to develop a human genome curriculum for-high school science and to provide education outreach to schools and community groups in the San Francisco Bay area. The Lawrence Berkeley National Laboratory's Human Genome Educators Program, sponsored by the Lawrence Berkeley National Laboratory's Human
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Genome Program, was an information network of education professionals with an active interest in all aspects of genetics research and education. This national group included scientists, researchers, educational curriculum developers, ethicists, health professionals, high-school teachers and instructors at college and graduate levels, and others in occupations affected by genetic research. Genome Educators was a unique collaborative effort dedicated to sharing information and resources to further the understanding of current advances in the field of genetics.
International Genome Centers and Programs In many countries worldwide, active genomic research was also being pursued by researchers and science funding agencies at both public and private institutions. Programs varied in the countries involved, depending on their particular concerns, capabilities, and funding. Some of the larger programs, in addition to those of the United States, were in Brazil, Canada, China, Denmark, the European Union, France, Germany, Israel, Japan, Mexico, the Netherlands, Russia, Sweden, and the United Kingdom. Several smaller countries also participated in international collaboration with larger countries. In addition, the European Commission established a multinational, coordinated Human Genome Analysis program to complement the various national initiatives in Europe. 28 The European Community (EC) played a significant role in the HGP. In 1988, the EC introduced a proposal entitled the Predictive Medicine Programme. However, a few EC countries, notably Germany and Denmark, claimed the EC proposal lacked ethical sensitivity Germany, in particular, had strong objections to the possible eugenic implications of the program. Because of such controversy, the initial proposal was dropped. However, it was later modified, renewed, and finally adopted in 1990 as the Human Genome Analysis Programme (HGAP). The HGAP had three objectives: First, to provide an improved study of the human genome for a better understanding of genetic functions and the prevention and treatment of human disease; second, to establish medical, ethical, social, and legal guidelines to ensure that the results of the research were not misused; and third, to ensure that modification of human characteristics by genetic engineering of germ cells and embryos is excluded from the program. 29 In 1989 the UK Secretary of State for Education and Science awarded £11 million ($21 million) to the Medical Research Council (MRC) for the initiation of a national Human Genome Mapping Project (HGMP) to coordinate and expand UK activities in human genome mapping and to provide a link with genome research in other countries. Program objectives included giving the United Kingdom a role in international genome research and ensuring that the nation would benefit from medical and commercial applications of genome work. The UK program concentrated on identifying and isolating as many genes as possible and characterizing them in biological terms. 30,31 The international scientific community involved in human genome work formed the Human Genome Organization (HUGO) to coordinate the international effort and to foster collaboration between scientists; to facilitate the exchange of data and biomaterials; to encourage debate on scientific, social, ethical,
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legal, and commercial implications of human genome projects; and to ensure that the results of research are freely available to all nations. 32
Mapping and Sequencing the Human Genome Mapping of human genes began early in the twentieth century; however, it had been extensively pursued only for the last few decades. The first meeting dedicated specifically to discussing the feasibility of mapping and sequencing the human genome was held in May 1985 at the University of California at Santa Cruz under the auspices of Robert Sinsheimer, Bob Edgar, Harry Noller, Bob Ludwig, and colleagues. In order to obtain sufficient quantities of DNA for study, it was necessary to reproduce the DNA fragments of interest. One way that this was done was by "cloning," whereby foreign D N A was inserted into a growing organism that was "tricked" into synthesizing the cloned DNA along with its own. Another way that DNA was reproduced was by the polymerase chain reaction (PCR). PCR results in the in vitro synthesis of large segments of a target D N A sequence, a technique utilized in research and clinical laboratories. Mapping of the genome involved locating and identifying the genes present within a strand of D N A (gene sequencing). The map facilitates the location of genes that segregate with specific disease states. After mapping was completed, the next step was to determine the base sequence of each of the ordered D N A fragments. Sequencing D N A was a long and excruciatingly difficult task. In the mid-1970s Frederick Sanger, a molecular biologist at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England, devised an elegant sequencing method that won him a second Nobel Prize in Chemistry. The HGP Mapping Project consisted of two major components—the Resource Center and the Directed Programme of Research. The first component, the Resource Center, acted as a national repository and site for systematic work, as well as distributary and reference center for human-mouse cDNA libraries, yeast artificial chromosomes (YAC), DNA probes, computer facilities, and relevant databases. In addition to the production of cDNA libraries and sequencing of new cDNAs, work at the center included nonradioactive sequencing, hybridization screening, polymerase chain reaction screening, oligonucleotide synthesis, and in situ hybridization. The second component, the Directed Programme of Research, served to expand work in various university departments and other institutions. In addition, it supported research in three broad areas: general mapping of interesting genomic regions, evaluation and design of enabling methodologies and equipment, and study of model organism genomes such as the mouse and the roundworm Caenorhabditis elegans. Currently, the speed with which disease genes are being identified continues to increase rapidly because of improved genetic and physical maps. By introducing detailed human genetic mapping techniques, human genes have been identified more rapidly. For example, Duchenne and Becker identified muscular
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dystrophy genes in 1986, entering a new era of medical treatment and diagnosis. Also, construction of an E. coli clone library was started to analyze the E. coli genome, and in 1988 the D N A polymerase chain reaction (PCR) was introduced. Three types of maps were used in the HGP—genetic, cytogenetic, and physical. The genetic map (genetic linkage map) consisted of thousands of landmarks that were short distinctive pieces of DNA, more or less evenly spaced along the chromosomes. Genetic maps had many uses, including identification of certain genes associated with genetic diseases. Genetic maps enabled researchers to identify an inherited disease by pinpointing the exact chromosomal location of important disease genes in diseases such as sickle-cell anemia and cystic fibrosis. The second type of map, physical maps, consisted of overlapping pieces of DNA spanning an entire chromosome. Physical maps were used to isolate and characterize individual genes and other DNA regions of interest. Physical maps consist of ordered landmarks at known distances from one another, much like a travel map indicating distances between cities along a highway. A physical map represented actual locations (as compared with relative locations on a genetic map) of identifiable landmarks. The completed physical map simplified the genetic analysis of human disease. The third type of map, cytogenetic maps, represented the appearance of a chromosome when examined microscopically. These maps served to identify specific chromosomes and chromosomal regions. 33 ' 34 Currently, gene sequencing involves taking DNA from human chromosomes, which is shredded into short segments. These are fed into an automated machine that reads each biochemical "letter" on the segment. Once the segments have been read, a computer puts them together by assembly—finding overlaps and matching adjacent pieces. This is complicated by the fact that similar sequences occur many times in many places. The final step involves annotation. This involves pinpointing the genes along the chromosomes. These genes make up about 3 percent of the genome. Once these are identified, researchers can figure out which ones make proteins that cause disease or protect health. Understanding how and when genes make proteins will give doctors new ways of looking at disease and lead to new treatment.
Results and Surprises Venter and his company, Celera, and Collins and the HGP team used different strategies and methods to complete sequencing the human genome. Venter used the whole-genome shotgun approach, whereas Collins and his HGP team used landmark mapping and sequencing. Importantly, both teams reached the goals that were set. In completing the HGP, there were three primary surprises: first, scientists found that the human genome has only about one-third as many genes—about 20,000 to 25,000 genes, rather than 100,000—as originally thought. Interestingly, this is about the same (20,000) as a nematode worm's (Caenorhabditis elegans) or a
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fruit fly's (Drosophila melanogaster) 14,000 genes. Surprisingly, in terms of genes, humans appear only five times as complex as the bacterium Pseudomonas aeruginosa. Interestingly, the 20,000 to 25,000 genes present about 90,000 or more distinct proteins encoded by the human genome. Genes build proteins to meet the demands of each of the body's 100 trillion cells. Yet, despite its apparently light load of genes, the human genome is large. Much of the human DNA does not contain human genes but rather is packed with remnants of snippets of ancient DNA that have replicated and inserted themselves into the genome many times over. This accounts for large chunks of duplicated sequences called junk DNA. The sequence tells us that we received more than 200 genes as gifts from bacteria that somehow infected a distant ancestor of ours and transferred some DNA. Second, scientists discovered that proteins, the most complex large molecules in nature, are much more complicated in humans than in animals or plants and that each gene makes two or three proteins, not one as originally thought. This is highly significant since it renders the one gene, one protein theory obsolete, at least in humans. Third, foreign DNA, derived from ancient microbial invaders, also populates large portions of the human genome. This is significant because it implies that humans share with bacteria some genes that regulate important processes such as metabolic functions or enzyme creation. The typical human gene likely has twice as many proteins as worm genes, giving the human cell an ability to build any kind of protein the cell might need. However, humans use them differently than do lower organisms. These protein domains have survived millions of years of evolution. 35 From the HGP work, two lines of evolution converged on humans. The first implies that one set of genes came from the first bacteria capable of living in an oxygen-rich atmosphere. The second set came from the single-celled organisms that gobbled up the bacteria and co-opted their ability to turn oxygen into energy. Interestingly, genes from those bacteria still live in the human genome, demonstrating the fusion of two different lines of evolution into the same genome. It was shown that hundreds of human genes appeared to have come from bacteria millions of years ago. Whether the bacteria infected humans or were carried by a virus is not currently known. Perhaps the most intriguing question to emerge from these analyses is this: How do relatively few genes build and maintain an organism as complex as a human, with 90,000 to 300,000 proteins and 100 trillion highly specialized cells? The HGP has shown that genetic information is not evenly divided on the chromosomes. Eric Lander of the Whitehead Institute Center for Genomic Research in Cambridge, Massachusetts, a lead researcher for the HGP, best described the genome as a "remarkably uneven landscape . . . Some chromosomes are chockablock with genes, [and] others are virtually devoid of genes. The weirdest chromosome in the genome is [number] 19. It's chockablock full of genes and other functional elements, far beyond what you'd expect, given its measly size. It's a mighty little chromosome there. Given its size, it has grand aspirations. In contrast, chromosomes 4 and 8 barely pull their weight." 36
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Impact of the Human Genome Project Completion of the HGP was a historic moment. No one will argue that mapping and sequencing the human genome, whatever method used, has provided us with useful, if not stunning, information. Leading to new drugs, new ways to prevent or treat many illnesses, and better forecasts of peoples' lives, the information generated by the HGP promises to be the source book in the twenty-first century, if not the third millennium. "Humanity has been given a great gift. With the completion of the human genome sequence, we have received a powerful tool for unlocking the secrets of our genetic heritage and for finding our place among the other participants in the adventure of life."37 The HGP has already begun to revolutionize the practice of biomedicine. Maps and sequences have aided scientists in finding genes, and thousands of known inherited disorders have been identified as a result of the HGP. Today, the HGP serves as a guide for scientists who are trying to find cures for diseases such as Parkinson's, Alzheimer's, multiple sclerosis, muscular dystrophy, diabetes and other diseases that afflict millions. Use of the HGP will enable scientists to find other genes involved in various other genetic diseases. Whereas mapping the human genome has increased our ability to understand and eventually prevent or cure diseases, it has also allowed scientists and others to develop techniques and instruments for rapid determination of gene sequences on DNA. For example, Eugene Chan, who received U.S. Patent 6,355,420 for what he calls the "Gene Engine," has invented a machine that deciphers the human genome in less than thirty minutes. Chan says his new machine takes genetic information, unwinds the information at extremely high speeds, and reads it at even higher speeds. The machine has a chip that allows the user to manipulate and control DNA at a very small scale. The chip has fluid channels inside it that stretch out the DNA and then read it with an amazing optical technology. Chan's machine has many uses. For example, when an individual is born, his or her genome can be scanned, analyzed, and stored and the information reaccessed later.38 With such stunning successes, scientists and clinicians have been given a powerful resource that allows them to study and treat humans in exceedingly more beneficial and sophisticated ways. In addition to its impact on biomedicine, the HGP has had a large impact on industrial activities in society in producing vaccines, interferon, and other useful pharmaceuticals. Researchers are now able to identify individuals predisposed to particular diseases and to devise novel therapeutic regimens based on new classes of drugs, immunotherapy techniques, avoidance of environmental conditions that may trigger disease, and possible replacement of defective genes through gene therapy. In April 2003 President George W. Bush issued the following statement upon completion of the HGP: "The HGP provides us with the fundamental platform for understanding ourselves from which revolutionary progress will be made in biomedical sciences and in the health and welfare of humankind." 3 9 The ability to compare complete genomic sequences also has enabled scientists to compare humans, worms, flies, and bacteria and has shown the commonality of life. Demonstrating obvious distinct differences, the HGP has provided
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researchers with the capacity to solve the mysteries of human development and evolution. In a 2005 experiment, Purdue University molecular biologists challenged a scientific law of inheritance that stood for 150 years. The scientists believe that plants sometimes select better bits of DNA in order to develop normally even when they inherited genetic flaws from their predecessors. Researchers found that a plant belonging to Arabidopsis thaliana, a member of the mustard and watercress family, sometimes corrected the genetic code it inherited from its flawed parents and grew normally like its unflawed grandparents and other ancestors. The discovery leads scientists to wonder whether humans may also have the potential to avoid genetic flaws or even repair them, proving that inheritance can happen more flexibly than previously thought. The conclusion by the Purdue scientists contradicts some basic rules of plant evolution believed to be absolute since the mid-1880s when Austrian monk Gregor Mendel proved that traits are passed on from one generation to another. Mendel's work earned him the title "Father of Genetics." Some scientists described the results of the Purdue experiment as "spectacular" because it reveals a novel way in which the genome can heal itself.
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PART II Beauty and the Beast The birth in England of Louise Brown, the world's first test-tube (in vitro fertilization) baby, marked a revolution in fertility treatment. In spite of the reproductive miracle, however, there existed in the minds of many a certain apprehension that the miracle of test-tube tots indicated the arrival of Aldous Huxley's unorthodox science. As a result, the conservative British government commissioned Dame Mary Warnock of Cambridge University to form the Committee of Inquiry into Human Fertilization and Embryology. The committee issued sixty-four official recommendations.
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4 LABDRATDRY BABIES New Biology, Old Morality The in vitro fertilization controversy divided physicians and researchers who were torn between the lure of a new dawn of knowledge as depicted in Brave New World and the safety of a traditional code of ethics. Dame Mary Warnock, Girton College, Cambridge University The creation and birth of the world's first in vitro fertilization (IVF, "test tube") baby was far from being an ordinary event. Its occurrence made headlines throughout the world because it was a new way of beginning life. However, behind the beauty of IVF there lurked a beast in the form of nightmares and concerns voiced by theologians, ethicists, lawyers, and philosophers who, on both sides of the Atlantic, warned that the medical miracle of IVF indicated the arrival of unorthodox medicine as forecast in 1932 by Aldous Huxley in his novel, Brave New World.
Huxley's Brave New World In Huxley's Brave New World, students tour the fictitious Central London Hatchery and Conditioning Centre where they observe various machines and techniques that promote the production and conditioning of embryos. Absent are fathers and mothers in the usual sense and family and marriage are nonexistent. Surrogate parental relationships with children are filthy and improper and feelings are obsolete. Overall, the book represents a society without moral controls—one
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where only carnal pleasures are pursued, and where any rituals are orgiastic in nature. While on the tour in Brave New World, students learn that the key to social control is the "Bokanovsky Process" in which a single human egg (ovum) could produce up to ninety-six identical twins, each mentally and physically identical to all others and all capable of contributing to a social stability. Although written more than seven decades ago, many of the technologies described in Brave New World have, at least in part, become realities. Huxley did not intend to evoke just how wonderful our lives could be if the human genome were rewritten, yet early in the twenty-first century we have already experienced in vitro fertilization and other assisted reproductive technologies, recombinant DNA technology (genetic engineering), mood-altering drugs, stem-cell research, and reproductive and therapeutic clonings, and have seen completion of the human genome project (HGP).
The Road to Oxford Huxley's Brave New World brought back memories. Leaving my home on the North Dakota prairies early one mid-July morning in 1985,1 boarded a jet to Minneapolis, where I embarked on a direct flight into London's Gatwick airport. From there, I proceeded by bus directly into the city of Oxford where I resided for several weeks at the Queen's College at Oxford University. A Bush Foundation (St. Paul, Minnesota) faculty development grant had enabled me to participate in an international science seminar, Medicine, Ethics, and Society, held at the Queen's College. Oxford is a university traditionally renowned for study of the arts and one of the world's great scientific universities as well. Each of the forty colleges comprising Oxford University has its famous alumni. The Queen's College, one of Oxford's oldest colleges, was founded in 1340 by Robert of Eglesfield, chaplain to Queen Philippa, wife of King Edward III. Like other Oxford University colleges, the Queen's College boasts of the famous pupils who once attended. John Wyclif, the English religious reformer and first translator of the Bible into English, attended during the years 1363-65 and 1374-81. King Henry V studied at Queen's while he was Prince of Wales prior to becoming King of England. During the seventeenth century, the noted playwright Wycherley attended, as did Edmund Halley, the Astronomer Royal after whom Halley's Comet is named. World-renowned philosopher Jeremy Bentham was an undergraduate in 1760, and during the nineteenth century the art critic Walter Pater was a student.
An International Forum Attracting some of the world's greatest philosophers and ethicists, the international forum Medicine, Ethics, and Society was attended by over one hundred persons representing seventeen countries and was designed to discuss social, moral, and ethical ramifications stemming from scientific breakthroughs in biology and medicine.
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The forum's key-note speaker, Dame Mary Warnock, Mistress of Girton College at Cambridge University and Senior Research Fellow, St. Hugh's College at Oxford University, addressed seminar participants in the spacious Examination Room of the Queen's College. Warnock told forum scholars that she had been commissioned by the conservative British government's Department of Health and Social Security to form a committee to conduct inquiry into human fertilization and embryology and to make recommendations. Need for the study, Warnock reported, evolved after the creation and birth of the world's first "test tube baby," Louise Brown—conceived and born in England. Warnock's committee was established in 1982 to examine the social, ethical, and legal implications of recent and potential developments in the field of human assisted reproduction. Warnock told forum scholars that when scientists first suggested that IVF might be applied in the treatment of infertile women, a heated debate arose in the United States (and to a lesser degree in the United Kingdom) about whether it was moral to use IVF technology with the intent to create a human baby: "For decades an intense IVF controversy divided physicians and researchers who were torn between the lure of a new dawn of knowledge as depicted in Brave New World and the safety of a traditional code of ethics." 1 As a result, for decades philosophers, theologians, ethicists, and lawyers on both sides of the Atlantic debated the morality of IVF, a technology centered mainly around promises, trust, and commitments. 2 In July 1984 the Warnock Committee issued its detailed report, Report of the Committee of Inquiry into Human Fertilization and Embryology in the United Kingdom.3 The report addressed topics of in vitro fertilization, surrogacy, the freezing and storage of reproductive materials, and the use of embryos for research. Considered a crucial text in the discourse on assisted reproductive technologies, the study was considered a point of reference to countries including the United States, Great Britain, Denmark, Germany, and France.
The World's First "Test Tube Baby" Born July 25, 1978, in Oldham, England, Louise Brown was a healthy five-pound, twelve-ounce baby girl, the first ever conceived outside a mother's body under controlled laboratory conditions. The IVF procedure was deemed necessary since Louise's mother had an inoperable blockage of the fallopian tubes which prevented her from getting pregnant in the usual way. The egg that produced Louise Brown was fertilized in vitro via embryo transfer, a process whereby an egg is taken from the mother's body, fertilized by the father's sperm, allowed to grow to embryo stage in the laboratory, and returned to the mother's uterus for further development. The merger of an egg and sperm is technically called a "zygote" and contains the full set of forty-six human chromosomes, twenty-three from the egg and twenty-three from the sperm. Today, more than twenty-five years after the birth of Louise Brown, IVF conceptions in a petri dish from a mother's egg and a father's sperm seem relatively natural. More than one million test tube (IVF) babies have been conceived and born healthy, and the debate now is nearly nonexistent. Governments all over the
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world have since adopted policies that allow the regulated use of IVF on the proven assumption that it produces more good than harm.
Drs. Edwards and Steptoe The British medical researchers who performed the first IVF procedure that created Louise Brown were Drs. Robert Edwards and Patrick Steptoe, who took it as their duty to satisfy the natural desire of every couple to have a child, by natural or artificial means. Edwards and Steptoe's partnership began in 1968 at the Centre for Human Reproduction in Oldham, England, where Edwards had succeeded in fertilizing the first human ova outside the womb. Over time this technology resulted in the births of thousands of IVF babies, including Louise Brown and her younger sister.4 Dr. Robert Geoffrey Edwards, born September 27, 1925, attended the Universities of Wales and Edinburgh, served in the British Army (1944-48) and worked as a physiologist and medical researcher at various universities in Britain and the United States. He began his work on the human egg in 1963 and his first paper on the subject was published in 1965 in the prestigious scientific journal Lancet.5 Dr. Patrick Christopher Steptoe was born on June 9, 1913, in Winey, Oxfordshire, England. He died on March 21, 1988, in Canterbury, Kent, the day before he was to be made a Commander of the Order of the British Empire. In 1939, Steptoe graduated from the University of London's St. George Hospital Medical School and joined the Royal Navy Volunteer Reserve, serving as a surgeon until his ship was sunk and he was taken prisoner and held by the Italians (1941-43). After his release, he continued his medical training in London, Dublin, and Manchester before becoming senior obstetrician and gynecologist at Oldham Hospitals (1951-78). While at Oldham, Steptoe conducted research on sterilization and infertility and published Laparoscopy in Qynecology (1967), concerning the use of the laparoscope, a narrow tube with a built-in fibre light. Edwards and Steptoe's first joint paper was published in 1970.6
A Huge Impact The birth of Louise Brown had a huge impact on the ethical and moral debate surrounding the use of IVF. Overall, there was a sense of pride in the technological achievement, as well as relief of anxiety for couples who were infertile. Yet, for some there was an uneasiness with a technique that presented an uncontrolled scientific advancement—one capable of manipulation. In describing IVF's rapid advancement, Warnock said: "There was a sense that events were moving too fast for their implications to be assimilated." 7 Other concerns arose, primarily over moral and ethical questions involving the possible creation and destruction of human beings, the normality of the offspring, a change in the natural patterns of human reproduction, and the potential for future genetic engineering in our species.
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Responses of people to IVF fell into three general categories. First, for many the anathema response existed—the entire innovation of laboratory procreation was morally unthinkable. Simply, science had become a beast that had gone too far! People had visions of moving assembling lines of test tubes and petri dishes in the biological laboratory where embryos were made and discarded by impersonal laboratory workers in full factory-like connotation, much like Brave New World. To those experiencing this kind of response, IVF represented a complete depersonalization of marriage and parenthood. Second, to those experiencing an assimilation response the goal was an ancient one—for childless couples to have children. Neither the ends nor the means involved in creating a test tube baby was a drastic departure. At the center of the response were questions such as: When is a human being a human being? Does life begin at conception when the egg and sperm unite? Is there valid scientific evidence when actual human life exists? Third, those who experienced an apprehension response believed that there were many things that happen to humans in life that are not welcome. Persons experience a pronounced uncertainty, one that is often poorly tolerated. In spite of these fears, by the 1980s several groups, including Carol Wood's group in Australia, were experimenting with human IVF and announcing more IVF pregnancies. Others believed IVF was unethical because it violated the sanctity of marriage and a proper family environment for child bearing. Still others argued that although sexual intercourse might well be an act of love that sanctified marriage, it did not guarantee a happy family environment. Proponents of the new technology argued that IVF demanded sacrifice on the part of both male and female partners far beyond anything required for normal procreation. Another concern of opponents of IVF was that the technology entailed unknown risks to potential children who could not give consent. Proponents of IVF believed that it was unlikely that the risks involved with IVF were substantially greater than they were with normal fertilization. Others believed that IVF was unethical because the technique made possible wholesale reconstructions of the human body. Opponents of IVF believed that IVF was unethical because science does not have the right to manipulate nature, whereas proponents argued that if it was ethically acceptable to seek medical care for a reproductive disorder, it was ethically acceptable to seek care that required IVF. When the wide-spread IVF controversy initially began, opponents of IVF were concerned that it was unethical because the risks of publicity to a child so conceived would not allow the normal development of the child. That idea is now known to be false, based on the normal development of Louise Brown and her sister, as well as thousands of other IVF babies. Louise Brown currently works as a postal employee and lives in Bristol, England. Because IVF has gained wide acceptance throughout the world, undue publicity is currently minimal.
Infertility: "Genetic Death" It is not difficult to imagine infertility, sometimes labeled "genetic death," as causing great anxiety to many couples, thus putting a strain on their marriage. As
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powerful as the innate will to survive, the desire to have children is one of humanity's strongest urges, symbolizing a human's attempt to achieve immortality and leave something of him or herself to posterity. Understandably, then, the desire of an infertile couple to seek help in creating their own children is also very powerful. One out of every six couples struggles to become parents. However, infertility is not confined to those who are married, but single women and men, widows and widowers, and homosexuals and lesbians, as well. For over a century, physicians have offered the practice of donor insemination as a means of providing children to infertile couples. Yet, despite greatly increased abilities to diagnose and treat the causes of infertility, many couples still remain involuntarily childless. It is not surprising, then, that IVF was a considerable breakthrough that opened new doors for the alleviation of infertility and the science of embryology. At the time of the IVF breakthrough, there were those who asked: W h y would anyone want to make babies via IVF? The answer is that, in many instances, the "natural" method is not possible. Infertility is an enormous problem worldwide and is not constrained by a high birth rate or an overpopulated nation. 8 The dramatic increase in the incidence of infertility over the last five decades has been attributed to a number of factors, including an increase in the incidence of venereal diseases that destroy the reproductive apparatus of both men and women. In addition, females are starting their families at a later age, when their natural fertility has already begun to decline. Another major increase in infertility has been attributed to the use and abuse of drugs and narcotics that play havoc with spermatogenesis (formation of sperm) and oogenesis (formation of eggs). The treatment of infertility has raised legal and ethical questions concerning equity and justice, falling roughly into two broad categories: questions of social justice and questions of individual justice. 9 In July 2002 it was announced that fertility clinics were under pressure to review security procedures after a white couple had black twins following an in vitro fertilization mix-up. The mix-up, it is believed, was due to human error and was the first of its kind in Britain. The fertility clinic, linked to a state-funded National Health Service hospital, somehow confused sperm, eggs, or embryos belonging to a black couple with those from a white couple. IVF experts say there were two main possibilities for the error: either Mr. B's sperm was used by mistake to impregnate Mrs. A's eggs, which were then implanted in her; or that an embryo created using Mr. B's sperm and Mrs. B's eggs was accidentally implanted in Mrs. A. Most experts believe the latter was the more likely.10
Donated Eggs Infertility may be due to reasons other than blocked oviducts, and because of this, successful donation of eggs is sometimes necessary. After superovulation is induced, a mature egg is recovered from a fertile woman donor and is fertilized in vitro, using the semen of the husband or male partner of the infertile woman. Another technique uses a mature normal donated egg with one set of chromosomes (twenty-three; haploid). The chromosomes are sucked out of the egg and
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the nucleus from a healthy body (somatic) cell with its forty-six chromosomes is injected into the empty egg, producing an egg with two sets of chromosomes (forty-six; diploid). To make the egg viable for fertilization one set of chromosomes is removed by shocking the egg electrically or injecting it with a chemical that pushes the extra set of chromosomes out. The mature egg is then ready for fertilization by a sperm. The resulting embryo can be implanted in the same woman from which the egg was obtained or donated to another woman (a gestational mother). If the embryo implants, the woman may carry the pregnancy to term.
Donated Sperm Sperm cryopreservation and sperm banking also have become a widely accepted part of our culture, and sophisticated procedures and techniques are available. As early as the 1940s cattle breeders and veterinarians used the process of cryopreservation of bull semen and artificially inseminating heifers. However, it wasn't until the 1950s that the methods for cryopreserving human semen and artificial insemination were refined, resulting in the first human birth. One of the first human sperm banks was started in the early 1980s. Today, sperm banks are commonplace and it has been experimentally shown that sperm motility, viability, and morphology are not affected by proper longterm preservation over many years. Sophisticated methods and techniques are currently available for freezing and storing human semen. Many reasons are given for men freezing and storing their semen. Those in high-risk occupations, as well as sports figures, at times elect to protect their future against possible injury that could affect their reproductivity. Vasectomy patients sometimes store their sperm prior to their procedure in case they may someday choose to father another child. Because surgery, chemotherapy, and radiation may render male patients who are undergoing cancer treatments sterile, many males opt to store sperm prior to these procedures. In September 2002 it was announced that U.S. and British scientists had put together a genetic profile ("fingerprint") of healthy sperm. Heralded as a major step in the understanding, diagnosis, and treatment of male infertility, the genetic "fingerprint" provides a necessary molecular "benchmark" against which to compare men with fertility problems. The profile is also useful in fertilizing eggs and in early embryo development. 11 A recent spectacular achievement was an offshoot of IVF called intracytoplasmic sperm injection. A single sperm is injected directly into the egg. This is particularly useful when the quality and number of sperm are low.
Surrogacy Surrogacy is the practice whereby one female carries a child for another with the understanding that the child will be handed over after birth. At times, surrogacy becomes necessary for the alleviation of infertility and is frequently used among
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women with uterine abnormalities that preclude normal pregnancy Surrogacy is also used by women who wish to hire gestational mothers in order to avoid interference with their careers or sports activities. W h o are the women willing to be surrogates? Often, child bearers are poor women who are willing to be surrogate mothers for good pay. However, even though money is an important motive for many surrogate mothers, for many it is not the primary motive. Other reasons given by surrogates include the love of children and the gratification offered by the children, empathy with the infertile female (a thoughtful act of generosity on the part of one woman to another), and the drive to generate parenthood for others. The contribution of the surrogate mother is great, intimate, and deeply personal. Many women believe that surrogacy is a feeling of self-actualization. This is especially true in cases where one female relative carries the pregnancy for another. For these couples, it offers them their only chance of having a child genetically related to one of them and may be the only way that the husband of an infertile woman can have a child. In the case of a relative gestating another's baby, certain questions surface: Whose child is he or she? Is the female morally justified in gestating another's child? How does the rest of the family feel about her giving birth for a relative? Will other members of the family feel obligated to perform the same act of kindness? Psychological and legal consequences in surrogate motherhood may be significant. Opponents of surrogacy believe that it is an attack on the marital relationship between couples because a third party is introduced into the process of procreation. Others believe that surrogacy is degrading because poor women are used by rich women to have their babies in order to avoid the discomfort of pregnancy. Opponents view surrogacy as inconsistent with human dignity and believe that a woman should never use her womb for financial profit. Others view surrogacy as buying and selling of human flesh, a process that is dehumanizing. Many believe surrogacy should be prohibited. Opponents believe that surrogacy is harmful to a child's future self-esteem because the child will have been purchased for money. Others feel that surrogacy distorts the relationship between mother and child because the woman allows herself to become pregnant, carries the child nine months, and then gives it up. As a result, the bonds of the child are with the carrying mother and the separation is damaging to the child. In the first known case in the United States in which a woman was paid to be a surrogate, a child was born in November 1980 to a thirty-eight-year-old mother of three children. Rather than using her real name, she used a pseudonym, Elizabeth Kane. For an undisclosed amount (reported to be between $5,000 and $10,000), Kane permitted herself to be artificially inseminated with the sperm of a man from Louisville, Kentucky, whose wife was infertile. Kane signed a formal agreement, releasing her parental rights to the baby. The parentsto-be were present at the birth of the healthy eight-pound, ten-ounce baby boy. Kane asked and received the couple's permission to briefly hold the baby and then handed him over to the parents, the baby's genetic father and his adoptive mother.
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In a later case, Mary Beth Whitehead, a twenty-nine-year-old homemaker from New Jersey, signed a contract paying her $10,000 to bear a child for Elizabeth and William Stern. Elizabeth Stern was infertile and the couple desperately wanted a baby. Whitehead allowed herself to be impregnated by the sperm of William Stern and agreed to carry the baby to term and to turn it over to the couple in return for the money. However, near the birth of the baby, Whitehead changed her mind and decided to back out of the legal agreement with the Sterns. The Sterns refused to let Whitehead out of the agreement and hired Noel Keane, a Dearborn, Michigan, attorney who owned and operated the first surrogacy agency. Keane, on behalf of the Sterns, demanded that Whitehead turn the baby over to them after it was born and give up custody to it. The litigation, known as the "Baby M " case, was heard in room 217 of the Bergen County Courthouse in Hackensack, New Jersey. The case captured national attention, mainly because it challenged traditional definitions of parenthood and tested the adaptability of the law to radical social change. At the time of the adoption, the six-page document that Whitehead and William Stern had signed placed them in a gray area of the law. Consequently, the judge ruled that Whitehead, as the surrogate mother, had to turn the baby over to the Sterns who had contracted her to carry the child because she had to "honor the contract" she signed with the couple. However, an appeal to a higher court reinstated some of Whitehead's parental visitation rights to see the child.
When Does Human Life Begin? At the heart of the IVF controversy is the question: When does human life begin? Some believe that life begins at conception, when an egg is fertilized by a sperm, whereas others believe that life is a developing process, coming into being only when the resulting mass of cells begins to appear human. Those who believe that life begins at conception say that what exists before conception is not life. They argue that since the sperm and the egg are sex cells (haploid cells, each containing twenty-three chromosomes), by themselves they do not constitute human life. Rather, they can become whole only when they unite to form the fertilized egg called the zygote (a diploid cell containing forty-six chromosomes). From the time of fertilization by the sperm, the egg takes on an entirely different destiny. The genotype conferred at conception does not merely start life, it defines life. From a biological point of view, life begins at conception, and the destruction of a fertilized egg or embryo constitutes the destruction of a human life. Others believe that life is a continuous process of development, beginning with a molecular thread of DNA, the "essence" of life and the basic material that forms the building blocks of life, the genes and the chromosomes. Those who believe this theory state that life begins well before conception and extends long afterwards. They believe that the egg and the sperm, each with its own genome of twenty-three chromosomes, are very much alive. Under normal conditions, fertilization of the egg by the sperm may not result in a person but rather into a cell mass that ultimately divides into two major
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components, the embryoblast and the trophoblast. The embryoblast becomes the fetus, and the trophoblast becomes the placenta, the umbilical cord, and the extraembryonic membranes. Some believe that the trophoblastic derivatives are alive and human, with the same genetic composition as the fetus. Since they are discarded at birth, many wonder whether they deserve the same moral standing as a fully developed human. Many argue that human embryos are biologically alive, even at the blastocyst stage (the blastocyst is the largest embryo and is barely visible to the naked eye). Others believe that the embryo, if not a human, is potentially a human, as are the egg and the sperm. Years ago, theologians particularized the human desire to identify personness. Many question when "ensoulment"—the moment when the soul (apparently a quality not shared by other species)—enters the embryo. Does it occur at conception, at implantation, at quickening, or at birth? There are those who claim that laboratory reproduction, such as in vitro fertilization, is no longer human reproduction and may be ethically correct only when the normal process of birth cannot take place.
Embryo Loss There has been considerable concern over embryo loss in females. Because in vitro fertilization is the deliberate creation of embryos, the most frequently voiced concern is that IVF is unethical because embryos are destroyed in the process or after transfer to the uterus, or that embryos that are not transferred are somehow destroyed. In creating Louise Brown, it was originally reported that Edwards and Steptoe transferred over 100 embryos before their first success.12 What happened to the excess embryos? Various pro-life groups believe that as horrible as it may be to discard embryos, it is far worse to perpetuate them in their laboratory existence. Numerous questions arise during the IVF process: What happens to the embryos that are discarded at the end of the day? Are they washed down the sink? Does this amount to abortion or murder? W h o decides the grounds to discard embryos? Are discarded embryos considered fit material for experimentation? Should they be donated to those who wish to have the otherwise unwanted embryo? Whose embryos are they? The woman's? The couple's? The geneticist's? The obstetrician's? W h o will the children be, and who will be their parents? What is their social definition? Some argue that embryo loss is not unusual—that there is a high rate of embryonic loss that occurs in women during the normal reproductive process. 13 They cite a similar phenomenon has been known for many years to occur normally in non-primates such as rabbits and pigs, and other mammals as well.14'15 Over a half-century ago, embryonic loss in women was recognized and it was observed that potentially abortive ova could be recovered from women who were considered to be normally fertile.16 Biggers estimated embryo wastage and concluded that by the time pregnancy was recognizable, half the embryos had been lost. With the IVF procedure, he determined, a larger proportion of the embryos was lost by the time a pregnancy was recognizable. Further, Biggers concluded
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that during the remainder of pregnancy, another quarter of the embryos perished and were aborted. 17 Pro-abortionists at times argue that even a significant number of fertilized eggs (zygotes) fail to implant and therefore do not result in pregnancy. They use this as "evidence" that even Mother Nature does not consider the fertilized egg genuine human life, any more than she does the hundreds of thousands of eggs and millions of sperm that are wasted.
Human Embryo Research Panel The subject of human embryo research has been highly controversial. In December 1994 the National Institutes of Health (NIH) appointed the Human Embryo Research Panel to make recommendations regarding human embryo research and to offer ethics-based advice on how the NIH should research the human embryo. The panel responded by trying to prove that the embryo's moral status is greater than that of other human tissue but less than that of a baby. In doing so, they hoped to convince officials that respect must be granted embryos as early human life, but not at the expense of promising research for the benefit of public health. The panel concluded that women should not be paid for donating eggs for research, although payment for egg donation to private fertility clinics could continue. The panel also proposed a ban to prevent the commodification of embryos and the exploitation of women. The ban, however, foreclosed a choice for women and had significant effects on the availability of eggs for researchers. The panel tried to prevent the development of a two-tier market for eggs— eggs from wealthy women in contrast to eggs from low-income women. Most often, eggs intended for fertility clinics were acquired from high-income women and usually had greater value in the market than eggs acquired for research purposes that were provided by poor women or women of color. The panel had a significant degree of concern for researchers in two areas. First, it recommended that researchers be allowed to continue to use preexisting embryos from fertility clinics despite the fact that donors were paid for these embryos. Second, the panel concluded that the profit motive was acceptable for researchers as long as subjects in federally funded embryo experimental protocols were informed of the financial interest of the researcher as part of the consent process.
Sperm, Eggs, and Embryos as Property As developments in reproductive technology advanced, new and difficult moral and ethical questions intensified and were presented to courts as legal issues of first impression. As a result, judges had to decide the law at the frontier of reproductive technology. The possibility of posthumous reproduction with preserved sperm was one such dilemma facing the courts. In the unique case of Hecht vs. Superior Court, the children of William Kane fought with Kane's lover over possession of sperm that
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Kane had deposited in a sperm bank. Kane had signed a legal document that Hecht, his girlfriend, could use the sperm to conceive children after he committed suicide. As a result, the court was faced with the unique question of whether sperm could be treated as property and whether sperm could be left to another by execution of a will. The analysis proceeded in three main parts. First, legally, property rights exist whenever a person has the ability to sell or transfer control of something. In order to answer the question of whether courts should honor Kane's intent to transfer control of his sperm to Hecht, it became necessary to address the moral issues of Kane's purpose—the ethical problems of posthumous reproduction. Second, legal and moral arguments existed against allowing posthumous reproduction. Protection of unborn children from potential harm is an inadequate basis for a morally based legal ban on posthumous reproduction. Third, arguments existed against commodification of body parts and against the commercialization of reproduction in particular. As a result, it was concluded that the transfer of sperm using a will does not implicate the concerns that justify opposition to commercial traffic in body parts and reproductive capacities. Concerns for individual autonomy and privacy in matters of reproduction justify the transfer of sperm by will. Various considerations arise. For example, sperm can last a long time when frozen. It might take a widow years to decide whether or not she wants to use the semen. In France, a court ruled that a man's sperm should be buried with him. These days, a greater number of families are being asked whether they want to harvest the sperm from a son in a coma or a husband who just died in an accident. Is this "cheating death" or is it more akin to rape? Consider the following hypothetical story with regard to unused embryos. Jack and Sally of Philadelphia, Pennsylvania, were married for six years before they decided to try to conceive a child. When they married, both had wanted to have children. However, after trying for several years unsuccessfully to have a child, the couple visited a fertility clinic to obtain help. Sally was induced to produce several eggs, which were fertilized by Jack's sperm. As a result of the fertilization, several eightcell embryos were artificially produced in vitro. Although Sally was implanted with the embryos several times, all attempts were unsuccessful. Several years later Jack and Sally's marriage deteriorated and, despite counseling, in the end they filed for divorce. At the time of divorce, they had twelve frozen embryos stored at a Philadelphia fertility clinic. Despite their divorce, Sally decided to keep the embryos for future use in producing a baby. Jack, however, wanted to donate the embryos to a private research company. Both Jack and Sally had signed a consent form at the fertility clinic that stated that any unused embryos would be donated to research. However, the embryos could not be released without the consent of both donors. The agreement stated that in case of divorce, ownership of the embryos would be determined in a property settlement or decided by a court of law.
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In Britain there is a law that says unclaimed frozen embryos are to be kept only five years. In the United States there are no such laws and few rules beyond consent forms. At some IVF clinics the time limit on embryos extends to the donor's menopause. Dramatic advances are occurring in reproductive science, particularly in cryogenic preservation of human sperm, eggs, and embryos. It is a time when courts and legislatures increasingly are called upon to reconcile property interests of the reproductive partners and their families and the rights of third parties. As clinical procedures improve and more individuals and couples use in vitro fertilization, cryogenic preservation, surrogacy, and single parent reproduction, traditional property and proprietary issues need to be reconciled. In these and other cases, reference to traditional property concepts will provide a valuable framework for the merging public policy debate. If reproductive material such as sperm is property, can this be left in wills? Would a child conceived posthumously share the estate with existing heirs? Ellen Goodman of the Washington Post Writers Group wrote the following: Lately, I have tried to imagine introducing my late grandmother to the 5-year old twins. Grandma, I would say, meet Michayla and Mackenzie Woodward. One of the girls has eyes just like her father. The other looks like her dad around the chin and the mouth. Oh, by the way, the girls were born two years after his death. My grandmother's attitude toward new reproductive technology never went beyond her repeated wish: "One man should have one baby!" How would she respond to this information from the frontier? With her signature huff of skepticism? "Hoo ha." For that matter, I would like to introduce the twins' mother Lauren to the Massachusetts legislators of 1836. These men thought they'd covered all bases, when they voted to allow a child born posthumously to inherit a father's estate. Hey, guys, what about a child conceived posthumously? Posthumous conception? Postmortem creation? We live in a world in which we can separate reproduction from sex. We have sperm and eggs and embryos stored away in the freezers of myriad reproductive clinics. And now we are learning that we can separate reproduction from death. The Woodward story was a mix of unplanned tragedy and planned parenthood. When Lauren's husband Warren was diagnosed with leukemia and faced chemotherapy, he banked his sperm for a future family. After Warren died at 30, Lauren created their family. Lauren called her girls "a miracle" and won the right to have her late husband called the father on their birth certificates. But when she sued for survivor's benefits under Social Security, the federal courts asked for a state ruling. Last week they got it. The Massachusetts Supreme Judicial Court, the highest court ruling so far on posthumous conception, said that children can be the legal heirs of a dead parent as long as (1) they are
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biologically related to the father and (2) he gave his consent both to creating children and supporting them after his death. "Posthumously conceived children may not come into the world the way the majority of children do. But they are children nonetheless," wrote Chief Justice Margaret Marshall. When Woodward proves her husband's consent in a district court, this will be a closed case. But a closed case with dozens of open ends. I confess to mixed feelings about deliberately reproducing children whose only relationship with a parent is through the genes. I was appalled when a California man left 15 vials of frozen sperm to his girlfriend before he committed suicide. At the same time, I understand the impulse to "cheat death," as another widow and mother once put it. I understand why some soldiers leave behind sperm when they go to war and some cancer patients store a family when they face death. 18
Questions and Answers; Lessons Learned It is doubtful whether the general public, at the time of Louise Brown's birth, appreciated the magnitude of the scientific achievement. Today it is quite different, and IVF is recognized as one of the great medical breakthroughs of our time by the general public and scientists alike. Medicine and technology have grown together over the years to overcome an obstacle of nature. Over a million test-tube babies have been conceived and the once-heated debate over IVF has dwindled to almost nothing. The average probability of an infertile couple taking home a baby after IVF is one in five, about the same chance that healthy couples have of conceiving naturally each menstrual cycle. What was new when the IVF method was first introduced was that sexual intercourse was no longer needed for generating new life. Rather, the new technology provided the corollary to the pill: babies without sex. In retrospect, Louise Brown's conception in a petri dish from her mother's egg and her father's sperm now seems relatively natural. After Louise Brown's birth a utilitarian response dominated. No moral evils were involved in IVF if all parties were freely consenting and there was a positive balance of benefits over harms. Since that time, governments all over the world have adopted policies that allow the regulated use of IVF on the proven assumption that it produces more good than harm. When IVF was first introduced, substantial moral issues in the new technology centered around promises, trust, and commitments. 19 Pointed questions were asked: When does human life begin? What is the value of the human embryo? Do humans have inherent properties that make them valuable and if so, when do they acquire these properties? What is the value of genetic reproduction? What are the human's genetic and personal rights and duties? Is there a direct connection between genetics and people with moral rights? Is geneticism, like racism and sexism, a valid case for arguing societal relationships?
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Other questions demanded answers: Whose right is it, a woman's or a couple's, to procreate? Is it a right to carry and deliver (i.e., only a woman's right) or is it a right to nurture and rear? Is it a right to have your own biological child? Is the inability to conceive considered a disease (if so, whose disease is it?) Does infertility demand treatment wherever found—in women over seventy? In virgin girls? In men? Can these persons claim either a natural desire or a natural right to have a child, which the new technologies might or must provide them? Does infertility demand treatment by any and all available means—by artificial insemination, IVF, extracorporeal gestation, parthenogenesis, cloning, stem-cell research?20 All human beings enjoy an unrestricted and fundamental right to procreative liberty. There is support for such a claim in the U.S. Constitution, the Universal Declaration of Human Rights of the United Nations, and declarations of human rights issued by various other national and international organizations. Newer technological methods for making babies require prevention of transmission of inherited diseases such as cystic fibrosis or missing or defective chromosomes to prospective children. Human embryo experimentation, whether it is utilizing embryos left over from IVF or more recently, the technology to harvest stem cells from human embryos, has serious moral and ethical implications that need to be addressed in any discussion of such experimentation. 21 Advances in human biomedicine have opened new avenues and given hope to many. Yet, an uncertainty exists whenever persons do not understand a situation and cannot predict the outcome. Because few people tolerate uncertainty well, it is important to remember that before we ask what a new medical technology will do for us, we need to ask what it will do to us.
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5 THE WARNDCK REPORT The task you set the Inquiry was not an easy one. The issues raised reflect fundamental moral, and often religious, questions which have taxed philosophers and others down the ages. Rightly, you chose a membership which encompassed not only the many professions with a concern in these matters but the many religious traditions within a society, so that as many viewpoints as possible could be brought to bear on the morally sensitive issues before us. Dame Mary Warnock's June 26, 1984, letter to the British government on behalf of the Committee of Inquiry The Committee of Inquiry into Human Fertilization and Embryology, also known as the Warnock Committee and the Inquiry Committee, convened in July 1982 and was chaired by Dame Mary Warnock, philosopher and Mistress of Girton College of Cambridge University. The remaining fifteen members of the committee included professionals in theology, medicine, natural science, social science, law, and ethics.
Tasks of the Warnock Committee The Warnock Committee was set up to examine, among other things, ethical implications of new developments in assisted reproductive technologies. In Great Britain, ethical committees such as the Warnock Committee were used to advise
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governments, with a general intention to include a fair number of different points of view.1 Acknowledging that there was no such thing as a moral expert, the committee's task was primarily to give advice to British Ministers, based on moral judgments. Committee members were obliged to interpret the concept of ethics in a rather restricted way and they were reluctant to appear to dictate on matters of morals to the public at large. As a result, the committee based its views on argument rather than on sentiment. In the introduction to her book, A Question of Life (1985), Warnock wrote: "Now, there are some respects in which a Committee of Inquiry such as ours has to argue on utilitarian presumptions, especially with regard to legislation. By themselves, then, neither utilitarianism nor a blind obedience to rules could solve the moral dilemmas the Inquiry was forced with. We were bound to have recourse to moral sentiment, to try, that is, to sort out what our feelings were, and to justify them." 2 The committee set the following terms of reference: "To consider recent and potential developments in medicine and science related to human fertilization and embryology; to consider what policies and safeguards should be applied, including consideration of the social, ethical and legal implications of these developments; and to make recommendations." 3 By setting terms as the interests of medical-legal authorities and the patriarchal nuclear family, the committee provided that social and medical control of reproductive technologies must be in the hands of expert medical specialists once acceptable boundaries were set by legislation or licensing authority guidelines. "Barriers, it is generally agreed, must be set up; but there will not be universal agreement about where these barriers should be placed. The question must ultimately be what kind of society can we praise and admire? In what sort of society can we live with our conscience clear?" 4 Warnock realized that the public was extremely anxious over activities that the committee was about to examine when she wrote: "Society, insofar as it is a single identifiable body, has here, perhaps uniquely, a corporate reaction. It is one of fear. People generally believe that science may be up to no good, and must not be allowed to proceed without scrutiny, both of its objectives and of its methods." 5 Because many expressed deep concerns about the development of the new human-assisted reproductive technologies, the committee sought evidence from various organizations and institutions, such as the Royal College of Obstetricians and Gynecologists (RCOG), reflecting as many different perspectives as possible. The committee also visited Bourn Hall, the private in vitro fertilization center of IVF pioneers Edwards and Steptoe, in order to get a first-hand perspective on the new technology. The committee realized that they were to examine new reproductive technology that included countries other than Great Britain, one that was in the process of developing and rapidly changing worldwide. However, they limited themselves to a Great Britain approach, rendering invisible the international scope of science and medicine and the link to international politics. Although the committee attempted to keep abreast of current developments, Warnock said that they found
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the task overwhelming because different countries had different cultural, moral, and legal traditions that resulted in contrasting views. In addition, countries were also at different stages in development—both of services and of a policy response. 6 Warnock's committee divided its tasks into two parts. The first was infertility and the second was the pursuit of knowledge designed to benefit society at large, specifically evolving scientific developments. Taking a pragmatic view that they could react only to what they knew and what they could realistically foresee, the committee identified four areas of major concern: (1) Infertility as a disease, the domain of medicine (2) The sanctity of the embryo (3) The ideology of motherhood (surrogacy) (4) The status of scientific (technological) knowledge 7
The Report The Warnock Report was first published in 1984. The recommendations were incorporated, with certain modifications, in research and medical guidelines by the Royal College of Obstetricians and Gynecologists, the British Medical Association, and the Medical Research Council. Able to reach agreement on most areas, the Committee eventually issued a list of sixty-four recommendations concerning artificial techniques for assisting human reproduction. Framing their recommendations in general terms, the committee left specific details to be worked out by the British government and other appropriate organizations. Although everything in the report seemed quite reasonable to most reviewers, not everything in the report was as it should be to many. Those who reviewed the Warnock Report were divided. Most critics were angry at what they viewed as unreasonable recommendations, whereas others viewed the Warnock Report as a compromise. 8 Despite their differences, Warnock praised her committee members as being extremely capable, as evidenced by their thorough investigation of scientific information and the careful wording of the Warnock Report, which proved to be a key text, not only in Great Britain but in other countries as well. Taken as a point of reference by medical, scientific, and legal professionals, the committee's recommendations are even today used by many as a model for committees and guidelines. Acknowledging sensitivity of the issues, Warnock in a June 26, 1984, letter to the British government wrote: Despite the way in which members have worked together, there remain nonetheless certain differences between us; indeed it would have been surprising if, on such sensitive issues, we had been united. These differences, presented in three formal expressions of dissent have, significantly, focused on the very subjects, surrogacy and research on human embryos, which, to judge from the evidence, arouse the greatest public
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anxiety. Thus even in our disagreement we have reflected the range of views within society 9 Regrettably, the committee did not feel that they were able to obtain as much evidence as they would have liked, particularly from minority and special interest groups. Rather than discussing in their report every situation that might arise and then relating it to existing law, Warnock said that they considered fundamental questions raised in relation to existing law, as well as essential legislative changes applied equally throughout Great Britain and Northern Ireland. 10 The committee was silent on the use of genetic technology by the military and was cautious on possible future developments in research—for example, trans-species fertilization, drug testing using embryos, cloning, parthenogenesis, nuclear substitution, and gene replacement. The committee also avoided making recommendations on abortion, contraception, and ectogenesis (artificial womb) because these topics were within the terms of reference. At the time that the committee wrote the report, they had agreed that cloning was too far in the future to require legislation. With regard to human embryo research, they replaced the question of When does life begin ("personhood")? with the ethical and legal question, How is it right to treat the human embryo?11
Infertility as a Medical Condition The committee heard arguments for and against treatment for infertility. The committee made known to the public that it thought of the family as a highly valued institution of society and that infertility was a medical condition worthy of study. Primary emphasis of the committee's recommendations was on fertility as a malfunction of couples, rather than malfunction of male or female. Views in favor of treating infertility by assisted reproductive technologies included a powerful urge to perpetrate an individual's genes through a new generation—a desire that could not be assuaged by adoption; social pressures such as the feeling that couples are unable to fulfill their own and others' expectations that they have children; and exclusion by contemporaries who had children and exclusion from activities of these families. Arguments against the treatment of infertility by assisted reproductive technologies included the view that the world was overpopulated and that it was wrong to create by assisted reproductive technologies more human beings who would eventually consume finite resources; that it was not only selfish to use assisted reproductive technologies but that it also interfered with nature and was against the will of God; and further, that the desire to have children by assisted reproductive technologies was no more than a wish; it did not constitute a need. The committee concluded that infertility was a malfunction of the human body and one that merited treatment. They agreed that, in general, everyone should be entitled to seek expert advice and appropriate investigation of his or her infertility. The committee recommended that the patient always be provided with a full explanation of the reasons he or she was denied treatment. However, no firm opinion was offered on the provision of help with children of lesbians.
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Overall, the treatment of infertility by assisted reproductive techniques was supported by the committee. Rejected was the need to restrict population growth. 12
Embryo Research The committee's major approach was embryo centered, as well as knowledge centered. All other issues were considered relatively trivial. Asked to recommend whether embryo research should be allowed at all because of public disapproval, the committee looked at the very earliest stages of human development, starting with in vitro fertilization (IVF) of the egg and sperm to form the zygote and eventually the first recognizable features of the embryo proper. Warnock wrote: "It was the development of IVF that, for the first time, gave rise to the possibility that human embryos might be brought into existence which might have no chance to implant because they were not transferred to a uterus and hence no chance to be born as human beings. This inevitably led to an examination of the moral rights of the embryo." 13 The committee defined limits of embryo research by making two categories of study. The first category was pure research and was designed to increase and develop knowledge of the very early stages of the embryo. The second category was applied research with direct diagnostic or therapeutic aims for the human embryo or for the alleviation of infertility in general. 14 Arguments were heard for and against the use of human embryos for research. The main concerns of opponents were the status of the embryo and fear of out-of-control science or the Frankenstein image. Opponents also had major concerns about scientists tampering with human life in order to create hybrids, or participating in selective breeding and eugenic selection. Feminists complained that the recommended restrictions on human embryo research concerned the humanity of embryos, not women. They felt that approval of human embryo research boiled down to approving the use of women as laboratory animals.15 Opponents of embryo research also felt that embryos were potentially human and thus should have the same status as a child or an adult and should have a chance for further development. They argued that to take the life of an innocent embryo for research was morally unacceptable. Opponents also believed it unethical to carry out any research on human embryos without first obtaining informed consent. Since embryos were not able to give consent, opponents felt they should not be used for research purposes. The committee gave moral approval to IVF only if each embryo that was produced was transferred to a uterus. Others felt that since embryos were potentially human persons, and if "personhood" had been established, it might be permissible for research to be undertaken. Supporters of human embryo research argued that a human embryo could not be thought of as an actual or even a potential person. They concluded that the embryo was a mere collection of cells that had no potential for development unless implanted in a uterus. Considering the embryo only as a cluster of cells, supporters believed that the embryo did not deserve the same respect as a human being. However, they argued that if beneficial results could be obtained from embryo research then it should be done. At the time of the study, the committee
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underestimated the speed with which it would be possible to use DNA probes for the diagnosis of the genetic health of an embryo. The committee had substantial difficulty in reaching an agreement on human embryo research. Warnock wrote: I do not believe that the question of individual freedom enters here into public thinking. A scientist who argued that he must be free to carry out whatever research he liked, by whatever methods, would not get much public support, if this involved the use of other human beings. Society feels, albeit obscurely, that its members, especially the most helpless, such as children and the very old, must be protected against possible exploitation by enthusiastic scientists; and embryos are brought into the category of those deserving protection, just as animals are. This is a matter of public, and widely shared, sentiment. 16 With regard to embryos being used for routine testing of drugs, Warnock wrote on behalf of the committee: "We feel very strongly that the routine testing of drugs on human embryos is not an acceptable area of research because this would require the manufacture of large numbers of embryos. We concluded however that there may be very particular circumstances where the testing of such substances on a very small scale may be justifiable."17 The committee considered biopsy as a possible future development to allow detection of genetic abnormalities and genetic selection of embryos. It was noted that the scientific definition of "genetic abnormality" was at the time expanding to include "abnormalities" like cleft palate, and that the desire for "perfect" babies was being exploited by IVF researchers who argued for the superiority of artificial reproduction. 18
Embryos and the Law Committee members agreed that human embryo research was a matter that needed to be legislated, and the extent to which embryos were used must be a decision based on law. Believing that the law must generally be seen to be beneficial, intelligible, and enforceable, Warnock wrote: "This was the task that, especially in the second part of the Report, the Committee had to tackle. It was a task, as I have suggested, which raised profound and far-reaching questions about the relation between the law and the morality of society." 19 The committee concluded that the human embryo should not be accorded the same status as a living person under current English law. They agreed, however, that human embryos should be afforded some protection in law. The committee recommended that research conducted on IVF embryos and the handling of such embryos should be permitted only under license and that any unauthorized use of an in vitro embryo would in itself constitute a criminal offense. In making its recommendation, the committee cited the Offenses Against the Person Act 1861, the Infant Life Preservation Act 1929, and the Abortion Act 1967.
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Committee members could not agree over the degree of protection that the law should afford to the human embryo. The question, according to Warnock, was not whether the embryo was alive and human, or whether, if implanted, might become a full human being. Committee members agreed that these things were true. Rather, they argued that because, in practical terms, a collection of four or sixteen cells was very different from a full human being, from a new human baby, or from a fully formed human fetus, it might quite legitimately be treated differently. The committee did agree, however, that in some circumstances an embryo at a very early developmental stage might be used for research purposes. The committee recommended that no live embryo derived from in vitro fertilization (frozen or unfrozen) should be kept alive, if not transferred to the uterus of a woman, beyond fourteen days after fertilization. They also recommended that it be a criminal offense to handle or use the embryo beyond that time. 20 The limit of fourteen days after fertilization was one of many criteria suggested to the Warnock Committee by consulting doctors and scientists. British embryologist Anne McLaren, a member of the Warnock Committee, presented a scientific explanation for the fourteen day limit. McLaren explained that for the first two weeks after fertilization the cells of the growing "pre-embryo" are engaged in making cells that eventually become the placenta and at fifteen or sixteen days the "primitive streak" appears, where the "definitive" embryo begins to form. Committee members recommended regulation of IVF, artificial insemination by donor (AID), human embryo research, and medical application of genetic technologies through a centralized licensing authority. Any nonlicensed activity, they concluded, would be a criminal offense. Some committee members did not make the same distinction between spare and deliberately generated embryos and argued that it made no difference whether the embryos just happened to be available or were created intentionally for the purpose of research. In either case, Warnock writes, there was no potential for human life since the embryos would not be transferred to a uterus. In either case, however, the fourteen day limitation would be in effect. The committee recommended that embryo research should be carried out wherever possible with the consent of the genetic parents. Deciding to allow cross-species experiments, the committee recommended that those embryos would have to be destroyed after the first cell division. The transfer of human embryos to the uteri of other species was banned outright. The committee requested that inspectors monitor laboratory work in humans using assisted reproductive technologies. Some feminist groups countered that the committee took the attitude of experts who state that human embryo research and IVF are the antithesis of abortion, the creation of life. However, Warnock Committee members argued that a moral couple uses technologies to avoid abortion. 21 The committee argued that, unlike a full human being, the embryo might legitimately be used as a means to an end that was good for other humans. Reasoning such as this became the committee's moral judgment. Warnock, in a compelling statement on behalf of the committee, wrote:
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What was being weighed up was certain human goods on the one hand and the status of these collections of cells on the other. One was to be valued against the other. The majority of the Committee was not moved by the argument that these cells could, if certain conditions were satisfied, become human beings. They did not rely, that is to say, as the minority did, on "potentiality", but on the consideration of what the embryo was at a particular time, its actual mode of existence immediately after fertilization. If, on broadly utilitarian grounds, the benefits from the use of embryos at this stage seemed very great, and not only was there no harm in the sense of immediately-felt pain to the embryo but also in addition there was no absolute outrage of general moral sentiment (as there would be, for instance, if even a very young or profoundly defective child were used for research) then the majority argued that the embryo might be used for research. The precise point of dispute within the Committee was not on the value that should be attached to human life in general, but to the value that should be attached to human life at its very earliest stage of development. It was here that it was necessary to invoke the law.22 The committee also discussed embryonic biopsy as a possible future research development to detect genetic abnormalities. This was considered by some as a eugenic approach to reproduction, and the committee directed the question of embryonic gene therapy to the proposed licensing authority, authorizing them to decide about such matters. Warnock wrote: Nevertheless, the argument runs, research on embryos may be justified, provided that the embryos used as subjects of research were brought into being, not primarily for research, but in order to alleviate a particular case of infertility. This argument in part rests on the doctrine known to philosophers as "double effect": an act which would be wrong if chosen for its own sake may be justified if it occurs as a byproduct of some other, well-intentioned act. According to this view, therefore, there would be no general acceptance of research on embryos, but acceptance only in the limited circumstance of the existence of "spare embryos". Those who hold this view would argue that it would be preferable on moral grounds that there should be no research on embryos rather than research regardless of the circumstances in which the embryos were brought into being. 23 The committee decided it would be morally wrong to bring human embryos into being with the sole intent that they be used for research. Members felt that once a foot was set on the "slippery slope" of deliberate creation of embryos, there would be no end to the dangers. In the case of "spare embryos," the committee recommended that no research should be carried out without the informed consent of the couple for whom the embryo was generated. The committee recommended a need to obtain consent to the method of use or disposal of spare embryos.
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Artificial Insemination by Husband or Donor The Warnock Committee voted to consider artificial insemination (AI) because it was neither accepted ethically nor regulated by law. Committee members decided to propose that artificial insemination by the donor (AID) be regulated for the same reasons and by the same licensing authority required to regulate IVF. This meant that females who ran self-insemination groups in Great Britain would be criminally liable. The committee concluded that AID should receive protection of the law and should be subject to certain conditions and safeguards, that a licensing authority to regulate provision of AID should be established, and that any nonlicensed activity should be a criminal offense.24 As to eligibility for AID, the committee recommended that physicians would be the final authority but would require a special license to offer AID. Researchers would have access to donated sperm for genetic studies, just as they would have access to gametes and embryos from IVF. This was interpreted by some feminist groups as the state's desire to reassert traditionalist male authority. 25 The committee recommended that artificial insemination by husband (AIH) or an IVF child not in utero at the date of the father's death should be disregarded for purposes of succession to and inheritance from the father. Anticipating unprecedented legal complications resulting from the use of frozen embryos, they added: for the purposes of establishing primogeniture the date and time of birth, and not the date of fertilization, shall be the determining factor.26 At the time the Warnock Report was written neither AIH nor AID was unlawful. However, in 1978 Conservative Member of Parliament Rhodes Boyson had demanded legislation to ban the use of AID by lesbians, saying: "To bring children into the world without a natural father is evil and selfish. This evil must stop for the sake of the potential children and society, which both have enough problems without the extension of this horrific practice." 27 The Warnock recommendations on eligibility concurred with the sentiments of Boyson. The committee recommended that a child born to a married couple as a result of AIH was the legitimate child of that couple. A child born as a result of AID, on the other hand, was illegitimate, and so was liable to suffer all the disadvantages associated with that status. In theory, the husband of the woman who bore an AID child had no parental rights and duties in law with regard to the child; rather, these in principle lay with the donor. The committee further recommended that on reaching the age of eighteen the child should have access to basic information about the donor's ethnic origin and genetic health and that legislation should be enacted to provide the right of access to this. The legislation should not be retrospective. 28 The committee heard strong arguments against AID. Most Warnock Committee members were concerned that a third party would be introduced into what ought to be an exclusive relationship between husband and wife. Some considered AID harmful to not only the family but to the spousal relationship because the child would be the wife and donor's biological child, excluding the husband from the procreation. However, others believed that it would provide stability in the family if the husband agreed to the procedure. After much discussion, the committee did not accept that the donor was necessarily a threat to the stability of the relationship. 29
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There were equally strong arguments in favor of AID. Supporters argued that the process allowed couples to have a child they otherwise would not have. Since the AID child was very much desired, the committee agreed that in all likelihood the child would strengthen the couple's relationship. The committee did not encourage the possibility of prospective parents seeking donors with specific characteristics by the use of whose semen they hoped would give birth to a particular type of child, but believed that the couple should be given sufficient information on the donor for their reassurance. 30
In Vitro Fertilization (IVF) With regard to infertility and in vitro fertilization (IVF), Warnock wrote: "In the days preceding in vitro fertilization the cause of infertility in a childless couple was generally attributed to the woman; only occasionally was it thought that there might be something wrong with the man." 31 Realizing the angst that infertility causes childless couples, Warnock, on behalf of the committee, wrote: "For those who long for children, the realization that they are unable to found a family can be shattering. It can disrupt their picture of the whole of their future lives." 32 The committee recognized that during the IVF pioneering days of Edwards and Steptoe there had been a great deal of concern and anxiety over IVF. Writing about the 1970s and the ethical debates over their pioneering IVF work, Robert Edwards commented: On the other hand I would not wish the reader to imagine we [Edwards and Steptoe] were overly vulnerable. I had been a member of a small committee for some years now that had been formed to clarify ethical issues arising from advances in biology. Its Chairman was Walter Bodmer, Professor of Genetics at Oxford University. It included a theologian, Gordon Dunstan, John Maddox, who was editor of Nature, and two politicians, Shirley Williams, a future Cabinet Minister, and David Owen, a future Foreign Secretary. Doctors and scientists like myself held numerous meetings and we called on many witnesses to discuss organ transplantation, the screening of fetuses for inherited disorders, artificial insemination and, of course, fertilization in vitro.33 The practice of IVF was commended by the committee, but within a framework of licenses because the overall rate of success at the time of the Warnock Report was still quite low. IVF had been originally proposed for use on women, like Louise Brown's mother, whose infertility was caused by blocked or absent fallopian tubes (oviducts). Today, among IVF candidates are fertile women whose partners have low sperm counts or who do not wish, for one reason or another, to be inconvenienced by a pregnancy. With regard to IVF the committee's most visible concerns were the status of the embryo and the problem of infertility in marriage. The committee approved
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the use of IVF for infertility treatment for cohabiting heterosexual couples when eggs that were taken from a woman were fertilized with the sperm of her partner. The committee cited medical risks of surgical removal of eggs as an argument against egg donation. Eventually, the committee approved egg donation because of its social value. Concern for the embryo was a prime argument of those who were against IVF. One concern included more embryos brought into existence than would be transferred to the mother's uterus—i.e., "spare embryos." Those opposed to IVF believed it was morally unacceptable to deliberately manufacture embryos that had the potential for human life and then to discard them if not needed or used. The primary argument in favor of IVF was that the successful technology would allow a childless couple to have a child. Having substantial concerns over IVF, Warnock's committee discussed many significant questions. They concluded that the medical risks of IVF were not necessarily more dangerous that those associated with surgical removal of eggs (both procedures carry dangerous risks). The committee wondered why IVF should be rejected. The evident reason, they ascertained, was the risk of unwanted pregnancy in the donor woman if the fertilized egg implants in her own uterine wall. The committee was perplexed by the question, what can society do with this other mother? The confusion of such relationships challenged the exclusivity of marriage. They considered the fact that two women would be sharing a pregnancy. If the donor woman became pregnant, it would be an undesirable outcome. It she decided to have an abortion, she would be considered not a good woman or mother. If she carried the child to full term and kept it, the father of her offspring would be someone else's husband. Considering these things, the committee eventually concluded that there would be no respectable place for this donor woman in the usual categories of motherhood. The only argument the committee cited in favor of IVF was that it would help infertile couples have children and was the only method by which some could have a child that was genetically entirely theirs. This exclusive nuclear family argument eventually convinced the committee of the importance of IVF. However, certain feminist groups countered that in the social terms of this discourse, women did not exist; rather, motherhood was what existed. There was a call for the creation of a new licensing authority to regulate both research and therapy pertaining to AID and both standard and nonstandard forms of IVF; a fourteen-day limit on the use of frozen embryos for either research or therapeutic purposes; the need to obtain consent from the donor for any interventions pertaining to embryos; and, perhaps most controversially, the criminalization of surrogacy.34
Egg Donation When the Warnock Committee studied egg donation, they found that it was open to the same kinds of objections as AID—the introduction of a third party into the marriage. They decided that egg donation interfered with the normal process of fertilization, much like IVF. Proponents of egg donation argued that it provided
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an opportunity for both partners to contribute to the birth of a child, allowing the couple the same experiences during the pregnancy as other couples have. The committee decided that egg donation provided an offspring which was genetically related to the husband. Egg donation also meant that women who carried heritable genetic disease could avoid having to make abortion decisions by using donor eggs. A physical risks argument was used to reject the technique of egg donation by uterine lavage, where the donor woman conceived in vivo (in her body), usually by artificial insemination with sperm from the husband of the receiving couple. In successful cases, the fertilized egg was "washed" from the donor's womb and placed in the womb of the receiving woman. The committee considered the consequences when a woman donated an egg for transfer to another. They concluded that egg donation should be treated as absolute and that, like a male donor, the female donor should have no rights or duties with regard to any resulting child. The committee recommended that when a child was born to a woman following donation of another's egg, the woman giving birth should, for all purposes, be regarded in law as the mother of that child, and that the egg donor should have no rights or obligations in respect to the child. 35 The Warnock Committee considered egg donation as ethically acceptable where the donor was properly counseled and made aware of any risks. The committee felt that the law should treat egg donation in the same manner as AID and IVF and that the same principles of practice should be applied to all. This included anonymity of the donor, limitation of the number of children born from the eggs of any one donor to ten, openness with the child about his/her genetic origins, the availability of counseling for all parties, and informed consent. 36
Embryo Donation The committee determined that embryo donation took two forms. The first involved the donation of both an egg and semen. The egg was fertilized in vitro with donated semen and allowed to develop to an embryo. The resulting embryo was transferred to a woman who was unable to produce eggs and whose husband was also infertile. The second method, called uterine lavage, did not involve removing the egg by surgical intervention. In this method the egg was released naturally from the ovary during the menstrual cycle. During the optimal time of ovulation the female was artificially inseminated with semen from the husband of the infertile woman or from a donor if the husband was also infertile.37 Three or four days later, before the start of implantation, the donor's uterus was "washed out" and the embryo was retrieved. The embryo was next transferred to the uterus of the infertile woman and allowed to implant, and the pregnancy carried to term. Arguments against embryo donation included the introduction of a third party into an exclusive relationship. The committee also considered the fact that when a semen donor was used neither of the nurturing parents had contributed genetically to the child. The committee felt that embryo donation was probably the least satisfactory form of donation. Believing that there would be a minimal number of embryo
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donations, the committee recommended that it be accepted as a treatment for infertility, subject to the same type of licensing and controls as AID, IVF, and egg donation. The committee also recommended that it should be accepted practice to offer donated gametes and embryos to those at risk of transmitting hereditary disorders. Primarily because of the risk to the egg donor, the committee did not recommend embryo donation by lavage.
Surrogacy In writing their official recommendations, the question of surrogacy presented the committee with some of the most difficult problems they were to encounter. After considerable discussion, the committee unanimously agreed that surrogacy for convenience alone—for example, where a woman did not want to undergo pregnancy because she was deeply involved with her career—was totally unacceptable. The committee concluded that the exploitation of another individual outweighed the potential benefits. The committee agreed that criminal law should be involved in the control of surrogacy and recommended that legislation be introduced to render criminal the creation or the operation of surrogacy. Recommendations included making criminally liable the actions of professionals and others who knowingly assisted in the establishment of surrogate pregnancy, and that it be provided by statute that all surrogacy agreements be illegal contracts and therefore unenforceable in the courts. Rejecting surrogacy, the committee reported that "the weight of public opinion is against the practice and recommends the criminalization of organized surrogacy arrangements, referring to the activity as 'recruitment of women.' " 38 Arguments against surrogacy all addressed the same issue—the meaning of motherhood and woman's sexuality: To introduce a third party into the process of procreation which should be confined to the loving partnership between two people, is an attack on the value of the marital relationship; it (surrogacy) is inconsistent with human dignity; the relationship between mother and child is itself distorted by surrogacy; this is the wrong way to approach pregnancy; since there are some risks attached to pregnancy, no woman ought to be asked to undertake pregnancy for another, in order to earn money. Nor, it is argued, should a woman be forced by legal sanctions to part with a child, to which she has recently given birth, against her will. 39 The committee drew a firm line on the practice of surrogate motherhood where the mothers did not intend to keep the child. They based their decisions chiefly on emotional and legal difficulties but also on fears of "commercial
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exploitation." 40 However, members of the committee did feel there was some place for surrogacy in special circumstances. In 1986, IVF pioneers Patrick Steptoe and Robert Edwards also suggested that surrogacy be allowed in special circumstances—for example, when a sister or relative of an infertile couple in their IVF program was willing to become a surrogate mother. For example, Steptoe and Edwards asked: "Why should a childless woman with a hysterectomy be denied the chance of a child with the willing help of another woman, perhaps a sister?" 41 In deciding on surrogacy, the committee agreed unanimously on the disapproval of surrogate motherhood, largely because of possible consequences for the child. They agreed, however, that surrogacy could not be prevented by law because of the intrusiveness of any law that would be impossible to enforce. By a majority vote, the committee recommended that the commercial use of surrogacy arrangements, as a way of making money for an agency, could and should be made a criminal offense. The 1985 Surrogacy Arrangements Act criminalized surrogacy in Great Britain. Two members of the committee, Wendy Greengross and David Davies, dissented from the majority opinion to ban surrogacy. However, they did express concerns over surrogacy, saying they believed it could lead to serious problems. They agreed with the rest of the committee that criminal law should prevent profit making using surrogates and that surrogacy for convenience should not be allowed. Many doctors and IVF practitioners opposed the committee's rejection of surrogacy, and in 1985 a small majority of members of the British Medical Association (BMA) voted in favor of surrogacy as a medical treatment for infertility, against BMA official policy. The committee reported that "supporting research on the prevention of genetic defect is one thing; supporting research for high tech, state controlled, artificial reproduction, at the expense of women's bodies, for the sake of producing superior offspring, is another." 42
Freezing and Storage of Human Semen, Eggs, and Embryos The committee did not object to the freezing of human semen, eggs, and embryos in the treatment of infertility and recommended the use of frozen semen in artificial insemination. However, subject to review by the licensing body, they recommended that the use of frozen eggs in therapeutic procedures not be undertaken until research showed that there was no risk. The committee also recommended that the clinical use of frozen embryos should continue to be developed under review by the licensing body. The committee recommended that five-yearly reviews of deposited eggs and semen be made. They also recommended that legislation provide that when a person dies during the storage period or cannot be traced at a review date the right of use or disposal of his or her frozen gametes should pass to the storage authority. It also discouraged the use by a widow of her dead husband's semen for artificial insemination.
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W i t h regard to storage of embryos for future use, the committee r e c o m m e n d e d a m a x i m u m of t e n years, after which t i m e t h e right t o use or disposal s h o u l d pass t o t h e storage authorities. However, the c o u p l e w h o stored t h e e m b r y o s h o u l d have limited rights t o t h e use and disposal of t h e e m b r y o . If t h e r e was a marital b r e a k d o w n , it was r e c o m m e n d e d that t h e use o r disposal of the e m b r y o s h o u l d pass t o the storage a u t h o r i t y as t h o u g h t h e ten-year p e r i o d h a d expired. T h e c o m m i t t e e r e c o m m e n d e d n o right t o o w n e r s h i p of a h u m a n e m b r y o , as directed by legislation. W i t h regard t o t h e q u e s t i o n of inheritance and succession, t h e c o m m i t t e e r e c o m m e n d e d t h a t for t h e p u r p o s e s of establishing p r i m o geniture t h e date and t i m e of b i r t h , and n o t the date of fertilization, s h o u l d be t h e d e t e r m i n i n g factor.
Official Recommendations T h e c o m m i t t e e acknowledged t h a t m a n y of its r e c o m m e n d a t i o n s were u n d u l y lax b u t were justified by their relevance t o beneficial medical t r e a t m e n t s for infertility. 43 Listed below are the c o m m i t t e e ' s official r e c o m m e n d a t i o n s : A. The licensing body and its functions 1. A new statutory licensing authority be established to regulate both research and those infertility services which we have recommended should be subject to control. 2. There should be substantial lay representation on the statutory authority to regulate research and infertility services and that the chairman must be a lay person. 3. All practitioners offering the services we have recommended should only be provided under license, and all premises used as part of any such provision, including the provision of fresh semen and banks for the storage of frozen human eggs, semen and embryos should be licensed by the licensing body. 4. AID should be available on a properly organized basis and subject to the licensing arrangements, to those infertile couples for whom it might be appropriate. The provision of AID services without a license for the purpose should be an offense. 5. The service of IVF should continue to be available, subject to the same type of licensing and inspection as we have recommended with regard to the regulation of AID. 6. Egg donation should be accepted as a recognized technique in the treatment of infertility subject to the same type of licensing and controls as we have recommended for the regulation of AID and IVF. 7. The form of embryo donation involving donated semen and egg which are brought together in vitro be accepted as a treatment for infertility, subject to the same type of licensing and controls as we have recommended with regard to the regulation of AID, IVF, and egg donation. 8. The technique of embryo donation by lavage should not be used at the present time.
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9. The use of frozen eggs in therapeutic procedures should not be undertaken until research has shown that no unacceptable risk is involved. This will be matter for review by a licensing body. 10. The clinical use of frozen embryos may continue to be developed under review by the licensing body. 11. Research conducted on human in vitro embryos and the handling of such embryos should be permitted only under license. 12. No live human embryo derived from in vitro fertilization, whether frozen or unfrozen, may be kept alive, if not transferred to a woman beyond fourteen days after fertilization, nor may it be used as a research subject beyond fourteen days after fertilization. This fourteen day period does not include any time during which the embryo may have been frozen. 13. Consent be obtained as to the method of use or disposal of spare embryos. 14. As a matter of good practice no research should be carried out on a spare embryo without the informed consent of the couple for whom the embryo was generated, whenever this is possible. 15. Where trans-species fertilization is used as part of a recognized program for alleviating infertility or in the assessment or diagnosis of sub-fertility it should be subject to license and that a condition of granting such a license should be that the development of any resultant hybrid should be terminated at the two-cell stage. 16. The licensing body be asked to consider the need for follow-up studies of children born as a result of the new techniques, including consideration of the need for a centrally maintained register of such births. 17. The sale or purchase of human gametes or embryos should be permitted only under license from, and subject to, conditions prescribed by the licensing body. B. Principles of provision 18. As a matter of good practice any third party donating gametes for infertility treatment should be unknown to the couple before, during and after the treatment, and equally the third party should not know the identify of the couple being helped. 19. Counseling should be available to all infertile couples and third parties at any stage of the treatment, both as an integral part of NHS provision and in the private sector. 20. O n reaching the age of eighteen the child should have access to the basic information about the donor's ethnic origin and genetic health and that legislation be enacted to provide the right of access to this. 21. In the case of more specialized forms of infertility treatment the consent in writing of both partners should be obtained, wherever possible, before treatment is begun, as a matter of good practice. Any written consent should be obtained on an appropriate consent form. 22. The formal consent in writing by both partners should, as a matter of good practice, always be obtained before AID treatment begins. A consent form should be used and thoroughly explained to both partners.
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T H E W A R N D C K REPORT 23. For the present, there should be a limit of ten children who can be fathered by one donor. 24. In cases where consultants decline to provide treatment they should always give the patient a full explanation of the reasons. 25. The NHS numbers of all donors be checked by the clinics where they make their donations against a new centrally maintained list of NHS numbers of existing donors, which is to be held separately from the NHS donor register. 26. There should be a gradual move towards a system where semen donors should be given only their expenses. 27. In relation to egg donation the principles of good practice we have already considered in relation to other techniques should apply, including the anonymity of the donor, limitation of the number of children born from the eggs of any one donor to ten, openness with the child about his genetic origins, the availability of counseling for all parties and informed consent. 28. It should be accepted practice to offer donated gametes and embryos to those at risk of transmitting hereditary disorders. 29. All types of "do-it-yourself" sex selection kits should be brought within the ambit of control provided by the Medicines Act with the aim of ensuring that such products are safe, efficacious and of an acceptable standard for use. 30. The use of frozen semen in artificial insemination should continue. 31. There should be automatic five-yearly reviews of semen and egg deposits. 32. There should be a maximum of ten years for the storage of embryos after which time the right to use or disposal should pass to the storage authority. 33. When one of a couple dies the right to use or dispose of any embryo stored by that couple should pass to the survivor. If both die that right should pass to the storage authority. 34. Where there is no agreement between the couple the right to determine the use or disposal of an embryo should pass to the storage authority as though the ten year period had expired. C. Service provision 35. Funding should be made available for the collection of adequate statistics on infertility and infertility services. 36. Each health authority should review its facilities for the investigation and treatment of infertility and consider the establishment, separate from routine gynecology, of a specialist infertility clinic with close working relationships with specialist units, including genetic counseling services, at regional and supra-regional level. 37. Where it is not possible to have a separate clinic, infertility patients should be seen separately from other types of gynecological patients, wherever possible. 38. The establishment of a working group at national level made up of central health departments, health authorities and those working in infertility, to draw up detailed guidance on the organization of services.
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39. Consideration be given to the inclusion of plans for infertility services as part of the next round of health authority strategic plans. 40. IVF should continue to be available within the NHS. 41. One of the first tasks of the working group, whose establishment we recommend, should be to consider how best an IVF service can be organized within the NHS. D. Legal limits on research 42. The embryo of the human species should be afforded some protection in law. 43. Any unauthorized use of an in vitro embryo would in itself constitute a criminal offense. 44. Legislation should provide that research may be carried out on any embryo resulting from in vitro fertilization, whatever its provenance, up to the end of the fourteenth day after fertilization, but subject to all other restrictions as may be imposed by the licensing body. 45. It shall be a criminal offense to handle or to use as a research subject any live human embryo derived from in vitro fertilization beyond that limit (i.e., fourteen days after fertilization). 46. No embryo which has been used for research should be transferred to a woman. 47. Any unlicensed use of trans-species fertilization involving human gametes should be a criminal offense. 48. The placing of a human embryo in the uterus of another species for gestation should be a criminal offense. 49. The proposed licensing body promulgates guidance on what types of research, apart from those precluded by law, would be unlikely to be considered ethically acceptable in any circumstances and therefore would not be licensed. 50. Unauthorized sale or purchase of human gametes or embryos should be made a criminal offense. E. Legal changes 51. The AID child should in law be treated as the legitimate child of its mother and her husband, where they have both consented to the treatment. 52. A change in the law so that the semen donor will have no parental rights or duties in relation to the child. 53. Following the English Law Commission, that it should be presumed that the husband has consented to AID, unless the contrary is proved. 54. The law should be changed so as to permit the husband to be registered as the father (see #51). 55. Legislation should provide that when a child is born to a woman following donation of another's egg the woman giving birth should, for all purposes, be regarded in law as the mother of that child, and that the egg donor should have no rights or obligations in respect to the child.
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56. The legislation proposed should cover children born following embryo donation (see #53 and #54). 57. Legislation should be introduced to render criminal the creation or the operation in the United Kingdom of agencies whose purposes include the recruitment of women for surrogate pregnancy or making arrangements for individuals or couples who wish to utilize the services of a carrying mother; such legislation should be wide enough to include both profit and non-profit making organizations. 58. Legislation should be sufficiently wide enough to render criminally liable the actions of professionals and others who knowingly assist in the establishment of a surrogate pregnancy. 59. It should be provided by statute that all surrogacy agreements are illegal contracts and therefore unenforceable in courts. 60. Legislation should provide that where a person dies during the storage period or cannot be traced at a review date the right of use or disposal of his or her frozen gametes should pass to the storage authority. 61. Legislation be introduced to provide that any child born by AIH who was not in utero at the date of the death of its father shall be disregarded for the purposes of succession to and inheritance from the latter. 62. Legislation be enacted to ensure there is no right of ownership in a human embryo. 63. For the purposes of establishing primogeniture the date and time of birth and not the date of fertilization shall be the determining factor. 64. Legislation be introduced to provide that any child born following IVF, using an embryo that had been frozen and stored, who was not in utero at the date of the death of the father shall be disregarded for the purposes of succession to and inheritance from the latter.44
Reactions to the Warnock Report T h e ancient Italian system says t h a t it is a g o o d thing that we have intuitions. In t h e case of t h e W a r n o c k R e p o r t , however, intuitive feelings ranged from outrage and shock t o intolerance and disgust. Public c o n c e r n s centered a r o u n d t w o major facets—the loss of e m b r y o s after transfer t o t h e u t e r u s (an essential step in t h e I V F process) and t h e loss of e m b r y o s t h a t were n o t transferred. W a r n o c k and h e r c o m m i t t e e were aware t h a t negative feelings challenged their r e p o r t . In a J u n e 26, 1984, letter t o the British g o v e r n m e n t , W a r n o c k said: It is n o t possible t h a t a r e p o r t like this s h o u l d b e equally well received in all q u a r t e r s , given s o m e of t h e controversial issues we have h a d t o consider. T h e r e is b o u n d t o be criticism t h a t we have gone t o o far, or n o t far e n o u g h . However, we have sought t o p r o v i d e o n t h e o n e h a n d a reasoned discussion of t h e issues which we h o p e will c o n t r i b u t e t o a high s t a n d a r d of public debate o n m a t t e r s which are of deep c o n c e r n t o t h e public, and o n t h e o t h e r a c o h e r e n t set of p r o p o s a l s for h o w public policy, rather t h a n t h e individual conscience, s h o u l d r e s p o n d t o
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a range of developments which many people will not wish to participate in, but which others find entirely acceptable. We have tried in short, to give due consideration both to public and to private morality.45 The heated and critical reactions that greeted the Warnock Report gave pause to those in the United States who believed that the time had come to initiate regulation or legislation with respect to in vitro fertilization. 46 Most Members of Parliament in Great Britain felt that the recommendations were too permissive, whereas many prominent scientists and scientific societies thought it too restrictive—particularly the recommendations concerning human embryo research. Legal authorities in particular did not like the committee's stance on surrogacy and the commercialization of in vitro fertilization. 47,48 Feminists were unhappy with parts of the Warnock Report, stating that although the public and others were invited to submit evidence no women's group had been asked to present oral evidence. This included the main artificial insemination (AI) agency in Great Britain (British Pregnancy Advisory Service) and the largest infertility clinic in Great Britain (Hammersmith Hospital). 49 Feminist groups challenged the committee's ruling that AID and IVF should be made available in Great Britain to treat infertility, but only for the heterosexual couple living together in a stable relationship. 50 In response to this concern, the Warnock Committee issued a statement saying that they believed as a general rule it was better for children to be born into a two-parent family, with both father and mother. 51 In general, the scientific community enthusiastically accepted regulation of AID. Although they argued for less regulation of human embryo research in the name of scientific freedom, they endorsed the recommendations to regulate AID. In one report, the editors of Nature said that the committee proposals on AID were "less stringent than they might be" because genetic data about donors should be available to researchers. 52 The scientific establishment's response to the Warnock Report was: less regulation for embryo research in the interests of science but more regulation for AID, again in the interests of science.
9D
P A R T III Fighting to Save a Gene Pool Ethnic history lies hidden within our DNA. The Human Genome Diversity Project (HGDP) began as an international study intended to collect and preserve genetic material from a portion of the world's indigenous peoples. Among the many values proposed for the HGDP were an understanding of human history and identity, human biological history, and biological relationships among various human groups. However, the HGDP has been enmeshed in massive controversy since its beginnings, with intense negative reactions from many of the indigenous peoples it had intended to study.
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6 THE HUMAN GENDME DIVERSITY PRDJECT The goal of the Human Genome Diversity Project is to increase the body of scientific knowledge about all the earth's peoples. Existing research efforts on human genetics have focused almost exclusively on citizens of the United States and Western Europe, yet we know that all populations—and, indeed, all humans,— are, to some extent, genetically distinctive. Much of that distinctiveness is disappearing, sometimes through physical extinction, more often through migration, assimilation, and intermarriage. Luigi Luca Cavalli-Sforza, Department of Genetics, Stanford University and Henry Greely, Stanford University Law School and Chair, HGDP North American Regional Committee's Ethics Subcommittee There is a marvelous diversity amongst human beings. A quick glance around any public gathering will attest to the physical diversity of the human population. This is what makes life and the human species so wonderful. In large measure, physical appearance is determined by our genes (packets of DNA), which make up forty-six chromosomes in each human cell. Collectively, these genes are known as the human genome.
Ethnic History Ethnic history, with its differences and similarities between various peoples and populations, lies hidden within our DNA. Regardless of where or how people
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live, each of their cells contains genes that transmit heritable traits from parents to children. As a result, in most groups of people, some will be tall, others short; some will have brown eyes, others green or blue. The study of this variation is the basis of the study of evolution, one of the principal aims of genetics.1 A wide enough sampling of DNA has made it possible to reconstruct human evolution, trace global migrations, and answer questions that have concerned anthropologists and historians for centuries. People who live in a certain area of the world, or who make up an ethnic group, a nation, or a population and share common ancestors are more likely to share certain kinds of genetic variants than people who do not share common ancestors. At times, particular genetic variants can lead to susceptibility or resistance to disease and may explain why some groups of people resist disease better than others. Because of this, genes are of great interest to medical researchers trying to improve human health and welfare.2 People within certain ethnic groups are genetically more different from each other than their group is from other groups. Researchers have shown that, in populations studied, Europeans were an admixture of primitive African and primitive Oriental populations. 3 Yet, as far as is currently known, no particular genes make a person Norwegian or Japanese or Cherokee. These are not genetic labels, but rather cultural ones. Although these people are more likely to have some variant genes in common, none will be found in members of one population and not in members of any other population. In effect, there is no such thing as a genetically "pure" human population. It is not surprising to find rare variations in populations. Hundreds of distinct ethnic groups and tribes are disappearing through intermarriage, famine, and disease. Whereas much of the world worries about pollution and saving the rain forests, another valuable source of biological diversity is quietly disappearing— the human being. It is estimated there are about 4,000-8,000 indigenous groups of distinct populations in the world, totaling over 600 million people, and that in the next three or four decades at least 500 groups will be gone. Along with their disappearance their genes will disappear, loaded with information about evolution and human physiology. 4
The Human Genome Diversity Project In 1991 a group of prominent Bay Area human geneticists and molecular biologists, led by population geneticist Dr. Luigi Luca Cavalli-Sforza of Stanford University, proposed to the scientific community that a five-year international project be undertaken to study variation in the human genome. The study was intended to be an effort to collect and preserve DNA from at least 500 of the world's endangered populations, such as the Yanomami of the Amazon rain forests and the Kurds of eastern Turkey. For many years, Cavalli-Sforza and other geneticists and anthropologists had collected blood and tissue samples from various ethnic groups around the world. Their mission at that time was to create a central repository and free representative database for scientists as to how different human populations are related to each other. 5 Cavalli-Sforza had worked for many years with populations in central
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Africa and had quickly discovered that many of the people he saw suffered from yaws, a rare but terrible skin disease. On subsequent trips, in a heartening humanitarian effort, he and his team brought large amounts of antibiotics to cure people of this affliction. In the 1980s Cavalli-Sforza and population geneticist Kenneth Kidd of Yale University collected samples from fifteen human populations, including African Pygmies, the Thoti of central India, Cambodians, Melanesians, and Ethiopian Jews. Cavalli-Sforza and Kidd removed white blood cells from each person in the study, cultured the cells in the laboratory, and then froze the cells in liquid nitrogen. Since each white blood cell contained DNA, the genes were preserved indefinitely for further study. For a very long time, scientists had been aware that each ethnic community may have a slightly different genetic composition. Because of this, they were interested in finding out if such variation in anatomy and physiology, as well as a variation in susceptibility to disease that they knew varied from one population to another, was caused by human adaptation to local environments or changes in genetic makeup. In 1991, Cavalli-Sforza and a number of colleagues wrote a letter to the editors of the scientific journal Qenomics, pointing out the need for a systematic study of the whole range of human genetic diversity: The populations that can tell us most about our evolutionary past are those that have been isolated for some time, are likely to be linguistically and culturally distinct and are often surrounded by geographic barriers. Such isolated populations are being rapidly merged with their neighbors, however, destroying irrevocably the information needed to reconstruct our evolutionary history. 6 The letter was signed by Cavalli-Sforza; molecular anthropologist Allan Wilson and geneticist Mary-Claire King, both of the University of CaliforniaBerkeley; Charles Cantor of Lawrence Berkeley Laboratory; and Robert CookDeegan of the Institute of Medicine in Washington, D.C. This led to an informational discussion among a group of individuals attending the International Congress of Human Genetics meeting in Washington in late 1991, which included representatives from the National Science Foundation, National Institutes of Health, and the Department of Energy. Walter Bodmer, a popular geneticist and at the time president of the Human Genome Organization (HUGO), a nonprofit, nongovernmental consortium of scientists involved in the Human Genome Project (HGP), responded to CavalliSforza's proposal for a diversity study. Bodmer suggested the establishment of an ad hoc subcommittee of HUGO, under the Chairmanship of Cavalli-Sforza, to consider how such a global project could be developed. In turn, the council nominated Bodmer to liaise with the committee on their behalf. Members of the ad hoc committee included: Dr. Julia Bodmer (UK), Dr. Walter Bodmer (UK), Dr. Luigi Luca Cavalli-Sforza (U.S.), Dr. Mary-Claire King (U.S.), Dr. Marc Feldman (U.S.), Dr. Ken Kidd (U.S.), Dr. Ken Weiss (U.S.), Dr. Alberto Piazza (Italy), Dr. Marcello Siniscalco (Italy), and Dr. Svante Paabo (Germany).
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The primary plan of the five-year diversity project was to select genetically distinct indigenous populations worldwide and then to collect DNA and search for DNA sequences that could potentially offer clues to genetically caused diseases and cures. In addition, project scientists planned to map human genetic diversity to give insights into the origins of modern humans as well as the movements of ancient populations. At a time when scientists were increasingly concerned with preserving information about the diversity of many species, Cavalli-Sforza emphasized that science should not ignore the diversity of our own species. In his letter to Qenomics Cavalli-Sforza noted that since many ethnic groups previously had been exploited by outsiders, it was possible that these same indigenous groups might view the diversity study as another form of exploitation. Because of this, HGDP organizers thought it essential that the diversity project promise to provide direct medical services as part of the sampling when it could do so.7 Cavalli-Sforza and colleagues asked for support from national funding agencies. In the United States these included the National Science Foundation, the National Institute of General Medical Sciences, the National Center for Human Genome Research, and the genome program at the Department of Energy. International organizations included UNESCO, World Health Organization, and United Nations Industrial Development Organization. It soon became quite evident that the project would be of interest to scientists and nonscientists alike—human geneticists, linguists, historians, bimolecular scientists, archaeologists, evolutionists, and anthropologists. Organized in midSeptember 1993, the project became known as the Human Genome Diversity Project (HGDP) and involved national and international scientific and nonscientific groups. The HGDP was really an initiative rather than a project, however, since it had no initial funding. In January 1994 the HGDP was formally brought under the auspices of the Council of HUGO. An international executive committee coordinated the HGDP, as well as a number of self-organized regional committees. Henry Greely, a lawyer at Stanford University, was selected to chair the ethics subcommittee of the North American Committee. The HGDP Executive Committee encouraged each region of the world to create its own regional HGDP committee responsible for raising funds and overseeing collection efforts in their own region. Some of the regional committees were successful in raising funds; others were not. For example, when it was first organized, the North American Regional Committee had no funding, but eventually was successful in collecting some money. On the other hand, the European Committee received substantial operational funding from the European Community, in addition to raising some on its own.
International Workshops A small series of international workshops was held in order to explore major scientific issues involved. The first two planning workshops were held in the United States in 1992. Help and support for the workshops were given by the National
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Science Foundation, the National Center for Human Genome Research, the National Institutes of Health (National Institute of Medical Sciences), the Center for Human Genome Research, and the Department of Energy. The first workshop, organized by Cavalli-Sforza and Marc Feldman, was held at Stanford University and was concerned with the statistical issues of sampling populations. The second workshop, organized by Ken Weiss, was held at Pennsylvania State University in November 1992 and focused exclusively on anthropological issues. The primary purpose of the Penn State workshop was to identify those issues most pertinent to representative populations from each area of the world that met the defined criteria. An additional meeting was held at the end of 1992 at the National Institutes of Health in Washington, D O , to discuss technical and ethical issues connected with the HGDP. Other discussions of the HGDP took place in various countries during 1992, under the auspices of the Council of HUGO. These included the Human Genome 92 meeting in Nice (France), the second H U G O Europe meeting in Porto Conte, Sardinia (Italy), and the first South/North Human Genome meeting in Brazil. The third and main workshop was held in Sardinia on September 11-12, 1993. With wide international participation, the meeting was devoted entirely to the global HGDP. Eighty people attended, representing twenty countries (including the United States). The meeting was organized by H U G O Europe and representative populations were also included in this workshop. Two parallel workshops were held on September 9-10, 1993. One of the parallel workshops was concerned specifically with the development of the global HGDP, whereas the other one was concerned with issues of importance to anthropologists and involved extensions of discussions that had begun at Pennsylvania State University. It was decided by participants at the workshops that pilot projects should be completed before beginning a full-scale HGDP. Pilot projects included improving DNA techniques and clarifying cross-cultural ethical and legal issues. It was also decided that pilot projects should investigate what was important to populations, particularly collection of tissue samples and cultural information. Relevant concerns involved identifying culturally appropriate contacts, negotiating contracts, maintaining continued interactions, and identifying participant concerns regarding use of data and samples. It was also decided that improvements would be needed to create affordable, distributable D N A banks.
Proposed Value of the HGDP Broad humanitarian benefits were the primary value of the HGDP since all human groups seemed interested in their origins and scientific evidence about those origins. In general, the HGDP was designed to help see how closely humanity is intertwined by collecting, studying, and preserving the diversity of the genetic inheritance of the human species. Other proposed specific values of the HGDP included the understanding of human history and identity, human biological history, and biological relationships among different human groups. These included the evolution and migration of
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different human populations—creating a definitive "family tree" of human populations. It was decided that some populations might be interested in what D N A samples had to present with regard to historical stories and would allow the populations to trace their connections to other populations and to their ancestors' migrations. In a July 8, 1993, statement supporting the HGDP, Greely and Cavalli-Sforzi issued the following statement: The goal of this project is to increase the body of scientific knowledge about all the earth's peoples. Existing research efforts on human genetics have focused almost exclusively on citizens of the United States and Western Europe, yet we know that all human populations—and, indeed, all humans—are, to some extent, genetically distinctive. Much of that distinctiveness is disappearing, sometimes through physical extinction, more often through migration, assimilation, and intermarriage.8 Although the primary purpose of the HGDP was cultural, it was proposed that HGDP data would be used to study diseases and to lend aid in the treatment and possibly the cures of these diseases, as well. Included were specific populations that were known to suffer from genetic diseases such as thalassemia in Mediterranean populations, diabetes mellitus in Native Americans, and sicklecell anemia in African Americans. On September 16, 1996, Mary-Claire King, representing the North American Regional Committee of the Human Genome Diversity Project, issued a statement to the National Academy of Sciences committee on the relevance of the HGDP: Good afternoon. Thank you for permitting me to speak in this public meeting. My colleague John Moore and I represent the North American Regional Committee of the Human Genome Diversity Project. I am American Cancer Society Professor of Genetics and Medicine at the University of Washington. My research and teaching interests lie in human genetics, in particular how molecular genetics and genomics can be integrated with approaches from population genetics and epidemiology to address problems of complex human diseases and questions of human evolution and diversity. I have been interested in these questions for 25 years, since I was a graduate student in Allan Wilson's laboratory at UC, Berkeley, where our work focused on human evolution at the molecular level. Since then, my lab has studied problems of complex human disease traits, especially breast and ovarian cancer, inherited deafness, systemic lupus erythematosus, and AIDS. We have tried to contribute to and use information about the human genome to identify genes critical to the development of diseases such as breast cancer, then to take the normal alleles of the same genes as the basis for developing cures. I'll return to this theme of complex diseases in a moment.
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In parallel with our work on specific diseases, we have had the opportunity to apply molecular genetics to problems of human rights. We have worked since 1983 with the Abuelas de la Plaza de Mayo to identify their grandchildren kidnapped by military squads in Argentina during the Dirty War, to learn who these children are, to return them to their families, and—in some cases—to bring their kidnappers to justice. As soon as PCR was developed, we applied mitochondrial D N A sequencing, in the context of human diversity, specifically to the project with the Abuelas. This was an outgrowth, of course, of the evolutionary studies based on mitochondrial D N A sequencing of PCR products in the Wilson lab.This human rights work in Argentina was one of the first projects supported by the then-verynew ELSI Committee of the Human Genome Project. It has also been supported by Amnesty International. The project continues to the present, with identification of now-adult children who represent themselves as possible members of the disappeared. We have applied the approaches we developed with the Abuelas to other problems of human rights, including identification of victims of military murders in Chiapas, in Salvador, and in Somalia, and to the identification of MIAs from World War II, Korea, and Vietnam. We are now working on behalf of the United Nations War Crimes Tribunal to identify murder victims from Bosnia and Rwanda. This work is supported by the United Nations through Physicians for Human Rights. What does all this have to do with the Human Genome Diversity Project? The connection is that we can use the tools of molecular genomics and population genetics to answer questions about ourselves. An important class of these questions are those of complex diseases of people. In recent years, there has been a great deal of progress in the identification of genes that influence diseases like cystic fibrosis, some rare familial cancers, some common cancers, some inherited blindness and deafness, and many others. We are beginning to learn how to use these genes for prevention and cure. The biggest challenges are the complex diseases: that is, diseases for which more than one gene, as well as environmental exposures, are likely to influence the appearance of symptoms in each ill person. Diseases like this include diabetes, rheumatoid arthritis, and hypertension, to name just three. How are we to disentangle the multiple causes of these diseases? An approach that is proving successful is to work with relatively isolated groups of people in whom the disease is common, with the hope that the picture may be clearer in a group in whom relatively few, relatively ancient mutations may be responsible for a portion of the genetic influence on the disease. Of many current examples of this approach, one published last week is a study of diabetes in a linguistically isolated community in the Botnian region of western Finland. In a subset of families with diabetes in this geographic area, in a segment of chromosome 12 about
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20 million base pairs in length appears to be shared by relatives with this disease. Now the problem is to close in on this gene and isolate it. However, for this and other complex diseases, isolating genes will be difficult, because no informative recombination events remain to decrease the size of the linked region. To identify these complex disease genes, then, one must rely on the association of genetic markers with diseases, or genetic disequilibrium. Genetic disequilibrium is the association of specific DNA sequences, or markers, with one another in populations. Genetic disequilibrium depends on (1) the physical distance between the marker and the disease allele; (2) polymorphism of the marker, or how variable the marker is; (3) mutation rate at the marker, or how fast the variation changes; and (4) recombination rate as a function of physical distance for this specific part of the genome. Some of these parameters depend, in turn, on features of populations; specifically (1) effective population size; (2) degree of endogamy; and (3) age of the disease allele in the population. Another way of phrasing this question is: given linkage and disequilibrium between markers and a hypothetical disease allele over a large genomic region, where is the best place in that genomic region to start looking for the disease gene? Twenty million base pairs is very large to scan for individual mutations, even when the genome sequence for one amalgamated person is known. In order to narrow the search, it will be important to know more about genomic structure at the population level. The way to learn genomic structure at the population level is to study various genomic regions in different populations, with each genomic region evaluated at markers very densely distributed. The goal of this approach is to evaluate disequilibrium among markers (at different distances apart and with different mutation rates) across the genome in populations differing in size, endogamy, and history. In other words, how is disequilibrium distributed in the genome, as a function of (1) features of individual variant sites, (2) chromosomal structure, and (3) organization of populations? How does the Human Genome Diversity Project contribute to this understanding? Wouldn't it be possible to carry out this analysis one population at a time, one chromosomal region at a time: for example, for chromosome 12 in western Finland? Of course. This is analogous to sequencing a part of the genome from one person with disease at a time. Indeed, this is where we stand right now with the Human Genome Project. Individual studies are a necessary interim solution. However, much more is to be learned, and the information will be more universally useful, if disequilibrium structure is studied for the genome as a whole and in populations with a range of historic features. Small numbers of people from many historically coherent populations, specifically including those without disease, are the best source of this information. W h y should anyone from any population—particularly indigenous populations exploited for lifetimes by outsiders—be willing to
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participate in such research? Good question. A fundamental tenet of those of us working on the North American Regional Committee of the HGDP is that any community, including in particular indigenous communities, should control research access to their own community, to their DNA, and to any possible commercial value from research with these resources, however remote the possibility of commercial value might be. In our research on breast cancer in families, many families choose to participate in our project; others decline. Similarly, in the Human Genome Diversity Project, it is to be expected that some communities would participate and others decline. It is obvious to me that individuals, families, and communities have the wisdom and intelligence to make these decisions for themselves, and the right to be provided with information that is useful for doing so. With these principles in mind, the North American Committee of the HGDP has developed a draft of a model ethical protocol for the collection of DNA samples for research. Your committee has, of course, obtained and discussed this draft protocol. We hope that the HGDP will break new ground in recognizing the autonomy of communities in making such decisions, and that this standard will be applied beyond HGDP to biomedical research generally.9 It was proposed that the information gathered through the HGDP would help clarify the history of specific populations of the human species as a whole because the frequencies of different variations in different populations could reveal how recently they shared a large pool of common ancestors. For example, frequencies such as these had potential to be used to see whether, for example, the Norwegians are more closely related to the Germans or the Danes. In addition, it was proposed that the HGDP had potential to yield significant information on major human migrations—where people came from, what geographical routes they took to get to their present territories, and what technological innovations they used to get there. Other information to be derived would be social interactions within their own group and with other groups, why and how different traits or languages developed and whether there were major population reductions due to disease or substandard living conditions. The project would potentially enable scientists to map the history of civilization. Certain ethnic groups were brought by different migrations from various parts of the world and the HGDP proposed to determine whether a single group was ancestral to all members of a group. Studying genetic variations of peoples around the world has the potential to provide a great deal of information about the development of the human species and to help understand relationships between different populations. In addition, the HGDP proposed to help settle the long debate about whether Homo sapiens evolved to modern humans in Africa or over the entire world. Organizers of the HGDP acknowledged early that variation could be explained by environmental factors such as climate, pollutants, diet, infectious diseases, and
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parasites. However, they also knew that DNA variation was a major contributor. By studying genetic variations in different populations, particularly those groups that have lived in isolation for thousands of years, scientists could understand how humans evolved and migrated over the planet. The study, organizers believed, had the potential to increase the likelihood of developing effective ways of treating and preventing diseases. The HGDP sought to provide answers by leading to a greater understanding of the differences between individuals and between human populations. The HGDP promised to make a significant contribution to the elimination of racism by showing that there is a continual graduation from one population to another and there is no such thing as a clearly defined race. The HGDP declared the potential to bring together people from many countries and disciplines. It promised to create a unique bridge between science and the humanities. Even populations that do not seek scientific explanations for their origins might reap long-term benefits from the discovery of useful medical information about their susceptibility to, or treatments for, disease.
Considering Populations It became apparent to HGDP organizers that not all populations could be studied in detail. However, scientists were determined that no group would be deliberately excluded. Therefore, it was decided that if certain populations did not wish to participate in the HGDP they would not be included. To achieve this goal, in October 1992 a planning workshop for the HGDP proposed examples of populations that were broadly representative of all major regions of the world. Some of the proposed populations were small, whereas others were very large. After much study, approximately 500-800 indigenous representative human world populations (including those in Europe and North America) were viewed as a potential group to make up the study.10 Among the indigenous groups suggested for study were peoples of the Sahara, of western, southern, and eastern Africa;11 the Etas of Japan, and insular populations in Malaysia and southeastern Asia. 12 ' 13 Other ethnic groups included minorities of China, Polynesians, aboriginal populations of Australia and Melanesia, the Kurds of eastern Turkey, peoples of the Caucasus, the Lapps, the Basques, other peoples in the Pyrenees, Appenines, Carpathians, and Alps, and the many Indigenous American populations. In addition, the Central Australian Aboriginal Congress (CAAC) reported that at least a dozen aboriginal communities throughout Australia were proposed to participate in the project. Among others suggested for D N A sampling were the Yukaghir of Siberia (about 100 people remaining in the group), the Dorasque of Panama (50 individuals remaining) and the Amazon's Akuriyo (50 survivors). Other communities included the Salsiat of Taiwan, Somalis in the faminestricken Horn of Africa, and the Onondagas, the Cayuga, the Delaware, and the Sarcee of North America (each numbering around 600 persons). Not all the proposed indigenous communities were thrilled by their inclusion and asked for an explanation of how populations were selected. The Onondagas
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were enraged to find their nation on the list, saying they had not been asked and wondered why they were named. A second Iroquois nation, the Cayuga, also made the list and was not happy.14 Representatives of the HGDP issued a statement staying that populations that were proposed were done so for historical, genetic, cultural, and other reasons. Some of the things, they declared, that made a population of particular interest included an unusual language, culture, or history; an indication of susceptibility to or immunity from particular diseases and possible extinction; or a possible relationship to another interesting population. The HGDP gave the following explanation: "One criterion for inclusion was imminent danger of extinction. This applies to about half of the selected groups, including the Hazda of Tanzania, the Yukaghir of Siberia and the Onge and Greater Andamanese of the Andaman Islands, Malaysia. Another objective was to choose groups whose genetic make-up could shed light on specific anthropological problems, such as how the Americas were first colonized, or the history of the Bantu expansion in Africa 2000 years ago." 15 The small size of the population was another important criterion. Henry Greely, on behalf of the North American Regional Committee's Ethics Subcommittee, issued the following statement: For example, one group in Tierra del Fuego reportedly has only two members. Should those people die, or, perhaps more likely, move to a city, sampling may be difficult or impossible. The actual collection of samples will depend on the willingness of the population to be sampled, as well as on the interest of an anthropologist or other person knowledgeable in the population's culture to ensure that the collection is done in a way that provides true informed consent and that comports with the population's culture. 16 Because prior research into variations among human populations appeared to be proceeding in a haphazard and invisible way, Greely and other organizers felt the HDGP was an effort to coordinate the work and make sure it was done with the highest scientific and ethical standards. 17
Sampling In light of equity, it was proposed by HGDP organizers that each region be given the opportunity to define its own local sampling procedures. It was decided that questions might be asked about various issues, including human history and identity that concerned geneticists, anthropologists, and historians. Questions might be raised by populations themselves which would include genome-wide, statistical, and locus-specific information. Miscellaneous questions would constitute an important part of the sampling. In order to preserve history, the HGDP proposed to collect DNA samples from hundreds of different populations, as well as demographic, historical, sociocultural, linguistic, and other data from all over the world. This would be in contrast to the
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Human Genome Project, where samples would come mostly from people of European origin. It was proposed that the collection and analysis of DNA samples, in conjunction with the necessary epidemiological data, would lead to the identification of genetic factors in certain human diseases and eventually to ways to treat or prevent those diseases. Participating health-care workers would provide some screening immunization, diagnoses, or treatment of medical conditions while working with populations, particularly those considered to be on the brink of near extinction. It was suggested that in some large linguistic or geographical populations multiple (rather than single) samples would be taken. DNA samples would be taken from blood, hair roots, cheek cells, and sputum, as well as other biological materials. All samples would be collected in culturally appropriate ways, with explicit informed consent from surveyed subjects. This type of sampling would allow communication with the population and allow participants to learn from findings of the research. Samples would be frozen and preserved in both central and regional repositories around the world. Regional laboratories would be set up for processing the specimens because samples would have a limited time of forty-eight hours to be processed. One example suggested for a regional repository was the American Type Culture Collections in Rockville, Maryland. Basic, preliminary analyses of the DNA samples would be carried out prior to freezing the samples. DNA samples would be preserved as cell lines in gene banks in order to obtain a large amount of duplicate DNA for study. These "immortalized cell lines" would be made available to any qualified scientists worldwide interested in doing legitimate research on them. Once the D N A samples had been analyzed, the results of the analyses would be put into a computerized database for distribution worldwide. Cavalli-Sforza urged that the study be started immediately, warning that if sampling were delayed, it might be too late for some discrete tribes such as the Yanomami, who were dying in large numbers from disease and environmental damage caused by gold mining in the Amazon forests.18 "It would be tragically ironic if, during the same decade that biological tools for understanding our species were created, major opportunities for applying them would be squandered." 19 Unfortunately, what began as a humanitarian and scientific effort—to coordinate and ascertain that the HGDP would be carried out only with the highest integrity and ethical standards—was met with considerable resistance by indigenous communities, who were upset with many aspects of the HGDP. Despite attempts to quell the uprising against the project, the debate continued to heat up.
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V T H E H G D P DEBATE After being subjected to ethnocide and genocide for 500 years, which is why we are endangered, the alternative is for our DNA to be stored and collected . . . why don't they address the causes of our being endangered, instead of spending $20 million for five years to collect and store us in cold laboratories? If this money will be used instead to provide us basic social services and promote our rights as Indigenous Peoples, then our biodiversity will be protected. Victoria Tauli-Corpuz, Cordillera Peoples' Alliance, The Phillipines The Human Genome Diversity Project (HGDP), dubbed the "Vampire Project" by opponents worldwide, has been enmeshed in substantial controversy since its beginnings, with intense reactions from many of the indigenous groups it proposed to study. When an article written by Luigi Luca Cavalli-Sforza et al. appeared in the scientific journal Qenomics, various indigenous peoples were appalled by what they perceived as an insensitive term used by the authors. The term "isolates of historic interest" was used to describe indigenous peoples purportedly selected for human DNA sampling. 1 Some indigenous groups suggested the term had the ring of eugenics.
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Concerns of Indigenous Peoples For several decades, indigenous peoples have had concerns of various kinds, so it was not a complete surprise that they were distressed when it was announced that a diversity project was planned. Upon the report that the HGDP wished to obtain DNA from the indigenous peoples, that concern intensified and became an acute issue. Because of language differences, it was of utmost importance to the HGDP organizers that the project be understood by the indigenous involved, not merely presented. In addition to translation problems, however, there was the potential for differences in ethnic views. In attempts to allay fears of the indigenous peoples, organizers of the HGDP declared openly that it was not their intent to inflict harm on indigenous peoples. Rather, they said, the project intended to "immortalize" endangered populations by establishing viable cell lines in the search for unique D N A sequences that could offer clues to genetically caused diseases and to potentially lucrative cures. HGDP organizers were questioned by conservationists, scientists, and organizations whose primary concern was that the indigenous peoples not be exploited when obtaining the DNA samples. Indigenous peoples questioned what was in it for them and repeatedly said they didn't need scientists or anyone else telling them where they came from, or, for that matter, where they were going. They made it quite clear that they had strong beliefs and knowledge about their creation and histories. Ray Apodaca of the National Congress of American Indians did not agree with what he termed the "pure science" justification of the HGDP, particularly with reference to the history of human migrations, saying: "We know where we came from, and we know who we are, and we think we know where we are going. W h y do we need to know anything else? I mean, is it for their benefit? It certainly isn't for ours." 2 Major concerns of indigenous peoples included possible violation of human rights, biological warfare, informed consent, biopiracy, and diversion of funds. Other issues surrounding the HGDP had indigenous peoples and support groups demanding that the project be halted until moral, ethical, socioeconomic, political, and physical implications were discussed and agreed upon.
Violation of Human Rights With regard to possible violation of human rights, the South and Meso American Indian Information Center (SAIIC) from the beginning stated that indigenous peoples from whom DNA samples were to be taken had not been consulted during any planning stage of the project. The SAIIC emphatically argued that indigenous peoples from whom samples were to be taken must be given information about risks, benefits, and alternative procedures, as well as information as to how the DNA samples would be used and the purposes of the HGDP research. Apodaca and others viewed drawing of blood samples as a sacrilege. They reminded scientists that obtaining blood samples and other tissues from indigenous
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peoples was not very different from studies of the last century when hundreds of Native American graves were robbed and skull sizes taken in a study to estimate racial intelligence. They cited those studies and others in an attempt to show indigenous peoples as victims of inhumane treatment and human rights violations. This was, they thought, especially true of those studies they believed belittled Native Americans as being inferior and less intelligent.
Biological Warfare and Ethnic Genes Some indigenous peoples' groups had concerns about biological warfare, in spite of HGDP organizers repeatedly stating that the HGDP had no implications for biological warfare. Because all humans share the same gene pool, specific ethnic groups are not defined by any specific genes and it seemed, at the time, next to impossible to create ethnic-specific genes. Quite likely, had this been possible, a large number of diseases would already have been eliminated. There was, indigenous groups stated, always the possibility that with technological advances, some unethical scientist might gain access to the desired information. Recorded in past history are cases of oppressed indigenous peoples in various regions of the world who have been the target of genocide. Uncovering such information would make it easier for individuals or governments to design and use biological weapons against populations.
Informed Consent One of the main concerns of indigenous peoples was the lack of informed consent. They wanted the right to decide, collectively, whether they would participate in the HGDP. They requested fully informed consent for population sampling. As a result, the HGDP organizers promised that only those populations, and individuals within the populations, who consented to the HGDP would participate. 3 Indigenous peoples raised a large number of ethical questions, including: How would scientists obtain informed consent from the people under study? W h o would own the resulting stockpile of genetic material? Would the individuals giving these samples know what happened to them? Were the donors consulted about further applications to the scientific findings? Were they assured of a share of any benefits? W h o was authorized to give consent? Should consent be granted by government officials of the nation-state in which the indigenous nation was located? Should consent be required only by the individual being sampled, or also include the governing body of that particular indigenous nation? Other questions were: How would permission be obtained for collection of samples from the dead, or for use of fetal and placental tissues as sources for genetic samples? How would the project be explained in the local language? Would the full scope of the project and the short- and long-term implications and potential uses of the samples be fully disclosed? Would donors be fully informed of the potential for profits that may be made from their genetic samples?4
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Biopiracy and Diversion of Funds Indigenous peoples were concerned that DNA specimens would be taken from indigenous individuals without rewards of any kind. The Rural Advancement Foundation International (RAFI), an international nongovernmental organization, was the most instrumental in aiding indigenous peoples against what they called "bio-colonialism" or "biopiracy." RAFI cited earlier cases in which Third World peoples previously provided biological materials and information without rewards of any kind. They reported that, repeatedly, western science had been exported to the Third World without prior consultation with those who were supposed to benefit. Examples included the wholesale collection of samples of crops and wild plants by foreign scientists, as well as by drug and chemical companies. 5 Indigenous groups believed that seed and drug companies from the developed world had long exploited the developing world's plant genetic resources. Some companies, it was charged, freely gathered plants from generations of indigenous farmers in undeveloped countries. These plants had been developed, domesticated, and maintained for hundreds of years. Without paying anything to the farmers or their countries, the pharmaceutical and seed companies used the plants to create products that were then patented and sold back to the developing world at high prices for high profits. Few, if any, of the profits, some indigenous groups believed, were returned to the patents' original users. The exploitation of the plant and animal genetic resources of the developing world played a major role in the 1992 Biodiversity Treaty. Advocates for indigenous peoples were concerned that the HGDP would be a human version of these plant-collecting expeditions. Emphatically, the HGDP promised that this would not happen. It also declared that it was committed to two propositions: first, that financial benefits should not go to the HGDP; and, second, that an adequate part of the financial gains, if any, would go back to the sampled populations. Unconvinced, RAFI cited another incident that had occurred on the small island of Tristan da Cunha in the South Pacific. In 1991 two researchers from the Mount Sinai Hospital in Toronto, Ontario, had visited the island, interested in researching residents with a high incidence of hereditary asthma. While on site, the researchers allegedly took blood samples from 272 of the island's 295 inhabitants. Shortly after the researchers returned to Toronto it was announced that Mount Sinai Hospital had formed a contract with Sequana Therapeutics, a biotechnology company that was to analyze the blood samples in attempts to identify the asthma gene. The contract stipulated that any patent profits would be shared by Sequana and the hospital, bypassing the island's citizens who had actually donated the blood. The contract included potential profits made from patenting human genes (particularly to large pharmaceutical companies) and diversion of any funds generated. 6 Citing other such cases, indigenous peoples worried that their most fundamental property (their own DNA and genes) would end up in the hands of almost anyone who wanted to experiment with them. Indigenous peoples argued that,
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like other companies in the past, the HGDP potentially could amount to widespread commercialization and potential misuse of samples and data. In defense of their study, organizers of the HGDP once again tried to assure the indigenous communities that the HGDP was not intended to be a commercial venture. Rather than profit, it sought knowledge. In September 1993, at its international congress, the HGDP formally announced that it would not profit from the D N A samples or data developed from the samples. However, in the event that it evolved into profit, the HGDP was committed to ensuring that any financial benefits would be given back to the donor populations. The HGDP also said it did not intend to patent DNA samples taken from indigenous peoples or any products made from the samples. However, the World Congress of Indigenous Peoples (WCIP) and RAFI each said that they believed that the HGDP was motivated by the potential to make profits from medical research more than by the pursuit of knowledge. George Annas, Professor of Medical Ethics at the Massachusetts Institute of Technology, issued a similar concern: "We're taking from them their DNA, which we now consider like gold. It's even worse than standard colonialism and exploitation because we are taking the one thing that we value. And after we take that we have no real interest in whether they live or die. We need to secure their future as peoples, not just immortalize their genes." 7
Patents and Indigenous Peoples In the United States, numerous patents had been issued by the U.S. Patent and Trademark Office (PTO) on created living animals, microorganisms, and human genes and tissues, breaking the long-standing policy that animate life forms were not patentable. In 1971 the General Electric Corporation and one of its scientists, Ananda Chakrabarty, filed a patent application for bacteria which could digest oil hydrocarbons. In determining whether to award the patent, whether it was alive or inanimate was seen as the major criterion. Initially, the U S . Patent Office rejected the application. However, the case was appealed to the courts and in 1980 the Supreme Court ruled, in a five to four opinion by Chief Justice Warren Burger, that the oil-eating microbe was not a product of nature but a humanmade invention. In 1987 the U.S. Patent Office decided that all multicellular living organisms, including animals, were held patentable. Since that time, the National Institutes of Health (NIH) has secured patent rights for fragmented gene sequences, allowing corporations and research institutions the right to secure patents on a substantial percentage of the entire human genome. The issue of patents on genetic samples obtained from indigenous peoples became a controversial subject and resulted in a heated written exchange between Henry Greely of the HGDP and Edward Hammond and others of RAFI. Reportedly, NIH patent claims on indigenous peoples' DNA were undertaken by the National Technical Information Service, a division of the U.S. Department of Commerce. 8
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The Guaymi Patent In 1993 U.S. Secretary of Commerce Ron Brown filed U.S. and world patent claims on a cell line of a twenty-six-year-old Guaymi woman from Panama. The cell line was of particular interest because it was known that some Guaymi people carried a unique virus in their cell lines and the antibodies to that particular virus were thought to be useful in AIDS and leukemia research. However, the Guaymi people viewed the patenting of humans and animals as fundamentally immoral and contrary to the Guaymi view of nature and their place in it. Because of their beliefs, the President of Guaymi, on behalf of his people, cited the patent as a violation of the integrity of life itself. Although the patent application had nothing to do with the HGDP, Henry Greely attempted to explain the American Type Culture Collections cell line patent in a July 21, 1993, letter to Pat Roy Mooney of RAFI: I have now talked with Dr. Michael Lairmore and have found out some more about the ATCC cell line you brought to my attention. I'm not sure what to make of that information, but I pass it along to you for your consideration. An NIH researcher working at the Gorgas Institute in Panama noticed that blood from a large percentage of a certain population in Panama showed some antibodies. He sent a sample to CDC for identification of the virus that had triggered the antibodies. It ended up with Lairmore [Dr. Michael Lairmore], who was then a CDC virologist. He and his colleagues discovered that the antibodies were being formed to the HTLV-II virus. This virus is closely related to the HTLV-I virus, which is known to cause some neurological and other symptoms and is common in the Caribbean and in American intravenous drug-using populations. HTLV-II has not been linked to any diseases or conditions. At CDC, they managed to create a cell-line from the same blood cells. That cell-line perpetually produced HTLV-II virus. They created the cell-line for the use of researchers interested in HTLV-II virus. Someone at CDC then told Lairmore that he should patent the cellline, so he and his colleague called the CDC's patent office and they put the process in motion. He doesn't know the financial side of the patent but assumes the federal government owns the patent and would be in a position to get any financial returns with perhaps a nominal sum going to the "inventors" (who were both government employees). All the interest in the cell-line, both scientific and, perhaps, commercial, has focused on the production of the virus by the cells. No one, as far as Lairmore knows, has paid any attention at all to the human genetic information in the cell line. As far as Lairmore knows, the patent has not been issued. He doesn't have much interest in it. It might conceivably become valuable as the source of a screening test for HTLV-II virus infection. However, that potential value has three drawbacks. First, right now it isn't known that HTLV-II virus infection causes any symptoms that anyone would
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want to screen against. Second, many other populations with endemic HTLV-II virus have now been found and they could just as easily be used to produce cell-lines that produced the virus. And third, the entire genetic sequence of that virus has now been determined, using that cell-line, and is about to be published in the August issue of the Journal of Virology (lead author, Diane Pardi). Now that the sequence (about 9,500 base pairs) is known, a source of the actual virus is probably less important for any commercial purpose. So, this is an example of a cell-line from a member of an indigenous group for which a patent has been sought. It does not seem to have a significant chance of having any commercial value, although that can't be ruled out. And it is not the human genes that are of any interest. Still, this does point out another way in which cell-lines have economic value and one I hadn't thought of. I agree we need to think harder about the economic value issues and I am still interested in your thoughts on an appropriate "fund-holder" for any royalties that might come in. I look forward to hearing from you. 9 The patent application was first discovered in August 1993. Pat Mooney of RAFI was examining a patent database primarily for agricultural information when he came across the application filed by United States Secretary of Commerce Ron Brown on the cell line of the twenty-six-year-old Guaymi Indian woman from Panama. Mooney, on behalf of RAFI, immediately contacted the Guaymi General Congress in Panama City about the patent claims. He also alerted the U S . Biotechnology Working Group, a group of international activists who had gathered in Geneva at the time. Very concerned, RAFI and others made known their beliefs that such patenting was a very dangerous trend toward commodification of humanity, whether it was by taking DNA samples from indigenous peoples or medicinal plants. RAFI requested that the United States withdraw its patent claims and return the cell line to the Guaymi people. In early October that same year, Mooney, representing RAFI, and the Guaymi president traveled to Geneva to protest the U.S. Guaymi patent claim at the intergovernmental meeting of the Biodiversity Convention, held October 10-15, and to the General Agreement of Tariffs and Trade (GATT) Secretariat. Isidro Acosta, President of the Guaymi General Congress, and Jean Christie of RAFI met with the GATT Trade Related Intellectual Property Rights Secretariat, and after much discussion, determined that human genetic material was not excluded from the GATT agreement. Intellectual property clauses of the GATT agreement required states to adopt patent laws covering microorganisms and (some form of protection for) plants. International precedent—under the Budapest Convention—led to the treatment of human cell lines as nothing more than a form of microorganism—in the same class as fungi, bacteria, or viruses. In so doing, the GATT mandated the patenting of human material. Later in October 1993, the European Greens introduced an emergency resolution into the European Parliament. Opposing the patent claims, they requested data on European patenting and called for a halt of the HGDP. Subsequent international protest and action by the Guaymi General Congress, RAFI, the World
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Council of Churches, the World Council of Indigenous Peoples (WCIP), and individuals, including Henry Greely of the North American Subcommittee of the HGDP, resulted in the withdrawal in November 1993 of the patent claims by the U.S. secretary of commerce. 10 On November 9, 1993, Nilo Cayuqueo, SAIIC Director, sent a fax to Henry Greely as chair of the Ethics Subcommittee of the North American Regional Committee: We have an array of serious concerns that, to date, have not been addressed at all: (1) The information you gather about our genetic make-up will be readily available to governments, foundations, and corporations. For the past 500 years, these institutions have waged an unbridled war of oppression and genocide against our people. The implications are potentially devastating for Indigenous Peoples all over the world. How are we going to be able to control these institutions from patenting and thereby owning the rights to our genetic material enabling them to make profits from our own blood? What kind of regulations are going to be set to ensure that this information is not going to be used against us in targeted biological warfare? (2) In your statement to us you say, "The populations that will be studied will be populations that choose to participate (and those individuals within the populations that also choose to participate)." How will the targeted populations be approached? How will the project be presented to them? What kinds of methods and tactics are going to be used to convince the communities that by "donating blood" they will benefit in some way? Given the history of the past 500 years, where and how does choice factor in? (3) The notion that the Guaymi sister in Panama "donated her blood" indicates the narrow and paternalistic way in which the people involved regard the situation. It is still not clear how she was approached and why the President of the Guaymi General Congress, Isidro Acosta, was not involved from the onset. To imply that the woman would have willingly given her blood sample had she known the U.S. government was going to then apply for a patent on her cell-line is ludicrous. Your description does not reflect the reality of the situation, Mr. Greely, and this is very dangerous. (4) The targeted Indigenous Communities have been referred to as "Isolates of Historic Interest." Due to the relentless oppression of the past 500 years, many of our peoples have been the victims of genocide and marginalization, our populations have dramatically decreased in size as our land has been overtaken and our way of life, our culture, our traditions totally overshadowed by the dominant capitalist mind set. In spite of this, we have endured and are 45 million strong in the Western hemisphere. Lest you think we are vanishing,
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we are not. We are living here and now under deplorable conditions imposed upon us by the oppressive government regimes that try as they may have not succeeded in exterminating us. With all the money and effort that is going to be expended to try to further exploit us, we believe the time, energy and money could be better put to much better use by: helping our communities in our struggle for self-determination; getting governments to acknowledge our way of life; honor broken treaties and allow us to reclaim our rightful territories; stopping the human rights violations against our people and our land; bringing proper sanitation and medical care to our impoverished communities; stopping the multinational corporations from exploiting and destroying our natural resources on which we all depend. We would like to make it clear, Mr. Greely, that we do not want to stand in the way of research that will be to the benefit of all humanity. However, we will not take part in any effort of the Human Genome Diversity Project until all of the moral, ethical, socioeconomic, physical and political implications have been thoroughly discussed, understood and approved by Indigenous Peoples. We do not want so called "experts" to come into our communities to try and convince us that for the sake of science we must allow the Human Genome Diversity Project to do whatever it wills. What we seek is open dialogue. Until this is granted, we will do everything we can to inform member organizations to refuse to cooperate with the project. We hope that our concerns will be addressed and that you will do whatever you can to ensure that respect guides your route. 11 In December 1993, Henry Greely, representing the HGDP, was invited to the World Council on Indigenous Peoples (WCIP) meeting, held in Guatemala. After several hours of intensive discussion, the WCIP unanimously voted to adopt a resolution to halt HGDP. Subsequently, it was discovered that two other patent claims had been filed by the U.S. Secretary of Commerce for cell lines of indigenous peoples, one claim from the Solomon Islands and the other from Papua New Guinea.
Solomon Islands Patent After discovering the patent for a cell line from residents of the Solomon Islands, the Solomon Islands government demanded withdrawal of the patent applications and repatriation of the genetic samples, citing an invasion of sovereignty, lack of informed consent, and moral grounds as the reasons for protest. However, U.S. Secretary of Commerce Ron Brown rejected the requested withdrawal, saying: "Under our laws, as well as those of many other countries, subject matter relating to human cells is patentable and there is no provision for
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considerations relating to the source of the cells that may be the subject of a patent application." 12 In September 1994 Dr. Jonathon Friedlaender, Physical Anthropology Program Director at the NIH, at the request of the Solomon Islands' ambassador to the United Nations, investigated the Solomon Islands patent application and advised the Solomon Islands government that both the Papua New Guinea and Solomon Islands patent applications would be either abandoned, withdrawn, or disallowed. However, it was later discovered the Papua New Guinea patent had been issued in March 1995.13 Greely issued a press release on October 26, 1995: In response to 1993 investigations by the Government of the Solomon Islands and RAFI, NIH's Jonathan Friedlaender wrote to the Solomon Islands Ambassador to the United Nations, allaying their concerns by saying that the patent applications "will likely be abandoned entirely or not allowed." Contrary to Friedlaender's indication, in the course of routine research prior to (Jean) Christie's trip to the Pacific RAFI discovered that the patent was issued 6 months ago. Friedlaender, who wrote that the patent would likely be withdrawn, participated in the development of the HGDP and was among those at its founding meeting. Within weeks of the patent's issue, Friedlaender returned to the Pacific on business related to the collection of blood samples. 14 In further defense of Friedlaender, Greely wrote: The similar patent application for cell-lines derived from the blood samples from the Solomon Islands was not prosecuted by the U.S. Government. It was "continued," which means "put on the back burner," last spring, and I am told that it has now been formally withdrawn. Dr. Friedlaender's letter to the Ambassador from the Solomon Islands was entirely accurate about the Solomon Islands application. It would also have been accurate about the [Papua New Guinea] PNG application, except that it did not foresee the strong request from the PNG Institute of Medical Research that the patent application from Papua New Guinea be prosecuted. 15 Friedlaender, who was also a tenured professor of anthropology at Temple University, said he had visited Papua New Guinea and the Solomon Islands after his stint with the NIH but said that he did not collect any blood samples. He did, however, admit to collecting various tissue samples for his academic research at the university.
Papua New Guinea Patent On March 14, 1995, the U.S. government, in an unprecedented move, issued to a group of five inventors U.S. patent number 5,397,696, called Papua New
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Guinea Human T-Lymphotropic Virus. The patent was on a cell line taken from an indigenous man of the Hagahai people from New Guinea's remote highlands. At the time, the Hagahai numbered a scant 260 persons. They had come into consistent contact with the outside world beginning in 1984. The cell line reportedly contained the virus variant called HTLV-1, and patent applications on the cell line were reported to be pending in nineteen other countries. 16 The team that patented the HTLV-1 virus variant was headed by 1976 Nobel laureate in medicine, Dr. D. Carleton Gajdusek, and Dr. Carol Jenkins, a U.S. citizen and widely respected medical anthropologist. The patent claimed as its "invention" the cell line, viral preparations made from the cell line, and bioassays made from the cell line. The patent did not make any ownership claims to that particular human DNA or to the information it contained. 17 RAFI was highly critical of the patent. Edward Hammond, Program Officer with RAFI-USA, located in North Carolina, issued the statement: "The thin veneer of the HGDP as an academic, non-commercial exercise has been shattered by the U.S. government patenting an indigenous person from New Guinea." 18 The patent did not give the U.S. government (or anyone else) any intellectual property rights on the DNA of any member of the Hagahai, although it did give the patentees exclusive commercial rights (in the United States) to one particular kind of cell line infected with a particular variant of a virus called HTLV-1 and on the possible uses of that cell line in developing diagnostic tests. No claim was made on any human genetic material. 19 Opponents of the patent argued that the Hagahai man's physical identity had been patented by the NIH. They argued that the patent, in claiming the cell line, also claimed the cell's contents—the viral strain and the human DNA derived from blood taken from the Hagahai man. Opponents asserted that the patent claimed a cell line containing the unmodified Hagahai DNA and several methods for its use in detecting HTLV-1-related retroviruses and in developing vaccines. As a result of the opposition to the patent, the NIH withdrew its application to patent the cell line. However, at the request of members of the Institute of Medical Research, an independent government institute in Papua New Guinea, NIH changed its decision. In an attempt to explain what was developing into a fiasco, on Friday, October 20, 1995, Henry Greely wrote: First, the NIH had decided to withdraw its application to patent the cell-line derived from blood from Papua New Guinea. The NIH changed its decision at the request of members of the Institute of Medical Research, an agency of the government of Papua, New Guinea. An Institute scientist is listed as a co-inventor on the patent application and, by agreement, her half of any proceeds from the patent are to go to the Hagahai—not to the co-inventor, the Institute, or the general government of Papua New Guinea. (The agreement is not part of the patent because patents do not include information on the distribution of the royalties they produce—they just describe the protected "invention".) The Institute and its staff have sterling reputations for service to the peoples of their country; this patent was issued as part of
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their service to the Hagahai. The Institute believed that it could best protect the interests of the Hagahai by a patent. That may or may not have been correct, but it certainly was not exploitation of the Hagahai—quite the contrary. 20 The Institute scientist who was coinventor on the patent application, Dr. Carol Jenkins, offered to donate her half of any proceeds from the patent to the Hagahai peoples themselves, not to the Institute or the general government of Papua, New Guinea. The Institute of Medical Research, with a sterling reputation internationally, believed it could best protect the interests of the Hagahai people by a patent. The Institute of Medical Research is considered an exemplary organization and the Papua New Guinea government has been extremely wise to support it. Their staff is international—meaning Australian, American, African, Indian, and Papua New Guinean, among others—and they have an outstanding record of biomedical research achievement and public health education. A few examples include the identification and cure of a formerly widespread and lethal disease ("pigbel"), very important malaria research, ongoing and important public health education efforts in nutrition, tuberculosis, AIDS, and ecological degradation. 21 Others who had been following the Papua New Guinea case issued statements, explaining what they termed "commodification of life." Some Americans, including Jeff Keohane of Stanford University, referred to taking genetic material from the Hagahai man from Papua New Guinea as "commodification": "That person's genes were commodified the instant they left his or her body and someone was willing to spend money for them. The NIH was granted a patent on a derivative of that material. It doesn't own anything within the person's skin. It doesn't own the person. It doesn't have any claim to so much as the sweat in their footprints." 22 Pat Roy Mooney, RAFI's executive director, issued the following statement: "This patent is another major step down the road to the commodifcation of life. In the days of colonialism, researchers went after Indigenous People's resources and studied their social organizations and customs. But now, in biocolonial times, they are going after the people themselves." 23 Once again defending the HGDP, Greely responded on Friday, October 20, 1995: As a member of the North American Committee of the Human Genome Diversity Program, I share RAFI's concern about the patenting of a cell-line derived from a member of the Hagahai population, or from anyone else, indigenous or non-indigenous, who may not have given fully informed consent to such use of his tissues or who may otherwise have been treated unfairly. But I am also concerned that the Human Diversity Project not be treated unfairly by RAFI. Its press release [Wednesday, October 4, 1995] contained such a host of misrepresentations and outright lies about that Project that I am compelled to respond.
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Fact 1. The HGDP had nothing to do with the collection, analysis, or patenting of the cell line from Papua, New Guinea or with patenting of any other cell lines, indigenous or otherwise. Fact 2. The HGDP is a regionally organized project. In most of the world, including the Pacific and the Americas, it remains entirely in the planning stage. In Europe and China, local researchers are engaged in pilot studies that might end up being part of the Project. Fact 3. The HGDP has stated, over and over, (a) that the Project will not try to capture for itself any commercial value that its samples or data may generate, through patenting or in any other methods, (b) but that should such value arise, the Project will seek to ensure that the sampled population gets a fair share of any benefits. Fact 4. The North American Committee of the HGDP has gone farther and stated that no patenting or commercial use of samples collected by the Project should be allowed without the express and informed agreement of the sampled population, provided by whatever authorities are appropriate within its culture. We expressly reject unfair and exploitative "gene hunting." Fact 5. The HGDP has not supported the U.S. government patent applications on cell lines from Indigenous Peoples. In fact, I personally helped the Guaymi General Congress and RAFI persuade the NIH to drop its patent application on a cell line from Panama. I discovered the nature of the patent application, the named inventors on the application, and the background of the patent and passed that information on to RAFI, which didn't know any of it. I wrote to and talked with the relevant federal officials in the efforts that led to the withdrawal of the Guaymi claim. I also offered to help the government of the Solomon Islands in the same manner. Fact 6. There is not, and never has been, an HGDP list of populations to be sampled. In October 1992, a planning workshop for the HGDP created a set of tables showing examples of the kinds of populations that would be of particular interest for studying the genetic diversity, and hence the genetic history, of humanity. The HGDP gave a draft copy of those tables to RAFI, which has proceeded for several years to refer to them as showing "targeted populations" and now as being "a hit list." As we have told RAFI often, these drafts were never completed and the idea of even discussing specific populations as examples was abandoned more than two years ago because of the way it was being misunderstood. Fact 7. When Edward Hammond of RAFI says, "The thin veneer of the HGDP as an academic, non-commercial exercise has been shattered by the U.S. government patenting an indigenous person from Papua New Guinea," he is, to be most charitable, grossly misinformed. The HGDP Project is N O T the United States government. It is an international effort by scholars from around the world to
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increase our understanding of our common human heritage. Although several years ago, it received minor federal funding for planning workshops, it has no current funding from the United States government. It hopes to get federal funding, but even then I am sure it would not accept funding that required the samples to be patentable without the informed consent of the populations involved.24 The debate intensified and RAFI moved to take the life patenting issue to the World Court at the Hague as well as to the Biodiversity Convention and relevant multilateral bodies. RAFI had been monitoring the patenting of indigenous peoples since 1993 when the patent was applied for (and subsequently withdrawn) by then-US. Secretary of Commerce Ron Brown on a cell line from the Guaymi woman. On October 2, RAFI's Jean Christie was in Port Moresby and telephoned Dr. Carol Jenkins at the Institute of Medical Research to discuss the patent. On her return from Honiara and Port Moresby, Christie issued a statement: "This outrageous patent has provoked anger in the Pacific and is a matter of deep concern worldwide." 25 Expressing belief that the HGDP was motivated to make profits on patenting genetic materials, in a newsletter of the Australian GenEthics Network, The Qene Report, Christie wrote that she believed that any money spent on collecting D N A samples from threatened indigenous peoples should be used to help these people to survive and improve their living conditions. The profit potential in indigenous germ plasm was brought home to drug companies this year when 30 people in the isolated Italian town of Limone were found to have a unique gene that codes against many cardiovascular diseases. Swedish and Swiss companies and the University of Milan have applied for patents. If the gene produces a marketable therapy, big profits are likely. Such patents may outlive the indigenous peoples from whose hair, blood and guts they are drawn. The National Institutes of Health (NIH) has already applied to patent more than 2800 genes and DNA fragments from the Human Genome Project's study of brain tissue, and H U G O teams in England and Japan plan to file for patents. 26 Other groups stepped in and voiced opposition to the HGDP. Alan Swedlund, head of the Anthropology Department at the University of Massachusetts, earlier announced that an increasing number of anthropologists were opposed to the HGDP because they felt there was a decline in social and cultural issues and an increase in genetic determinism. Swedlund said that HGDP managers "have hitherto ignored the plight of aboriginal peoples but now want to swoop in, collect blood for their own scientific goals, and then leave people to their fate." 27 Edward Tilton, project officer for the Central Australian Aboriginal Congress (CAAC), issued the following statement: "The HGDP is immoral and has no beneficial purpose to the Aboriginal peoples in the sense that it's just treating people as mere sources of genetic information. Aboriginal people will have no
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control over these samples, which will be frozen someplace in the United States where they'll be kept for decades, even centuries. So people won't have any control over how their genes are used. It's very much a continuation of the research on people rather than the research with people approach." 28 The HGDP responded that genocidal use of genetics was not possible with what was then current technology and, further, based on what they knew of human genetic variation, it seemed impossible that it would ever be developed. The HGDP condemned and barred any effort to use its data for such purposes. The best ways to implement those commitments depended on some complex issues of patent and contract law that had not been entirely resolved at the time, as well as on some decisions by the sampled populations or their representatives on how best to proceed. The HGDP declared its plans to implement their decisions after consultation with representatives. The commitments they made promised to be firm. Once again, the HGDP promised that it would not profit from any samples obtained from indigenous peoples and that it would do its best to make sure the financial profits, if any, were returned to the sampled populations.
Calls for a Halt The HGDP was heavily criticized by various indigenous groups, as well as by anthropologists, geneticists, and psychologists. Leonora Zalabata, spokeswoman for the Arhuaco people of northern Columbia, was particularly wary of the HGDP and its possible exploitation, saying: "Our land, our culture, our sub-soil, our ideology and our traditions have all been exploited. This could be another form of exploitation, only this time they are using us as raw materials." 29 As early as May 1993 RAFI had begun to sound an alarm about potential abuses and commercialization of human genetic material. At that time RAFI made accusations that the HGDP was planning to collect and "immortalize" human tissue from 722 human populations (10,000-15,000 actual persons) which included indigenous peoples around the world. RAFI made known its objections to the HGDP when it notified the World Council of Indigenous Peoples (WCIP), the First International Conference on the Intellectual and Cultural Property Rights of Indigenous Peoples, and other Indigenous Organizations. Chief Leon Shenandoah, of the Council of Chiefs of the Onondaga Nation, believing that the HGDP was violating human rights of indigenous peoples, sent the following message to the National Science Foundation: "Your process is unethical, invasive and may even be criminal. It violates the group rights and human rights of our peoples and Indigenous Peoples around the world. Your project involves the very genetic structures of our beings." 30 In June 1993, the WCIP and RAFI raised pointed questions about HGDP at the United Nations Human Rights Conference in Vienna and asked for a halt of the HGDP until the project could be further studied. This was followed by RAFI's discovery in August that the U.S. government had applied for U.S. and world patents on the cell line of the twenty-six-year-old Guaymi Indian woman from Panama.
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On Thursday, November 4, 1993, Henry Greely received an e-mail from Pat Roy Mooney, the Executive Director of RAFI, in which Mooney stated: We still believe that the Human Genome Diversity Project must be approved by Indigenous Peoples' organizations and must function under the auspices of the United Nations. We continue to be concerned that commercial benefits could arise from the Project and that they may not be shared equitably. We are justifiably concerned that intellectual property rights might be applied related (directly or indirectly) to human cell lines collected under the Project. We are further concerned that the information acquired could lead to further discrimination against Indigenous Peoples or even be used for population-targeted biological weapons. 31 The Third World Network received information from RAFI that U.S. HGDP scientists had started to collect human DNA samples from indigenous communities throughout the world. Subsequently, there was a call by indigenous peoples' groups to mobilize public opinion against the case of human communities as material for scientific experimentation and patenting. The SAIIC asked that representatives of the HGDP hold a meeting with the World Indigenous Council so that fair and open dialogue could take place and the peoples involved would be able to voice their needs and perspectives as active participants. 32 Various indigenous groups around the world called for an immediate halt of the HGDP and its activities. The groups made known to the world that they had a right to be recognized as fully human communities with full human rights, including the right to decide how other countries related to them. Indigenous groups were asked to write or call President Clinton, the U.S. National Institute of Health, and respective indigenous governments to demand that the U.S. government withdraw its support of the HGDP. The South and Meso American Indian Information Center (SAIIC) on October 20, 1993, sent out a memo requesting immediate halt of the HGDP, quoting a statement of RAFI: "The sampling of human genetics for scientific research has serious implications for Indigenous Peoples." 33 At the Beijing Women's Conference, Sami indigenous women from the Nordic countries added their voices to those organizations that denounced the HGDP as a violation of their rights. 34 O n December 10, 1993, the World Council of Indigenous Peoples (WCIP), with headquarters in Ottawa, Ontario, issued the following resolution:
Resolution of World Council of Indigenous Peoples (WCIP) Considering the preliminary discussions undertaken with the Human Genome Diversity Project; Considering the presentation of the Chairperson of the Ethics Panel of the North American Region of the Human Genome Project to
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this the VII International Conference of Indigenous Peoples on 08.12.93; Recognizing the reaction to this Conference to that presentation; W E RESOLVE TO CATEGORICALLY REJECT AND C O N D E M N THE H U M A N GENOME DIVERSITY PROJECT AS IT APPLIES TO O U R RIGHTS, LIVES AND DIGNITY. We also resolve to monitor, follow up and, if necessary, to take action against this project in all its manifestations, and to encourage Indigenous Peoples worldwide to do the same; Based on the aforementioned, we as representatives of Indigenous Peoples in the WCIP, are required to inform our Peoples, as a preventative measure, about the Project for the Study of the Diversity of the Human Genome. In the event that we become aware of the carrying out of this Project despite the rejection by Indigenous Peoples, we will go to the respective international human rights entities to ask for justice in this case.35 The WCIP Resolution was followed by a declaration on February 19, 1995, by the Indigenous Peoples of the Western Hemisphere:
Declaration of Indigenous Peoples of the Western Hemisphere We are the original peoples of the Western hemisphere of the continents of North, Central, and South America. Our principles are based upon our profound belief in the sacredness of all creation, both animate and inanimate. We live in a reciprocal relationship with all life in this divine and natural order. Our responsibility as Indigenous Peoples is to insure the continuity of the natural order of all life is maintained for generations to come. We have a responsibility to speak for all life forms and to defend the integrity of the natural order. In carrying out these responsibilities we insure that all life in its natural process and diversity continues in a reciprocal relationship with us. We hold precious all life in its natural form. The harmonious progress of the natural order in the environment shapes and defines healthy genetic diversity. The principle of harmony requires that we do not violate the principles of Creation by manipulating and changing the natural order. Given that our natural relationship has been interfered with by foreign or non-indigenous external forces in a long history of destruction we have never abandoned those responsibilities.
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In the long history of destruction which has accompanied western colonization we have come to realize that the agenda of the non indigenous forces has been to appropriate and manipulate the natural order for the purposes of profit, power, and control. To negate the complexity of any life form by isolating and reducing it to its minute parts, western science and technologies diminished its identity as a precious and unique life form, and alters its relationship to the natural order. Genetic technologies which manipulate and change the fundamental core and identity of any life form is an absolute violation of these principles, and creates the potential for unpredictable and therefore dangerous consequence. Therefore, we the Indigenous Peoples and Organizations participating in this meeting from North, Central, and South America reject all programs involving genetic technology. We particularly oppose the Human Genome Diversity Project which intends to collect and make available our genetic materials which may be used for commercial, scientific, and military purposes. We oppose the patenting of all natural genetic materials. We hold that life cannot be bought, owned, sold, discovered, or patented, even in its smallest form. We denounce and identify the instruments of intellectual property rights, patent law, and apparatus of informed consent as tools of legalized western deception and theft. We denounce all instruments of economic apparatus such as NAFTA, GATT, and the World Trade Organization (WTO) which continue to exploit people and natural resources to profit powerful corporations, assisted by governments and military forces of developed countries. We demand that scientific endeavors and resources be prioritized to support and improve social, economic, and environmental conditions of Indigenous Peoples in the environments, thereby improving health conditions and raising the overall quality of life. We reaffirm that Indigenous peoples have the fundamental rights to deny access to, refuse to participate in, or to allow removal or appropriation by external scientific projects of any genetic materials. We demand the Human Genome Diversity Project and any other scientific projects cease any attempts to seduce or coerce participation in their project through promises of benefits and financial gain in order to obtain consent and participation of Indigenous Peoples. We demand an immediate moratorium on collections and/or patenting of genetic materials from Indigenous persons and communities by any scientific project, health organization, governments, independent agencies, or individual researchers. We demand that nation-state governments and their departments do not participate, fund, or provide any assistance to the Human Genome Diversity Project or any related programs or seek to hold
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patents or otherwise benefit from the genetic materials taken from Indigenous Peoples. We call on religious communities, human rights, social justice and environmental organizations, funding agencies, all individuals, and institutions to refuse to participate, fund, or provide other assistance to the Human Genome Diversity Project and any related programs. We extend our support and solidarity to all those who are resisting these efforts, or are seeking the repatriation of genetic materials already taken or removed from their control. We urge the international community and the United Nations to participate with Indigenous Peoples in developing international policies and conventions which protect all life forms from genetic manipulation and destruction. We call on our brothers and sisters of the indigenous nations around the world and concerned peoples in the international community to stand up and unite in our efforts to protect the natural diversity and integrity of all life. The support of all humans in this Declaration would protect the sacredness of all life, the natural order, and would provide a healthy future for generations to come. As declared by the undersigned participating organizations in Phoenix, Arizona on February 19, 1995: Amazanga Institute, Provincial de Pastaza, Ecuador Association Kunas Unidos Pro Napguana, Panama Coorinadora de Mujeres Indigenous de Bolivia, Las Pas, Bolivia CONIC Consortium, Albuquerque, New Mexico Council of Athabaskan Tribal Governments, Stevens Village, Alaska En'owkin Center, Penticton, British Columbia, Canada Independent Traditional Seminole Nation of Florida, Immokalle, Florida Indigenous Environmental Minnesota
Network,
National
Indigenous Environmental Oklahoma
Network,
Oklahoma
Office,
Bemidji,
Region,
Tulsa,
Indigenous People's Alliance, Phoenix, Arizona Indigenous Peoples Support Network, London, Ontario, Canada Indigenous Women's Network, Lake Elmo, Minnesota; Ponsford, Minnesota; Boulder, Colorado Inter-Ethnic Association of the Peruvian Rain Forest (AIDESEP), Peru International Indian Treaty Council, San Francisco, California South and Meso American Information Center (SAIIC), Oakland, California
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Sovereignty People's Information Network, British Columbia, Canada Tonantzin Land Institute, Albuquerque, New Mexico Tonatierra, Phoenix, Arizona 36 On November 12-13, 1997, twenty-seven indigenous peoples' organizations and their delegates from fifteen different nations met at an HGDP workshop in the community of Ukupseni, Kuna Yala and issued the following declaration.
Declaration of Ukupseni, Kuna Yala The Indigenous Peoples' organizations, gathered in the community of Ukupseni, Kuna Yala, with regard to the Human Genome Diversity Project (HGDP) declare: Considering that for Indigenous Peoples, life constitutes a set of elements forming a small universe with relationships and inseparable harmonic dependencies, and after giving careful consideration to the Human Genome Diversity Project and other independent investigations on the human genome, we conclude: (a) That this research and other research projects on Indigenous Peoples' genome go against human life and, in particular, violate the genetic integrity of Indigenous Peoples and their values. (b) The process of genetic collection, based on deception and exploitation of poverty and marginalization, violates fundamental human rights and collective rights, often with the consent of governments. (c) This research is an act of piracy and theft, and consists of an assault again Indigenous Peoples. (d) We consider that all funding for this research constitutes an assault against humanity and an open violation of Indigenous Peoples' rights. (e) Having evidence that intense research already has been carried out and continues to be done in our communities, we demand the immediate suspension of these activities and the repatriation of all genetic collections, original genetic material, isolated cell lines, and the data obtained in this research. (f) We request that the international scientific community condemn any research that has been carried out contrary to recognized human values and moral principles, and that violates the international codes of ethics described in the Nuremberg Code and the World Medical Association Declaration of Helsinki. (g) We condemn all attempts to commercialize genetic material, or genetic cell lines of human beings, and in particular those of Indigenous Peoples. (h) We reject the use of existing mechanisms in the legalization of intellectual property and patent systems use of existing mechanisms including intellectual property rights and patents to legalize
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the appropriation of knowledge and genetic material, whatever their source, and especially that which comes from our communities. (i) For us, the concept of "individual consent" is a violation of our cultural norms and ignores our collective rights. (j) Indigenous Peoples do not oppose development and use of new technologies provided they do not violate our harmonic relationships, principles of solidarity, and universally recognized fundamental rights. (k) We also condemn the active participation of some universities and NGO's who, in complicity with large transnationals, attempt to violate the spiritual, material and political integrity of Indigenous Peoples. The Indigenous Peoples gathered in Ukupseni, Kuna Yala declare that our millennial existence has been based on the principles of respect, solidarity and harmony with the natural elements. In this context, our declaration is a contribution to all of humanity.37 On December 13, 1994, the Cordillera People's Alliance, an alliance of 120 indigenous peoples' organizations in the Cordillera region in the northern Philippines, with the support of Asian and other indigenous and nonindigenous organizations, issued their call for a halt to the HGDP.
Statement of the Cordillera People's Alliance 1. This is a more sophisticated form of collecting and preserving Indigenous Peoples like those collections of yet unreturned mummies taken from their burial caves in violation of Indigenous People's rights. 2. The $23-35 million to be spent over five years can be better put to providing basic social services needed for Indigenous Peoples' survival and rights protection. Fund raising for the HGDP endangers further the chances of receiving funding for more crucial projects. 3. After the rest of the world have squandered their own resources, the resources that Indigenous Peoples have sacrificed lives and limb to maintain are suddenly being made common heritage for the appropriation of transnationals that rarely benefit Indigenous Peoples. Developed drugs are often sold to Indigenous Peoples at exorbitant rates. 4. Research projects done amongst Indigenous Peoples have often been used against them. The potential biological warfare uses are great. 5. Indigenous Peoples used as subjects are often not fully briefed— many indigenous women have been sterilized or injected with drugs without being informed. There is a likelihood that Indigenous Peoples' poverty will be exploited to acquire test subjects.
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6. The Biodiversity Convention and the Biotechnology Chapter of Agenda 21 and the trade-related intellectual property rights of GATT will facilitate the issuance of patents to transnational developers of biotechnology. Many indigenous developed goods have suffered such a fate putting them beyond the reach of IPs. The Philippine Solidarity Group of Toronto (PSG), cognizant of these reasons, fully supports the call to halt the Human Genome Diversity Project. To emphasize the urgency of this call, we note two revealing points. The HGDP draft insensitively referred to Indigenous Peoples as "isolates of historic interest" and Luigi Luca Cavalli-Sforza wrote in Qenomics (11:1991): "the genetic diversity of people . . . may lead to clues of the evolution of our species. . . . " Taken together with the trend of this project, Cavalli's phrase has the disturbing ring of eugenics—a discredited field that seems to keep returning like the phoenix. Further, PSG encourages other groups to show solidarity for Indigenous Peoples struggles for aboriginal land rights and for selfdetermination. It is precisely because of ethnocide—the land grabbing, the destruction of Indigenous cultures and outright physical elimination of Indigenous communities for transnational and local big corporate and financial interests—that Indigenous Peoples become "extinct." In Solidarity, Philippine Solidarity Group-Toronto 3 8
National Research Council (NRC) Panel In September 1996 a fifteen-person National Research Council (NRC), commissioned by the National Institutes of Health and the National Science Foundation, heard testimony from the HGDP's organizers as well as proponents and critics. The panel was composed of ethicists, anthropologists, geneticists, and others and was instructed to examine issues surrounding the HGDP. 39 The NRC heard testimony that the HGDP has been awarded approximately $500,000 in seed monies from the U.S. government and private foundations, including the Chicago-based MacArthur Foundation. Although funding was an important consideration, a major concern was the biological significance of the HGDP. Judith Greenberg, director of the National Institute of General Medical Sciences division of genetics and developmental biology, questioned whether the HGDP was the best way to get information about complex disorders or susceptibility to disease. Henry Greely and Mary-Claire King, American Society Professor at the University of Washington School of Medicine, as well as HGDP founder and member of the North American regional committee, responded by presenting the document "Model Ethical Protocols for Collecting DNA Samples." The document detailed issues such as gene patenting and informed consent. Hope Shand, research director of RAFI, reminded the panel of past abuses of indigenous peoples and inherent potential abuses associated with the HGDP. She argued that many moral and ethical issues needed to be brought forth and resolved
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before the HGDP could proceed in good faith. Other critics of the HGDP included representatives from the Edmonds Institute (Edmonds, Washington) and RAFI, as well as Colombia and the Solomon Islands.
Current Status of the HGDP It is difficult to know exactly where the HGDP stands at the present time. Since 1991 when it was first proposed by Cavalli-Sforza and his colleagues, much has happened to dampen the spirits of some of those who first proposed the project. This author, not involved in any way with the HGDP or with any group opposing it, finds it difficult to compare stories from one side to the other. Accurate information is often difficult to obtain and compare since it is dispersed in so many different sites around the world. Access to these is often not easy. Funding remains a major problem for organizers of the HGDP. Although there has been some limited funding, it has not been sufficient to sustain the original purpose and goals of the HGDP. The United Nations Educational, Scientific, and Cultural Organization (UNESCO) did not endorse the HGDP in 1995. In 1997, a report from the National Academy of Sciences recommended that the United States National Science Foundation and National Institutes of Health not fund the HGDP. 40 ' 41 Political and public controversies have also reduced the size and scope of the HGDP. Some of the project's strongest supporters, including Hiraku Takebe, professor at the Atomic Energy Research Institute at Kinki University in Osaka, Japan, appear to be somewhat pessimistic about the project. Takebe told the Human Genome Organization (HUGO) meeting in Vancouver in 2000 that he feared the HGDP was "almost aborted" and that H U G O had not been actively pursuing the HGDP in recent years.42 Even with H U G O ' s backing, there have been serious efforts to thwart the project. Tactics included countries such as India forbidding the exportation of blood samples containing DNA, and New Guinea charging a fee for each sample taken. Other projects simulated the HGDP and drew large amounts of monies from both private and public sources. Some of the original backers of HGDP, including HUGO, have questioned the organization's structure. Some view the HGDP as having ambiguous goals and questions. However, most of the organizers continue to believe keeping the (DNA) cell lines alive for future study, as technology develops even further, to be a good idea. "The HGDP has been a catalyst for consideration of the ethical issues that arise during population genetics research, but itself has been plagued by the concerns to the point where the original plan is unlikely to be completed because technical strategies have evolved to help reduce the number of persons who need to be sampled." 43 In recent e-mail correspondence from Henry Greely at Stanford University, he writes: The Project never received any substantial funding. The HGDP itself has only been able to collect samples in two of its international regions—China and Southwest Asia—thanks to local funding in those
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regions. About the only thing the HGDP is actively doing right now is collaborating with the Center for the Study of Human Polymorphisms (CEPH) in Paris, to make DNA available from over 1,000 cell-lines from people around the world. Except for some of the cell-lines from China and all of the cell-lines from Southwest Asia, these cell-lines were not collected by the HGDP but were contributed by various researchers. The HGDP did examine the background of the collections to assure that each cell line had been collected with the informed consent of the individual subjects for the use of their DNA to study broad questions of human genetics or human history. None of the cell lines in the HGDP-CEPH collection is from US Native Americans. 44 The HGDP has had problems carrying out its ideas and research on populations that do not share Western ideals. Because of the current political climate worldwide, it seems poor timing to suggest what might next be possible for the HGDP. Yet, it appears that proponents of the HGDP remain optimistic, believing that with time and more visible work, support for the HGDP will grow.
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P A R T IV Threading an Ethical Needle The stem cell debate entails huge ethical principles, morality, and scientific potential. Proponents maintain that the new technology offers great benefits for humankind. Opponents bitterly oppose stem-cell cloning because the human embryo is destroyed when stem cells are removed. In arriving at a consensus on the value of stem-cell research we must look to the past, examine the current research, and project the merits of the technology for the good of society.
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s STEM-CELL RESEARCH Our intention is not to create a cloned human being, but rather to make life-saving therapies for a wide range of human disease conditions, including diabetes, strokes, cancer, AIDS, and neurodegenerative disorders such as Parkinson's, Alzheimer's, and multiple sclerosis. Robert Lanza, Director of Medical Research, Advanced Cell Technology Stem-cell research took a giant leap in April 2001 when Dr. Judson Somerville, a forty-year-old Texas physician paralyzed from the chest down as a result of a cycling accident, took a cigar-cutter and cut a chunk of skin from his right calf for a cloning experiment. The goal was to grow a new organ such as a heart for a heart patient, some brain tissue for an Alzheimer's patient, or some diabetic cells for a diabetic patient from the skin cells, or perhaps even providing some neurons (nerve cells) that would cure his own paralysis.1 Although Somerville does not believe in cloning humans, he has a firm belief in stem-cell research. "I don't want another one of me. I want my own neurons so I can walk again or feel below my chest." 2
Offering Hope Stem cells, obtained from human embryos, are useful in repairing and replacing damaged cells such as Somerville's neurons and offer the promise of curing many individuals with various diseases, including but not limited to cancer, Alzheimer's,
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Parkinson's, multiple sclerosis, chronic heart disease, rheumatoid arthritis, osteoarthritis, liver failure, diabetes, amyotrophic lateral sclerosis, muscular dystrophy, and spinal-cord injuries. Other examples of potential cures, using embryonic stem cells, include skin damaged by burns and bone mass depleted by osteoporosis. In addition, genetically engineered stem-cell cultures potentially may be used for both transplants and evaluating drugs in labs. This often overlooked, but profoundly important, procedure has the potential to rule out dangerous drugs before they are tested on humans. Embryonic stem-cell cloning is of great interest to scientists and physicians who believe they have a moral obligation to improve the lives of future generations. Yet, as with any scientific or technological advancement, the most important question that needs to be asked is whether or not the gains outweigh the potential losses. Stem-cell cloning allows a patient's own DNA to be used to develop advanced medicine and offers hope to the nearly 100 million Americans who suffer from diseases and the thousands who die each day as a result of incurable diseases. Unfortunately, while the huge controversy continues over cloning using embryonic stem cells, thousands of individuals die each each day as scientists and policy makers continue to study the issue and attempt to make decisions. "Three thousand Americans die every day of diseases that therapeutic cloning could treat. It would be wrong of us to abandon those people because we're afraid of controversy." 3 Whereas opponents of embryonic stem cell research have a great deal of empathy for those who suffer with various diseases, at the same time they bitterly oppose stem-cell cloning because the human embryo is destroyed when stem cells are removed. Stem-cell cloning is a technique used by researchers and animal breeders to split a single embryo into two or more embryos. The most unique feature of embryo cloning is that scientists can grow undifferentiated stem cells and transform them into more than 200 of the body's specialized cell types that humans need for development. In 1998 scientists discovered how to isolate and grow embryonic stem cells so that the cells maintained their pluripotency—they remain a seemingly endless source of any kind of cell. Recently, Dr. John D. Gearhart and his team at Johns Hopkins University figured out how to turn human embryonic stem cells into an infinite number of different kinds of cells, including heart muscle, skin cells, and T cells of the immune system. However, even though embryonic stem cells are able to differentiate into other cell types, they are not able to differentiate into a complete individual. All human embryos in their earliest stages of development contain stem cells that have a capacity to replace almost any damaged or defective tissue in the body. By cloning human embryos for the production of stem cells that perfectly match a patient's cells, transplant organs can be grown that provide a perfect genetic match. Importantly, embryonic stem cells are unspecialized (undifferentiated) and are not attacked by the person's own immune system. There is potential for millions of people worldwide to reap the benefits of embryonic stem-cell research. Among those who will benefit are children with
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Type I, juvenile insulin-dependent diabetes who could be supplied with the pancreatic islet, insulin-producing cells they now lack. In August 2001 a team in Israel, using human embryonic stem cells developed by scientists at the University of Wisconsin, reported they had programmed embryonic stem cells to produce insulin. 4 Another prime example of how stem cells offer great hope is regeneration of neurons in treatment of diseases such as amyotrophic lateral sclerosis (Lou Gehrig's disease), multiple sclerosis, and spinal-cord injuries. Gearhart and colleagues at Johns Hopkins University programmed embryonic stem cells to begin functioning like neurons. Gearhart injected programmed stem cells into the cerebrospinal fluid which surrounded injured spinal cords of rats. Three months later, many of the once paralyzed rats were able to walk again. In another significant study, Harvard scientists used embryonic stem cells in mice that had a multiple-sclerosis-type disease. Scientists used the stem cells to repair myelin, the fatty material that covers central nervous system neuronal axons. 5 Stem-cell-derived neurons also have the potential to treat Alzheimer's and Parkinson's diseases and to repair spinal-cord injuries. Using stem cells, scientists have done a great deal of work in providing Parkinson's patients with new brain cells. In Parkinson's disease people lose brain cells that produce dopamine, a chemical (neurotransmitter) responsible for controlling nerve signals that regulate movement. In treating Parkinson's patients, surgeons drill through the skull and implant reprogrammed stem-cell-derived neurons. Transplanting dopamineproducing neurons alleviates the tremors and impaired balance that are among the major symptoms of Parkinson's. Another example of embryonic stem cell use is in stem-cell-derived heart muscle cells (cardiomyocytes) that have the potential to repair or replace a damaged heart. Heart patients could receive programmed cardiac cells that would enable scientists to grow new cardiac tissue rather than having to rely on a mechanical heart or a heart transplant. In early September 2002 it was announced in Amsterdam, the Netherlands, that a three-year-old blond, blue-eyed boy named Wilco Conradi had been treated with embryonic stem cells. Wilco had been born with severe combined immunodeficiency (SCID), a disease that occurs in about one of every 15,000 births. SCID, which is carried by women but afflicts only boys, had plagued Wilco's family for generations, killing one of his uncles and two cousins. SCID makes the immune system ineffective against microorganisms ordinarily harmless in people with normal resistance. In order to give Wilco a normal immune system, he was injected with genetically modified embryonic stem cells. Wilco had been treated as a baby at the Hospital Necker Enfants Malades in Paris and had lived his first months in a germ-proof plastic enclosure to protect him from infections that would have been fatal to him. Previously, bone-marrow transplants had been the method of choice to help victims of SCID, followed by monthly intravenous infusions of immune globulin antibodies taken from donated blood. The potential for embryonic stem-cell research is not limited to those who suffer from life-threatening diseases. Stem-cell research also presents a realistic potential to curing some of the diseases that accompany aging. Gerontologists
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are especially optimistic about the prospects of using embryonic stem cells to replace cartilage destroyed by arthritis in the elderly. In early times, researchers never even came close to knowing the secret of aging and some of its manifestations: "English scientists of the 13th century therefore believed that the breath of a virgin would rejuvenate old men, while a physiologist in 1920's Vienna theorized that elderly men would find renewed vigor and extra years by having the testicles of younger men grafted onto their original equipment. Neither approach, needless to say, worked. But today's researchers are thinking along the same lines. To replace and repair cells damaged by the diseases of aging, go to the youngest of the young: days old human embryos." 6
Other Recent Breakthroughs Recently, in a significant breakthrough, it was reported that embryonic stem cells can be coaxed to transform themselves into eggs for stem-cell cloning. Researchers at the University of Pennsylvania reported they were able to cause stem cells from mouse embryos to transform into oocytes (eggs) and to further develop into primitive embryos. The embryos cannot be used to reproduce mice because they contain an incomplete set of chromosomes; however, the eggs can be used for embryo cloning. The study, conducted by Hans Scholer and colleagues of the School of Veterinary Medicine at the University of Pennsylvania, suggests that eggs can be made in the laboratory from stem cells. This is highly significant because it would eliminate the need for embryo donors and lead to an almost limitless supply.7 Although embryos are the choice for obtaining stem cells, adult stem cells are found in many tissues, including blood, liver, brain, nerve tissues, adult fat, umbilical cords, and placentas. In addition, multipotent adult progenitor cells (MAPCs), also known as "master cells," have been found in the bone marrow. MAPCs have the potential to be a major source of stem cells. The chief disadvantage of adult stem cells is that they do not have the same versatility as embryonic stem cells to differentiate into specific cell or tissue types. Another disadvantage is that adult stem cells can double only a few times in culture, allowing replication of only a few stem cells. Millions, or perhaps billions, of stem cells are needed for major organ repair, made possible by culturing embryonic stem cells. Efforts are currently underway to try to coax adult stem cells back to an embryonic state. Recently, at the Stem Cell Institute at the University of Minnesota, Dr. Catherine Verfaillie and her team reported that certain bone-marrow cells taken from adult humans give rise to a variety of other cell types in the test tube. The study, done in test tubes and mice, suggests that adult stem cells might be an alternative to embryonic stem cells, at least in some cases. A new discovery in 2004 is using stem cells to grow new adult teeth to replace lost or diseased ones. Scientists at the National Institute of Dental and Craniofacial Research have used human adult stem cells from extracted molars to grow new tooth buds that are implanted into animals' jaws and develop into new teeth. Another research team, directed by Paul Sharpe of King's College in London,
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grew new teeth in mice from nondental mouse stem cells. The team began experiments in 2005 with human cells. Another recent development in stem cells was effected by scientists at the University of Toronto and Miami University in Ohio, who transplanted stem cells from a human retina into the eyes of day-old mice and chick embryos. When the animals' eyes developed fully, the scientists found that many of the human cells had survived and grown into specialized cells needed for sight. The researchers examined the eyes, which appeared to be normal. It is now thought that the retinal stem cells from healthy mice will continue to develop when transplanted into blind mice. The research is a key advance in the use of stem cells to treat disorders such as macular degeneration and retinitis pigmentosa. In yet another noteworthy development, surgeons at the Justus-Liebig University Medical School in Giessen, Germany, used stem cells from a seven-year-old girl's fat to help repair severe damage to her skull. This was the first time that researchers have generated bone in a person by using the fat-derived cells. This is an example of the use of adult stem cells rather than embryonic stem cells to treat disease. The girl, a victim of a severe fall two years prior to the treatment, was missing nineteen square inches of her skull. After the stem-cell surgery, the girl's skull was reported smooth to the touch, the missing parts replaced by thin but solid bone. In May 2005 it was announced that South Korean scientists were speeding up the process of creating human embryonic stem cells, growing new batches that were, for the first time, a genetic match for injured or sick patients. Patients were male and female, as young as age two and as old as fifty-six, suffering with spinal cord injuries, diabetes, or genetic immune diseases. The Seoul researchers, led by Woo-Suk Hwang and Shin Yong Moon of Seoul National University, eliminated the use of mouse "feeder cells" that were used to nourish human stem cell lines, causing concerns about animal contamination. The researchers collected eggs that were donated by unpaid volunteers and removed the gene-containing nucleus from each egg. The scientists inserted into the eggs DNA from skin cells of the patients and electrically stimulated cellular division. Thirty-one early stage embryos (blastocysts) of 100 cells each successfully grew. From those, the scientists harvested eleven stem cell lines. Each line was a genetic match to the patient who donated the skin snippet, and each has the potential to form other tissues, such as brain cells or bone cells. The use of skin cells is not only easier but extends the technology to both males and females. The procedure, called nuclear transfer or therapeutic cloning, is permitted in the United States under Proposition 71, passed in November 2004 in California. The advance does not, however, change the fact that the human embryo must be destroyed to obtain stem cells. Leon Kass, M.D., chairman of the President's Council on Bioethics and professor metaphysics and moral philosophy at Georgetown University, described the Korean research as "morally troubling." Unlike the United States, the South Korean government supports financing stem cell research. The same is true in Singapore where $1.5 billion is given by the government to its renowned Biopolis research center. The Biopolis has many cutting-edge laboratories and has recruited top researchers from around the world. In August 2004, Britain granted its first license to Newcastle University for human cloning, joining South Korea on the leading edge of stem-cell research.
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Obtaining Stem Cells Different procedures are used to obtain stem cells. When therapeutic cloning (also known as somatic cell nuclear transfer technology) is used, scientists remove the nucleus of an egg cell and replace it with materials from the nucleus of a somatic (body) cell such as Dr. Somerville's skin, a nerve, heart, or any other nongerm cell. Scientists then stimulate the cell by electrical or chemical means to begin cell division. The resulting cells are never transplanted into a womb for subsequent development into a human being, but rather are kept in a petri dish in the laboratory where they are eventually used to obtain embryonic stem cells. For a few days, each embryonic stem cell is a "blank page," awaiting a complex set of genetic instructions to determine precisely which organs, bone, and specialized tissues and cells to form. What the stem cells actually become depends on which of the 30,000 or so genes (individual in every human cell) are turned on. For example, if genes characteristic of pancreatic cells turn on, while genes characteristic of all other cells remain turned off, the stem cells grow into pancreatic cells. If genes characteristic of dopamine-producing neurons turn on while other genes are turned off, the specific stem cells grow into dopamineproducing cells. Sexual fertilization is used for stem-cell production. After a sperm fertilizes an egg the embryo is allowed to develop and the stem cells are removed from the four-to-six-day-old embryo. Removing the stem cells kills the blastocyst (preembryo), a hollow ball of 200 cells. After removal from the blastocyst, stem cells are nurtured in a medium of proteins and enzymes where they divide indefinitely, creating a lineage of specialized cells called an embryonic stem-cell line. So far, scientists have revealed three established sources of human embryos needed for stem-cell cloning. Each of these methods crosses different moral, ethical, and legal lines. Excess (surplus) frozen embryos currently are obtained mostly from in vitro fertility clinics and are donated by infertile couples who no longer want them for pregnancy. Frozen embryos are the most widely accepted source of embryos. Destined to be destroyed, the few-daysold frozen embryos are thawed and the inner cell mass containing the stem cells is removed. Various groups on the Christian Right and the Roman Catholic Church regard frozen in vitro fertilized embryos as human beings. Fresh embryos (contrived conception) are created specifically for research by fertility clinics that gain consent from donors to fuse an egg and a sperm for the intentional purpose of creating an embryo, specifically for harvesting stem cells. Cloned (coupled and copied) embryos are created by combining donor eggs and cells using experimental cloning techniques. Using an electrical current, cells from a donor (preferably the person to receive the stem cells) are fused with an egg stripped of its nucleus. Reprogrammed with the donor's genetic material, the egg is tricked into developing
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and yielding stem cells. The stem cells are harvested and reprogrammed into dividing and forming colonies identical to the parent cells. Antiabortion activists and various religious groups consider all three techniques unethical, saying they result in the destruction of human life. However, proponents of stem cell research argue that these days-old, undifferentiated cells cannot be viewed as human since they will never be implanted in a woman with the intent to produce babies. In a newer technique, called pre-implantation analysis, actual cases like the following hypothetical one may soon become commonplace: Maya and Dick Anderson of Lakewood, California, went through in vitro fertilization and genetic testing of son David's embryo to make sure he did not have the gene for the always-fatal disease, Fanconi's anemia, that his sister, Susie, had. The Andersons also wanted to make sure David could provide transplant cells for Susie after he was born. Geneticists examined fifteen embryos that had been created using eggs and sperm from the Andersons and determined that David's embryo did not carry the Fanconi's anemia gene. Thus, they implanted David's embryo in Maya Anderson's uterus and allowed David to develop into a full-term baby. The remaining embryos were frozen. David was born in August 2003 and stem cells were taken from his umbilical cord blood and implanted into his sister Susie. Physicians at Duke University, where the transplant took place, said results were successful.
Leftover Embryos Frequently, there is little interest on the part of couples who create embryos as what to do with their embryos that they no longer need or want. Unable to face the difficult decision for one reason or another, many couples leave their embryos frozen, often paying hundreds of dollars each year in storage fees, some as high as $1,000 or more per month. It is estimated that there are over one million early embryos (blastocysts) leftover worldwide from in vitro fertilization, waiting to be discarded. The following hypothetical case is an example: In vitro fertilization brought Lori and Joe Haley two sons and a daughter but left them with a dilemma: what to do with three extra embryos left frozen in a Los Angeles clinic. It often takes several tries to get an embryo to attach to the uterus and grow into a fetus, so fertility specialists routinely collect and fertilize as many eggs as possible and then choose the healthiest. As a result, leftover embryos are frozen to try again later or in cases like the Haleys who have all the children they want, the frozen embryos remain. The Haleys did not want to throw their embryos away now that they had no further need for them. In addition to disposal of the embryos, their options included donating
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them to research or giving them to another couple who were trying to have a baby. Some embryo donors cannot abide with the prospect of their genetic children being raised by someone else, whereas others worry that one of their children might unknowingly meet and fall in love with a brother or sister. Others have long-term guilt in throwing away their embryos; some have guilt for the rest of their lives. For many couples, donating unwanted embryos for stem-cell research appears to be a more comfortable option than donating them to a couple for family building.
Stem Cell Debate The stem cell debate is about huge ethical principles, morality, and scientific potential. The debate over embryonic stem-cell use intensified with word that scientists at Advanced Cell Technology Inc. (ACT) in Worcester, Massachusetts, had cloned for the first time a six-cell human embryo for its stem cells. Officials at ACT repeatedly emphasized that the cloned human embryo was created to provide genetically compatible matched cells for patients suffering from a wide range of diseases, rather than to create a cloned human being: "Our intention is not to create cloned human beings, but rather to make life-saving therapies for a wide range of human disease conditions, including diabetes, strokes, cancer, AIDS, and neurodegenerative disorders such as Parkinson's and Alzheimers disease." 8 In general, opponents of stem-cell research believe that destroying an embryo, even for curing diseases, is morally repugnant, unethical, and medically unnecessary and view it as an evil act that can never be justified. The Roman Catholic Church has led opposition to human embryonic stem-cell research because of what it calls the "sanctity of life." Catholic doctrine holds that life begins at conception, which means that an embryo, even at its very earliest stage of development, is regarded as human life. Others fear that creating embryos for their stem cells will get out of control or in the hands of evil persons. Still others argue that embryonic stem-cell research must not be established in law because people, no matter their size or stage of life, are not products to be used for the benefits of others, no matter how noble the intentions. Some believe that if the Hippocratic Oath taken by physicians is abandoned, it will signify that the end justifies the means—that it is permissible to kill some people so long as physicians intend to do good for others. Yet, most physicians and scientists who are proponents of stem-cell cloning agree that it offers treatment and cures for many diseases and that they owe it to posterity to pursue it. With the potential to ease a great deal of pain and suffering, physicians and scientists also believe that stem-cell cloning would help not only those individuals who suffer from terrible ailments, but would also include victims' families and friends. Dr. Bert Vogelstein of the Johns Hopkins University School of Medicine, who chaired a National Academy of Sciences Report that endorsed stem-cell research, wrote: "The scientific obstacles surrounding stem-cell research are just as
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real as the ethical or legal concerns. If the nation wants to reap the benefits of stem-cell research, then these barriers must be overcome." 9 The prevailing view among scientists is that it is acceptable to destroy embryos for medical research as long as the embryos are destined to be destroyed anyway. The National Institutes of Health established guidelines during the Clinton administration that permitted federal funding of research on surplus frozen embryos from fertility clinics. This required the consent of couples who had the embryos created for the purpose of having a baby. The American Society of Reproductive Medicine, representing the nation's fertility doctors, issued a statement saying that it was ethical to create embryos for research. The argument set forth by fertility doctors was that it was a more "ethically pure" way to conduct the research than to ask couples to donate embryos. The U.S. government supported the work of medical researchers who were using human stem cells obtained from sources that did not require the destruction of human embryos. Current NIH guidelines ban funding of embryos that are created specifically for research. Part of the hysteria of embryo cloning is a misunderstanding of what an embryo actually is. Michael West, visionary for ACT, said: "If you ask the average person, they will tell you it's a tiny little person with buggy eyes. But in fact, these are just a few reproductive cells, not much different than eggs or sperm. They are the raw materials of life, but they are not a person." 10 However, David Oderberg, a professor of philosophy at the University of Reading in the United Kingdom, has a different view: "An embryo is a human being and may not be destroyed for any purpose, any more than a baby or an adult can be. Every innocent human being, no matter how big, small, healthy or sick they are, has an inalienable right to life."11 Oderberg's statement begs the question, is there an inalienable right to life? If so, why are embryos an exception? But ethicists argue the fact that embryos created in vitro (in a petri dish) and in vivo (in the body) are different, a term called nonenablement. Another serious obstacle standing in the way of successful medical treatment with human embryonic stem cells is immune system rejection. Both frozen and fresh stem cell lines are from donors unrelated to the patient who would receive the cells as transplants. Patients would be required to take antirejection drugs, which could have serious side effects. To circumvent rejection, scientists have to make the cells acceptable to a recipient's immune system. There is also controversy over whether taxpayer monies should be used to fund research that many people consider morally wrong. Although U.S. Federal law currently prohibits the use of taxpayers' money for the cloning of human beings, privately funded companies such as ACT are not affected by the ban.
Leading the Way Many companies are currently involved in stem-cell research. Leading the way with transfer of human DNA into human eggs and the growth of the eggs into six-cell embryos was Advanced Cell Technology (ACT), a small biotech company
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in Worcester, Massachusetts Founded in 1994, ACT since has offered a wide array of genetic services, including in vitro fertilization and cloning for cattle. The first of three men at ACT to be credited with pioneering embryo cloning was Jose Cibelli. Considered the "instigator," Cibelli, a native of Argentina and a doctoral student working in the laboratory of James M. Robl at the University of Massachusetts-Amherst, was instrumental in stem-cell cloning. Robl, a professor of veterinary and animal science, had previously cloned cattle, pigs, and rabbits. After joining ACT, Cibelli described what he perceived as the "future of medicine"—human stem-cell cloning. 12 The second man involved with stem-cell cloning at ACT, geneticist Michael West, was considered the "visionary." ACT's focus shifted to humans in 1998 when West took over the company. A "creationist," West had a passion for alleviating suffering, using stem-cell cloning: "If God is about love and life, then we should do everything we can to end suffering and death." 13 West had reincorporated his late father's truck-leasing business as a biotech firm called Geron (Greek for "old man"), with a primary goal to reverse aging and some of its main afflictions: macular degeneration, cancer, Alzheimer's, and heart disease. West's wife, a prominent scientist in her own right, had previously cloned the gene for telomerase, the enzyme that extends the life of telomeres, structures in the cell that decide whether a cell is to age and/or die. 14 West joined forces with Cibelli, who had demonstrated an alternate way to engineer an embryo by coaxing a human egg to divide and develop into an embryo without any kind of fertilization—either by a sperm or outside genetic material (DNA)—a process known as parthenogenesis (Greek for "virgin birth"). Cibelli tricked the eggs into keeping copies of their chromosomes for development. Human parthenogenesis had never been reported before; however, certain lizards, microbes, insects, and other animals naturally reproduce through parthenogenesis. Cibelli and his colleagues believed that stem cells had the potential of being retrieved from a parthenogenetic embryo in women of childbearing age because they could produce a sufficient number of eggs. The scientists speculated that it would be possible to replace the egg's D N A with genes from sperm and the egg then could be activated to become a parthenote.15 The third man at ACT, Robert Lanza, was considered the "activist." As a young scientist he was mentored by some of the scientific giants—psychologist B. F. Skinner, immunologist Jonas Salk, and heart transplant pioneer Christian Barnard. Highly regarded by his peers and mentors, Lanza became director of medical research at ACT in March 1999. Lanza had strong beliefs that cloning could end transplant rejection, and persuaded sixty-seven Nobel laureates to sign a letter that was sent to President Clinton in support of embryonic stem-cell research. However, over a two-year period (1999-2001), West, Cibelli, and Lanza lost some respect throughout the scientific community. Called "mad scientists," "baby killers," and "monsters," among other names, they were put on antiabortion assassination lists on the Web and warned by the FBI of threats on their lives. A bill presented to the House of Representatives declared them federal criminals deserving of ten years in prison and a $1 million fine.16 Some of their
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troubles came as a result of ACT's work with human embryos, since embryos could be implanted into a womb and grown into a fetus. However, the ACT scientists preferred the term uovum sum,11 to embryo.
Potential to Heal Today, most U.S. stem-cell research is done in private labs and biotech companies that are not affected by federal guidelines. Each company employs different, but sometimes controversial, techniques to harvest embryonic stem cells. Various well-known universities are working to create stem cell lines with funds from private organizations such as the Juvenile Diabetes Research Foundation, the Christopher Reeve Paralysis Foundation, the Michael J. Fox Foundation for Parkinson's Research, and Stanford University's Institute for Cancer/Stem Cell Biology and Medicine. Christopher Reeve (who died in 2004) suffered a spinal cord injury and Michael J. Fox is a Parkinson's victim. In 1998 James Thompson pioneered research on human embryonic stem cells at the University of Wisconsin-Madison. Thompson created five colonies of stem cell lines from human embryos. WiCell Research Institute, a nonprofit company formed in 1999 by the Wisconsin Alumni Research Foundation (WARF), also further advanced research in the area of stem cells. Founded in 1925, WARF patents research discoveries at the University of Wisconsin-Madison and manages patents and technology transfers to industry. Because federal law prohibits public funding of human embryo experiments, Thompson used private funding from Geron Corporation, located at Menlo Park, California, to buy leftover frozen embryos from fertility clinics. Since that time, Geron has announced plans to obtain its stem cells by cloning proteins in eggs that would lead to the creation of stem cells. Michael West, president of ACT, announced that his company intended to clone human embryos as sources of stem cells using a new technique that would provide an alternative to creating embryos as sources of stem cells. He announced that a patent was pending on the technique, called ooplasmic transfer, which would allow scientists to create stem cells directly without first making an embryo. Working with university labs, ACT has shown some very promising stem-cell research. In animals, body cells have been taken and cloned to generate embryos. Stem cells have been extracted from the embryos to grow new tissues and some diseases have been cured. For example, in sheep, replacement neurons have cured spina bifida. Old cows have been given new "young" immune system cells. Tiny kidneys, grown from cloned cells, reportedly have functioned properly for three months in cows. Embryonic stem cells have been injected directly into sheep and become disks of bone and perhaps the replacement for liver and brain cells. Patches of heart muscle, skeletal muscle, skin, and cartilage have been grown from cloned embryos and transferred back into the parent cows. ACT hopes to be able to change DNA, removed from a body cell, before it is placed into an egg, by adding factors—genes for immune cells that would make a person resistant to diseases.17
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Other private companies have established collaborative arrangements with Universities. Boston in Vitro Fertilization, the country's largest infertility clinic, has provided embryos to Harvard University scientists, who extract stem cells from the embryos. Boston IVF contacts thousands of couples with long-frozen embryos to ask whether they want to donate their embryos for stem-cell research. The project has been financed by the Howard Hughes Medical Institute. Using donated sperm and eggs, human embryos have been created by the Jones Institute for Reproductive Medicine, located in Norfolk, Virginia. The institute fertilizes them with the same techniques used for generating embryos for infertile couples. Created solely for research purposes, the embryonic stem cells were available under President Bush's guidelines because the embryonic cells are created with informed consent of donors from excess embryos originally intended for human reproduction. In early December 2002 Stanford University became the first U.S. university to publicly announce that it had plans to develop stem-cell research through a highly experimental scientific method. The research is taking place at Stanford's new Institute for Cancer/Stem Cell Biology and Medicine and is led by Irving Weissman, a leader in stem-cell research. 18 Stanford's new institute is privately funded to avoid any conflict with President George W. Bush's policy against using federal funds to create new stem-cell lines. The institute and its scientists are reportedly opposed to human reproductive cloning. Other scientists are involved in an emerging field of medicine that involves control of blood vessel growth by stem cells. In August 2002 an article published in the medical journal Lancet was the first to report that patients' own stem cells were injected into their leg muscles to create new blood vessels (therapeutic angiogenesis), eliminating pain from bad circulation and helping to prevent gangrene or amputations. The main focus of such research is on the heart, limbs, and brain. Another major use of angiogenesis are sores that fail to heal, in the case of diabetes. Findings such as these offer hope to millions of people worldwide who suffer pain in their limbs because of clogged arteries but cannot have an operation. 19
The Political Side On September 22, 2001, Governor Gray Davis of California, believing stem-cell research was essential to keep California at the forefront of medical research, signed a bill authored by Senator Deborah Ortiz to allow embryonic stem cell research in California. Governor Davis was joined at the ceremony by actor Christopher Reeve, who was paralyzed in a horse riding accident in 1995. The bill allowed for both the destruction and donation of embryos. In addition, the bill required clinics that perform in vitro fertilization procedures to inform women that they have the option to donate discarded embryos to research; the bill banned the sale of embryos. Ortiz's bill was openly opposed by the Roman Catholic Church and antiabortion groups because the embryo is destroyed in the process. Because obtaining embryonic stem cells for research destroys human embryos, the practice is viewed by many as immoral. Although stem cell research
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came at an ethical cost for society, it came as a political cost for President George W Bush from his most conservative political and religious supporters. The president's decision on embryonic stem-cell research represented the most socially acceptable means of sacrificing embryos for research. In making his decision, President Bush balanced the issues. The president reassured conservatives that he would never permit federal funding of stem-cell research that required the destruction of human embryos. The president promised to allow funding for research on only a limited number of existing stem-cell "lines."
How Far? How Fast? How far, and how fast, stem-cell research progresses will depend mostly on the outcome of the heated political battle that continues over the use of human embryos as a source of stem cells. Realistically, it will probably be many years before the research yields a viable product. A good example of how slowly science proceeds is that scientists started working with genetic engineering in the early 1970s and it took more than a decade before recombinant DNA products hit the market. It took in vitro fertilization even longer before it was accepted into society. Although currently banned in the United States, human embryo research continues overseas. In February 2004 South Korean scientists cloned an embryo and extracted the stem cells from it. In another case, Professor Song Chang-hun of Chosun University treated a thirty-seven-year-old spinal-cord patient with umbilical cord stem cells. The patient had been in a wheelchair for nineteen years, and forty days after treatment stood up and walked with the help of a walker. Researchers hope eventually to create insulin-producing cells that could be transplanted into diabetics. Regardless of the political dispute and its outcome, stem-cell research will go forward in the United States with private, if not public, financing. Scientists owe it to posterity to pursue stem-cell research, proceeding with great care, vigilance, and restraint. The technology has enormous potential and benefits for those suffering from many devastating diseases.
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At its core, this issue [stem cell research] forces us to confront fundamental questions about the beginnings of life and the ends of science. President George W. Bush
In a long-awaited decision that resulted in a passionate political and ethical debate, President George W. Bush, in an August 9, 2001, prime-time speech to the nation, gave the go-ahead for limited federal funding on existing human embryonic stem cells. In the eleven-minute speech, the president was deliberate and well grounded and came across as thoughtful and serious: Good evening. I appreciate you giving me a few minutes of your time tonight so I can discuss with you a complex and difficult issue, an issue that is one of the most profound of our time. . . . My administration must decide whether to allow federal funds, your tax dollars, to be used for scientific research on stem cells derived from human embryos. A large number of these embryos already exist. They are the product of a process called in vitro fertilization, which helps so many couples conceive children. When doctors match sperm and egg to create life outside the womb, they usually produce more embryos than are implanted in the mother. Once a couple successfully has children, or if they are unsuccessful, the additional embryos remain frozen in laboratories. Some will not survive during long storage; others are destroyed. A number have been donated to science and used to create privately
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funded stem-cell lines. A few have been implanted in an adoptive mother and born, and are today healthy children. . . . You should also know that stem cells can be derived from sources other than embryos—from adult cells, from umbilical cords that are discarded after babies are born, from human placentas. And many scientists feel research on these types of stem cells is also promising. Many patients suffering from a range of diseases are already being helped with treatments developed from adult stem cells. However, most scientists, at least today, believe that research on embryonic stem cells offers the most promise because these cells have the potential to develop into all of the tissues in the body. . . . Research on embryonic stem cells raises profound ethical questions, because extracting the stem cell destroys the embryo, and thus destroys its potential for life. Like a snowflake, each of these embryos is unique, with the unique genetic potential of an individual human being. As I thought through this issue, I kept returning to two fundamental questions: First, are these frozen embryos human life and therefore something precious to be protected? And second, if they're going to be destroyed anyway, shouldn't they be used for a greater good, for research that has the potential to save and improve other lives? . . . At its core, this issue forces us to confront fundamental questions about the beginnings of life and the ends of science. . . . Researchers are telling us the next step could be to clone human beings to create individual designer stem cells, essentially to grow another you, to be available in case you need another heart or lung or liver. I strongly oppose human cloning, as do most Americans. We recoil at the idea of growing human beings for spare body parts, or creating life for our convenience. . . . I have friends whose children suffer from juvenile diabetes. Nancy Reagan has written me about President Reagan's struggle with Alzheimer's. My own family has confronted the tragedy of childhood leukemia. And, like all Americans, I have great hope for cures. I also believe human life is a sacred gift from our Creator. I worry about a culture that devalues life, and believe as your president I have an important obligation to foster and encourage respect for life in America and throughout the world. . . . Embryonic stem cell research offers both great promise and great peril. So I have decided we must proceed with great care. As a result of private research, more than 60 genetically diverse stem cell lines already exist. They were created from embryos that have already been destroyed, and they have the ability to regenerate themselves indefinitely, creating ongoing opportunities for research. I have concluded that we should allow federal funds to be used for research on these existing stem cell lines, where the life and death decision has already been made. . . .
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I also believe that great scientific progress can be made through aggressive federal funding of research on umbilical cord, placenta, adult and animal stem cells, which do not involve the same moral dilemma. . . . I will also name a President's council to monitor stem cell research, to recommend appropriate guidelines and regulations, and to consider all of the medical and ethical ramifications of biomedical innovation. . . . As we go forward, I hope we will always be guided by both intellect and heart, by both our capabilities and our conscience. 1
The President's Main Concern In arriving at his decision, the president had a moral and ethical concern because he believes life begins at conception. From the beginning, he made it clear that he believed the risks and ethical issues associated with human cloning outweighed any potential benefits to science. Addressing a White House audience filled with supporters of a ban on cloning, the president stated: "Our children are gifts to be loved and protected, not products to be designed or manufactured. No human life should be exploited or extinguished for the benefit of another." 2 The president's decision was not a total restraint, but rather a compromise. Accepting stem-cell lines in existence as of his August 9 speech, the president said he would not allow taxpayer money to go toward creating more stem-cell lines because it would involve destruction of more human embryos. Attempting to thread an ethical needle, the president's compromise allowed him to address concerns about the willful destruction of potential human life, while at the same time gave hope to those suffering with destructive diseases that might potentially be cured by embryonic stem-cell research. In forming his resolution, the president decided that a few stipulations must be followed. First, human embryos must have been created for in vitro fertilization (IVF) and no longer wanted for that purpose. Couples with leftover embryos could still donate them for research, but only if privately funded. Private groups operating without federal funds could still create and clone embryos. Second, informed consent must have been obtained for the donated human embryo cells. President Bush announced that he would offer half of the federal money for research on human embryonic stem cells to the University of Wisconsin Alumni Research Foundation, a biotechnology company known as the WiCell Research Institute, and Geron Corporation of Menlo Park, California, to pay royalties and licensing fees on patents.
Not an Easy Decision It was not an easy determination for the president, especially from a spiritual, scientific, and political standpoint. Describing the issue as "one of the most profound of our time," the president made his final decision after meeting with his
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top aides at his ranch in Crawford, Texas, telling them that the decision was as agonizing as sending U.S. troops into combat: "It is important that we pay attention to the moral concerns of the new frontier. I have made the decision and I pray it is the right one." 3 Ari Fleischer, at the time White House Press Secretary, told an audience that he believed the president made the right decision: "This is a very sensitive issue that divides American society. It involves the promise of life and the destruction of life. The President made a principled decision that he stands proudly behind. Progress will be made without destroying life. The President and his administration support alternative routes to obtain stem cells, including use of adult cells. So, in effect, the President's decision was a compromise. President Bush has made it clear that cloning humans is 'morally wrong' and we should not create life to destroy it." 4 President Bush repeatedly assured conservatives that he would never permit federal funding of stem-cell research that required the destruction of human embryos. In addition to his belief that life begins at conception, the president emphasized that he opposes abortion and that he believed destruction of embryos for stem-cell research is the same as ending human life by abortion. This position is also held by the Roman Catholic Church. Repeating his decision, the president said that he would allow funding for research on existing stem-cell lines, but would not allow funding for the creation of additional stem-cell lines from existing or future human embryos because it involved extraction of stem cells from embryos and subsequent destruction of embryos.
Considerable Input President Bush consulted many individuals and groups and read widely before reaching his decision. Ethicists, physicians, religious leaders, abortion foes, lawmakers, and health activists offered their views to the president. For several weeks prior to making the decision, three of President Bush's top aides—Secretary of Health and Human Services Tommy Thompson, Chief of Staff Andrew Card, and political advisor Karl Rowe worked to help the president find a solid compromise, one that would please both the pro-human-embryo-research community and those opposed to human embryo cloning. Leading up to the president's decision, leading conservatives had urged him to reject any kind of funding for embryonic stem-cell research. Nancy Reagan, wife of former President Ronald Reagan (an Alzheimer's victim) sent word to the White House that she supported embryonic stem-cell research, although as an opponent of abortion, she also supported former President Reagan's value of human life and the need to protect it at all stages. O n behalf of Nancy Reagan, former Reagan aides Kenneth Duberstein and Michael Deaver delivered a message to then U.S. House Speaker Dennis Hastert and U.S. Senate Republican leader Trent Lott: "This would mean an awful lot to Nancy, especially for a cure for Alzheimer's, even if it's not for the President, but for future generations." 5 However, President Bush's final decision to allow funding for limited embryonic stem-cell research was shaped by, more than anyone else, Leon Kass, a
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University of Chicago bioethicist. Earlier, Bush had named Kass to head a White House Commission to oversee stem-cell research and set practical guidelines. Sharing the president's views, Kass is an opponent of human cloning who also shared the president's concern that research on embryonic stem cells needs rigid controls. "Anyone truly serious about preventing human reproductive cloning must seek to stop the process from the beginning, at the stage where the human somatic cell nucleus is introduced into the egg."6 In formulating his decision, President Bush kept returning to two fundamental questions: "First, are these frozen embryos human life and therefore something precious to be protected? Second, if they're going to be destroyed anyway, should they be used for a greater good, for research that has the potential to save and improve other lives?"7 President Bush had repeatedly said that he believed that killing to cure is morally repugnant and must not be established in law and that people, no matter their age or stage of life, are not products to be used for the benefits of others, no matter how noble the intentions. In effect, the president said that he believed that even the most noble acts do not justify any means. Prior to making his decision, the president met with Pope John Paul II on Monday, July 23, 2001, at the pope's summer retreat (Castel Gandolfo) in the foothills southeast of Rome. During the meeting the Pope denounced embryonic stem-cell research, telling the president that destroying embryos to obtain stem cells amounts to ending a life: "A free and virtuous society, which America aspires to be, must reject practices that devalue and violate human life at any stage from conception to human life. Experience is already showing how a tragic coarsening of consciences accompanies the assault on innocent human life in the world." 8 During the same meeting, the pope also repeatedly denounced euthanasia, infanticide, and proposals for the creation of human embryos for research purposes. The president's own United Methodist Church previously pleaded with him to use extreme caution in proceeding with activities that would result in the destruction of human embryos. In support of human embryonic stem-cell cloning, eighty Nobel laureates sent the president a letter urging federal funding for research that could produce novel therapies for a range of serious and currently intractable issues. Other supporters of embryo donation (embryo adoption) offered it as an alternative to embryo destruction. President Bush also carefully reviewed past legislation and action taken with regard to embryo research and noted that in 1979 with bipartisan support, Congress had approved a moratorium on experiments using human embryos fertilized in laboratories. Also, in 1985 Congress had denied funds for experiments that had the potential to do harm to embryos in the womb. In 1994 President Clinton's Commission on Stem-cell Research recommended caution but suggested that stem-cell research held great potential to cure disease. At that time, the Clinton administration allowed federal money for stemcell research as long as embryonic cells were extracted with private money rather than with federal funds. During this time legislators also became involved. Representative Jay Dickey (R-Ark.) sponsored the first Dickey amendment, which was added in 1996 to a
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House appropriations bill. The amendment banned federal funds for experiments that destroy human embryos. Current law (The Dickey Amendment, in Public Law 106-554) prohibits federal funding of any research in which human embryos are destroyed, discarded, or knowingly subjected to risk of injury or death. The law embodies the principle that nonconsenting human beings must not be subjected to harmful medical experimentation. In 1998 researchers at the University of Wisconsin (WiCell Research Institute Inc.) and at Johns Hopkins University in Baltimore, using federal funds, extracted and grew stem cells from human embryos. The five stem-cell lines developed by Wicell were offered to the National Institutes of Health (NIH) for research purposes. The agreement stipulated that NIH scientists be allowed to publish freely and retain ownership of any new intellectual property that resulted from stem-cell research. A Memo of Understanding (MOU), a "Simple Letter of Agreement," governed the transfer of cell lines to individual laboratories with minimal administrative burden. WiCell retained commercial rights to the stem cells, as well as a fee to cover the handling and distribution expenses in supplying the cell lines.9 In the year 2000, at the prompting of the Clinton administration, officials at NIH agreed to fund stem-cell experiments, provided that the embryos were created without government funding; supporters of the Dickey amendment protested. In February 2001, President George W. Bush attempted to reverse policy by ordering a review of guidelines issued by President Clinton that would have allowed spending taxpayer money on stem-cell research. After a complete review, President Bush halted all NIH-funded stem-cell research. In July 2001, Advanced Cell Technology (ACT), a private research firm, announced that it had created embryos for stem-cell research using private funds. ACT had approached donors and informed them that their eggs and sperm would be used to develop embryos for stem-cell research. That same month, the U.S. House of Representatives banned cloning of human beings to create stem cells for research. Senator Bill Frist (R-Tenn.), Senate Majority Leader, suggested a plan that would ban the creation of embryos for stem-cell research but would permit federal funding for experiments on excess embryos from fertility clinics. Frist's plan was in direct contrast to a rival plan by Health and Human Services Secretary Tommy Thompson, which would fund only research that used existing stem-cell colonies.
Reactions to President Bush's Decision President Bush's decision to allow limited federal funding for existing human embryonic stem-cell research won mixed reviews, outraging some abortion opponents and leaving many lawmakers and scientists dissatisfied. Those who hoped to be helped by stem-cell cloning said that the president's opposition to stem-cell cloning was misplaced and totally unfair. However, the president defended his decision, saying that it was a compromise between the sanctity of life and the urgency of stem-cell research that meant hope to those who battle serious diseases.10 After thoroughly studying the human embryo cloning issue, the president said that the embryo cloning process would require "massive" numbers of
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women's eggs, potentially turning women's bodies into commodities and creating a national market for women's eggs. In further defending his proposal, the president argued that once cloned embryos were created for research, it would be "virtually impossible" to prevent a scientist from implanting an embryo in a woman who was willing to carry the clone to term. 11 White House spokesman Scott McClellan said that the president made his decision based on what he believed was in the best interest of the American people. Supporting the president, Scot Red, a Republican strategist, argued that Bush had succeeded in finding the right balance in his decision. Red said that the decision would not unduly alienate the president's conservative base, and would in fact appeal to some moderate voters. However, abortion opponents in the Republican party criticized the decision as a "bitter loss" because the president did not ban embryonic stem-cell research altogether. Roman Catholic leaders were dismayed with the president's decision, saying it had gone too far. Houston Bishop Joseph A. Fiorenza, president of the U.S. Conference of Catholic Bishops, was particularly harsh in his condemnation of the president's decision: "The trade-off he has announced is morally unacceptable: the federal government, for the first time in history, will support research that relies on the destruction of some defenseless human beings for the possible benefit to others." 12 The bishop said he opposed the president's decision primarily because existing stem-cell lines were obtained through the destruction of human embryos: "We consider the stem cells that are now in possession to be what we could compare to ill-gotten goods. For the government to allow funding for this experiment makes the government complicit in what we consider to be wrongdoing." 13 The American Life League took out a full-page newspaper ad that likened President George W Bush's promise on stem-cell research to the elder Bush's "Read my lips: no new taxes" pledge in the 1988 campaign. Surprisingly, Christian Coalition founder Pat Robertson said he was satisfied with George W Bush's plan because there was no killing of new life. Robertson, who has always opposed abortion, said he favored the research using existing stem-cell lines: "It is just a practical reality that this is a very useful science that has been held up because the desire of all of us to prevent the destruction of human life."14 The National Right to Life Committee, an antiabortion group that strongly opposed embryonic stem-cell research, said it mourned the embryos already destroyed by stem-cell research and issued the following statement: "We are delighted that President Bush's decision prevents the federal government from becoming a party to the killing of any further embryos for medical experimentation." 15 The Church of Jesus Christ of Latter-day Saints is neutral on the subject, although it opposes abortion as unjustified killing except possibly in cases of incest, rape, or serious peril to the mother. The Union of Orthodox Jewish Congregation favors stem-cell research if it involves frozen embryos that are left over from test-tube baby treatments. Jewish religous law places high value on the principle that everything possible must be done to save lives. In Islam, many jurists accept work with embryos to seek medical therapies. The Religious Coalition for Reproductive Choice advocates full access to
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abortion on behalf of mainline Protestants, Conservative and Reform Jews, Unitarians, and others. The coalition believes the medical potential justifies research that employs the test-tube leftovers or aborted fetuses. However, they are concerned about programs that create cloned human embryos in order to destroy them and acquire stem cells. This is morally problematic for the coalition. The California Council of Churches supports a state program that involves stem cell harvesting through destruction of cloned embryos. On the opposite side of the religious spectrum, the Roman Catholic Church teaches that the life of every human being is to be respected once a sperm and egg unite. It vehemently opposes destroying embryos, whether through abortion or for research. Eastern Orthodox and evangelical Protestant churches generally agree. Adding further support for President Bush's decision, Tommy Thompson, a Roman Catholic and secretary of Health and Human Services, stated that the president's decision was moral because it allowed federal funding only on embryos that had already been destroyed. Thompson issued the following statement: President Bush opened the door to embryonic stem-cell research in an ethical and morally sound manner. The immediate challenge for us is to conduct the vital basic research. Before we can talk credibly about therapies for diseases, we must do the fundamental research to fully understand how those cells work. This basic research will take years, but can now occur with federal funding with an adequate supply of lines. There is value in research at all stages. Very valuable basic research can be done on stem cells at all stages of development. Researchers will now be able to use federal dollars to work on further developing some of the existing lines. We need to get to work. We have a historic opportunity for research that did not exist at this level until now. Although we certainly want to seize the moment, we must not lose sight of the fact that the research we do must be conducted in an ethical manner. The only place we're going to find definitive answers to all of these questions is in the laboratory. The lab door is now open; let's get to work. 16 Most of the president's supporters praised his decision as a reasonable, statesman-like compromise for stem-cell research. However, others who supported the president's decision believed it was motivated by his deeply-held personal and religious beliefs, in addition to his political beliefs. At a July 19, 2001, news conference with British prime minister Tony Blair, President Bush referred to stem-cell cloning when he announced: "This is way beyond politics. This is an issue that speaks to morality and science and the juxtaposition of both." 1 7 The president's decision on human embryonic stem-cell research also affected many lawmakers personally. Although some key lawmakers were encouraged by the decision to allow federally funded embryonic stem-cell research, others expressed concerns that it failed to meet scientists' needs. Senator Edward Kennedy (D-Mass.) issued the following statement: "Restrictions on this lifesaving research will slow the development of the new cures that are so urgently needed by millions of patients across America." 18
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Senate Majority Leader Tom Daschle (D-S.D.) and Senator Patrick Leahy (D-Vt.) reported that, while they opposed human cloning, they would support human embryonic stem-cell research. Senator Daschle issued the following statement: "I support cloning for research purposes, but we vehemently oppose any cloning for purposes of human replication." 19 Dan Perry, executive director of the Alliance for Aging Research, a Washington advocacy group for research on aging, said that the president's decision, albeit important, fell far short of what researchers and suffering patients really need. After hearing the president's decision, Perry said that patient advocacy groups regarded the decision not as the end of the debate but as the beginning of a new battle. Many believed that human embryonic stem-cell research had been taken from behind the walls of private laboratories and placed in the public spotlight for the first time. There was also fear that without federal funding, stem-cell research would be developed solely by private companies lacking necessary ethical safeguards. Others were concerned that without public funding in the United States, human embryonic stem-cell research would progress at a snail's pace or be driven overseas.
How Many Stem Cell Lines? Prior to the president's August 9, 2001, decision, controversy intensified over the number of available stem-cell lines that researchers had to work with. Aware of wide differences in the scientific community as to how many stem-cell lines existed, the White House asked Secretary of Health and Human Services Tommy G. Thompson, to contact the National Institutes of Health (NIH) and ask for their help in conducting a worldwide survey to determine the number of available stem-cell lines. In response to the president's request, NIH researchers cataloged a Human Embryonic Stem Cell Registry of stem cell lines existing worldwide and reported to the White House that it had found at least sixty "genetically diverse" cell lines (possibly as many as sixty-five), with about thirty of them in the United States. Based on the NIH finding, Tommy Thompson reported back to the president and his administration that the world's supply of available human embryonic stemcell lines would be adequate to allow scientists to conduct effective embryonic stem-cell research: "The President's decision balances our deepest respect for life but also our highest hopes for alleviating human suffering. But the decision has spawned the question of whether the existing stem-cell lines are adequate to conduct effective research. The more than 60 stem-cell lines are diversely robust and they're viable for research." 20 However, leading scientists continued to dispute the number of stem-cell lines in existence and available to researchers. Most argued that even if there were sixty or more cell lines the number would, in no way, be sufficient to treat a diverse population of patients. The reason, scientists pointed out, was that while there may be that many cell lines available today, tomorrow there may be significantly fewer because most cells are unstable over a long period due to contamination.
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Convinced that the NIH cell-line numbers were accurate, the president reported to the nation that there existed at least sixty genetically diverse stem-cell lines and that there would be enough cell lines to explore the promise and potential of stem-cell research without crossing a fundamental moral line. 21 However, many scientists did not believe the president and thought instead that only a small number of cell lines were on the federally approved list and available to academic researchers. One such scientist was Ronald McKay, a senior investigator at the NIH in Bethesda, Maryland, who said: "Just because the President says something doesn't mean it happens tomorrow. It actually takes time to grow these cells. Good science takes time." 22 Defending the president, White House spokesman Ari Fleischer argued for the availability of stem cells, saying: "This is a new field, and it is unreasonable to expect instant action on something that is so promising, so untested and so new. What's important is that progress is being made and will be made." 23 Following President Bush's announced decision and, given the uncertain number of stem-cell lines, the American Association for the Advancement of Science (AAAS) issued a statement asking for disclosure of the exact number and sources of existing cell lines. The AAAS also requested information about the ownership and intellectual property status of the cell lines. They asked that the cell lines be released for evaluation so that it could be determined whether the cell lines could be accessed freely for future research and possible medical use. On September 5, 2001, amid growing skepticism, Health and Human Services Secretary Tommy Thompson admitted that a mistake had been made and that fewer than thirty cell lines were available for stem-cell research, not nearly enough to ensure the wide-ranging research that President Bush had promised in his speech on August 9, 2001. Some called it a deliberate lie on the part of the Bush administration; others called it shoddy research on the part of the NIH. Whatever the reason, because of the limited number of cell lines many scientists felt that eventually researchers would run short on research materials, sending prices skyward. Arthur Caplan, bioethicist at the Center for Bioethics at the University of Pennsylvania, agreed that prices would probably rise, saying: "There's nothing to stop them from charging what they want. And, worse, they can add conditions demanding a share on any discovery or therapy made down the road. This compromise threatens to push stem-cell work far into the private sector." 24 Calling for public funding, Caplan said he believed that private research would continue in "uncontrollable Wild West fashion" unless more funding from public sources was allowed. 25
National Academy of Sciences Report A September 17, 2001, report from the National Academy of Sciences (NAS), an independent panel of experts that advises the president, suggested that the stemcell research program that President Bush approved was not sufficient to produce significant results. In the NAS report, scientists declared that not allowing new stem-cell line development could result in inferior research. The NAS report indicated that a large amount of work remained before treatments could be devel-
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oped and encouraged researchers to aggressively pursue stem-cell work. This angered opponents of stem-cell research and bolstered critics who said that the president's plan did not go far enough. Most scientists agreed that the number of available cell lines was insufficient and that only by studying hundreds of embryonic cell lines could universally available treatments be developed. They pointed out that the low numbers of available stem-cell lines (less than thirty) actually available meant that the genetic diversity of the cells would be severely curtailed. Diversity is considered essential to develop treatments for millions of patients, each with a unique genetic structure. Harold Varmus, former director of the NIH and at the time head of the Memorial Sloan-Kettering Cancer Center, made it known that it would be a very cruel investment if scientists learned to grow cells for transplantation but did not have access to enough cell lines to treat patients effectively. The president's decision did not allow new supplies of stem cells to be generated using public funds nor did it encourage him to revisit his decision to limit federal funding for embryonic stem cell research, according to Health and Human Services Secretary Tommy Thompson: "The president will not equivocate. He made a very strong statement on that." 26 Thompson also said that the president believed basic research should continue before any legislation was sought to allow broader federally financed embryonic stem-cell research. On April 10, 2002, the president conducted an East Room ceremony at the White House promoting the anticloning bill. He continued to press the U.S. Senate to ban cloning of human embryos for research, saying science must not rush ahead without an ethical compass. "We can pursue medical research with a clear sense of moral purpose, or we can travel without an ethical compass into a world we could live to regret. How we answer the question of human cloning will place us on one path or the other. Life is a creation, not a commodity." 27 In late April 2002 the biotech lobby mobilized in Washington to fight antihuman-cloning legislation. At this time a survey of 800 adults by the The Polling Company showed 63 percent of the populous totally agreeing with President Bush's strong anticloning statement and 29 percent disagreeing. Sixty-eight percent of women agreed with the president as compared to 53 percent of men.
An Ethical Compass Politicians rose to the occasion. Senator Mary Landrieu (D-La.) and Senator Sam Brownback (R-Kans.) cosponsored an anticloning bill titled the Human Cloning Prohibition Act of 2003 (S.245). In turn, President Bush solicited support for the Brownback/Landrieu bill. U.S. Senator Bill Frist (R-Tenn.), a highly respected heart-transplant surgeon and Senate Majority Leader, issued a statement in support of the Brownback/Landrieu ban on human cloning: "Once cloned embryos are available, implantation will take place. Even the tightest regulations and strict policing would not prevent or detect the birth of cloned babies." 28 However, late in July 2005 Frist endorsed government-funded research on human embryonic stem cells, breaking with President Bush and the religious conservatives. In speaking against the Brownback/Landrieu bill, Senator Edward Kennedy
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(D-Mass.) issued the following statement: "We must not let the misplaced fears of today deny patients the cures of tomorrow. Congress was right to place medicine over ideology in the past, and we should do the same again as we confront the issue of cloning." 29 Other senators also voiced opposition to the ban on human embryo cloning. Senator Arlen Specter (R-Pa.) said that he believed a ban on human embryo cloning would criminalize legitimate research, tie the hands of medical science in the twenty-first century, and cause an enormous brain drain out of the United States to Europe. 30 Senator Tom Daschle (D-S.D.) urged lawmakers to listen to forty Nobel laureates who supported cloning research. 31 Senators Dianne Feinstein, Ted Kennedy, Orrin Hatch, Arlen Specter, and Tom Harkin also introduced a bill, the Human Cloning Ban and Stem Cell Research Protection Act of 2003. The Christian Legal Society (CLS) called on the U.S. Senate to defeat the Feinstein/Hatch Act and instead enact the Landrieu/Brownback bill. The CLS, founded in 1961, is a national membership organization of nearly 3600 Christian attorneys, judges, law professors, law students, and supportive lay people. The major difference between the two bills is that the Feinstein/Hatch bill would allow therapeutic cloning while the Landrieu/Brownback bill would criminalize certain types of promising medical research. In May 2005 the U.S. Congress debated several stem cell research bills. President Bush has threatened to veto any bill that involves the use of cloned human embryos, no matter how they are produced. The U.S. House approved one bill by a vote of 238 to 194, far short of the two-thirds majority that would be needed to override a veto. An alternative offered by Republican leaders that would fund research using stem cells derived from adults and umbilical cords rather than from embryos passed 430 to 1, with Representative Ron Paul (R-Tex.) the lone opponent. A more controversial bill, sponsored by Representatives Mike Castle (R-Del.) and Diana DeGette (D-Colo.), would lift President Bush's 2001 ban on federal funding for new research using stem cells from embryos that had not been destroyed before August 2001. The House vote on the Castle-DeGette bill was intended mostly on a show of force to help propel it through the Senate and, the sponsors hope, into compromise talks with the White House. The Castle-DeGette bill deals with embryonic stem cells. Representative Chris Smith (R-NJ.) believes that there are other ways to get where we want without cloning and using human embryos or aborted babies. In May 2005 he introduced a bill called the Stem Cell Therapeutic and Research Act of 2005. The bill would create a national program that would use cells from umbilical cords. Umbilical cord transplants have proved effective for treating patients suffering from inherited immune diseases like sickle-cell anemia and leukemia, even when those transplants are from unrelated donors. In August 2005, Harvard scientists announced that they had discovered a way to fuse adult skin cells with embryonic stem cells, a breakthrough that could lead to allpurpose stem cells. These cells could be created without harming embryos. In effect, embryonic stem cells could reset adult cell genes through the cell fusion.
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PART V To Clone or Not to Clone: That Is the Question On July 5, 1996, Drs. Ian Wilmut and Keith H. S. Campbell cloned Dolly the sheep—the first large creature ever cloned from a differentiated adult cell. The remarkable breakthrough was heralded as one of the most significant scientific accomplishments of the twentieth century. Now, there is the expertise and technology to clone a human. Cloning of humans is at an ethical and moral crossroads, and most scientific inquiries and bioethical conversation about human cloning are on the subject of pro-life politics and religion. The fundamental concern centers around the moral status of the embryo.
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ID REPRODUCTIVE CLDNING Three cloned mice, Three cloned mice, See how they run, See how they run. They all ran after the scientist, W h o cut them out of a blastocyst. Did you ever think such a thing could exist As three cloned mice? Bernard Mergen, Washington Post, Sunday, January 11, 1981 In January 1981 it was announced publicly that three healthy mice had been cloned. After seeing the story in the New York Times on January 4, with its headline "Three Mice Cloned in a Laboratory," Bernard Mergen, a professor of American Civilization at George Washington University in Washington, D.C. wrote the above rhyme. Dr. Peter Hoppe of the Jackson Laboratory in Bar Harbor, Maine, and Dr. Karl Illmensee of the University of Geneva were the scientists who allegedly cloned the mice by transplanting the nuclei of mouse embryos into mouse eggs. However, when other scientists tried to duplicate the experiments, they found that the cloning results could not be replicated. Rather than all three mice being produced from the same embryo, it was discovered that the three mice came from three different embryos. Following public announcement of the mouse experiment, leading scientists called for a ban on human cloning, asking: if cloning is successful in mice what is
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to stop someone from trying it on primates, and then on humans? Today, cloned mammals include mice, pigs, primates, sheep, cattle, and horses, as well as humans.
Cloning Not New The word "cloning" makes people nervous. Yet, cloning is not new. It has been going on the natural world since the beginning of time. Because there is nothing a priori unnatural about cloning many say there are no scientific grounds per se to ban cloning. Others disagree. More clones are present in the world than one would imagine. For example, in nature there are clones that everyone is familiar with—plants and algae, some insects, and certain unicellular organisms that conduct mitosis or binary fission. Amoebas clone themselves when they divide. Interestingly, the armadillo litter is always a batch of eight octoplets, an eight-clone. Earthworms cut in half have the ability to regenerate the missing parts of their bodies, resulting in two distinct worms with the same set of genes in each clone-twin. Plants clone themselves when they reproduce by budding or by sending up new shoots. All human tissue is potentially a source for cloning and some tumors are considered clones, derived from one aberrant cell that no longer obeys the normal rules of growth control.
Human Clones W h e n most people hear the word cloning, the first thing they think of is human reproductive cloning (duplicating babies). Most people are opposed to that type of cloning, yet in the strict sense biological human clones, for example identical twins, have existed as long as humanity itself. Human monozygotic twins are natural clones of each other, splitting from a single embryo. With individual characters, they have the same exact genetic information due to the division of the embryo early in development. Because sex is the normal means by which new genetic material is introduced during procreation, clones have the same genes as their single parent. 1 At least 8 million identical, or monozygotic, twins are alive in the world. Some consider identical twins as one person born with two bodies. As identical twins, clones have individual differences, separate identities and separate souls. Natural twins are much more alike than clone-twins because natural twins are exactly the same age, whereas a clone-twin and the DNA donor may be decades apart in age. In effect, a clone-twin is a time-delayed identical twin of another person. Whether produced naturally or artificially, clones are identical only physically because human selves, unlike human cells, can never be cloned. Environmental influences render them different, sometimes even before birth. "If clones are simply identical twins by another name, there is no reason to believe they will be any more similar than such twins are. In fact, because clones and their adult forebears would be born into different generations from different wombs, and have different arrays of environmental choices, there is every reason to think they will be even more different from each other than identical twins are." 2
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Some scientists have considered experiments that combine human genes with animal genes to make a half-and-half breed. Geep (half sheep and half goat) have already been born. Combining humans and monkeys, to make a half-and-half breed called a humonkey, would not be difficult (although not desirable), requiring the combination of two balls of growing cells in the preembryo stage. The genetic code for primates (including chimpanzees and monkeys) and humans is 99 percent identical, which means that less than 1 percent of the code determines individual differences. Because primates and humans share most of their genes in common, theologians frequently pose the following questions: • Would humonkeys be able to receive salvation like humans? • Would humonkeys be recognized as morally responsible individuals before the law if they were able to talk? Recently, scientists have fused rabbit eggs with human DNA, used human stem cells to make paralyzed mice walk, and created pigs with human blood. But the co-mingling of animal and human cells is now becoming of more concern, particularly with the mixing of brain cells. The question arises, What if human brain cells (neurons) were found in brains of nonhuman species? Does this mean the human mind could be contained within the sheep's brain? Charles Darwin, in his book The Expression of the Emotions in Man and Animals, cites one of "Father of Eugenics" Sir Francis Galton's anecdotes: A gentleman of considerable position was found by his wife to have the curious trick, when he lay fast asleep on his back in bed, of raising his right arm slowly in front of his face, up to his forehead, and then dropping it with a jerk so that the wrist fell heavily on the bridge of his nose. . . . Many years after his death, his son married a lady who had never heard of the family incident. She, however, observed precisely the same peculiarity in her husband; but his nose, from not being particularly prominent, has never as yet suffered from the blows. One of his children, a girl, has inherited the same trick. 3 It seems there may be more in our genes than we often realize.
Kinds of Cloning There are several different kinds of cloning which involve three distinct paths: adult-cell (somatic or body cell) cloning, natural and artificial embryo cloning, and stem-cell (therapeutic) cloning. In adult-cell cloning the development of an entire animal such as Dolly the sheep is obtained from a single body (somatic) cell, other than an egg or sperm, of another animal. In the first step of somatic cloning the nucleus of an egg (ovum) containing the maternal genes is removed (enucleated). Next, DNA from a cell from the individual to be cloned is implanted into
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the empty egg, creating a cell with a perfect set of genes. The egg is activated in a manner similar to natural fertilization, allowed to develop into an embryo, implanted into the womb of a female for further development into a fetus, and allowed to develop to a full-term baby. In natural embryo cloning an egg and a sperm are joined in vivo (in the body) and allowed to grow and divide in the body. In the laboratory, artificial (deliberate) embryo cloning begins with joining a sperm and an egg in a petri dish (in vitro fertilization) to form a fertilized egg called a zygote. After union, there is a natural division of the zygote; normal cell division occurs into two, four, eight cells, etc. If an egg splits, identical twins are the result. In stem-cell (therapeutic) cloning an embryo is deliberately created in order to obtain and use its stem cells. Stem cells are coaxed into replicating into any desired tissue or organ in the body and have great potential in treating persons suffering from diseases such as Alzheimer's, Parkinson's, and cancer. Some believe that cloning is simply an extension of in vitro fertilization, but although there are many similarities, cloning goes beyond that. Cloning, like in vitro fertilization, takes the same type embryo and destroys its originality through duplication. There is no doubt that research on in vitro fertilization has helped to improve cloning techniques.
A Brief History of Cloning The first attempts at artificial cloning were as early as the late 1890s and were exercises in artificial twinning. By splitting the embryos of frogs, sea urchins, salamanders, fish, and other animals, scientists found that they could produce additional embryos that would develop into small but otherwise normal larvae. However, scientists discovered that the technique worked only at a very early stage of development, when the fertilized egg had divided into no more than eight cells. Beyond the eight-cell stage (and sometimes even before), cloning failed, primarily because each of the subdivided cells contained too little cytoplasm, the material surrounding the nucleus. 4 In the late 1890s Adolph Eduard Driesch let the eggs of a sea urchin develop into the two-blastomere stage, separated the blastomere by shaking the flask, and allowed the cells to grow. Driesch selected sea urchins because they had large embryo cells and grew independently of their mothers. Eventually, the cells developed into whole dwarf sea urchins. His original goal was not to create identical animals, but to prove that DNA was not lost during cell division. At the time, Driesch could not explain his experiments, became discouraged, and gave up embryology for philosophy. In 1902 the German embryologist Hans Spemman used a thin hair taken from his blonde son, who was less than nine months old, as a knife to separate an eight-celled salamander embryo. Later, he isolated a single cell from a sixteencelled salamander embryo. In each experiment, both the large and small embryos developed into identical adult salamanders. In removing the D N A from an adult cell, Spemman used the D N A to grow another adult salamander, theorizing, as had Driesch, that no D N A was lost as cells grew and divided.
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The first successful implantation of a nucleus into an egg occurred in 1952. Robert Briggs, a zoologist at Indiana University, and Thomas J. King of the Institute for Cancer Research and Lankenau Hospital Research Institute (now known as the Fox Chase Center) in Philadelphia, described a way of transferring a nucleus, and with it the DNA, of a leopard frog's (Rana pipiens) embryo, into another Rana egg. The procedure, called nuclear transplant, involved taking an immature frog cell, at a late stage of its development (before it began the final round of divisions that produce mature eggs), and pricking it with a glass needle to activate its first division cycle. With another glass needle, the egg's nucleus was removed microsurgically. Next, Briggs and King took the blastula, an early embryonic stage of another frog, and sucked up one of its cells with a micropipette. After breaking the cell's membrane, they injected the ruptured cell onto the top of the enucleated egg. The scientists transplanted the entire cell containing both the nucleus and the cytoplasm because they considered the nucleus too fragile to survive the procedure on its own. The cytoplasm of the egg cell "reprogrammed" the new blastula nucleus, resetting its genes so that they functioned as original genes of the egg cell. The nuclei from the undifferentiated cells came from late-stage blastulas, hollow balls of cells. Each frog egg cell, with a full set of chromosomes, began to divide and form normal embryos that developed into normal tadpoles and normal young frogs. Today, modern developmental biologists consider this procedure cloning. Briggs and King chose frogs to use in their experiments because frog eggs were more abundant and much larger than those of mice, sheep, or humans. Because frog embryos were easy to rear (all a fertilized egg needed was a dish of water), they developed in the open with their early divisions in plain view. All Briggs and King's experiments began with embryonic cells (undifferentiated) or cells specialized for a particular physiological function. In 1953 Briggs and King expanded their experiments to successfully transplant nuclei from early-stage gastrula cells. A gastrula is a three-layered structure consisting of the ectoderm (outer layer), the mesoderm (middle layer), and the endoderm (inner layer). The scientists selected endodermal cells for their experiments because, of the three germinal layers, the endoderm had the largest cells and was the easiest layer to handle. Their experiments, however, produced many abnormal embryos. Although Briggs and King worked with frog eggs and embryos, their groundbreaking techniques paved the way for mammalian clonings, including Dolly the sheep. In 1972 they were awarded the Charles Leopold Mayer Prize by the French Academy of Sciences; they were the first Americans to receive the highest biology award given by the academy. In 1956 Dr. John Gurdon began graduate work at the University of Oxford, England, under the supervision of developmental biologist Michael Fischberg. Gurdon worked on nuclear-transplant experiments in %enopus laevis, the South African clawed frog. In 1958 Gurdon teamed with Fischberg and Thomas R. Elsdale to develop nuclear-transplant embryos in sexually mature Rana pipiens adult frogs, demonstrating that the nuclei of cells that had undergone development remained totipotent, not just pluripotent. In addition, the scientists were also able to get normal development with much older donor tissue than had previously been reported with Rana. 5 In 1960 Gurdon reported that normal nuclear-transplant embryos, including
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some that developed into feeding tadpoles, grew from endoderm cells of tail-bud tadpoles, not just from the cells of gastrulas. He concluded from his work with Xenopus that the specialization of cells was not necessarily accompanied by a loss or deadening of gene expression—a conclusion that differed from the one reached by Briggs and King.6 Although Gurdon's results proved puzzling at the time, work done by Marie A. Di Berardino of the Medical College of Pennsylvania-Hahnemann School of Medicine, Allegheny University of the Health Sciences in Philadelphia clarified the situation. Di Berardino showed that all embryos that died before the feedingtadpole stage of development possessed visibly abnormal chromosomes and that the more severe the developmental disorder, the more severe the prior chromosomal defects. In addition, Di Berardino showed that the Xenopus nuclei or chromosomes were more resistant to damage during transplantation. 7 In 1970 developmental biologist Sally Hennen of Marquette University in Milwaukee, Wisconsin, added a protein called spermine to the nuclear-transfer medium and performed the transplant at a lower temperature. She found that this greatly improved the results of nuclear-transplant experiments with nuclei from the endoderm of Rana pipiens.8 In the early 1970s other scientists around the world became successful with nuclear transfer experimentation. For example, scientists in France and Switzerland successfully cloned fertile fruit flies. At about the same time Chinese biologist T. C. Tung and his successor Yan Shaoyi, both of the Institute for Developmental Biology of the Academia Sinica in Beijing, conducted a series of successful experiments with teleost fish. In 1975 Gurdon, Ronald A. Laskey, and Raymond Reeves wrote a scientific paper to which the Roslin scientists who cloned Dolly the sheep would refer twenty-two years later. Gurdon, Laskey, and Reeves successfully injected the nuclei of skin cells (keratinocytes) from the foot webs of adult frogs and transferred them into frog eggs from which the nuclei had been removed. Some of the injected eggs developed into swimming tadpoles. 9 In explaining their experiment, Gurdon wrote: We used skin cells from the adults' foot webs. When small pieces of the foot web are cultured, a single layer of cells grows outward from the excised tissue. We treated those monolayers with an antibody that binds keratin, a protein made only by specialized cells, and we found that 99.9 percent of the cells in the monolayers bound to the antibody, thus revealing that they contained keratin. Nuclear-transplant experiments done with those cells yielded heartbeat-stage tadpoles with welldifferentiated eyes and other organs. The probability that those clones originated from the 0.1 percent of the donor-cell population unproved to contain keratin was less than one in 10 billion. We felt justified in concluding that "cell specialization" does not involve any loss, irreversible inactivation or permanent change in chromosomal genes.10 Although all of Gurdon, Laskey, and Reeves's experiments fell short of cloning an adult animal from the nuclei of cells derived from an adult animal, the
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scientists were able to conclude that cell differentiation did not involve any permanent or stable change in the chromosomes and that cell differentiation took place though the controlled expression of genes. Later, they postulated that cell differentiation was the foundation on which Dolly's cloning stands, and it made the cloning of other adult vertebrates possible. A few years later, in the early 1980s, developmental biologists James McGrath and David Solter at the Wistar Institute of Anatomy and Biology in Philadelphia cloned mice by fusing donor cells with mouse eggs. Based on prior procedures for cloning frogs, their experiments included important innovations. Following McGrath and Solter's experiments other laboratories around the world began to turn out impressive numbers of newborn mammals cloned from embryonic nuclei—among them calves, rabbits, pigs, rats, goats, and lambs. In 1983 Di Berardino and developmental biologist Nancy Hoffner Orr of the Allegheny University of the Health Sciences transplanted donor nuclei into oocytes (immature egg cells from the ovary), rather than into mature egg cells that had already been released from the ovary. Di Berardino and Orr allowed nuclei that had been transplanted into an oocyte twenty-four hours' exposure to the cytoplasm of the oocyte before cleavage. The success of their experiments was attributed to the much longer time than nuclei transplanted into mature eggs. This allowed the cytoplasm to reset the cell-division cycles. These techniques led to transplantation successes with Rana comparable to those obtained with Xenopus.11 In 1984, embryologist Dr. Steene M. Willadsen, at the Agricultural and Food Research Council Institute of Animal Physiology in Cambridge, England, announced that he had successfully cloned nuclei from early-stage sheep embryos. Later, he cloned embryos that were in the 64-128 cell stage and suggested that perhaps nuclear transfer might be possible with specialized (differentiated) cells. A decade later, Dr. Neal First cloned four cows by nuclear transfer from more developed embryos. These experiments, like those of Willadsen, began with undifferentiated cells that had no particular physiological function. This was followed by an experiment by Dr. Robert J. Stillman and colleagues at the George Washington Medical Center in Washington, D.C. They publicly announced the cloning of seventeen human embryos in order to encourage public discussion about human cloning. In July 1995 Scottish scientists Dr. Ian Wilmut and Dr. Keith H. S. Campbell cloned two sheep named Megan and Morag from differentiated embryo cells. Their new technique involved starving the donor embryo of the nutrient serum they fed the cells. The advantage of this, they later ascertained, put the cell in the right moment in the cell cycle, thus allowing the D N A to be accepted more easily by the egg cell. This proved to be the essential step in nuclear transfer.
Hello, Dolly! Well, Hello Dolly! On July 5, 1996, Wilmut and Campbell delivered lamb number 6LL3, or "Dolly," as she was named (after country music entertainer Dolly Parton), in a shed near the Roslin Institute near Edinburgh, Scotland. Not a genetic mutant, Dolly was
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the first large creature ever cloned from a specialized (differentiated) adult cell, rather than an unspecialized embryonic cell. Looking like a normal soft-eyed sheep, behaving like a sheep, and weighing fourteen pounds, Dolly was described as a "beautiful lamb with a gentle disposition." With her typical sheep-like nose, she wandered around her cage and nuzzled photographers and visitors who came to view her. Dubbed the "lone clone," Dolly had no father, but she made up for it by having three mothers—a nuclear mother, an egg mother, and a womb mother. Roslin scientists had used three different breeds of sheep to produce Dolly as compared to one or two when in vitro fertilization was used. Wilmut and Campbell's remarkable breakthrough in producing Dolly grabbed world headlines and was heralded as one of the most significant scientific accomplishments of the twentieth century. The cloning offered a new and unique way of reproducing and genetically modifying animals. Interestingly, the visceral reaction of the public to the announcement of Dolly's cloning was heralded by some as more interesting than the scientific achievement itself.12 Dolly was the world's first successfully cloned adult mammal born to a surrogate mother, cloned not from sex cells but from mature mammary cells with no reproductive function. Using sophisticated microsurgery, Dolly was grown from an egg cell whose nucleus had been replaced with DNA from mammary gland cell of a pregnant six-year-old ewe. As a result, the recipient egg contained a complete set of genes, just as it would had it had been fertilized by a sperm in the natural process. Previously, it had been thought that a whole mammal could not be regenerated from mature body (somatic) cells specialized for something other than reproduction. A nuclear marker present in the donor cell from which Dolly was cloned showed that Dolly resembled the breed of the nuclear donor. Analysis of Dolly's DNA confirmed that Dolly was in fact the clone of her nuclear donor, a fact that made Dolly immediately accepted by the scientific community as a valid clone. 13 Dolly was essentially her mother's physical twin. However, scientists have pointed out that even identical twins are not totally identical because not all of the cell's DNA lies in the nucleus. Some DNA is also found in the cell's mitochondria ("powerhouses of the cell" that produce energy), which are found in the cytoplasm of the cell. In reality, Dolly was an exact genetic copy or clone of the sheep that provided the transferred nucleus, not of those that provided the egg. Wilmut and Campbell started the Dolly cloning experiment with 434 sheep oocytes. Because the procedure was very labor-intensive, it took 277 nuclear transfers to produce Dolly. Of the original 434 oocytes, 157 failed to fuse with the transplanted donor cells and were discarded. The 277 successfully fused cells were grown in culture, but only 29 embryos lived long enough to be transferred to surrogate mothers. During gestation the investigators detected 21 fetuses with ultrasound scanning, but gradually all were lost except Dolly. With a success rate of only one out of 434, it was clear that there were other unsolved complicating factors.14 Another interesting fact was that frozen cells, not fresh cells, were used to clone Dolly. This was a little known fact until after her birth and was significant because it meant that the DNA donor need not be alive when cloning occurred and the individual could be cloned long after birth. The Roslin experiment con-
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firmed that adult cells do in fact contain a workable version of all the genes necessary to produce an entire organism. In 1986 Wilmut had worked on a project to create a sheep that produced a certain chemical in milk. In the experiment, he had altered cells and cloned them to produce animals with altered genes all throughout their bodies. The experimentation was extremely valuable and provided Wilmut and his team with the needed techniques to clone Dolly. However, what really enabled Wilmut and his team to succeed where so many others had previously failed was a simple modification of prior techniques. Wilmut's colleague, Keith Campbell, suggested that the reason so many cloning experiments had failed was that the cells were in incompatible stages of life. Eventually, both Wilmut and Campbell concluded that the key to their success was in starving the mammary cells for five days and forcing the cells into a kind of hibernation prior to removing their nuclei. They later determined that this quiescent phase of the cell division cycle made the chromosomes more susceptible to the programming that initiates growth of a new organism. During this time they realized that cellular differentiation was not a factor in cloning. Wilmut and Campbell chose sheep for cloning because sheep proved more easily cloned than mice or frogs. They realized that researchers had tried for decades to clone frogs and mice with no luck. Generally, frogs cloned from adult frogs died in the tadpole stage, whereas cloned mice did not develop far beyond an undifferentiated ball of cells. Scientists concluded at the time that there was just not enough time in the mouse's lifespan for the extensive reprogramming of gene activity that was required. 15 On April 13, 1998, Dolly became a mother when she gave birth to a healthy lamb named Bonnie. Then, on Wednesday, March 24, 1999, Dolly gave birth to three more healthy lambs, all conceived the "old-fashioned way." Unexpectedly, in May 1999, Wilmut discovered that Dolly's cells were six years older than her chronological age. This meant that Dolly was over six years old when she was born (the equivalent of a human being in her early thirties). Dolly's nuclear mother was a six-year-old female sheep when the somatic mammary cell was removed and placed in frozen storage in Wilmut's laboratory. Cells have an internal mechanism that keeps track of their age. It is thought that in Dolly's case the age mechanism of the donor cells was not reset to zero when Dolly was conceived. This was of interest to many gerontologists who were researching antiaging and progeria (a medical condition that causes infants to age prematurely). After determining Dolly's age, scientists asked: • Was Dolly really a six-year-old clone that at birth carried the DNA of a sixyear-old sheep? • Was Dolly's secondhand DNA as good as new? • Was Dolly as old as her body age . . . or as old as her genes? Several valuable pieces of new information were derived as a result of Dolly's cloning. Scientists measured key pieces (telomeres) of Dolly's DNA and found that
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the telomeres were shorter than those found in other three-year-old sheep, but the same length as her mother's. This suggested that Dolly was older than her birth date. Another discovery was that Dolly's nuclear DNA did not carry lethally damaged genes. This was considered significant because it indicated to scientists that in the future they might be able to take a person's D N A and insert it into cells in the laboratory, then grow tissue that could be transplanted back into that person without the danger of rejection. 16 There were other lessons learned from the cloning of Dolly. For example, Wilmut and Campbell showed that differentiated cells of one kind could be programmed to produce every kind of cell necessary for a complete organism. For example, white blood cells (leukocytes) could be harvested and reprogrammed into whatever cell type was needed. 17 It was also ascertained from Dolly's cloning that cells taken from a young and healthy person could potentially be stored for future production of replacement organs should a person need them because of illness or old age. It became possible that an individual's own tissues could be used to grow replacement organs for his or her own worn-out parts. This would be particularly useful to elderly or diseased persons who needed tissue and organ replacement and who had not stored their youthful tissues. However, such individuals would possibly not get much benefit from cloned organs because such persons carry much more damaged DNA in their cells than Dolly's donors did. 18 Sadly, at the age of six, Dolly had to be euthanized after being diagnosed with a virus-induced, slowly progressive lung disease. No treatment was available for the disease. It was thought that Dolly contracted the disease from other sheep that she was housed with. Dolly's body was willed to the National Museum of Scotland and has been put on display in Edinburgh. Scientists could not confirm that her illness was attributable to being a clone.
Other Animal Clonings Since the 1996 announcement of the cloning of Dolly, scientists worldwide have duplicated and advanced the work of Wilmut and Campbell in a variety of species. Credit also is given animal husbandry and agricultural research for the many breakthroughs in animal cloning. As a result, there are now hundreds of cloned animals; however, many more attempts have ended in failure.19 Some animals have been cloned using slight variations in the technique used to clone Dolly. Campbell and others from the Roslin Institute reported in 1996 that nuclei from embryonic cells grown in culture created viable cloned lambs, making largescale production of genetically engineered animals and organs possible for the first time. 20 On March 2, 1997, officials at the Oregon Regional Primate Research Center announced that they had cloned sibling rhesus monkeys using cells from different embryos. The cloning experiment proved that the technology for producing identical animals was now available. Don Wolf, senior scientist at the Oregon Regional Primate Research Center, was cautious and did not call the procedure cloning, saying: "That is not what I am calling it. Cloning in the strict sense of the word is us-
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ing an adult cell so you get an exact replica of the adult. That is not what we are doing. The procedure called nuclear transfer can be done in humans." 21 In the Oregon experiment, scientists harvested eggs from a female adult monkey and fertilized each of the eggs in vitro. After three days, each embryo divided into an eight-cell stage of development. Employing sophisticated microsurgery, scientists teased apart the cells and removed one full set of chromosomes from each egg cell, which they then inserted into each fresh egg that was enucleated. Nine successfully developed embryos were then implanted in adult females. Of these, three pregnancies and two live births resulted. In another significant experiment on October 3, 1997, Cumulina, a mouse, was cloned from cumulus cells (cells that surround developing egg cells). The nucleus was taken from a cumulus cell and implanted in an egg cell from another mouse. The new cell was then treated with a chemical to make it grow and divide. Scientists repeated the process for three generations, yielding over fifty mice that were virtually identical. On February 20, 1998, the Korean Times reported that researchers at the Seoul National University had successfully cloned a calf using methods identical to those that produced Dolly. Korea became the fifth country in the world to clone an adult animal after the United Kingdom, Japan, New Zealand, and the United States. On July 22, 1998, Dr. Ryuzo Yanagimachi of the University of Hawaii announced the cloning of seven out of twenty-two mice that were clones from the cell of a single mouse. Although scientists have been highly successful in cloning mice, they have only recently overcome a quirk in rodent physiology that had thwarted many attempts to genetically duplicate the rat. In the latter part of 2003, however, led by researchers at the National Institute of Agricultural Resarch at Joy en Josas, France, scientists cloned both male and female rats and then mated them and produced normal, healthy pups. This was hailed as exceptional research because white laboratory rats with special genetic changes could be developed and used for drug testing and other therapies to aid human patients. White laboratory rats are among the most frequently used animal models for human disease research. In producing the pups, scientists used a new technique called somatic cell nuclear transfer. Researchers first produced two male rat pups. In the second round of cloning, they got two female pups. The pairs were later mated and produced normal, healthy rats. The research is significant because it will enable researchers to genetically tailor laboratory animals for studies of specific disorders that affect humans.
Cloning Barnyard Animals Following other numerous animal cloning experiments, Harold Shapiro, chairman of the National Bioethics Advisory Committee, declared in November 1998 that cloning research was rapidly progressing in a successful manner. On December 8, 1998, Japanese researchers from Kinki University in Nara, Japan, using techniques similar to those that produced Dolly, cloned eight calves from a single adult cow's DNA. However, four calves died shortly after birth due to environmental factors.
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Other scientists also entered the barnyard to clone animals. In October 2000 they cloned a Holstein cow named Mandy, which eventually won several awards at an auction ring at the World Dairy Expo in Madison, Wisconsin. Mandy was described as having strong legs, a broad chest, and a large udder, as well as being a milk producer at nearly twice the rate of the average cow. Her unborn clone fetched $82,000 at the auction. Recently, scientists in Italy reported that they created the world's first cloned horse. The horse is in excellent health. This raises the possibility of the next Seabiscuit or a carbon copy of Kentucky Derby champion Smarty Jones. Texas A & M veterinarians have also cloned a horse. Scientists at the Laboratory of Reproductive Technology in the northern Italian city of Cremona reported that they have created their second cloned horse, produced from the DNA of a gelded thoroughbred Arabian race champion. The foal, named Pieraz-Cryozootech-Stallion, born on February 25, 2005, weighed ninety-three pounds and was "in excellent health." The young stallion was cloned from Pieraz, retired to a stable in the United States after winning endurance championships in 1994 and 1996. The birth preserves the lines of a world-class race horse. Italian scientists used DNA from skin cells obtained from the former champion, employing the same technique as that used to clone the sheep Dolly.
Cloning Pets Cloning was soon moved from the barnyard to the living room. On December 22, 2001, CC (Copy Cat) was born—the first household pet cloned. CC was a calico domestic shorthair cloned from a cat named Rainbow by Dr. Mark Westhusin at Texas A & M ' s Veterinary Medicine School at College Station, Texas. CC's creation was funded by Genetic Savings and Clone, a company that made its money from people who wanted to duplicate their favorite pets. Rainbow was a typical calico with splotches of gold, tan, and brown on white, whereas CC, her clone, had a striped gray coat over white. CC differed from its genetic donor in its color pattern because color pattern is not strictly determined by the lineup of genes. Prior to cloning, geneticists explained to the owners that CC would not necessarily bond with them. CC and Rainbow were different in other aspects, as well. Rainbow was moderately reserved by nature, whereas CC was playful and curious. Rainbow was chunky; CC was sleek. Although D N A test results showed that CC was indeed a clone, CC was not an exact copy, proving that cloning does not lead to exact duplication. In another case, a couple requested that scientists clone their eleven-year-old dog, Missy. Willing to pay over $2.3 million to have another dog just like Missy, the couple requested that Texas A & L M University veterinarians clone Missy. At the time, veterinarians explained to the couple that cloning a dog was a complex procedure when compared to other animals because the reproductive system of a dog is rather complicated. Previously, proponents of dog cloning had claimed that it would be a definite benefit to society, particularly the cloning of exceptional guide, rescue, or search dogs.
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In late December 2004 the first cloned-to-order pet sold in the United States was delivered to a Texas woman. The kitten, "Little Nicky," cost its owner $50,000 and was created from D N A from her cat who had died the previous year. The company was Sausalito-based Genetic Savings and Clone. The cloning has fueled a fierce ethics debate. In August 2005 South Korean scientists, led by Hwang Woo-Suk, successfully cloned Snuppy, a male Afghan dog.
Cloning Endangered Species Scientists also considered cloning endangered species to increase their populations. On October 17, 1999, a team of Russian, French, and Dutch paleontologists successfully airlifted a twenty-three-ton male wooly mammoth from its grave in Siberia. The mammoth had been frozen for more than 20,000 years and was almost complete except for its head, which had been exposed to air. At the time, scientists proposed that attempts be made to breed a living mammoth from the DNA taken from the mammoth's tissues or bones, or sperm or cell nuclei retrieved from the carcass. Unfortunately, thawing out the animal tended to destroy the cell nuclei, making cloning nearly impossible. In August 2005, it was announced in New Orleans that two previously cloned tabby wildcats had naturally mated. This is the first time that clones of two wild species, or any cats, have done so. Ditteaux, clone of the male African wildcat Jazz, fathered eight kittens on two clones of Nancy, a female unrelated to Jazz. The five kittens born July 26 to Madge and three born August 2 to Caty will be moved to the Audubon Center for Research of Endangered Species.
Transgenic Animals Human beings use animals for various purposes. For example, we kill animals for food, and this seems to justify many other uses. But when we clone animals, particularly warm and furry pets, it prompts most of us to ask questions about the way we are using animals. Transgenic animals offer a decided advantage for animal cloning because it allows an unlimited number of cells to be frozen for a long period of time if needed, then thawed without loss of unique, favorable traits for future use, if desired. Other advantages include sheep that produce milk with beneficial proteins for patients with diseases such as cystic fibrosis, and cloned livestock that produce biological proteins that could help people who have diabetes or Parkinson's. On April 20, 1999, Japanese researchers at the Snow Band Dairy in Hokkaido, Japan used a mammary cell extracted from colostrum (the milk produced by a cow shortly after giving birth) to clone twin calves. A week later, on April 27, Nexia Biotechnologies Inc. of Montreal, Quebec, announced that they had cloned the world's first triplet goats named Arnold, Danny, and Clint. Nexia's goal was to produce transgenic goats with a human gene that would produce milk
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containing spider-silk proteins to be used for artificial tendons and ligaments, tissue repair, wound healing, and sutures. The world's first cloned pigs were born on March 5, 2000, for the purpose of organ transplants. Scientists worked to remove the gene that produces the alpha 1,3 galactose sugar in pigs which causes an extreme rejection of animal tissues by the human immune system. The cloning of piglets lacking the gene is important because of the prospect of providing humans with an endless supply of compatible organs for transplantation. Because of a severe shortage of human organs, many people worldwide die while waiting for transplants. In late August 2002, PPL Therapeutics PLC, the Scottish company that helped clone Dolly, announced that four healthy piglets were born July 25 at the company's U.S. subsidiary in Blacksburg, Virginia. A fifth piglet died shortly after birth of unknown causes. Such piglets are of great medical value because they have corresponding human organs. But they are also considered of value because they are not susceptible to mad cow disease and related afflictions that can be passed on to humans. When it was first suggested, there was a major concern in transplanting pig tissues into humans. Scientists feared that human cells could be infected with porcine endogenous retroviruses (PERVs) that exist in all pig cells. In culture, pig pancreatic islets produce viruses that infect human body cells, but not blood cells. This was bad news for diabetes researchers who had thought that the pig pancreatic islet cells and pig cells were a possible alternative in a treatment for insulin-dependent diabetes mellitus. Because of this problem, the race to develop pigs for animal-tohuman transplants, which are known as xenotransplants, has been slowed. However, cloning has a great potential benefit for the livestock industry because scientists can genetically alter bovine adult cells easily. Scientists clone only the cells that are transformed. Harvesting and growing adult cells is preferable when compared to embryos and enables manufacturers to produce quality biological products such as proteins for humans. ABS Global, Inc., a small company specializing in reproductive services in DeForest, Wisconsin, reported that a black bull calf named Gene was the result of cloning a relatively undifferentiated (unspecialized) stem cell from a thirty-dayold calf fetus. This was a different process from Dolly's where they had to reset genes. Cloned cattle such as Gene are useful because they can be genetically manipulated to produce drugs or other valuable substances in their milk. Genetic engineering has been credited as the key precursor to cloning: "Whatever one's own personal views about using animals as vehicles for human drug production or as a source for replenishing defunct human organs, it is important to realize that it is mammalian transgenesis and not cloning that has opened the door for such practices. Cloning would have little future, and certainly be of little commercial value, without genetic engineering." 22
Safety of Transgenic Animals Advanced Cell Technology (ACT) of Worcester, Massachusetts, and Infingen Inc. of DeForest, Wisconsin, have released data on cloned cattle showing that milk
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taken from cloned cows is identical to normal cow's milk and is safe for human consumption. Animal husbandry has produced gene-altered domestic animals for centuries, suggesting that genetically engineered animals should be regulated like other farm animals. However, Consumer Reports magazine warned that not enough is known about the health effects of genetically engineered foods and has called for labeling of all genetically engineered or cloned fish, poultry, and meat for consumers. To assure safety of transgenic animals, the Food and Drug Administration asked the National Research Council (NRC), chartered by Congress, to define science-based risks to human health involving gene-altered or transgenic animals. This concerns two types of genetically-engineered animals. First are the bioreactors, which are animals prized for proteins in their milk or other products useful in agriculture, such as semen from a cloned prize bull such as Gene. Second are food sources such as pigs nursed by a sow that is bred with a gene that lets it make more milk.
Thinking Ahead Reproductive cloning and gene therapy are already becoming an important part of our society. However, there is a pronounced fear that it will progress to human cloning, most likely because the technology has progressed so far and so rapidly. Wilmut and Campbell's cloning of Dolly raised three important questions about the prospect of human cloning: 23 • Is it possible to undertake the same operations on human cells? • Will cloners be able to reduce the high rate of failure? • What is the relation between a clone obtained through nuclear transplantation and animals, born in the usual way, from which the clone is derived? When we consider reproductive cloning, we are reminded of the same primitive thoughts of those who first opposed in vitro fertilization, genetic engineering, organ transplantation, open-heart surgery, and other significant breakthroughs: Indeed many medical developments have been at least temporarily halted because of ethical qualms. Religious leaders found vaccines objectional because they interfered with God's plan for those who should get sick, and in vitro fertilization was condemned in the 1970s by many of the same conservative ethicists who today oppose therapeutic cloning. Organ transplants were once seen as objectionable. And recombinant DNA technology—the ability to create synthetic genes—was banned from top universities like Harvard and MIT for years, for fear that horrible and dangerous creatures would be produced. But much of the opposition melted when the technology was used to create a synthetic form of insulin to treat diabetics, and today recombinant DNA is used in virtually every research laboratory in the world. 24
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11 CLONING A HUMAN Mary had a little lamb, whose fleece was slightly gray, Didn't have a father, just borrowed some DNA. Sort of had a mother though the ovum was on loan, Was not so much a lamb kin as a little lamby clone. Soon it had a fellow clone and soon there were some more, They followed her to school one day, all cramming through the door. It made the children laugh and sing and thrilled them to the soul. But there were just too many lambs for Mary to control. No one else could herd the sheep, their imprints didn't vary, The cloners sought to fix it up by simply cloning Mary. So clone they did and Newsweek said it was extraordinary, But now they don't know what to do with Mary, Mary, Mary . . . author unknown Cloning has always caught the public imagination. Throughout the twentieth century and now into the early twenty-first century, newspapers and various reports, books, movies, television, and conversation have focused on the implications of cloning humans. The possibility of cloning a human has resulted in a media frenzy with thoughts of a Utopian society much like Aldous Huxley's Brave New World. As a result, many fear that Huxley's fiction of yesterday might become today's reality. Mary Midgely, widely respected senior lecturer in philosophy at Newcastle University in England, once asked why anyone would want to clone humans even if they could. She advised readers to forget fears like those raised in Brave New World and suggested instead they concentrate on real-life research.
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For many the mere mention of human cloning tends to inspire paranoid visions of many Hitler clones. In the political-science fiction book and film, The Boys from Brazil, two clones of Hitler were purportedly produced from a cell containing Hitler's DNA. The cell was in turned joined with an egg, and an embryo was formed that contained solely the genes of Hitler, with only the necessary ones coming from the woman. 1 The science fiction-like experiment in The Boys from Brazil was done for many reasons. One of the reasons was to bring the world under Nazi domination, but the experiment was primarily intended to test the clones' behavior away from one another and to see if any particular kind of attitude could be passed on from one clone to another. Results showed that the cloned boys had Hitler's genes and both displayed Hitler's violent psychotic personality, despite being raised apart and with totally different lifestyles. In 1978 science writer David Rorvik wrote in the book In His Image that in 1973 a millionaire asked to have himself cloned. After two years of experimentation, the procedure was carried out in secret. A single cell was taken from the millionaire's body and fused with an egg that had its nucleus and DNA removed. The resulting embryo was implanted into a surrogate woman's womb and a baby was born. The alleged cloning was said to have occurred somewhere in the Orient, in an unnamed laboratory, by unnamed scientists. In addition, the child was unnamed, as were his mother and father.2 No corroborating evidence could be shown to prove Rorvik's story. Not even Lippincott, the publisher of the book, supported Rorvik's story, and the case resulted in a $7 million lawsuit. In his ruling, the judge of U.S. District Court in Philadelphia ruled that Rorvik's book was a work of fiction and that the cloning experiment described in the book never took place. Rorvik did not contest the ruling.
The Good and Bad of Human Cloning There are pros and cons to every issue and human cloning is no exception. Because ethical implications of human cloning balance on a fine line, there is currently a heated debate over the potential cloning of a human. Many who have followed the human cloning debate believe that the real argument is about politics, not science. Yet, the primary debate over human cloning is fundamentally and undeniably about life. Beyond a shadow of doubt, certain aspects of human cloning already have become a part of our current society. Initial reactions of ethicists to human cloning were that it was unconscionable, even though in many countries it is not explicitly illegal. Some believe that human cloning is unnatural; however, unnatural does not necessarily mean bad. Others fear that human cloning has progressed so quickly that it is not sophisticated enough. In human fertility cloning the male donates a body (somatic) cell and the female donates an egg cell (ovum) from which the DNA has been removed (enucleated egg). The DNA from the male's body cell is implanted into the female's enucleated egg cell. In so doing, the majority of the genetic material is obtained
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from the male but a minute amount of DNA is left in the enucleated egg. As a result, the resulting child is potentially a partial genetic mix. Numerous reasons are given by proponents for cloning a human, but one of the most obvious and understandable reasons is replacing a dead or dying child. Consider the following hypothetical case: Conception had been difficult for Jim and Ann Thomas, both thirtytwo, but eventually Ann gave birth to their son Brad. He was the center of their lives. Then, one day, while watching an outdoor baseball game, Brad was struck by lightning and died. Understandably, Jim and Ann were devastated. Searching for a glimmer of hope, they asked scientists to take a cell from Brad's body, clone it, and implant the clone in Ann's uterus so that she might be able to give birth to Brad II. The procedure was successful and Brad II became the center of the Thomas family, bringing much happiness. Although the story has a happy ending it raises the following questions: • Was it moral to allow Ann to bear a cloned replacement for Brad? • Should grieving parents like Jim and Ann be denied the opportunity to clone an identical copy of Brad? Consider another case: In April 1991 Bob and Mary Smith of St. Paul, Minnesota, began living through every parent's nightmare. Susan, their fifteen-year-old daughter, was diagnosed with acute lymphoblastic leukemia, a fatal blood disease. Sadly, Susan died within a few months of the horrendous diagnosis. Both Bob and Mary were devastated and decided to ask that Susan be cloned. The cloning was successful and the twinclone, Susan II, became a part of the elated Smith family. The Smiths' story, like that of the Thomas's story, had a happy ending, yet other questions surfaced: • Is it right for a couple to use one child to clone another? • Can someone brought into the world for such a well-defined purpose ever feel that she is loved for who she is? • Should the Smith and Thomas families have been allowed to exercise the cloning option? No doubt, cloning from an already existing child is controversial any way it is looked at. Opponents of human cloning, understandably sympathetic to the Thomas and Smith families' losses, question whether or not this is an appropriate way to deal with human loss. They argue that human cloning to replace a dying or dead child is unreasonable, not only from an ethical and moral standpoint,
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but also because there are currently so many children worldwide who need adoption. Unlike the process of cloning embryos, cloning from an already existing human allows the parents or the individual donor to know exactly what the twinclone will look like ahead of time. In the case of both Brad II and Susan II, cloning produced exact physical replicas of the dead children. Understandably, personality and other factors cannot be replicated because environment plays a huge role in shaping a person's identity, even before humans are born. Another justification given by proponents of human cloning is to provide a child to a couple who cannot produce a child naturally because of infertility. Human cloning is considered by many scientists to be superior to in vitro fertilization for treating infertility because any health problems in the child can be eliminated from the beginning, ensuring a couple a healthy child. Opponents of human cloning believe that allowing even limited human cloning could result in a national black market for women's eggs. This could result in unethical (rogue) scientists producing cloned infants. Opponents say that it is as if the "birds and the bees" have been rendered irrelevant. A third major reason for cloning humans is vanity. The following question is frequently asked: Will humans someday be genetically engineered and cloned exclusively for vanity reasons? The answer, for many, is "yes" because society will do all kinds of things for money. In vanity cloning, it would be possible to clone someone famous, a departed loved one, a spouse, or even oneself, providing the person with exceptional talents he or she did not possess while living. This might include creating persons with small body size and weight for space flight or to be winning jockeys, or those cloned for their musical talents or athletic abilities. Even though cloning is a costly form of technology, it is likely that wealthy people such as movie stars and athletes would be willing to pay high prices for a clone of themselves or someone dear to them. Today, even middle-income couples spend a great deal of money on in vitro fertilization, and it is likely they would be willing to pay as much or more to clone their children, grandchildren, pets, or others close to them. Proponents of vanity cloning argue that if living persons want to clone themselves or others dear to them and can afford to be cloned, it should not be prohibited or considered a crime. Proponents of human cloning argue that there would be ultimate potential value to society if exceptional athletes, scientists, and musicians were cloned and educated in the twenty-first century. The prospect of cloning superstar basketball players Michael Jordan and Shaquille O'Neal or tennis stars Venus and Serena Williams; or replicating the great scientist, Albert Einstein, seem real. Or imagine cloning past political leaders like Abraham Lincoln, John F. Kennedy, Winston Churchill, or Franklin and Teddy Roosevelt, or reproducing the physical beauty of Elizabeth Taylor or Julia Roberts. Certainly no one will dispute the fact that leadership and good looks are assets to not only an individual, but to society in general. No one will argue that these and other clonings would add greatly to society's cultural value, making life more valuable for their twin-clones. Although physically like the cloned individual in beauty, height, and build, it is highly unlikely that the cloned twin would have the same personality, soul, spirit, behavior, thoughts, or any other characteristics as the person he or she was cloned from. It
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is a well-known fact that identical twins conceived in the natural way and raised under the same roof by the same parents turn out to be quite different because their personalities and identities are shaped by environment. Just as identical twins conceived in the natural way live separate lives and have separate souls, clone-twins would as well. Erik Parens, a bioethicist at the Hastings Center in Briarcliff Manor, New York, believes proponents and opponents of human cloning share the same mistaken idea that you can clone a "self." "But as everyone knows, you can't clone a self because a self is a function of infinitely more than one's own genetic material." 3 Another reason given for cloning humans is more efficient communication. Society would benefit both culturally and financially from human cloning because it has the potential to create more efficient communication among people. Clones who are alike in traits, including beauty, great genius, etc., would improve the species, making life more pleasant by having a better understanding of each other. Proponents also list as a definite advantage to human cloning the ability of clones to serve as "human banks" to provide spare parts for organ transplants. This would include production of embryonic replicas of a person, to be frozen until needed as a source of organs for transplantation to their genetically identical twin. After obtaining a person's DNA, scientists would insert it into cells, grow the desired new limbs, organs, skin, and so on, and then transplant the tissue back into the same person. The procedure would allow clones to be genetically engineered with special immune system genes that would allow organs to be transplanted without rejection. In 1997 Dr. Patrick Dixon, author of The Qenetic Revolution and an authority on the ethics of human cloning, predicted that sometime in the future headless human clones would be used to grow organs and tissues for transplant surgery. He made the prediction after it was reported that British scientists had created a frog embryo without a head. Dixon believes that the technique used to create the headless frog might be modified to grow human organs such as liver, hearts, pancreases, and kidneys in an embryonic sac living in an artificial womb. 4 According to Dixon: "I believe that there will be great pressure to combine technology with the creation of partial fetuses, missing heads, arms or legs, as organ factories for tomorrow's people. These will be developed on an experimental level somewhere in the world in countries where there is little or no gene legislation within the next 5-10 years because of overwhelming demand. International inconsistencies on various aspects of genetic engineering, including human cloning, urgently need to be ironed out." 5 Later, speaking on BBC World Service, Dixon commented: We will see the creation of human beings which are growing, yet technically dead, because they have no brain-but is that the kind of world we want to live in? Hundreds of these humanoids could be made. Their creation will raise profound questions. The real issue is not Dolly the cloned sheep, or now the headless frog. It is how we want society to use gene technology now that we have the ability to do more or less whatever we like with life, designing all kinds of bizarre creatures or hybrids. I am far more concerned by tomorrow's headlines
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than today's, and by the fact that most people are years behind reality when it comes to thinking through the impact of what is going to happen next. 6 Growing select human organs became a reality in the laboratory when scientists at Advanced Cell Technology (ACT) in Worcester, Massachusetts, reported that they had used cells derived from cloned cow embryos to grow kidney-like organs that functioned and were not rejected when implanted into adult cows. Scientists took a single skin cell from a cow's ear and fused it with a cow's enucleated egg to make a cow embryo. Stem cells were removed from the embryo, programmed to develop into kidney cells, and allowed to mature until they functioned like a miniature kidney. Scientists then implanted several of the mini-kidneys under the skin of the cow that had donated the ear cell. The mini-kidneys produced urine that drained into attached synthetic bags (bladders) for several months. Whether the mini-kidneys performed all of the jobs performed by normal human kidneys is not known. The ACT research was the first to show that cells taken from a newly created clone could be made to grow personalized, genetically matched organs, working together as a functioning organ, and coexisting with the body's immune system. 7 Opponents of human cloning remind us, however, that just as it is possible to clone the good and desirable, the same technology can be used to clone the evil. Imagine how appealing cloning would be to a dictator or terrorist like Osama bin Laden or Saddam Hussein, who would revel in watching numerous copies of themselves grow up to populate the world with what they perceived as a new race of genetically superior people. Human clones could result in cloned armies of people to work assembly lines; to supply large military troops for war such as those bred for war by the evil Saruman in The Lord of the Rings; or to run the world. Such clone wars would result in a lack of morality or immorality since killing or being killed would have no great meaning. Opponents of human cloning also remind society of the ramifications of flaws and failed experiments. Fritz Lang's 1926 science-fiction classic Metropolis, the first film to portray an artificially constructed evil twin-clone, depicts the story of cloning gone awry. In the story, clones turn out to be different from their originals in some pivotal, often destructive way; and the cloners usually overestimate their power to control the clones. 8 Today's opponents of human cloning worry about failed experiments as in Lang's Metropolis, saying that human cloning technology has not yet been perfected and could lead to death or malformation of the fetus. Opponents cite many animal cloning experiments that have produced high failure rates resulting in birth defects, multiple miscarriages, or mental and emotional problems. Opponents cite very low success rates of only about 1 percent of attempted clones in animals that result in a successful pregnancy. This is despite years of attempts after the cloning of Dolly, with a considerable amount of time and research money put into it. Opponents of human cloning remind us that it took Wilmut and Campbell 434 oocytes to produce Dolly. This raises a startling question: Suppose the survival rate for appendectomies was one in 434; would surgeons be anxious to operate?
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Admittedly, with such a potentially low survival rate it would be a game of genetic roulette. Cloning a baby would require hundreds of egg cells—more than a woman is physically capable of donating—and in nearly 100 percent of the cases cloning would give rise to abnormal embryos and fetuses, almost all of which would abort. Based on statistics, at least one abnormal child would be born. 9 Other problems would likely surface even if scientists were able to induce complete nuclear programming 100 percent of the time. This is because abnormal adult donor cells during their lifetimes are exposed to a number of stressors including carcinogens, radiation, and chemical mutagens. If cells were grown in culture (in vitro), quite likely there would be additional mutations, making it impossible to select normal donor cells. However, proponents of human cloning argue that it is ridiculous to ban human cloning just because the procedure is considered by some to be not perfectly safe. They are quick to remind opponents that there is no area of human activity free of accidental death and that human cloning is no exception. Citing statistics that reveal thousands of persons die each year in automobile, motorcycle, and plane accidents, proponents remind us that society would never think of banning automobiles, motorcycles, or airplanes. Proponents believe that the possibility of a cloned child with abnormalities would not be any different from the possibility of having a child with abnormalities born by in vitro fertilization. Like in vitro fertilization in the past, proponents believe that cloning procedures will be perfected to the point where the risk of miscarriage or death to the baby will be the same as for any birth. Another reason given by opponents not to clone humans is that cloning would cause males to be reproductively obsolete because cloning requires only oocytes, any somatic cell, and a woman's uterus to develop in. They believe that it would allow control of the sex of future children since the sex of the cloned offspring is the same as that of the adult from whom the donor nucleus is taken. 10 One of human cloning opponents' greatest fears is that cloning technology might be used irresponsibly to create large sets of genetically identical copies of humans, resulting in loss of diversity and human uniqueness. It is not for society to end evolution; diversity is our best hope. The uniqueness of each individual, and the consequent variability among individuals in biological populations of sexually reproducing organisms, provides the sine qua non for evolution by Darwin's mechanisms of natural selection. 11 Worldwide, there would be thousands of people identical to you, different from each other only by names and perhaps dress. Walking down the street as one clone among hundreds would be a disaster. This would have drastic long-term effects on society's self-perception and would overall cause the ratio of sexes to fluctuate wildly—too many men or too many women. Natural selection works only if individuals of a population are distinctively different, one from the other. Darwin's theories require that variability be conferred by genetic distinctiveness. Darwin's process works by selective elimination and preservation—by imparting higher reproductive success to a subset of individuals fortuitously better adapted to changing local environments. By reproductive process, a lineage continues by making more members; sex provides variability among individuals by mixing the DNA of the male and female parents in each of the offspring.12
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Scientists remind us that if everyone has the same DNA somewhere in the future we would lose the ability to clone because it would be necessary to resort to natural reproduction, causing a considerable amount of inbreeding. This would cause many problems: for example, occurrence of diseases that could wipe out an entire population. However, others argue that unlike in vitro fertilization, cloning would allow replication of the healthy to bypass the risk of genetic disease contained in the lottery of sexual recombination. With regard to human cloning, Stephen Jay Gould posed the following questions: 13 • Are clones distinct individuals? • Does each member of a clone have a soul? • Am I still a distinct individual if I clone a daughter from a cell scraped from the inner lining of my cheek? Gould believes that such fears about human cloning are misplaced because the above questions have clear answers. Because identical twins share mitochondrial as well as nuclear DNA, gestate in the same womb, and usually grow up in the same environment, they are much closer than twin-clones. They become distinct individuals because of environmental influences. Gould further believes that human cloning should be studied and debated with enthusiasm and interest. "We can spell out unacceptable scenarios for human cloning, and we should pursue our ethical debate on this subject with rigor and vigilance." 14 George Will, syndicated columnist, recently wrote: "There are some things humanity cannot get used to without jeopardizing its humanness—without becoming beastly. Creeping toward us, as on little cat feet—little monkey feet, actually—is perhaps the gravest imaginable crisis, one that could result in the end of history as a distinctively human, and humane, story." 15 Will was referring to ANDI, the first genetically-modified primate created. ANDI was a baby rhesus monkey with jellyfish DNA that glows green in the dark. The Oregon Health Science University researchers who created ANDI said their goal was not to tinker with the human blueprint but to use monkeys such as ANDI to advance medical research and wipe out diseases. Rhesus monkeys such as ANDI share 95 percent of their genes with humans. According to Will, "ANDI was created, not begotten; the result of manufacture, not procreation. Humans are primates, which makes us (humans) next in line for genetic 'enhancement.' " 16
The Eugenics Connection Whenever human cloning is discussed, invariably the topic of "eugenics" comes up. The idea of eugenics (improving the race through breeding) can be traced back to Plato's Republic or even before. In Mendel's time, eugenics was a primary objective of experimentation, and after publication of Darwin's Origin of the Species in 1859, there was renewed interest in the study and application of eugenics.
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However, interest in eugenics probably originated with Francis Galton, a first cousin of Charles Darwin, who coined the word eugenics (meaning "good genes"). To many, the term "eugenics" invokes a sense of horror, mainly because the historical record of eugenics is not encouraging. In Germany and other countries, interest in eugenics flourished after the turn of the twentieth century. There was fairly widespread interest in the theory of eugenics, which advocated that the human race could be improved if "genetic purity" or ethnic cleansing was encouraged. The horrors of Nazi Germany represent the most extreme case of eugenics. Hitler's goal was to improve the human gene pool by large-scale elimination of select groups of people in his attempts to raise a perfect "master race." Hitler's extermination policies began with the large-scale elimination of people with disabilities; however, the darkest period for eugenics occurred when Nazis embarked on a "final solution" to the Jewish "problem": the Holocaust. The smell of Auschwitz remains with us today. Nazi Germany justified its horrendous actions by saying that it demanded the sacrifice of the minority to advance the interests of the majority. Syndicated columnist Cal Thomas, wrote: "We need to return to a uniform life ethic covering the unborn, the handicapped, the elderly, racial and religious minorities, in short, all human life. We still recoil at what Hitler did to the Jews, gypsies, homosexuals, and the sick." 17 Ethnic cleansing continues today in various parts of the world. Opponents of human cloning believe that the technology has the potential to become a major part of ethnic cleansing. However, supporters of human cloning argue that it offers the chance of a new life for those whose lives ended prematurely or unjustly. They believe that eugenics offers the potential for partial restitution of great inequities of the past. For the first time, they say, eugenic cloning would offer Jewish people a time to reconstruct, as millions of victims of the Holocaust could be cloned to recover lost genetic strains. In Russia, human cloning could have the potential to replenish the gene pool that was diminished by Stalin's mass executions of millions, many of whom were Russia's most skilled and brightest. Today, gene technology has made it possible to isolate, splice, insert, rearrange, recombine, and mass produce genes and to bypass natural selection. Scientists are able to insert any gene, or gene combination, into the human genome. This includes genes for skin color, muscle development, mathematical or scientific abilities, musical skills, or intelligence. Such genetic enhancement has made it potentially possible to improve the appearance or abilities of individuals and has allowed scientists to remove individual genes from one individual and introduce them into another, even of another species. To many, fabricated (designed) individuals are seen as a step down the road to Huxley's Brave New World and the production of cadres of "gammas" and "deltas" where parents can selectively abort their unborn children until they obtain a child with a genetic profile characterized by high intelligence, exceptional sports or musical skills, or other desired characteristics. Such genetic manipulation raises serious moral and ethical concerns, particularly for indigenous groups who believe that any violation of the natural order is abhorrently wrong. To breed blue-eyed blonde babies, much like radishes grown and nourished in the family garden, or to genetically boost the skills and physical strength of a dictator's army are potential consequences of human cloning.
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Currently, a company called Clonaid, run by the religious sect Raelians and headed by Dr. Brigitte Boisselier, advertises its selection of human embryos, each guaranteed free of all genetic defects. Described in detail in the advertisement are the gender, IQ, eye color, and other traits of each embryo, a prime example of contemporary aggressive eugenics. Kevin Fitzgerald believes that such control is a prime example of the loss of freedom. "When we attempt to control all the various elements of our lives to the extent that this technology seems to indicate, we have in a sense chosen to relinquish some of that freedom (whether we are successful or not). We can no longer now be the creatures we were before." 18
President Clinton's 1995 National Bioethics Commission Responding to what he termed the "troubling prospect" of cloning human beings, President Clinton convened the National Bioethics Advisory Commission (a panel of experts in medicine, science, law, ethics, and theology) to review the ethics and legality of human cloning and the ramifications cloning would have for humans. Created in October 1995 by President Clinton's executive order, the eighteen members of the commission were appointed for terms ranging from two to four years. Harold T Shapiro, economist and president of Princeton University, served as the commission chair. President Clinton asked the commission to provide general and contextual advice on human cloning. He also requested that the commission make recommendations to the National Science and Technology Council and other government entities regarding bioethical issues arising from human biological and behavioral research, as well as the clinical applications of such research. The president asked the commission to report back to him in ninety days on the implications of human cloning on what he called "the sacred family bond at the very core of our ideals." The president's request was hailed by scientific experts as an important first step toward insuring that reproductive technology be neither diminished or allowed to get out of control in the United States. Opponents of human cloning were disappointed, saying that President Clinton and the Bioethics Commission did not go far enough. Soon after, opponents called for a complete ban on human cloning, which they feared would rob the human race of its individuality. Legalities aside, the prospect of human cloning gave rise to profound ethical questions for the commission to consider. The foremost question was: What are the psychological impacts of being born as a genetic duplicate of one's parent? Hearing from biologists, lobbyists, and ordinary citizens, the commission reported back to the president in ninety days with a three-part recommendation. First, the current moratorium on human cloning (mandatory for those with federal grants, voluntary for everyone else) should be extended. Second, a federal law should ban human cloning outright. Third, a "sunset clause" should limit the life of any anti-cloning law.19 As a result of the commission's recommendations, as well as the news that researchers at the Oregon Health Science University had cloned two rhesus monkeys
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from embryos, President Clinton decided to restrict the use of federal funds for human cloning. Defending the experiment, Oregon researchers said they created the monkey clones to make cloning research more efficient and economical and had no intent to clone humans.
Prior Regulatory Commissions The Clinton Commission was not the first set up to regulate ethical and moral issues. The first National Bioethics Commission was created in 1974 to address research on human fetuses and issued its report by its expiration date of 1978. The 1974 commission created widely respected reports on the protection of human research subjects, including prisoners and children; those recommendations also became law. The first federal ethics board, created by Congress in 1985, quickly turned into a battlefield over abortion issues. The board expired in 1989 without issuing a single report. In 1994, a National Institutes of Health panel concluded that certain types of human embryo research were not justified, whereas other types were ethically acceptable. Among the accepted types of research were those embryo research projects that would provide insights into genetic diseases.
President Clinton's Cloning Prohibition Act of 1997 President Clinton's Cloning Prohibition Act of 1997, modeled on the recommendation of the National Bioethics Advisory Commission, outlawed any somatic cell nuclear transfer intended to create a human being. However, it also included a five-year sunset clause and was careful not to restrict other important and promising work—the right to clone molecules, DNA, cells, tissues, or animals. 20 In considering the Act, President Clinton recognized the great potential for advances in medicine and agriculture when he decided not to recommend that cloning animals and human genes be outlawed. Realizing that human cloning had the potential to be used for evil purposes, the president felt that other forms of cloning held potential to do great things for humanity. The dilemma, Clinton said, was resolving the desire to use cloning as a means for curing diseases, which the president said was possible "without raising the kind of ethical implications that, in effect, we're in the business where people are trying to play God." 21 President Clinton compared human cloning to splitting of the atom during the nuclear age and recommended that scientists move with caution and care: "Each human life is unique, born of a miracle that reaches beyond laboratory science. I believe we must respect this profound gift and resist the temptation to replicate ourselves." 22 Some religious groups warned that human cloning was disrespectful and unnatural and that scientists and others who supported it were playing God. Warning against trying to play God, President Clinton imposed a ban on federal funds for human cloning experiments, saying, "Any discovery that touches upon human creation is not simply a matter of scientific inquiry. It is a matter of morality and spirituality, as well." 23
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The accusation of "playing God" has been a vague but recurring criticism every time there is a major advance in biomedicine and was used when advances in birth control pills, in vitro fertilization, and heart transplants occurred. Therefore it was not surprising that the accusation was made when scientists advocated human cloning. President Clinton asked for a voluntary moratorium on human cloning experiments in the United States until legal and ethical issues could be sorted out. The President declared that only a voluntary moratorium would ensure that ethical issues were fully debated. He excluded from his directive any privately funded research. Marie Di Berardino, distinguished Professor Emerita at Allegheny University of the Health Sciences in Philadelphia, supported a ban on human cloning, saying, "There are these characters around who are going to go ahead with human cloning despite the strong public sentiment against it. We have to permit legislation. A ban on human cloning would not hamper basic research. That's a red flag that very liberal scientists are holding up." 24 Taking a firm stand against human cloning, Di Berardino emphatically stated that cloning research should proceed with other animals, but not with human material.
National and International Concerns The concern as to whether human cloning should be allowed really began in 1993 at George Washington University Medical Center in Washington, D.C. Dr. Jerry Hall and colleagues experimented with human cloning and in doing so opened a Pandora's box of moral and ethical questions. Hall and his team first announced they had created sixteen human embryos in a laboratory dish and separated them into forty-eight individual cells. In the experiment, two of the separated cells survived a few days and developed into new embryos of thirty-two cells each. However, each embryo was declared defective and destroyed shortly thereafter. When Hall's experiment was announced, the public was outraged, with outcries coming from both sides of the Atlantic. One German magazine called Hall's cloning research "unscrupulous." Even proponents of human cloning at the time admitted that the experiments were premature, but that it was quite likely a possibility for the future. The Vatican condemned Hall's experiment, calling it "perverse." Two Roman Catholic doctrines—natural law and ensoulment—dictated a closed position on the issue and the Roman Catholic document Instruction on Respect for Human Life (1987) presented a reasoned plea for society to follow natural methods of human procreation. The Roman Catholic Church cited human cloning as contrary to moral law and in opposition to the dignity both of human procreation and of the conjugal union. Instruction on Respect for Human Life speaks of the embryo as the unborn child who must be cared for, to the extent possible, in the same way as any other human being. Ensoulment, the second relevant Catholic doctrine, is the belief that at conception God imbues each human with an immortal soul. 25 The Jewish faith took a liberal stance on human cloning, encouraging people
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to view God's act of creation as a transformation process. In a Hastings Center report, Jonathan Cohen wrote that God invites humans to become created cocreators in His ongoing creation. Given this charge, and in view of widespread human disease and the promise of biotechnology, Cohen questioned: Would it not, in fact, be morally wrong to bypass the modern development? 26 Ian Wilmut, who cloned Dolly, expressed his views on human cloning at a cloning forum organized by the American Association for the Advancement of Science. Expressing his views, Wilmut used a slide (all in capital letters) to emphasize his views on human cloning: W E SHOULD N O T COPY PEOPLE BECAUSE W E SHOULD TREAT EACH CHILD AS AN INDIVIDUAL AND N O T AS A COPY OF ANOTHER PERSON 27 Later, Wilmut added, "It would be naive to say that we can completely prevent this. I don't find that frightening. I find it sad." 28 Wilmut also pointed out various other benefits of cloning, especially where pharmaceutical manufacturing, animal husbandry, and organ transplants were concerned. Xenotransplantation (the use of animal organs in people) was among Wilmut's expressed interests: "Cloning will provide, for the first time, an opportunity for precise genetic modifications to farm animals." 29 In 2005 Wilmut and motor neuron expert Christopher Shaw of the Institute of Psychiatry in London were given a license by the British government to clone human embryos for medical research into the cause of motor neuron disease. The experiments do not involve creating cloned babies. The decision by the Human Fertilization and Embryology Authority means a step closer to medical research that has the potential to revolutionize the treatment of motor neuron disease. The project does not use stem cells to correct the disease, but the cells will help scientists develop future treatments. On February 11, 1997, a bill was brought before the U.S. Senate that would have criminalized human cloning at the federal level. However, protests from the scientific community about the Republican leadership's haste in bringing the bill forward killed the bill. Shortly thereafter, on February 23, 1997, Dolly the sheep was displayed to the media, the first large cloned animal using DNA from another adult. Several months later, in June 1997, messengers to the annual meeting of the Southern Baptist Convention passed a resolution supporting a U.S. government ban on funding human embryo research and asked that human cloning be prohibited.
Setting Off a Furor In December 1997 the nation was dealt a bombshell when Chicago physicist Richard Seed announced plans to clone a human on National Public Radio's All Things Considered. The announcement set off an emotionally charged national
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debate. As a result of Seed's announcement, President Clinton immediately renewed efforts for federal legislation to outlaw both public and private attempts to clone a human. When congress reconvened in January 1998, Republican leaders promised quick action to ban human cloning but not existing human scientific research. A bill titled The Human Cloning Prohibition Act was sponsored by Christopher S. Bond (R-Mo.). The bill was stopped by opponents who used a parliamentary procedure to prevent debate. Although supporters sought to force a debate on the bill they failed to muster the three-fifths majority required to override the objections. Forty-two Senators supported consideration of the bill and fifty-four opposed it. Under Bond's bill someone found guilty of using cloning technology with human cells would face fines and ten years in prison. 30 The major lobbying effort against Bond's bill was by President Clinton's administration and various scientific groups including the American Cancer Society, Association of American Medical Colleges, the Federation of American Societies for Experimental Biology, American Council for Cell Biology, and the Biotechnology Industry Association. In addition twenty-seven Nobel Prizewinning scientists also wrote to President Clinton and members of Congress to oppose the bill. Other foes of Bond's bill were Senators Dianne Feinstein (D-Calif.) and Edward Kennedy (D-Mass.) who introduced their own bill. The Kennedy-Feinstein bill prohibited the placement of cloned human embryos in a uterus (reproductive cloning), but allowed the use of clones in research (therapeutic cloning). Their bill included fines but no prison terms for violators and had a life of ten years. In general, the scientific community favored the Kennedy-Feinstein bill over the Bond bill. Dr. David Baltimore, Nobel Prize-winning scientist, said that he believed that someday human cloning would be morally acceptable as a technological means to aid infertile couples. He recommended that the U.S. government follow the 1980s regulation of genetic engineering. Although there was considerable opposition to genetic engineering at the time it was first proposed, Baltimore said he believed that it was now an accepted technology of medical science. 31 Calls went out throughout the world for greater government control of human cloning experiments. Vatican officials, as well as members of the U.S. Congress, called for a total ban on cloning humans. Pope John Paul II criticized scientific experiments such as human embryo cloning that threatened the dignity of human life. In a strong statement, the pope condemned human embryo cloning and urged physicians to "defend without compromise life and the dignity of people, operating with respect to moral law. True humanism can never allow methods and experiments that constitute threats against life."32 The fifteen-member European Union, which had previously banned human cloning, asked a scientific committee to consider whether other forms of genetic manipulation should be regulated. However, Harold Varmus, then head of the National Institutes of Health (NIH), told lawmakers that cloning a human being was not consistent with traditional ideas of Darwinian biology concerning human individuality and diversity. Varmus suggested that interference with the genetic diversity of an entire population would be a disaster.
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Varmus further suggested that there were hidden risks in making a person from a cell that was already many years old because of accumulated mutations. He suggested that the U.S. government not support human cloning, and he and others called for a need to legislate the rights and privileges of such clones. Discussion of human cloning also centered around U.S. laws, as well as laws in other democratic countries, to control the behavior of rogue dictators in totalitarian countries. Meanwhile, the Southern Baptist Convention continued its effort to eliminate human cloning. On June 16, 1999, the Convention passed a resolution repeating its request for the U.S. government to continue its ban on federal funding for human embryo research and asked that privately funded researchers also stop their research voluntarily. In early August 2000 the U.S. House of Representatives voted 265-162 to ban all forms of human cloning with violations punishable by fines of $1 million or more and up to ten years in prison. The vote to criminalize cloning was backed by 200 Republicans, 63 Democrats, and 2 Independents. However, many scientists, patients' groups, and the biotechnology industry opposed the ban because it outlawed therapeutic cloning for potential disease treatments. In 2001 the National Academy of Sciences (NAS) panel concluded that human cloning should be banned because of significant risks. Maxine Singer, president of the Carnegie Institution, who chaired the NAS panel, said, "Studies of the cloning of animals have indicated very real safety concerns both for the clone and the mother. It seems unwise to proceed to clone a human being." 33 Despite impassioned opposition, some scientists continued to explore and perform human embryo cloning.
Eve: The First Human Clone? On December 26, 2002, an allegedly cloned, healthy seven-pound girl of American nationality and nicknamed "Eve" by scientists was delivered by Caesarean section at an undisclosed location somewhere outside the United States. The baby, according to scientists at a company called Clonaid, was an exact genetic duplicate of its mother, a thirty-one-year-old with an infertile husband. To date, the cloning of Eve has not been officially confirmed by experts. Clonaid was founded in the Bahamas in 1997 by Claude Vorilhon, a former French journalist and leader of a sect called the Raelians. Vorilhon claimed that a space alien visited him in 1973 and revealed that extraterrestrials had created all life on earth through genetic engineering. Dr. Brigitte Boisselier, who identified herself as a Raelian "bishop," said she accepts Vorilhon (known as Rael) as her spiritual leader. In the past, Vorilhon had claimed to be a race car driver, racing journalist, and author of Let's Welcome Our Fathers from Space. Dr. Boisselier, science director at Clonaid, said FDA officials encouraged her to sign an agreement stating she would not attempt to clone a human in the United States until the law on such procedures was clarified. Disappointed, Boisselier closed her U.S. laboratory, saying, "It's a pity that cloning could not happen in the United States because it is the most advanced country for science." 34
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The Food and Drug Administration (FDA) asserted jurisdiction over human cloning and after Eve's birth investigated whether the alleged cloning violated U.S. law. The FDA contended that its regulations forbid human cloning without prior agency permission. At the time, the United States had no specific law against human cloning. In April 2001 Boisselier was investigated by a grand jury in Syracuse, New York, after she testified before Congress that her company planned to clone a human. Parents of a baby boy who died at ten months were said to be the primary financial backers of Clonaid. With plans to use the boy's DNA to clone the dead baby, Boisselier said, "My goal is, as it has always been, a very healthy baby. The right of an individual to use his own genes as he wants is a basic human freedom." 3 5 Not a medical doctor, Boisselier claimed two doctorates in chemistry and had taught at Plattsburgh State University and Hamilton College in New York. She was previously marketing director for a chemical company in France.
An Infamous Cloning Trio Others made early news headlines with their announcement that they planned to clone a human. Among these were a team of three controversial fertility researchers—Rome-based embryologist Severino Antinori, director of the International Research Institute in Italy, fertility researcher Panayiotis (Panos) Zavos, director of the Andrology Institute of America in Lexington, Kentucky, and Israeli physician Avi Ben-Abraham. The scientists said in early August 2001 that they planned to clone humans. Antinori first gained notoriety by helping a sixtytwo-year-old woman have a child in 1994. The three scientists told a panel at a scientific conference on human cloning that they had recruited 200 infertile volunteers from different countries for their cloning project. Like Boisselier, the investigators had relocated their laboratories to undisclosed locations outside the United States. In early April 2002 Antinori announced that he had cloned a human embryo, which had been implanted into a surrogate mother. But a leading bioethicist and outspoken critic of human cloning, Arthur Caplan, director of the Center of Bioethics at the University of Pennsylvania Health System, called the announcement "nothing more than hype and sizzle. . . . I don't believe this is even practical. They claim to have 200 couples lined up to bring to some remote location and perform IVF [in vitro fertilization] procedures using cloned cells and then take care of all the pregnancies that might result. It just doesn't sound plausible." 36
A Look Ahead Scientists have done the job they were asked to do and there is now the technology to clone a human. Yet, many fear human cloning, most likely because the technology has progressed so far so quickly. Others, however, believe that the only real threat is our own narrow complacency.
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Much of the fear of human cloning appears similar to those of previous breakthroughs. For example, there was a time when birth control was viewed as a moral sin, in vitro fertilization was unthinkable, and heart transplants were morally and ethically unacceptable. Even general surgery at one time was objected to on the grounds that it interfered with God's creation. Because animal cloning yields high failure rates, reproductive experts believe it highly likely that human cloning would result in some birth defects, stillbirths, and a high rate of miscarriages. All this has the potential to cause social nightmares. Because of this no responsible U.S. scientist or public policy maker appears to favor human cloning. There are some who say, however, that creating a human clone is not all that difficult. They say that all that is needed is the same setup as that used for in vitro fertilization and because of this, the risks are minimal. Cloning of humans is at an ethical and moral crossroads, and most scientific inquiries and bioethical conversation about human cloning are on the subject of pro-life politics and religion. Human cloning is not prohibited by some religions or by the Bible or the other holy texts of major religions. The fundamental concern, as it has always been, centers around the moral status of the embryo. Whereas abortion involves the termination of life, cloning involves the creation of a new life. It is now up to our politicians and society in general to determine whether human cloning should be permitted and, if so, how it should be used. If human cloning moves forward, we will need to protect the rights and dignity of any human beings who might result from cloning techniques by ensuring that good laws are in place and that human cloning does not result in deformed individuals. Writing for the Ethics Board of the Department of Health, Education, and Welfare, Sid Leiman said, "If what is intended is the creation of human clones whose organs would be designated for transplantation purposes, I fail to see by what ethic or law any clone could be designated a donor rather than a recipient. And if experiments are being undertaken whose intended result is the cloning of a human being, we had better legislate now regarding the rights and privileges of such clones." 37 One cannot accurately predict what developments in human cloning will occur in the future, let alone when. However, it is wise to remember that what is not acceptable today may well be in the near future. This will demand that we look first to the past, and then to the present to determine whether human cloning is beneficial for the future of our society. In so doing, there are two important questions that need to be asked: Can we safely clone humans? Should we clone humans?
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NDTES Chapter 1. Recombining DNA Molecules 1. Watson 1968, 1. 2. Watson 1990, 44-49. 3. Watson and Crick 1953, 737-38. 4. Krimsky 1982, xiii. 5. Jackson, Symon, and Berg 1972. 6. Krimsky 1982, xiii. 7. Grody and Hilborne 1992, 166-71. 8. Zilinskas and Zimmerman 1986. 9. Chang and Cohen 1977, 4811-15. 10. Cohen 1977, 654-57. l l . R e i n h o l d 1969. 12. Glassman 1970, 963-64. 13. Beckwith 1970, 46-58. 14. Glassman 1970, 963-64. 15. Gershon 1983, 3-16. 16. Jackson and Stich 1979, 99-126. 17. Witt 1990. 18. Bergetal. 1974,303. 19. Krimsky 1982. 20. Bergetal. 1974,303. 21. Singer and Soil 1973. 22. Krimsky 1982. 23. Bergetal. 1974,303. 24. Ibid. 25. Cohen 1977, 654-57. 26. Wade 1975.
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27. Gershon 1983, 3-16. 28. Sinsheimer 1978. 29. Bergetal. 1974,303. 30. Bergetal. 1975,991-94. 31. Emery 1984. 32. Zimmerman 1978, 273-301. 33. Chargaff 1976, 938-39. 34. Peattie 1995. 35. Singer 1976, 257-58. 36. Javits and Kennedy, quoted in Swazey, Sorenson, and Wong 1978, 1019-78. 37. Swazey, Sorenson, and Wong 1978, 1019-78. 38. Federal Register 1987, 49596-9609. 39. Nightingale, quoted in Sun 1982, 1079-80. 40. Baltimore, quoted in Sun 1982, 1079-80.
Chapter 2. Splicing Life: Technological Revolution or Pandora's Box? 1. Chargaff 1977,32-35. 2. Zimmerman 1978, 273-301. 3. Chang and Cohen 1977, 4811-15. 4. Bender and Leone 1990. 5. Culliton 1990a, 974-76. 6. Culliton 1990b, 1373. 7. Miller 1990, 1368. 8. Swinbanks 1989, 398. 9. Roberts 1992, 677-78. 10. Brenner 1978, 2-3. 11. Watson 1978. 12. Emery 1984, 273-301. 13. Witt 1990. 14. Zilinskas and Zimmerman 1986. 15. Task Force on Human Life and the New Genetics 1982. 16. General Secretariats 1982. 17.Emanuel 1984, 266-69. 18. Ibid. 19. President's Commission for the Study of Ethical Problems in Medicine and Biomedical Research 1982. 20. Ibid. 21.Stichl978, 187-205. 22. Swinbanks 1989, 398. 23. Sharpies and Davis 1987, 1329-35. 24.Ibid. 25. Roberts 1992, 677-78. 26. Palca 1989, 398. 27. Zilinskas and Zimmerman 1986. 28. Mooney and Risser 1989, 297.
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Chapter 3. The Book of Life: The Human Genome Project 1. Netting and Wang 2001. 2. Dash 1991, 94. 3. Burke, Carle, and Olson 1987, 806-8. 4. Watson and CooloDeegan 1991, 8-11. 5. Saikietal. 1988,487-91. 6.Jaroff 1989, 62-67. 7. CookT)eegan 1989, 661-63. 8. U.S. Congress, Office of Technology Assessment 1988. 9. Dulbecco 1986, 1055-56. 10. Pines 1986. l l . L e w i n l 9 8 6 , 157-60. 12. Alberts 1985, 337-38. 13. U.S. Congress, Office of Technology Assessment 1988. 14. DeLisi 1988, 488-93. 15. U.S. Congress, Office of Technology Assessment 1988. 16. Leder 1990, 1-3. 17. Annas 1989, 19-21. 18. Grisolia 1991, 404-5. 19. U.S. Department of Health and Human Services and U.S. Department of Energy 1991-95. 20. Watson 1990, 44-49. 21. U.S. Department of Health and Human Services and U.S. Department of Energy 1991-95,5. 22. McKusick 1990, 73-74. 23. Collins and Galas 1993, 43-46. 24. Barnhart 1989, 651-60. 25. Watson 1989. 26. Watson 1990, 44-49. 27. Cantor 1990,49-51. 28. Ferguson-Smith 1991, 61-65. 29.Ibid. 30. Barnhart 1989, 657-60. 31. McKusick 1989a, 910-15. 32. Bodmer 1991,73-74. 33. Pinkel, Straume, and Gray 1986, 2934-38. 34. Licter, Tang, and Call 1990, 64-69. 35. Sternberg2001,9A-B. 36. Lander, quoted in Sternberg 2001, 9A-B. 37. Jasny and Kennedy 2001, 1153. 38. Chan 2002. 39. Bush 2003.
Chapter 4. Laboratory Babies: New Biology, Old Morality 1. Warnock 1985a. 2. Englehardt 1986, 239-41. 3. Warnock 1985b, 4. 4. Edwards and Steptoe 1980, 115-16.
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5. Edwards 1965, 926-29. 6. Steptoe and Edwards 1970, 683-89. 7. Warnock 1984, 4. 8. Fishel 1988, 54-72. 9. Caplan 1986, 241-53. 10. Morris 2002. 11. Ostermeier 2002, 772-77. 12. Edwards, Steptoe, and Purdy 1980, 737. 13. Roberts and Lowe 1975, 498-99. 14. Hammond 1914, 263-77. 15. Robinson 1921, 137-51, 209-31. 16. Hertig and Rock 1949, 968-93. 17. Biggers 1981,336-42. 18. Goodman 2002. 19. Engelhardt 1986, 239-41. 20. Kass 1972. 21. Berg 1999, 293.
Chapter 5. The Warnock Report 1. Singer and Wells 1984. 2. Warnock 1985b, ix-x. 3. Ibid., 4. 4. Warnock 1984, 3. 5. Ibid., xiii. 6. Ibid., 6. 7. Spallone 1986, 544. 8. Editorial 1984a. 9. Warnock 1984, vi-vii. 10. Ibid., 10. 11. Editorial 1984b. 12. Ibid. 13. Warnock 1985b, 60. 14. Ibid., 61. 15. Spallone 1986, 543-50. 16. Warnock 1985b, xiv. 17. Ibid., 71. 18. Corea 1985. 19. Warnock 1985b, xvi-xvii. 20. Spallone and Steinberg 1987, 166-83. 21. Ibid., 170. 22. Warnock 1985b, xv. 23. Ibid., 67-68. 24. Warnock 1984, 5. 25. Spallone and Steinberg 1987, 172. 26. Warnock 1984b, 55. 27. Boyson 1978. 28. Warnock 1985b. 29.Ibid. 30.Ibid.
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NOTES 31. Warnock 1985b, 8. 32. Ibid. 33. Edwards and Steptoe 1980, 115-16. 34. Caplan 1986, 241-53. 35. Warnock 1985b. 36.Ibid. 37.Ibid. 38. Warnock 1984, 44, 67. 39. Ibid., 44, 45. 40. Editorial 1984b. 41. Edwards and Steptoe 1980, 115-16. 42. Spallone 1986, 548. 43. Editorial 1984b. 44. Warnock 1985b, 80-86. 45. Ibid., vii. 46. Caplan 1986, 241-53. 47. Sattaur 1984, 12-17. 48. Editorial 1985, 417. 49. Campbell 1984. 50. Warnock 1984, 10. 51. Ibid., 11. 52. Editorial 1984a.
Chapter 6. The Human Genome Diversity Project 1. Bowcock and Cavalli-Sforza 1991, 491-98. 2. Smith 1993. Cayuga and Onandaga leaders were suspicious of a scientific study that wanted DNA samples from their nations. 3. Bowcock et al. 1991, 839-43. 4. C h i u l 9 9 1 . 5. Cavalli-Sforza et al. 1991, 490-91. 6. Ibid. 7. Ibid., 491-98. 8. Greely and Cavalli-Sforza 1993. 9. King 1996. Allan Wilson's group at Berkeley collected a different form of genetic material known as mitochondrial DNA. Inherited over time, it was useful in tracking evolutionary relationships. Wilson's studies of mitochondrial DNA led him to the controversial theory that all humans descended from a single woman who lived in Africa 200,000 years ago. 10. Cavalli-Sforza et al. 1991, 490-91. 11. Vigilant et al. 1990, 9350-54. 12. Stoneking et al. 1990, 717-33. 13. Stoneking and Wilson 1989, 215-49. 14. Smith 1993. 15. Johnson 1991, 44-48. 16. Greely 1993a. 17. Greely 1993b. 18. C h u i l 9 9 1 . 19. Cavalli-Sforza et al. 1991, 490-98.
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NOTES Chapter 7. The HGDP Debate 1. Cavalli-Sforza et al. 1991, 490-98. 2. Apodaca, quoted in Holland 1995. 3. Greely 1995a. 4. Harry 1994. Debra Harry is a Paiute Indian from Nevada who has researched issues related to the HGDP. 5. Australian Genethics Network 1994. 6. Ibid. 7. Annas 1995. 8. Hammond 1995. 9. Greely 1993c. 10. Harry 1995. 11. Cayuqueo 1993. 12. Brown 1995. 13. Hammond 1995. 14. Greely 1995b. 15.Ibid. 16. Hammond 1995. 17. Greely 1995b. 18. Hammond 1995. 19. Greely 1995b. 20. Greely 1995c. 21. Friedlaender 1995. 22. Keohane 1995. 23. Mooney 1993. 24. Greely 1995c. 25. Christie 1995. 26.Ibid. 27. Swedlund, quoted in Brown 1993. 28. Tilton, quoted in Brown 1993. Brown served as project officer for the Central Australian Aboriginal Congress. 29. Zalabata 1995. 30. Shenandoah, quoted in Bereano 1995. 31. Mooney 1993. 32. South and Meso American Indian Information Center (SAIIC) 1993. 33.Ibid. 34. Hammond 1995. 35. World Council of Indigenous Peoples (WCIP) 1993. 36. Indigenous Peoples of the Western Hemisphere 1995. 37. Ukupseni, Kuna Yala 1997. 38. Cordillera People's Alliance 1993. 39. Kreeger 1996, 1. 40. Butler 1997, 373. 41.Wadmanl997,774. 42. Smaglik2000, 912. 43. Macer 1999, 287-89. 44. Greely 2003.
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NOTES Chapter 8. Stem-cell Research 1. Fischer 2001, 52. 2. Somerville, quoted in Vergano 2001, 6D. 3. Lanza, quoted in Fischer 2001, 52-63. 4. Vergano 2001, 6D. 5. Begley 2002, 84-86. 6. Ibid. 7. Scholer 2003. 8. Lanza 2001b, 6 D At the time, Dr. Lanza was Vice-President of Medical and Scientific Development at Advanced Cell Technology, Inc. (ACT). 9. Vogelstein 2000. Dr. Vogelstein is a researcher at the Johns Hopkins University School of Medicine. 10. West, quoted in Fischer 2001, 60. 11. Oderberg, quoted in Weise 2002b, 3A. 12. Fischer 2001, 54. 13. West, quoted in Fischer 2001, 57. Dr. West was an executive/researcher for ACT and was considered a "visionary." 14. Fischer 2001, 57. 15. Ibid., 59. 16. Ibid., 57. 17. Ibid., 62. 18. Weise 2002a, 3A. 19. Ostermeier 2002, 772-77.
Chapter 9. A Major Decision 1. Bush 2001a. 2. Bush 2001b. 3. Bush, quoted in Lindlaw 2001. 4. Fleischer, quoted in Weise 2002c, 5D. 5. Duberstein and Deaver, quoted in Cloud 2001, 24. Duberstein was former Chief of Staff for President Ronald Reagan. 6. Kass 2001. Dr. Kass is a University of Chicago biomedical ethicist. A conservative, he was appointed by President Bush to head a commission to oversee stem-cell research. 7. Bush, quoted in Lindlaw 2001. 8. Pope John Paul II, quoted in Meckler 2001. 9. National Institute of Health 2001, 650. 10. Mohammed 2002. 11. Willing 2002. 12. Fiorenza2001. 13. Fiorenza, quoted in Keen 2001, 5A. 14. Robertson, quoted in Keen 2001, 5A. Robertson is founder of the Christian Coalition. 15. National Right to Life Committee, quoted in Mohammed 2002. 16. Thompson 2001a, 14A. Thompson was U.S. Secretary of Health and Human Services. 17. Bush, quoted in Page and Hall 2001, 4A. 18. Kennedy, quoted in Meckler 2001.
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NOTES 19. Daschle, quoted in Kenen 2001. 20. Thompson 2001b. U.S. Secretary of Health and Human Services. 21. Weise 2002c, 5 D 22. McKay, quoted in Weise 2002c, 5D. McKay is a senior investigator at the National Institute of Neurological Disorders and Strokes at the National Institutes of Health in Bethesda, Maryland. 23. Fleischer, quoted in Weise 2002c, 5D. 24. Caplan, quoted in Manning 2001, 8 D 25. Caplan, quoted in Jacoby 2001, 14-16. 26. Thompson 2001a. 27. Bush, quoted in Ross 2001. 28. Frist, quoted in Ross 2001. 29. Kennedy, quoted in Ross 2001. 30. Specter, quoted in Ross 2001. 31. Daschle, quoted in Ross 2001.
Chapter 10. Reproductive Cloning l.Beddingtonl997. 2. Bouchard 1997, 52-57. Bouchard is a professor of psychology at the University of Minnesota in Minneapolis. He was president of the Behavior Qenetics Association from 1993 to 1994. 3. Ibid. 4. Di Berardino and McKinnell 1997, 32-37. Di Berardino is Professor Emerita of Biochemistry at the Medical College of Pennsylvania-Hahnemann School of Medicine, Allegheny University of the Health Sciences in Philadelphia. McKinnell is a professor of genetics and cell biology at the University of Minnesota in St. Paul. Both authors are considered experts on the cloning of normal and cancerous frog cells. 5. Gurdon 1997, 26-31. Gurdon was chair of the Wellcome Trust/Cancer Research Campaign Institute at the University of Cambridge in England. 6. Ibid. 7. Ibid., 29. 8. Ibid. 9. Ibid., 26-31. 10. Ibid., 30. 11. Ibid., 26-31. 12. Lutz 1997, 10-11. 13. Di Berardino and McKinnell 1997, 32-37. 14.Ibid. 15. Beddington 1997. 16. Hart, Turturro, and Leakey 1997, 47-62. Hart is a biogerontologist. Turturro is a biologist and biophysicist. Leakey is a biochemist at the National Center for Toxicological Research in Jefferson, Arkansas. 17. Ibid., 51. 18. Ibid. 19. Fischer 2001, 52-63. 20. Hart, Turturro, and Leakey 1997, 47-62. 21. Wolf 1997, 1. Wolf is senior scientist at the Oregon Regional Primate Research Center. 22. Beddington 1997.
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NDTES 23. Kitcher 1997, 58-62. 24. Fischer 2001, 52-63.
Chapter 1 1 . Cloning a Human 1. Levin 1976. 2. Rorvik 1978. 3. Parens, quoted in Lutz 1997, 10-11. 4. Dixon 1993. 5. Dixon 1997. 6. Ibid. 7. Weiss 2002, A04. 8. Ribalow 1997, 38-42. 9. Di Berardino, quoted in Kiernan 1998, A40-41. 10.Ibid. 11. Purcell and Gould 1997, 14-15. 12.Ibid. 13. Purcell and Gould 1997, 16. 14.Ibid. 15. Will 2001. 16.Ibid. 17. Thomas 2000. 18. Fitzgerald, quoted in Thomas 1991. 19. Bilger 1997, 17. 20. Ibid., 18. 21. Clinton, quoted in Ross 1997. 22.Ibid. 23. Clinton, CNN Interactive 1997. 24. Di Berardino, quoted in Kiernan 1998, A40-41. 25. Walters 2001, 9-11. 26. Cohen 1999, 7. 27. Wilmut, quoted in Bilger 1997, 17-19. 28.Ibid. 29.Ibid. 30. Kiernan 1998, A40-41. 31. Baltimore, quoted in Kiernan 1998, A40-41. 32. Pope John Paul II, quoted in Associated Press 2001. Meeting with President George W. Bush. 33. Singer, quoted in Friend 2002, 5D. 34. Boisselier, quoted in Willing 2001b. 35.Ibid. 36. Caplan, quoted in Friend 2001, 5D. 37.Leiman2001.
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BIBLIOGRAPHY Alberts, B. M. 1985. Limits to growth: in biology, small science is good science. Cell 41: 337-38. Annas, George J. 1995. A new film on human genome hunting (February 23). http://www .gene-watch.org/Campaign/signers.html. . 1989. W h o ' s afraid of the human genome? Hastings Center Report (July/ August).T9-21. http://www.thehastingscenter.org. Associated Press. 2001. Meeting with President George W. Bush at Castel Gandolfo to discuss human cloning. Pope condemns human cloning (July 23). Australian GenEthics Network. 1994. The Human Genome Diversity Project. QenEthics News 10 (December 13). Barnhart, B. J. 1989. The DOE human genome initiative. Qenomics 5:657-60. Beckwith, J. 1970. Social and political uses of genetics in the United States: past and present. Annals of the NY Acad Sciences 265:46-58. Beddington, Rosa. 1997. Cloning. Mill Hill Essays. Bethesda, Md.: National Institute for Medical Research. http://omni.ac.uk/browse/mesh/D014183.html. Begley, Sharon. 2002. Fountains of youth. Newsweek 138(1 lA):84-86. Bender, D. L., and B. Leone. 1990. Qenetic engineering: opposing viewpoints. San Diego, Calif.: Greenhaven Press. Bereano, Phil. 1995. Regarding Papua New Guinea patents,
[email protected] (October). Berg, Laurence C. 1999. The ethics of using embryos. Laboratory Medicine 30(5):293. Berg, Paul, et al. 1975. Asilomar conference on recombinant DNA molecules. Science 188:991-94. Berg, Paul, David Baltimore, Herbert W. Boyer, Stanley Cohen, Ronald W. Davis, David S. Hogness, Daniel Nathans, Richard Roblin, James D. Watson, Sherman Weissman, and Norton D. Zinder. 1974. Potential biohazards of rDNA molecules. Science 185:303. Letter to the editor.
BIBLIDGRAPHY
Biggers, J. D. 1981. In vitro fertilization and embryo transfer in human beings. The New Eng]Med304(6):336-42. Bilger, Burkhard. 1997. Cell block. The Sciences 37(5): 17-19. Bodmer, Walter F. 1991. H U G O : the human genome organization. FASEB J 5:73-74. Bouchard, Thomas, Jr. 1997. Whenever the twain shall meet. The Sciences 37(5):52-57. Bowcock, Anne, and L. L. Cavalli-Sforza. 1991. The study of variation in the human genome. Qenomics 11:491-98. Bowcock, A., J. Kidd, J. Mountain, J. Herbert, L. Carotenuto, K. Kidd, and L. CavalliSforza. 1991. Drift, admixture, and selection in human evolution: a study with D N A polymorphisms. Proc Nad Acad Sci USA 88:839-43. Boyson, Rhodes. 1978. Protest to newspapers over tone of lesbian report. Times (London) (January 7). Brenner, S. 1978. A framework for assessing the potential risks of recombinant D N A research. Nature 276:2-3. Brown, Anthony. 1993. Genome project causes controversy (November 10). http://www .native-net.org/archive/nl/9311/0147.html. Burke, D. T , G. F. Carle, and M. V. Olson. 1987. Cloning of large segments of exogenous D N A into yeast artificial-chromosome vectors. Science 236:806-8. Bush, George W. 2003. Completion of the Human Genome Project. White House press release (April 14). . 2001a. Prime-time speech to the nation regarding his decision on stem-cell cloning (August 9). . 2001b. White House address to supporters to ban human stem-cell research and human cloning (August 8). . 2001c. News conference with British Prime Minister Tony Blair (July 19). Butler, Declan. 1997. Genetic diversity proposal fails to impress international ethics panel. Nature 377:373. Campbell, Beatrix. 1984. Why didn't they ask women? Quardian (London) (November 7). Cantor, C. R. 1990. Orchestrating the Human Genome Project. Science 248:49-51. Caplan, Arthur L. 1986. The ethics of in vitro fertilization. In Primary care 13. Philadelphia, Pa.: W. B. Saunders. 241-53. Cavalli-Sforza, L. L., A. C. Wilson, C. R. Cantor, R. M. Cook-Deegan, and M. C. King. 1991. Call for a worldwide survey of human genetic diversity: a vanishing opportunity for the human genome project. Qenomics 11(2):490-91. Cayuqueo, Nilo. 1993. SAIIC Director. Fax to Henry Greely, Stanford Law School, and Chair of HGDP Ethics Subcommittee (November 9). Chan, Eugene. 2002. Unraveling the genome. Newsweek (June 24):76. Chang, S., and S. N. Cohen. 1977. In vivo site-specific genetic recombination promoted by EcoRI restriction endonuclease. Proc Natl Acad Sciences of the USA 74:4811-15. Chargaff, Erwin. 1977. Uncertainties great, is the gain worth the risk? Chemical and Engineering News 55:32-35. . 1976. O n the dangers of genetic meddling. Science 192:938-39. Letter to the Editor. Chiu, Glenda. 1991. Fighting to save a gene pool: samples sought from dying tribes. San Jose Mercury News (July 23). Christie, Jean. 1995. Open letter. The Qene Report. Australian GenEthics Network (October 5). Cloud, John. 2001. Bush's no-win choice. Time (July 23):22-26. CNN Interactive. 1997. Clinton bars federal funds for human cloning research. Sci Tech (March 4). Cohen, Jonathan. 1999. In God's garden: creation and cloning in Jewish thought. Hastings Center Report 29(4):7.
2D4
BIBLIOGRAPHY
Cohen, Stanley N. 1977. Recombinant DNA: fact and fiction. Science 195:654-57. Collins, F , and D. A. Galas. 1993. A new five-year plan for the U.S. Human Genome Project. Science 262:43-46. Cook-Deegan, R. M. 1989. The Alta Summit, December 1984. Qenomics 5:661-63. Cordillera People's Alliance. 1994. Statement (December 13). Corea, Gena. 1985. The mother machine. New York: Harper and Row. Culliton, Barbara J. 1990a. Gene therapy: into the home stretch. Science 249:974-76. . 1990b. Gene therapy begins. Science 249:1373. Dash, Joan. 1991. The triumph of discovery. Englewood Cliffs, N.J.: Messer. DeLisi, C. 1988. The Human Genome project. Am Scientist 76:488-93. Di Berardino, Marie, and Robert G. McKinnell. 1997. Backward compatible. The Sciences 37(5):32-37. Dixon, Patrick. 1997. Headless human clones will grow organs in next ten years. BBC World Service Press Assoc. text (October 19). . 1993. The genetic revolution. New York: Kingsway. Dulbecco, R. 1986. A turning point in cancer research: sequencing the human genome. Science 231:1055-56. Editorial. 1985. Warnock proposals in trouble. Nature 313:417. . 1984a. Artificial fertilization made natural. Nature 310:269. . 1984b. Legal restraints proposed for United Kingdom. Nature 310:266. Edwards, Robert G. 1965. Maturation in vitro of human ovarian oocytes. Lancet 2:926-29. Edwards, Robert, and Patrick Steptoe. 1980. The sindy in Washington. In A matter of life. London: Hutchinson. 115-16. Edwards, R. G., P. C. Steptoe, and J. M. Purdy. 1980. Establishing full-term human pregnancies using cleaving embryos grown in vitro. Br J Obstet Qynaecol 81:131. Emanuel, E. J. 1984. The ethics of splicing life. Dissent 31:266-69. Emery, Alan E. H. 1984. An introduction to recombinant DNA. New York: Wiley. Engelhardt, H. T 1986. The foundations of bioethics. New York: Oxford University Press. Federal Register 42(1987):49596-609. Ferguson-Smith, M. A. 1991. European approach to the Human Genome Project. FASEB ] 5(l):61-65. Fiorenza, Joseph A. 2001. Statement to ABC's This Week (August 13). Fischer, Joannie. 2001. The first clone. U.S. News and World Report (December 3):52-63. Fishel, Simon. 1998. Assisted human reproduction and embryonic surgery: the ethical issues. In Biomedical ethics: An Anglo-American dialogue. Edited by Daniel Callahan and G. R. Dunstan. New York: New York Academy of Sciences. 530:54-72. Friedlaender, Jonathon. 1995. Open letter (October 25). Friend, Tim. 2002. Scientist says he will begin human cloning. USA Today (August 14):5D. General Secretariat. 1982. Letter to Jimmy Carter. Qenetic Technology News. 1991. Wholesale gene patenting by NIH sirs up a storm. 11(11):2. Gershon, E. 1983. Should science be stopped? The case of rDNA research. The Public Interest 71:3-16. Glassman, J. K. 1970. Harvard genetics researcher quits science for politics. Science 167:963-64. Goodman, Ellen. 2002. We need to tame our reproductive wild west. Boston Qlobe (January 10). Greely, Henry. 2003. E-mail to Dr. Rose M. Morgan (June 27). . 1995a. Open letter (October 29). . 1995b. Letter in Defense of Dr. Jonathon Friedlaender (October 26). . 1995c. Open letter (October 20).
2D5
BIBLIOGRAPHY . 1993a. Re: DNA probe angers the "endangered." Open letter (October 12). . 1993b. Human Genome Diversity Project organizer's response. Open letter (September 8). . 1993c. Letter to Pat Roy Mooney of RAFI (July 21). Greely, Henry, and L. L. Cavalli-Sforza. 1993. Open letter (July 8). Grisolia, Santiago. 1991. UNESCO program for the Human Genome Project. Qenomics 9:404-5. Grody, Wayne W , and Lee H. Hilborne. 1992. Diagnostic applications of recombinant nucleic acid technology: genetic diseases. Laboratory Medicine 23(3): 166-71. Gurdon, J. B. 1997. The birth of cloning. The Sciences 37(5):26-31. Hammond, Edward. 1995. RAFI press release: indigenous person patented (October 5). Hammond, J., Sr. 1914. O n some factors controlling fertility in domestic animals. J Agric Sci 6:263-77. Harry, Debra. 1995. The Human Genome Diversity Project: implications for indigenous peoples. Abya Yala News 8(4). Hart, Ronald, Angelo Turturro, and Julian Leakey. 1997. Born again? The Sciences 37(5):47-62. Hertig, A. T , and J. A. Rock. 1949. A series of potentially abortive ova recovered from fertile women prior to the first missed menstrual period. Am ] Obset Qynecol 58:968-93. Holland, Luke, prod. 1995. The gene hunters. Zif Productions, UK. Indigenous Peoples of the Western Hemisphere. 1995. Declaration (February 19). Jackson, D. A., and S. P. Stich, eds. 1979. Biological, social and political issues in genetic engineering. In The recombinant DNA debate. Englewood Cliffs, N.J.: Prentice Hall. 99-126. Jackson, D. A., R. H. Symon, and P. Berg. 1972. Biochemical method for inserting new genetic information into DNA of simian virus 40: circular SV40 D N A molecules containing lambda phage genes and the galactose operon of Escherichia coli. Proc Natl Acad Sci USA 69:2904-9. Jacoby, Susan. 2001. Brave New World. AARP (September): 14-16. Jaroff, L. 1989. The gene hunt. Time 20:62-67. Jasny, Barbara R., and Donald Kennedy. 2001. The human genome. Science 291:1153. Jeffords, James M., and Tom Daschle. 2001. Political issues in the genome era. Science 291:1249-51. Johnson, Julie. 1991. The oldest DNA in the world. New Scientist (May 11):44—48. Kass, K. R. 1972. Making babies—the new biology and the "old" morality. Public Interest 26:18. Kass, Leon. 2001. Discussions with President George W. Bush. Keen, Judy. 2001. Bush says line is drawn at embryo destruction. USA Today (August 13):5A. Kenen, Joanne. 2001. A biotechnology firm's announcement it has set limits on science frontiers. Associated Press (November 25). Keohane, Jeff. 1995. Re: RAFI press release: indigenous person patented. Keohane@ stanford.edu (October 9). Kiernan, Vincent. 1998. Senate rejects bill to ban human cloning. The Chr Higher Ed (February 20): A40-41. King, Mary-Claire. 1996. Relevance of the Human Genome Diversity Project. Statement to the National Academy of Sciences committee charged with evaluating the Human Genome Diversity Project (September 16). Kitcher, Philip. 1997. Whose self is it, anyway? The Sciences 37(5):58-62. Kotaro, Nawa. 1992. Patenting human DNA. Law in Cyberspace: Niigata University. Delivered to the Second International Bioethics Symposium.
2D6
BIBLIOGRAPHY Kreeger, Karen Young. 1996. Proposed Human Genome Diversity Project still plagued by controversy and questions. The Scientist 10(20).T. Krimsky, Sheldon. 1982. The social history of the recombinant DNA controversy. Cambridge, Mass.: MIT Press. Lanza, Robert. 2001. Embryo cloning breakthrough. Sci Tech, BBC News (November 25). Leder, Philip. 1990. Can the human genome project be saved from its critics . . . and itself? Cell 63:1-3. Leiman, Sid. 2001. Report for the Ethics Board of the Department of Health, Education, and Welfare. Levin, Ira. 1976. The boys from Brazil. Philadelphia: Lippincott. Lewin, R. 1986a. Molecular biology of Homo sapiens. Science 233:157-60. . 1986b. Proposal to sequence human genome stirs debate. Science 232:1598-600. Licter, P., C. J. Tang, and K. Call. 1990. High resolution mapping of chromosome 11 by in situ hybridization with cosmid clones. Science 247:64-69. Lindlaw, Scott. 2001. Bush backs limited medical research on cells. Associated Press (August 10). Lutz, Diana.1997. Hello, hello, Dolly, Dolly. The Sciences 37(3):10-11. Macer, Darryl R. J. 1999. Ethical opportunities offered by the Human Genome Diversity Project. Politics and the Life Sciences 18(2):287-89. Manning, Anita. 2001. Stem-cell limits questioned. USA Today (August 14):8D. McKusick, Victor A. 1990. Mendelian inheritance in man. Baltimore, Md.: Johns Hopkins University Press. . 1989a. Mapping and sequencing the human genome. New Eng ] Med 320:910-15. . 1989b. The human genome organization. FASEB J 5:73-74. Meckler, Laura. 2001. Stem-cell debate far from over. Associated Press (August 11). Mergen, Bernard. 1981. Three cloned mice. The Washington Post (January 11). Miller, S. K. 1990. Genetic privacy makes strange bedfellows. Science 249:1368. Mohammed, Arshad. 2002. Bush's stem-cell decision gets mixed reviews. Yahoo News (August 10). Mooney, H. A., and P. G. Risser. 1989. The release of genetically-engineered organisms: a perspective from the Ecological Society of America. Ecology 70(2):297. Mooney, Pat Roy. 1993. Letter to Henry Greely (November 4). Morris, Steven. 2002. Baby mishap shifts focus to security. Internet News, theage.com.au (July 10). Nash, Madeline. 1998. The case for cloning. Time 151(5):81. National Institute of Health Briefings. 2001. NIH signs stem-cell research agreement with WiCell Research Institute Inc. Laboratory Medicine 32(11):650. Netting, J., and L. Wang. 2001. The newly sequenced genome bares all. Science News 159:100-101. Ostermeier, G. C. 2002. Spermatozoal RNA profiles of normal human men. Lancet 360:111-11. Page, Susan, and Mimi Hall. 2002. Compromise may bring flak from both sides. USA Today (August 10):4A. Palca, J. 1989. Go ahead for gene transfer experiment. Nature 339:398. Peattie, Debra. 1995. The politics of genetic engineering. Harbus Online, www.harbus.org (December 4). Pines, M. 1986. Shall we grasp the opportunity to map and sequence all human genes and create a human gene dictionary? Paper presented at the meeting of the Trustees of the Howard Hughes Medical Institute, Bethesda, Md. Pinkel, D., T. M. Straume, and J. W. Gray. 1986. Cytogenetic analysis using quantitative, high sensitivity, fluorescence hybridization. Proc Natl Acad Sci USA 83:2934-38.
2D7
BIBLIOGRAPHY
President's Commission for the Study of Ethical Problems in Medicine and Biomedical Research. 1982. Splicing life. Washington, D C : Government Printing Office. Letter to Ronald Reagan. Purcell, Rosamond, and Stephen Jay Gould. 1997. On common ground—individuality: cloning and the discomforting cases of Siamese twins. The Sciences 37(5): 14-16. Reinhold, R. 1969. Scientists isolate a gene; step in heredity control. The New York Times (November 23). Ribalow, M. Z. 1997. Take two. The Sciences 37(5):38-42. Roberts, C. J., and C. R. Lowe. 1975. Where have all the conceptions gone? Lancet 1: 498-99. Roberts, L. 1992. Sequencing venture sparks alarm. Science 255:677-78. Robinson, A. 1921. Prenatal death. Edinburgh Med J 26:137-51, 209-31. Rorvik, David. 1978. In his image. 2nd ed. Philadelphia: J. B. Lippincott. Ross, Sonya. 2001. Pushing the cloning ban. Associated Press (April 11). . 1997. Clinton nixes cloning research. The Washington Post, http://www .washingtonpost.com (March 4). Saiki, R. K., D. H. Gelfand, S. Stoffel, S. J. Scharf, R. Higuchi, G. T Horn, K. B. Mullis, and H. A. Erlich. 1988. Primer-directed enzymatic amplification of D N A with a thermostable DNA polymerase. Science 239:487-91. Sattaur, O. 1984. New conception threatened by old morality. New Scientist 103:12-17. Scholer, Hans R., Karin Hubner, Guy Fuhrman, Guy Christenson, Lane Christenson, James Kehler, Rolland Reinbold, Rabindranath De La Fuente, Jennifer Wood, Jerome R Strauss III, and Michelle Boiani. 2003. Derivation of oocytes from embryonic stem cells. Science 300:1251-57. Shannon, T 1985. What are they saying about genetic engineering? Mahwah, N.J.: Paulist Press. Sharpies, R E., and B. Davis. 1987. Policy forum. Science 235:1329-35. Shenandoah, Leon. 1995. Letter to National Science Foundation (October). Singer, Maxine. 1976. Recombinant D N A research. Proc Conf on NIH Quidelines for Research on Recombinant DNA Molecules 1:257-58. Singer, Maxine, and Dieter Soil. 1973. Guidelines for DNA hybrid molecules. Science 181:1114. Singer, P., and D. Wells. 1984. The reproductive revolution. New York: Oxford University Press. Sinsheimer, L. R. 1978. Two lectures on recombinant DNA research. In The recombinant DNA debate. Edited by D. A. Jackson and S. P. Stich. Englewood Cliffs, N.J.: Prentice Hall. 99-126. Smaglik, Paul. 2000. Genetic diversity project fights for its life. Nature 404:912. Smith, Robert L. 1993. DNA probe angers the "endangered." Syracuse Post Standard (September 9). South and Meso American Indian Information Center (SAIIC). 1993. Open letter (October 20). Spallone, Patricia. 1986. The Warnock Report: the politics of reproductive technology. Women's Studies Int Forum 9(3):543-50. Spallone, Patricia, and D. L. Steinberg. 1987. Reproductive technology and the state: the Warnock Report and its clones. In Made to order: the myth of reproductive and genetic progress. Oxford: Pergamon Press. 166-83. Steptoe, Patrick, and Robert Edwards. 1970. Laparoscopic recovery of preovulatory human oocysts after priming of ovaries with gonadotrophins. Lancet 1:683-89. Sternberg, Steve. 2001. Decoding the mysteries of life. USA Today (February 12):9A-B. Stitch, S. P. 1978. The recombinant D N A debate. Phil Pub Affairs 3:187-205.
2DB
BIBLIOGRAPHY
Stoneking, M., L. B. Jorde, K. Bha'Tla, and A. C. Wilson. 1990. Geographic variation in human mitochondrial DNA from Papua New Guinea. Qenetics 124:717-33. Stoneking, M., and A. C. Wilson. 1989. Mitochondrial DNA. In Colonization of the Pacific: a genetic trail. Edited by A. Hill and S. Serjeanston. Oxford: Oxford University Press. 215-49. Sun, Marjorie. 1982. D N A rules kept to head off new laws. Science 215(26): 1079-80. Swazey, J. P., J. R. Sorenson, and C. B. Wong. 1978. Risks and benefits, rights and responsibilities: a history of the recombinant DNA research controversy. Southern California Law Review 51:1019-78. Swinbanks, D. 1989. Rifkin tries to block human gene transfer experiment. Nature 337:398. Task Force on Human Life and the New Genetics. 1982. National Council of Churches, Washington, D C . Tauli-Corpuz, Victoria. 1994. Open letter. QenEthics News 10. Thomas, Cal. 2000. If abortion is legal, why not cloning? Syndicated column (January 4). . 1991. Human cloning: why not. Syndicated column (November 28). Thompson, Tommy. 2001a. Door to research is open. USA Today (September 7): 14A. . 2001b. Statement to Associated Press (August 10). Ukupseni, Kuna Yala. 1997. Declaration (November 12-13). U.S. Congress, Office of Technology Assessment. 1988. Mapping our genes—the genome projects: How big, how fast? OTA-BA-373. Washington, D C : Government Printing Office. U.S. Department of Health and Human Services and U.S. Department of Energy. 1991-95. Understanding our genetic inheritance: the first five years, FY 1991-1995. DOE/ER-0452P. Springfield, Va.: National Technical Information Service. Vergano, Dan. 2001. Donor's age, health limit cloning options. USA Today (November 26):6D Vigilant, L., R. Pennington, H. Arepending, T D. Kocher, and A. C. Wilson. 1990. Mitochondrial DNA sequences in single hairs from a southern African population. Proc Nad Acad Sci USA 86:9350-54. Vogelstein, Bert. 2000. Report on stem cell research. Washington, D C : National Academy of Sciences. Wade, Nicholas. 1975. Genetics conference sets strict rules to replace moratorium. Science 187:931-35. Wadman, Meredith. 1997. Genome study maps chemical sensitivity. Nature 389(6653):774. Walters, James. 2001. Is cloning moral? Signs of the Times (August):8-ll. Warnock, Mary. 1985a. Medicine, ethics, and society international forum. Address to seminar participants, the Queen's College of Oxford University. . 1985b. A question of life: the Warnock report on human fertilisation and embryology. Oxford: Basil Blackwell. . 1984. Report of the committee of inquiry into human fertilisation and embryology. London: HMSO. Watson, James D. 1990. The human genome project: past, present, and future. Science 248:44-49. . 1978. The Washington Post (May 14). . 1968. The double helix. New York: Times Mirror Signet. Watson, James D., and R. M. Cook-Deegan. 1991. Origins of the human genome project. FASEBJ5(1):8-11. Watson, James D , and F.H.C Crick. 1953. Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid. Nature 171(6921):964-67. Weise, Elizabeth. 2002a. Stanford plans controversial stem-cell work. USA Today (December 11):3A.
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BIBLIOGRAPHY
. 2002b. Stem-cell research gets off to a slow start. USA Today (August 7):5D. . 2002c. Ethics and "surplus" embryos: the right-to-life question that won't go away. USA Today (August 7):5D. Weiss, Rick. 2002. Scientists claim an advance in therapeutic cloning. The Washington Post Online (January 30):A04. Will, George. 2001. Syndicated column (January). Willing, Richard. 2002. Bush: No to human cloning. USA Today (April 11). . 2001a. Human cloning banned by House. USA Today (August 1):1. . 2001b. Human cloning company to leave USA. USA Today (February 7). Witt, Stephen C 1990. Biotechnology: microbes and the environment. San Francisco, Calif.: Center for Science Information. Wolf, Don. 1977. Scientists grow monkeys from cloned embryos. Sci Tech, BBC (March 2):1. World Council of Indigenous Peoples (WCIP). 1993. Open resolution (December 10). Zalabata, Leonora. 1995. Open letter (February 23). Zilinskas, Raymond A., and Burke K. Zimmerman, eds. 1986. The gene splicing wars: reflections on the recombinant DNA controversy. New York: Macmillan. Zimmerman, B. K. 1978. Beyond recombinant DNA—two views of the future. In Recombinant DNA: science, ethics and politics. Edited by J. Richards. New York: Academic Press. 273-301.
2 1 D
INDEX
A b r a m , M o r r i s B., 19, 26-27 ABS Global, Inc., 172 Acosta, Isidro, 111 ACT. See Advanced Cell Technology Inc. (ACT) action groups, 20-22, 27-29 Adams, Mark, 41 adult-cell cloning, 161, 166-67, 172 Advanced Cell Technology Inc. (ACT), 138-40, 150, 172, 180 aging and genetic research, 133-34, 167-68 Alberts, Bruce, 39 American Association for the Advancement of Science (AAAS), 154 American Life League, 151 American Society of Reproductive Medicine, 139 A m m a s h , H u d a h , 32 A m p l i C h i p CYP450, 30 A N D I , 182 angiogenesis, 142 animals: cloning of, 159-60, 162-73, 180, 182, 191; stem cells and, 141; transgenic, 171-73 Annas, George, 109 annotation, 49 Antinori, Severino, 190 Apodaca, Ray, 106
artificial insemination (AI), 62, 79-80 Asilomar Conferences, 7, 9-12, 31 "Baby M " case, 63 bacteria, 8, 17, 22-23, 28; genomes and, 36, 42, 50. See also E. Coli Baltimore, David, 8, 15-16, 37, 188 Barrell, Bart, 37 Becker muscular dystrophy, 37 Beckwith, Jonathan, 6 Ben-Abraham, Avi, 190 Berg, Paul, 6-10, 38 Biggers, J.D., 64-65 Biodiversity Convention, 111, 118, 126 biohazards of r D N A , 5-18 biological warfare, 5, 3 1 - 3 3 , 107, 125 Biological Weapons Convention, 33 biomedicine, 51. See also diseases, disorders and genetic research biopiracy, 108-9 BiPolis research center, 135 blastocysts, 64, 135-37 blastulas, 163 Blattner, Fred, 42 blood vessels and stem cells, 142 Bodmer, Julia, 95 Bodmer, Walter, 80, 95 body cell cloning. See somatic cell cloning
INDEX Boisselier, Brigitte, 184, 189-90 Book of Life. See H u m a n G e n o m e Project Boston In Vitro Fertilization, 142 Botstein, David, 3 6 - 3 7 , 3 7 Bouchard, Thomas, 200n2 Boyer, Herbert, 7, 22-23 Boys from Brazil, The, 176 Boyson, Rhodes, 79 Brave New World (Huxley), 55-56 Brazilian Society of Biochemistry and Molecular Biology, 41 Brenner, Sydney, 22 Briggs, Robert, 163 British Medical Association (BMA), 73, 84 Brown, Louise, 57-59, 64 Brown, Patrick, 42 Brown, Ron, 110, 113-14 Bush, George W., 5 1 , 143; reaction to decision of, 150-53; stem cell research a n d , 1 4 5 - 5 1 , 152, 155 Califano, Joseph, 22 Callahan, Daniel, 20, 22 Cambridge, City of, 12-13 Campbell, Allan, 15-16 Campbell, Keith H. S., 165-68 cancer, 6, 8, 17, 38 Cantor, Charles, 95 Caplan, Arther, 154, 190 Card, Andrew, 148 Carter, Jimmy, 25 Cavalli-Sforza, Luigi Luca, 9 3 - 9 8 , 104-5, 126 Cayuqueo, Nilo, 112-13 c D N A . See complementary D N A Celera Genomics, 43 cell lines: commercialization of, 124; patents, 110-19; stem, 141, 146-48, 153-55 cells: cumulous, 169; differentiated/specialized, 165-68; multipotent adult progenitor (MAPCs), 134. See also stem cells Central Australian Aboriginal Congress (CAAC), 102 Chakrabarty, Ananda, 2 2 - 2 3 , 109 C h a n , Eugene, 51 Chang, S., 20 Chargaff, Erwin, 3, 11-12, 20 Christian Legal Society (CLS), 156 Christie, Jean, 111, 118 chromosomes, 36, 50, 6 0 - 6 1 , 99-100; maps and sequencing of, 22, 40, 4 2 - 4 3 , 49
212
C h u r c h , George, 37 churches. See religions and genetic research Cibelli, Jose, 140 Clinton, William, 29, 44, 149-50, 184-86 Clonaid, 184, 189-90 cloning, 48, 74; animal, 159-60, 162-73, 180, 182, 191; combining species and, 161, 182; embryos and, 136-38, 141, 143, 147, 162; history of, 162-68; h u m a n (see h u m a n cloning); kinds of, 161-62; in nature, 160; reproductive, 159-73; stem cell, 132, 162; therapeutic, 135-36, 162 C o h e n , Daniel, 42 C o h e n , Jonathan, 187 C o h e n , S. N., 20, 22-23 C o h e n , Stanley, 7, 10 Cold Springs H a r b o r Laboratory meetings, 38-40 Collins, Francis, 4 2 - 4 4 , 49 commercialization, 65-66, 83-84, 109, 119, 124,178 C o m m i s s i o n for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research, 25-27 C o m m i t t e e of Inquiry into H u m a n Fertilization and Embryology in the United Kingdom, 57; report of, 71-90 commodification, 65-66, 111, 116, 151 complementary D N A , 42, 48 conception, 63, 136, 138, 147 Conradi, Wilco, 133 containment, 10, 14—16 controversy: decade of, 4 - 7 ; H G D P and, 105-28; over cloning, 176-91; over in vitro fertilization, 57-59, 6 2 - 6 9 ; r D N A and, 2 0 - 3 3 , 27-29; stem cell research and, 129, 136-39, 142-43, 148-53; surrogacy and, 6 2 - 6 3 . See also environmental concerns; ethical concerns; political debates Cook-Deegan, Robert, 95 Cordillera People's Alliance, Statement of, 125-26 Crick, Francis, 3 cryogenic preservation (cryopreservation), 61, 67. See also freezing cytogenetic maps, 49 Daschle, Tom, 153, 156 Dausett, Jean, 40 Davies, David, 84 Davis, Bernard D , 28-29
INDEX Davis, Gray, 142 Davis, Ronald, 36 Deaver, Michael, 148 DeLisi, Charles, 39 D e p a r t m e n t of Agriculture, 38 D e p a r t m e n t of Energy (DOE), 38-42, 45 "designer bugs," 32 diabetes, 99-100, 133, 172 Diagnostic Development Branch, 46 Diamond vs. Chakrabarty, 23 Di Bernardino, Marie, 164-65, 186, 200n4 Dickey, Jay, 149-50 diseases, disorders and genetic research, 98-102, 104, 131-35, 141-42; blood vessels and, 142; diabetes and, 99-100, 133, 172; eyes and, 135; heart repair and, 133; neurons and, 133; teeth and, 134-35 disequilibrium, genetic, 100 diversity, 155, 181-82; Project, H u m a n G e n o m e (HGDP), 93-104; protection of bio, 105 Dixon, Patrick, 179 D N A : cloning and, 48, 161-62; complementary (cDNA), 42, 48; ethnicity and, 93-94; foreign, 48, 50; in h u m a n genome, 35; junk, 50; mitochondrial, 99, 197n9; polymerase chain reaction (PCR), 37, 48-49; recombining (rDNA), 3-18; sampling, 103-4; sequencing, 36, 4 8 - 4 9 , 99; and stem cell research, 141. See also H u m a n G e n o m e Project D O E . See D e p a r t m e n t of Energy (DOE) Dolly (cloned sheep), 165-68 Donis-Keller, Helen, 37 dopamine and stem cells, 133 "double effect," 78 double helical structure, 3 Driesch, A d o l p h Eduard, 162 Duberstein, Kenneth, 148, 199n5 (chap. 9) D u c h e n n e muscular dystrophy, 37, 48 Dulbecco, Renato, 38 E. Coli, 6, 10, 15, 20; genome, 36-37, 42, 49 ecological communities, 28-29 Edgar, Bob, 48 Edwards, Robert, 58, 64, 80, 84 eggs: d o n a t i o n of, 6 0 - 6 1 , 65, 81-82, 176; as property, 65-68; from stem cells, 134 Elsdale, T h o m a s R., 163 embryoblast, 64 embryos, 64-69; cloning of, 136-38, 141,
143, 147, 162; d o n a t i o n of, 8 2 - 8 3 ; and the law, 76-78; leftover ("spare"), 64, 66-67, 77, 8 1 , 137-38; loss of, 6 4 - 6 5 , 89; as property, 65-68; research on, 65, 74-78, 90; sources of, 136-37; stems cells and destruction of, 132, 136-37, 148-50, 152 endangered species cloning, 171 ensoulment, 64, 186 environmental concerns, 28-29, 32-33 Ethical, Legal, and Social Issues (ELSI) Branch, 45, 99 ethical concerns: cloning and, 183, 186-87, 191; and genome research, 4 0 - 4 1 ; and r D N A , 5-18, 23-27; in vitro fertilization and, 58-59, 63-69, 75, 78; in W a r n o c k Report, 71-90. See also controversy ethnic cleansing, 183 ethnicity and genetic variants, 93-94 ethnocide, 126 eugenics, 2 1 , 126, 182-84 European government and organizations, 4 7 , 9 6 , 111, 188 evolution: and D N A , 9 4 - 9 5 , 97-98; two lines of, 50 exploitation: of indigenous peoples, 96, 100-101, 105-8, 113, 119, 125, 197n2; of plant and animal genes, 108 Fauci, Anthony, 43 federal funding and research, 139, 145-50, 153-54 Federal Interagency Advisory C o m m i t t e e on Recombinant D N A Research, 15 Federation of American Scientists (FAS), 21 Feldman, Marc, 95, 97 feminist concerns, 75, 77, 79, 8 1 , 90 fertility clinics, 65-66, 72 fertilization, in vitro (IVF), 55-69 field testing, 28-29 Fiorenza, Joseph A., 151 First, Neal, 165 Fischberg, Michael, 163 Fitzgerald, Kevin, 184 Fleischer, Ari, 148, 154 Fleischmann, Rob, 42 Food and Drug Administration (FDA), 29, 190 Ford, Gerald, 15 Foundation o n Economic Trends, 27-29 Fox, Michael J., 141 Franklin, Rosalind, 3
213
INDEX Fraser, Claire, 41-42 Friedlaender, Jonathan, 114 Frist, Bill, 150, 155 frozen semen, eggs and embryos, 6 1 , 8 4 - 8 5 , 136,166-67 fruit flies: cloning of, 164; genome, 36, 43-44,50 funds: diversion of and HGDP, 108-9; research and federal, 139, 145-50, 153-54 Gajdusek, Carleton, 115 Galton, Francis, 183 gastrulas, 163 GATT. See General Agreement of Tariffs and Trade (GATT) Gearhart, John D , 132-33 GenBank database, 42 General Agreement of Tariffs and Trade (GATT), 111, 126 General Electric C o r p o r a t i o n , 109 genes: maps of, 44; muscular dystrophy, 37; shuffling of, 36; splicing of, 19-33, 183 (see also recombining D N A ) gene therapy protocols, 28-29 "genetic death," 59-60 genetic disequilibrium, 100 genetic engineering, 12-13, 18, 23-26, 27-28, 179, 188; of animals, 172-73. See also recombining D N A genetic flaws, repair of, 52 genetic information, 21, 50-51 Genetic Manipulation Advisory G r o u p ( G M A G ) , 22 genetic maps, 49. See also mapping Genetic Savings and Clone, 170-71 genetic tests, 30 genocide: genetics and, 119. See also ethnocide genomes, 36-37, 42-44; genes in h u m a n , 49-50; Project, H u m a n , 35-52 genomic regions, 100 Germany, 18; Nazi, 183 G e r o n C o r p o r a t i o n , 141, 147 Gilbert, Walter, 13, 36-38 G o o d m a n , Ellen, 67-68 G o r d o n Research Conference o n Nucleic Acids, 7-8 G o t t e s m a n , Susan, 16 G o u l d , Stephen Jay, 182 Greeley, Henry: and H G D P debate, 109-18, 126-28; and H G D P formation, 93, 96, 98, 103
214
Greenberg, Judith, 126 Greengross, Wendy, 84 Guaymi General Congress, 111 Guaymi patent, 110-13 Quidelines for Research Involving Recombinant DNA Molecules (NIH), 10 G u r d o n , John, 163-65, 200n5 Hagahai people, 115 Hall, Jerry, 186 H a m m o n d , Edward, 109, 115, 117 Harry, Debra, 198n4 Hart, Ronald, 2 0 0 n l 6 Haseltine, William, 4 1 , 4 3 Hastings Center, 20-22 Hayashizaki, Yoshide, 42 hazards of r D N A , 5-18 Health and Environmental Research and Advisory C o m m i t t e e (HERAC), 39 Healy, Bernadine, 29, 41 Hecht vs. Superior Court, 65-66 H e n n e n , Sally, 164 HGDP. See H u m a n G e n o m e Diversity Project (HGDP) HGP. See H u m a n G e n o m e Project (HGP) Hitler, Adolf, 176, 183 Holocaust, 183 H o o d , Leroy, 37 Hoppe, Peter, 159 Howard Hughes Medical Institute (HHMI), 38-39, 142 HTLV viruses, 110-11, 115 H u d s o n , Thomas, 42 H U G O . See H u m a n G e n o m e Organization (HUGO) h u m a n cloning, 175-91; alleged success in, 189-90; ban on, 150-51; Bush and, 146-47, 155; diversity issues and, 181-82; eugenics and, 182-84; failure rates and, 180-81, 191; good and bad of, 176-82; growing organs and, 180; headless, 179-80; " h u m a n b a n k s " and, 179; o p p o n e n t s of, 180-82, 184-86, 188-89; p r o p o n e n t s of, 177-79, . 181-83, 188; twins and, 160, 182 H u m a n E m b r y o Research Panel, 65 H u m a n Eugenics Advisory Committee, 21 H u m a n Gene Therapy Subcommittee (HGTS), 28 H u m a n G e n o m e Analysis Programme (HGAP), 47 H u m a n G e n o m e Diversity Project (HGDP), 93-104; calls for a halt to, 119-26;
INDEX concerns of indigenous peoples about, 106-9, 112-13; current status of, 127-28; debate over, 105-28; defense of, 116-18; ethnic history and, 93-94; funding and, 108-9, 127; history of, 94-96; h u m a n rights and, 106-7, 113, 119-20, 122, 124; informed consent and, 104, 107, 117-18, 125; international workshops for, 96-97; N R C panel on, 126-27; patents and, 108-19; populations for, 102-3, 117; sampling and, 103-4; value of, 97-102 H u m a n G e n o m e Education Program (HGEP), 46 H u m a n G e n o m e Educators Program, 46-47 H u m a n G e n o m e Initiative, 39-40 H u m a n G e n o m e Mapping Project (HGMP), 47 H u m a n G e n o m e Organization ( H U G O ) , 4 1 , 47-48, 118; H G D P and, 95-97, 127 H u m a n G e n o m e Project (HGP), 35-52; feud within, 43-44; foundation of, 36-37; funding of, 45; goals of, 4 4 - 4 5 ; history of, 3 7 - 4 3 ; impact of, 51-52; international centers and programs, 47-48; mapping and sequencing in, 48-49; results and surprises of, 49-50; U.S. centers and programs, 45-47 h u m a n life, beginning of, 63-64, 136-38, 147 h u m a n rights: and genetics, 99; and indigenous peoples, 106-7, 113, 119-20, 122,124 Hussein, Saddam, 32 Huxley, Aldous, Brave New World, 55-56 Illmensee, Karl, 159 indigenous peoples: declarations and resolutions of, 120-26; exploitation of, 96, 100-101, 105-8, 1 1 3 , 1 1 9 , 1 2 5 , 197n2; as focus of HGDP, 93-104; genetic technology and, 122-23; and H G D P debate, 105-28; n u m b e r s of, 94; patents and, 108-19, 122; World Congress of, 109, 112-13, 119-21 infertility, 59-60, 69, 74-75, 80-81 Infingen Inc., 172 informed consent: and H G D P sampling, 104, 107, 117-18; "individual consent" and, 125; and reproductive technologies, 59, 77-78, 147 inheritance, 67-68, 79, 85 Inquiry Committee. See W a r n o c k Report
Institute for Genomic Research (TIGR), 41 Institute of Medical Research (PNG), 114-16, 118 insulin and stem cells, 133 interest/action groups, 20-22, 27-29 International M o u s e Mutagenesis C o n s o r t i u m , 36 intracytoplasmic sperm injection, 61 in vitro fertilization (IVF), 55-69; infertility and, 59-60; responses to, 59, 68; techniques of, 60-62, 82; W a r n o c k R e p o r t and, 75, 8 0 - 8 1 ; world's first, 57-59 "isolates of historic interest," 105, 126 IVF. See in vitro fertilization (IVF) Jacob, Francois, 37
Japan, 42 Javits, Jacob, 15 Jenkins, Carol, 115-16, 118 Jewish faith, 151, 186 Joint G e n o m e Institute, 42 Jonas Institute for Reproductive Medicine, 142 Kass, Leon, 135, 148-49, 199n6 (chap. 9) Kelly, Bishop Thomas, 23 Kennedy, Edward, 10, 15, 20, 152-53, 155-56 Keohane, Jeff, 116 Kidd, Kenneth, 95 King, Mary-Claire, 95, 9 8 - 1 0 1 , 126 King, T h o m a s J., 163 Klausner, Richard, 43 laboratory babies, 55-69 Lairmore, Michael, 110 Lander, Eric, 4 2 - 4 3 , 50 Lanza, Robert, 131, 140, 199n8 (chap. 8) Laskey, Ronald A., 164-65 Lawrence Berkeley National Laboratory, 46-47 Leahy, Patrick, 153 Leakey, Julian, 2 0 0 n l 6 legal issues, 63, 65-68, 76-78, 84 legislation and regulation, 21-22; cloning and, 185, 188; current efforts toward, 155-56; e m b r y o destruction and, 149-50; scientists' responses to, 11, 20, 90, 153-54; on surrogacy, 84. See also W a r n o c k Report Leiman, Sid, 191 Lipscomb, William, 16
215
INDEX Los Alamos National Laboratory, 38 Ludwig, Bob, 48 M a m m a l i a n Genomics Branch, 46 M a n d e l b a u m , Rabbi Bernard, 23 mapping, 37, 4 4 - 4 5 , 48-49; of history of civilization, 101 Mapping Project of HGP, 48-49 Mapping Technology Branch, 46 Maxam, Allan, 36 Mayo, Frederico, 40-41 McClintock, Barbara, 36-37 M c G r a t h , James, 165 McKay, Ronald, 154, 200n22 (chap. 9) McKinnell, Robert, 200n4 McLaren, Anne, 77 Medical Research Council (MRC), 47, 73 Medicine, Ethics, and Society forum, 56-57 Mendel, Gregor, 52 Mergen, Bernard, 159 Mertz, Janet, 6 mice: cloning of, 159-60, 165, 169; genome of, 36, 43 Midgely, Mary, 175 migrations and D N A , 9 4 - 9 5 , 9 7 - 9 8 , 101-2 M o n a d , Jacques, 37 Mooney, Pat Roy, 110-11, 116, 120 moratoria, 7-10, 13, 21-22, 27, 40, 122, 186 M o u n t Sinai Hospital (Toronto), 108 Murray, Jeffrey, 42 muscular dystrophy genes, 37 myelin and stem cells, 133 National Academy of Sciences, 22, 39, 127, 154-55, 189 National Bioethics Advisory C o m m i s s i o n (NBAC), 29, 184-85 National Center for H u m a n G e n o m e Research ( N C H G R ) , 40, 42, 45 National Council of Churches Task Force, 23-25 National H u m a n G e n o m e Research Institute, 42 National Institutes of Health (NIH): e m b r y o research and, 65, 185; guidelines, 10, 14-17, 28, 139; H G P and, 3 8 - 4 3 , 45-46; N C H G R , 40, 42, 45; patents and, 109, 115-16, 118; R A C , 9 - 1 1 , 21-22, 25, 28-29; stem cells and, 150, 153-54 National Research Council (NRC), 39, 126-27, 173 National Right to Life Committee, 151
216
National Science Foundation (NSF), 38 natural law, 186 N C H G R . See National Center for H u m a n G e n o m e Research ( N C H G R ) neurons and stem cell research, 133, 187 Nexia Biotechnologies Inc., 171 Nightingale, Elena, 16 N I H . See National Institutes of Health Noller, Harry, 48 N o r t h - S o u t h G e n o m e Conference, 41 NRC. See National Research Council (NRC) nuclear transfer/transplant, 135-36, 163-69, 185 Oderberg, David, 139 Office of Technology Assessment (OTA), 39 Olson, Maynard, 41 Onandagas, 102-3 ooplasmic transfer, 141 " o p e r o n , " 37 Orr, Nancy Hoffner, 165 Ortiz, Deborah, 142 ova. See eggs Paabo, Svante, 95 Page, David, 42 Papua New Guinea Patent, 114-19 Parens, Eric, 179 parental rights and responsibilities, 25, 79 parthenogenesis, 140 patents: cell line, 110-19; Guaymi, 110-13; indigenous peoples and, 108-19, 122, 124-25; life forms and, 2 2 - 2 3 , 109; Papua New Guinea, 114-19; S o l o m o n Islands, 113-14 Patrinos, Aristides, 44 Peattie, Debra, 12-13 pedigree analysis, 37, 44 Pena, Sergio, 41 Perry, Dan, 153 p e r s o n h o o d , 63-64, 74-75 pets and cloning, 170-71 P h i l i p p i n e Solidarity G r o u p of Toronto, The (PSG), 126 physical maps, 49 Piazza, Alberto, 95 Plunkee, Guy, 42 Points to Consider documents, 28-29 political debates, 2 0 - 2 3 , 27-29, 142-43, 155-56, 188-89 Pollack, Robert, 6 polymerase chain reaction (PCR), 37, 4 8 - 4 9 , 99
INDEX Pope John Paul II, 149, 188 populations: D N A and history of, 98, 101-2; for HGDP, 102-3, 117; indigenous, 94, 100-101 p o s t h u m o u s reproduction, 65-68, 79, 84 PPL Therapeutics PLC, 172 preimplantation analysis, 137 primogeniture, 79, 84 privacy and reproduction, 66 proteins, 50, 164 protocols, 28-29, 101 Pseudomonas bacteria, 22-23, 28, 50 public policy issues: Asilomar Conference and, 3 1 ; cloning and, 185-86, 188-89, 191; commissions and, 25-27, 29, 184-85; interest/action groups and, 20-22; r D N A and, 19-33; stem cell research and, 142-43, 145-56. See also controversy; political debates Question of Life, A (Warnock), 72 RAC. See Recombinant D N A Molecule Program Advisory C o m m i t t e e (RAC) racism, 102, 107 RAFI. See Rural Advancement Foundation International (RAFI) Randall, Claire, 23 r D N A . See recombining D N A Reagan, Nancy, 148 Recombinant D N A Molecule Program Advisory C o m m i t t e e (RAC), 9 - 1 1 , 21-22, 25, 28-29; guidelines, 10, 14-17, 28 recombining D N A (rDNA), 3-18; academic involvement in, 12-13; arguments for and against, 27; Berg letter on, 9; commissions on, 25-27, 29; conferences on, 7-12, 14; containment and, 10; contributions of, 30; controversy over, 4 - 7 , 20-25, 27-29; discovery of, 7; safety guidelines for, 10; social implications of, 3 0 - 3 1 ; Third World and, 31 Red, Scot, 151 Reeve, Christopher, 141-42 Reeves, R a y m o n d , 164-65 regulation. See legislation and regulation rejection, i m m u n e system, 139 religions and genetic research, 23-25, 111-12, 136, 138, 149, 151-52, 186-87 Religious Coalition for Reproductive Choice, 151-52
Report of the Committee of Inquiry into Human Fertilization and Embryology in the United Kingdom, 5 7 , 7 1 - 9 0 reproduction: p o s t h u m o u s , 6 5 - 6 8 , 84; privacy and, 66 reproductive cloning, 159—73 reproductive technologies: artificial insemination (AI), 79-80; egg donation, 6 0 - 6 1 ; frozen semen, eggs and embryos, 6 1 , 8 4 - 8 5 ; informed consent and, 59, 77-78; inheritance and, 67-68, 79, 85; sperm banks, 6 1 ; surrogacy, 6 1 - 6 3 ; techniques of, 60-62, 82; in vitro fertilization (IVF), 55-69; W a r n o c k Report on, 71-90 "restriction endonucleases," 4 Rifkin, Jeremy, 21-22, 27-29 Robertson, Pat, 151, 199nl4 (chap. 9) Robl, James M., 140 R o m a n Catholic Church, 136, 138, 151-52; Instruction on Respect for Human Life, 186 Rorvik, David, 176 r o u n d w o r m (nematode) genome, 36, 43, 49 Rove, Karl, 148 Rubin, Gerald, 44 Rural Advancement Foundation International (RAFI), 108-11, 115-20 SAIIC. See South and M e s o American Indian Information Center (SAIIC) Sanger, Frederick, 36, 48 Scholer, Hans, 134 Science for the People, 6 Scientific Coordinating C o m m i t t e e (SCC), 41 Seed, Richard, 187 Sequana Therapeutics, 108 sequencing, 42-44, 48-49, 99 Sequencing Technology Branch, 46 severe combined immunodeficiency (SCID), 133 Shand, Hope, 126-27 Shapiro, Harold, 169, 184 Shapiro, James, 5-6 Sharpe, Paul, 134-35 Sharpies, Frances E., 28-29 Shaw, Christopher, 187 Shenandoah, Leon, 119 Shin Yong M o o n , 135 sickle-cell anemia, 30 Singer, Maxine, 8, 14, 189 Siniscalco, Marcello, 95
217
INDEX Sinsheimer, Robert, 10, 37, 48 Skolnick, Mark, 36 Smith, Chris, 156 Smith, Hamilton, 42 social implications: of genome research, 4 0 - 4 1 ; of r D N A , 30-31 Society for Social Responsibility in Science (SSRS), 21 Soil, Dieter, 8 S o l o m o n Islands patent, 113-14 Solter, David, 165 somatic cell cloning, 161, 166, 169, 176, 185 Somerville, Judson, 131 Song Chang-hun, 143 S o u t h and M e s o American Indian Information Center (SAIIC), 106, 120 S o u t h e r n Baptist Convention, 187, 189 Specter, Arlen, 156 S p e m m a n , Hans, 162 sperm, donated, 6 1 ; inheritance and, 67-68, 79, 85; as property, 65-68 Splicing Life (Carter Commission), 25 splicing of genes, 19-33 Stanford University, 141-42 stem cell research, 131-43; o n animals, 141; benefits and breakthroughs of, 131-35, 141-42; Bush decision on, 145-56; debate over, 138-39; federal funding and, 139, 145-50, 153-54; leaders in, 139-41; o p p o n e n t s of, 132, 138, 149-51; overseas, 143; s u p p o r t e r s of, 149-50, 152-55 stem cells: adult, 134-35; cloning and, 132, 162; embryonic, 131-37; lines of, 141, 146-48, 153-55; obtaining, 136-37 Steptoe, Patrick, 58, 64, 84 Stevenson, Adlai, 20 Sulston, John, 3 7 , 4 1 , 4 3 surrogacy, 6 1 - 6 3 , 83-84 SV40 virus, 6 Swedlund, Alan, 118 Takebe, Hiraku, 127 Tauli-Corpuz, Victoria, 105 telomeres, 140, 167-68 "test t u b e " babies, 55, 57-58 Thomas, Cal, 183 T h o m p s o n , James, 141 T h o m p s o n , Tommy, 148, 150, 152-55 Tilton, Edward, 118-19 transgenic animals, 171-73 trophoblast, 64
218
Tung, T. C , 164 Turturro, Angelo, 2 0 0 n l 6 U k u p s e n i , Kuna Yala, Declaration of, 124 U N E S C O , 4 0 - 4 1 , 127 United Kingdom, 47, 143; W a r n o c k R e p o r t of, 71-90 United Nations Education, Scientific, and Cultural Organization. See U N E S C O U.S. Congress, 10, 22, 39-40, 45; cloning and, 187-89; stem cell research and, 149-50, 155-56 U.S. government. See individual departments and agencies uterine lavage, 82-83 "Vampire Project," 105. See H u m a n G e n o m e Diversity Project (HGDP) Varmus, Harold, 155, 188-89 Ventor, Craig, 41-44, 49 Verfaillie, Catherine, 134 Vogelstein, Bert, 138-39, 199n9 (chap. 8) Vorilhorn, Claude, 189 Wade, Nicholas, 10 Wald, George, 6 W a r n o c k , D a m e Mary, 55, 57-58, 71-77, 80, 89-90; A Question of Life, 72 W a r n o c k Report, 73-90; official recommendations of, 85-89; reaction to, 89-90; task of, 71-72; views of, 74-85 Waterston, Robert, 37, 43 Watson, James D , 3, 22; H G P and, 35, 37, 40-41,43 WCIP. See World Congress of Indigenous Peoples (WCIP) Weiss, Ken, 95, 97 Weissman. Irving, 142 Wellcome Trust, 43 West, Michael, 139-41 Westhusin, Mark, 170 W h i t e , Ray, 36-37 whole-genome shotgun sequencing, 42-44 WiCell Research Institute, 141, 147, 150 Wilkins, Maurice, 3 Will, George, 182 Willadsen, Steen M., 165 Wilmut, Ian, 165-68, 187 Wilson, Allan, 95, 197n9 Wisconsin A l u m n i Research F o u n d a t i o n (WARF), 141, 147
INDEX Wolf, Don, 168-69, 200n21 (chap. 10) Woodward Case, 67-68 Woo-Suk Hwang, 135 Workshop on International Cooperation for the Human Genome Project, 40 World Congress of Indigenous Peoples (WCIP), 109, 112-13, 119-21 Wyngaarden, James, 40 xenotransplantation, 172, 187
Yanagimachi, Ryuzo, 169 Yan Shaoyi, 164 yeast genome, 36, 42 Zalabata, Leonora, 119 Zavos, Panayiotis, 190 Ziff, Edward, 7-8 Zinder, Norton, 40 zygote, 57, 63, 162
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About the Author ROSE M . M O R G A N , Ph.D., is Professor Emerita of Biology at Minot State University. She has published over 50 articles in refereed national and international scientific journals, as well as several other books. She is listed in Who's Who in Science and Engineering, Who's Who in Medicine and Healthcare, and Who's Who in America. Currently, she is an independent scholar.
