Germ Theory (Science Foundations)

science f o u n dat i o n s

Germ Theory

SCIENCE FOUNDATIONS The Big Bang Evolution The Genetic Code Germ Theory Gravity Heredity Light and Sound Natural Selection Planetary Motion Plate Tectonics Radioactivity Vaccines

science f o u n d at i o n s

Germ Theory Natalie Goldstein

Science Foundations: Germ Theory Copyright © 2011 by Infobase Publishing All rights reserved. No part of this book may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage or retrieval systems, without permission in writing from the publisher. For information, contact: Chelsea House An imprint of Infobase Publishing 132 West 31st Street New York, NY 10001 Library of Congress Cataloging-in-Publication Data Goldstein, Natalie. Germ theory / by Natalie Goldstein. p. cm. — (Science foundations) Includes bibliographical references and index. ISBN 978-1-60413-041-6 (hardcover) ISBN 978-1-4381-3520-5 (e-book) 1. Germ theory of disease—Popular works. 2. Epidemics—Popular works. I. Title. II. Series. RB153.G65 2010 614.4—dc22 2010015730 Chelsea House books are available at special discounts when purchased in bulk quantities for businesses, associations, institutions, or sales promotions. Please call our Special Sales Department in New York at (212) 967-8800 or (800) 322-8755. You can find Chelsea House on the World Wide Web at http://www.chelseahouse.com Text design by Kerry Casey Cover design by Alicia Post Composition by EJB Publishing Services Cover printed by Bang Printing, Brainerd, MN Book printed and bound by Bang Printing, Brainerd, MN Date printed: October 2010 Printed in the United States of America 10 9 8 7 6 5 4 3 2 1 This book is printed on acid-free paper. All links and Web addresses were checked and verified to be correct at the time of publication. Because of the dynamic nature of the Web, some addresses and links may have changed since publication and may no longer be valid.



1 “Civilizing” Disease



2 The “Not So Good” Old Days

23



3 A Tiny Universe Revealed

38



4 Contagion

48



5 Sour Wine

55



6 Silk and Chickens

64



7 Cultural Developments

72



8 “Magic Bullets” and Antibiotics

87



9 Life in the Age of Antibiotics

97

10 Looking Forward

7

106



Glossary

115



Bibliography

119



Further Resources

120



Picture Credits

122



Index

123



About the Author

127

“Civilizing” Disease

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here is no doubt that for as long as there have been organisms on Earth, there have been diseases that plagued them. From plants to platypuses, fish to fowl, dinosaurs to donkeys, all living things have always been subject to, and sometimes killed by, diseases. Humans, like all other organisms, have always been vulnerable to disease. There is no evidence of how prehistoric early humans perceived or reacted to disease, or what they thought caused it. There is evidence that they were far less prone to disease than modern people, and their lifestyle ensured that they were generally also far healthier than people today.

From Nature to Agriculture For hundreds of thousands, even millions, of years, early humans were hunter-gatherers who lived in small groups. Each group wandered through its environment gathering plants or hunting animals for meat. The wandering bands were exposed to the diseases in their environment, most likely from contact with animals they hunted. Yet there were generally not enough people living in one place to allow human-specific diseases to develop and cause widespread disease, or an epidemic. An epidemic is an outbreak of a disease that afflicts a large population living in a given region. An epidemic cannot get a foothold when a population made up of small groups of people is dispersed over a wide area.



  Germ Theory Experts have reported that early humans suffered from far fewer diseases than people today. Studies have shown that the diet of early humans was extremely varied. This wide-ranging diet kept them very fit and healthy. Even the most ordinary of modern diseases, such as the common cold, may have been unknown among early humans. Most of today’s diseases flourish where people are crowded together. These diseases had little or no chance of succeeding among small bands of hunter-gatherers. Experts speculate that the diseases that did afflict early humans were probably associated with eating meat and hunting. For example, eating an animal that had a disease might have transferred the disease to people. Undercooking meat might have caused trichinosis or similar meat-related diseases. Early humans might also have been prone to mosquito-borne malaria or to diseases carried by flukes, worms, and other parasites that thrive in freshwater. Studies have shown that most early humans died from accidents or hunting-related injuries, not from illness. As early humans developed important skills and tools that helped them survive—the ability to control fire, for instance—the human population grew. By about 100,000 years ago, humans had colonized most of the habitable corners of the globe. For the next 60,000 years, humans used their big brains to improve the tools they used to find, gather, and kill food. These tools helped early humans obtain more food, which could feed more people. As their access to food improved, the human population began to grow rapidly. By about 12,000 years ago, the human population had increased so much that small bands of people could no longer support themselves by hunting and gathering. There was too much competition among the larger and more numerous bands of people to permit this lifestyle to continue. By this time, people had learned which plants provided the most nutritious and tastiest seeds (grain) from wild grasses, fruits and berries from trees and bushes, and plant roots. They had already domesticated, or tamed, wolves. These domesticated dogs lived with people and helped them find and bring down the animals they hunted. Humans used their knowledge of plant and animal foods to begin growing the best-tasting and most nutritious plants and raising the tamest and tastiest animals for meat. In other words, they started farming. The Agricultural Revolution of 12,000 years ago was probably the most significant and momentous change in human history

“Civilizing” Disease   because it completely altered the course of human development. “Such a transition was indisputably the most important event ever engineered by humankind,” according to one historian quoted in the Cambridge Illustrated History of Medicine. No longer were humans simply animals sharing the planet and its resources with other animals. With the Agricultural Revolution, humans began manipulating the Earth to suit their own needs and desires. People stopped being hunter-gatherers and started to settle down, mainly in places where the soil was rich and could support repeated plantings of crops. Humans planted grasses, such as wheat

Vitamin C Humans are one of the few species of animal whose body cannot make its own vitamin C (ascorbic acid). Vitamin C is vital for health because it aids in the absorption of iron and in building a tough, structural protein called collagen, which is used in forming bones, cartilage, muscles, and blood vessels. Most scientists believe that the varied plant diet of a distant ancestor of humans (and many other primates) caused it to lose the ability to make vitamin C. Early humans ate such an enormous array of different types of plants that they were certain to get all the vitamin C they needed from the food they ate. So the job of making vitamin C was “given up” a long time ago, because way back then it was no longer needed. Today, of course, the human diet is far more limited. Yet our bodies inherited the inability to make vitamin C. Modern humans will get a potentially deadly disease called scurvy if they do not eat foods with enough vitamin C. For hundreds of years, sailors with the British navy fell ill or died from scurvy. When their illness was finally traced to a lack of vitamin C, the navy began provisioning their ships with large stores of limes. Limes are citrus fruits, like oranges, that contain lots of vitamin C. Sailors from other nations, who did not know any better, made fun of the limes the British sailors ate and referred to the sailors as “limeys.”

10  Germ Theory or rice, that produced the most and the best-tasting grains. Year after year, agricultural lands were expanded and produced increasing amounts of grain and vegetables. Humans learned how to domesticate animals they had once hunted for food. The wild boar became the domesticated pig. Wild sheep, cattle, goats, and fowl (chickens) were tamed and bred on the farm for food. No longer did people have to go out searching for food. They grew it or raised it themselves.

The Rise of Cities Soon, farming communities were producing far more food than only the farmers could eat. This excess food allowed cities to develop. Farmers sold their grain to early city dwellers, the first population of humans that was completely uninvolved in food production. Because city people did not have to spend their time looking for food, they could turn their attention and their talents to other things. The rise of cities brought about advances in trade, the arts, architecture, music, mathematics, philosophy, writing, technology (improved tools), and most other artistic and intellectual activities people take for granted today. Human civilization as we know it was a direct result of the rise of agriculture and the growth of cities. Unfortunately, many of the diseases to which humans became subject also arose from these advances. In cultivating crops, people also cultivated a host of previously unknown diseases. One historian analyzed the diseases that adapted from their original animal hosts to infect humans. According to the Cambridge Illustrated History of Medicine, beginning about 12,000 years ago, humans suddenly became subject to

• • • • • •

65 diseases that originated in dogs, 50 diseases that originated in cattle, 46 diseases that originated in sheep and goats, 42 diseases that originated in pigs, 35 diseases that originated in horses, and 26 diseases that originated in fowl.

For the first time, diseases ran rampant among people. Farmers lived among their livestock, often keeping the animals in the farmhouse. Livestock diseases adapted to infect humans. Farmers kept

“Civilizing” Disease  11

Figure 1.1â•… This ancient Egyptian tablet, found in the Tomb of Menna in Thebes, Egypt, shows early agricultural practices around 1500 to 1400 b.c. Among the activities portrayed are gathering sheaves of grain, herding cattle, using cows to plow fields, and collecting and preparing food.

stores of grain and other crops. These food stores attracted mice and rats, which ate the food but also passed on disease. Rodents and other animals also took advantage of the cozy warmth of the farmhouse and lived in every corner of it. This, too, aided in the transfer of disease from animals to humans. Agriculture itself led to an increase in disease. Malaria, a disease carried by mosquitoes that breed in standing water, predates the Agricultural Revolution. Yet the widespread irrigation of farm fields vastly increased the area in which mosquitoes could breed,

12  Germ Theory and malaria exploded after the Agricultural Revolution. Furthermore, even the simple act of plowing up undisturbed soil brought people into contact with worms, insects, and other soil organisms that gave them diseases they had never had before. City dwellers lived cheek-by-jowl with each other in small, crammed-together buildings. Urban housing of the time may have been extremely cramped, but here, too, human dwellings provided shelter for mice, rats, and other assorted creatures looking for a home and attracted by scraps of available food. These house pests passed on the diseases they harbored to humans. Parasites, such as head lice, became specialists in infecting people. As many pet owners know, dogs (and other domesticated creatures) are hosts for fleas, which can also harbor diseases that have adapted themselves to attack humans. Nearly all early cities were not only overcrowded, but also were dirty and unhealthful. Streets ran with human bodily waste. Piles of garbage could be found everywhere. Both conditions fostered diseases that almost constantly plagued early city dwellers. As people abandoned living off nature (hunting and gathering) in order to manipulate it for their own purposes, they unleashed a whole universe of new human diseases. Diseases that once were confined to nonhuman species began to evolve to take advantage of their new intimacy with people. Cities became “disease heaven” for germs because so many people lived crowded together and sanitation was so poor. Over time, diseases that had once been unknown in humans became able to target and devastate human populations.

Early Epidemics: A Brief Overview Civilization made epidemics possible. Civilizations developed all over the world, from South America and Mexico to China, North Africa, Europe, and the Near East, the birthplace of agriculture. Everywhere, increasing agricultural food production led to the rise of cities and tremendous growth in the human population. Crowded, unsanitary cities became breeding grounds for disease. Any disease able to infect humans could easily sweep through a city, sickening or killing many of its inhabitants. The rise of cities and surpluses of regional crops led to the development of an early type of “global trade.” Caravans of camels carried

“Civilizing” Disease  13 silk and rice from China and the Far East to the Near East and on to North Africa and Europe. Traders exchanged these goods for wheat, gold, and other valuables, and the camels lugged them back to Asia. Along with spices, silks, and other products, long-distance trade transported diseases from one part of the world to the other. Diseases that had once been limited to one region were carried to parts of the world where they were previously unknown. These new diseases devastated entire populations. Wars also spread disease. As the human population grew, limited agricultural technology could not keep up with the growing demand for food. Wars of conquest were frequently triggered by one people’s need for more land to grow more food. Armies that marched to faraway lands with a view to conquering them often returned home carrying new diseases they had picked up on distant battlefields. Epidemics that wiped out large populations have occurred for thousands of years. The most frequent and widespread epidemics were caused by smallpox, measles, and bubonic plague.

Smallpox and Measles Smallpox is a truly horrific and deadly disease that is believed to have evolved from the less lethal cowpox. Over time, the cowpox carried by farmers’ cows changed into smallpox, a far more virulent disease that specializes in infecting humans. Measles is most likely a deadly human variation of distemper in dogs. Epidemics of both diseases devastated human populations in earlier times. Nearly 2,000 years before biblical times, Egypt and its pharaohs were felled by an epidemic that was almost certainly smallpox. A war between the Egyptians and the ancient Hittites carried the smallpox epidemic to the area that is now modern-day Turkey and Syria. Ancient Indian texts from 1,600 years ago describe an epidemic disease—very likely smallpox—that swept through India and killed many thousands of people. More of Alexander the Great’s soldiers were killed by a smallpox epidemic in India in 327 b.c. than died during the fighting there. From India, smallpox made its way to China, where, in 243 b.c., it spread throughout the nation, killing untold thousands of people. Smallpox epidemics occurred on and off in China for more than 400 years, in some places killing 50% or more of the population.

14  Germ Theory One of the worst plagues of ancient times struck Greece in 430 b.c., during the Peloponnesian War, when Athens was fighting Sparta. The Greek historian Thucydides described the horrific epidemic, which had started in Africa and was carried to Greece by trading ships from Egypt. At that time, Athens was at the height of its glory and power. When the disease (probably smallpox) reached Athens, it rampaged through the crowded city-state. Thucydides, who survived the disease, describes high fever, bleeding from the mouth, and a wracking cough. These symptoms were followed by painful sores that broke out all over the body. The sores became ulcers that were so agonizing that people could not bear any touch, even that of a mattress or clothing. Crazed by thirst, the afflicted staggered naked through the streets, seeking water. Many died in the streets, and corpses were everywhere. Most animals avoided the corpses, but those that feasted on the dead also soon died. The epidemic raged through southern Greece for four years, killing an estimated 25% of the population. A few hundred years later, the Roman Empire extended over much of Europe and North Africa. Controlling such a huge empire made it necessary to post legions of soldiers in “barbarian” lands far from Rome. When these soldiers returned to Rome, they brought new or foreign diseases with them. In the second century a.d., the Antonine plague left up to one-third of the Roman population dead. After that, about 200 smallpox epidemics periodically ravaged the Romans. The disease-wracked Romans, reeling from mass death and disruption, were easily conquered by “barbarian” invaders. Thus, the disease-weakened Roman Empire eventually collapsed. Of course, Roman soldiers posted throughout the empire also carried smallpox with them. Epidemics of smallpox and/or measles flared in most of Europe during the height of Roman power, as well as following the Roman collapse. Traders carried smallpox to Japan in the sixth century, and the disease afflicted that nation’s population for centuries. When the ferocious Huns rode out of Central Asia to conquer the Roman Empire, they, too, fell victim to smallpox, which some of them later carried home when they returned to Asia. As dreadful as these epidemics were, they pale in comparison with the effect smallpox had on the peoples of the New World. Native peoples of North, Central, and South America had no immunity,

“Civilizing” Disease  15 or inborn resistance, to diseases such as smallpox and measles. When the Spanish, Portuguese, and English explorers landed in the New World, they brought these diseases with them. Only one native person needed to be exposed to smallpox to infect an entire tribe. Lacking any innate defenses against smallpox, native peoples suffered a staggering death toll. It is estimated that between 90 and 112 million people died, including almost 90% of many native populations. This decimation of native populations led to the collapse of their cultures and societies and made conquest of their territory that much easier for the Europeans. (Note, however, that these early smallpox epidemics were not deliberately caused by the Europeans. That did not happen until the eighteenth century in North America, when smallpoxinfected blankets were sent to native peoples to weaken them.)

The Plague In general terms, a plague is any widespread, severe disease or epidemic. When people talk about the plague, they are referring to the bubonic plague, one of the most terrible and deadly diseases ever to afflict humankind. In this book, the word plague will refer to any severe epidemic, and the phrase the plague will refer to bubonic plague. Bubonic plague is very lethal because it is essentially a disease of animals, not humans, so people have little or no resistance to it. Bubonic plague is believed to have originated millions of years ago among rodents in the foothills of the Himalayas in Asia. From there, it spread to rodents residing in China, then on to the Middle East and North Africa. When it was confined to rats, the plague had little effect on people. Then, about 2,000 years ago, climate conditions changed, producing a bumper crop of grains that fed people but also attracted hungry rats. The rat population soared, and infected rats spread the disease throughout the exploding rodent population. Pretty soon, the plague was passed on to the Indian black rat, which by then was well adapted to living in crowded human settlements. The plague is passed from one infected rat to another via fleas that feed on the rats’ blood. When a flea-ridden host rat dies from the plague, its fleas hop off its carcass to look for another living host. Ordinary rats were host to fleas that did not bother humans. But black rats were host to fleas that also had a taste for human blood.

16  Germ Theory

Figure 1.2 A health care provider tends to a child’s smallpox rash in the Republic of Benin, West Africa, in the 1970s. Many famous historical figures also suffered from the disease, including Lakota Chief Sitting Bull, composers Wolfgang Amadeus Mozart and Ludwig van Beethoven, Soviet Communist leader Joseph Stalin, and U.S. presidents George Washington, Andrew Jackson, and Abraham Lincoln. After a large-scale vaccination campaign, the World Health Organization certified that smallpox had been eradicated by December 1979.

When black rats died of the plague, their fleas hopped onto humans. In the process of biting humans and then drinking human blood, the fleas transmitted the plague to people. At first, bubonic plague could only be transmitted to people by the rats’ fleas. It could not be transmitted from person to person. At this stage, people contracted only bubonic plague. But then a period of very cold weather caused the disease to change. The new form of the disease was no longer limited to the lymph nodes of an infected person but could also settle in the lungs. The lung-based form of the plague, called pneumonic plague, could be transmitted from an infected person to other people via coughing or sneezing, just like

“Civilizing” Disease  17 the common cold. Once the plague could be transmitted in both of these ways, it became an unstoppable, deadly force. Trade via ships was primarily responsible for spreading the plague, as virtually every ship that plied the seas was infested with rats. In every port, rats would scurry off the ship by running along mooring ropes, and rats on the shore would board the ship in the same way. Thus, European ships in Chinese ports were invaded by Chinese rats, which were carried to North Africa and Europe, where they debarked

The Horrors of Quarantine Though no one in medieval Europe had any real knowledge of contagion, or how disease spreads, the populace was understandably wary of any contact with a person who had the plague. This fear of contact led to the widespread practice of quarantine that, in plague time, was a fate worse than the plague itself. When one member of a family was stricken with the plague, city or town officials would round up all the other family members. Every family member was forced into their house with their sick, dying relative. Then the door to the house was barricaded or securely locked from the outside. The intent was to lock the disease in and keep it from getting out to infect others in the community. So great was the fear of the plague that even perfectly healthy children were locked into the “plague” house. Everyone in the plague house died. Some died from the plague, which they caught from their infected relative. Others died from thirst or starvation. Even if a family member never contracted the plague, he or she would be unable to get any food or water, for the door was never unlocked for any reason. Those imprisoned in a plague house might be heard begging and pleading for water or food, but everyone outside ignored them. No one would open a plague house door until the plague was long gone. Even then, plague houses were often burned with their doors still bolted shut rather than risk having the bubonic plague escape and possibly begin its killing spree again.

18  Germ Theory

Figure 1.3â•… With its high mortality rate (80% to 90% of those stricken died), the medieval bubonic plague could decimate a city within weeks. Outbreaks often inspired panic in large cities, as depicted in this image of a Roman city in the sixth century. As the dead lie in the street outside a temple, they are shunned by passersby, who are terrified of being infected.

and spread their deadly infection. The first verifiable epidemic of bubonic plague began in Egypt in a.d. 540. The disease spread down the Nile River and was carried by ship to Constantinople in today’s Turkey. It is estimated that half the affected population perished. Bubonic plague begins with a fever. After a day or two, lymph glands under the arms, in the neck, and other places on the body begin to swell. The fever gets worse, and the swellings, called buboes, grow fantastically large. Then they turn black. The buboes are extremely painful, and as the fever rises, the brain is affected and the sick person becomes disoriented or deranged. By the fifth day, the sufferer, mercifully, dies. About 60% of people who contracted bubonic

“Civilizing” Disease  19

Figure 1.4 This map traces the spread of the Black Death from the Mediterranean region north to England and Scandinavia in the years 1347 to 1352.

plague died of the disease. During cold weather, the disease struck most often as pneumonic plague. Infected people died coughing up and vomiting large quantities of blood. Their coughing ensured that the disease was passed on to others. Untreated pneumonic plague killed 95% of the people who contracted it. The most famous bubonic plague pandemic was the Black Death that wiped out about half of Europe’s population around

20  Germ Theory 1348. Again, the black rat was the culprit that transferred its infected fleas to humans. By the 1330s, the plague had already spread from Asia to the Middle East. Italian traders brought black rat stowaways on their ships returning from Central Asia. One by one, each Italian port at which the ships docked was soon ravaged by the plague. From Genoa to Venice, and from Italy to other Mediterranean countries, the plague broke out with a murderous vengeance. By the winter of 1347, bubonic plague was making its way inland from port cities. As cold weather settled over Europe, the disease adopted its pneumonic form, and the pestilence spread like wildfire. It sped westward to reach England in 1348 and eastward to Moscow. Plague sufferers were everywhere during these terrible years. In summer, buboes on infected people swelled to the size of oranges. The swellings spread all over the body and turned black. When purple spots also covered the skin, death was near. The pneumonic form of the plague that struck Europe at this time was so virulent that a person could get up in the morning feeling fine, be overwhelmed by the plague’s symptoms a few hours later, and be dead by sundown. As always, so many people died that there were few to bury the dead. Many dead were tossed onto the street and picked up whenever a “death cart” happened to pass by. Hundreds of corpses at a time were dumped into quickly covered mass graves. In the wake of the Black Death, 25 to 40 million people perished.

Other Disease Epidemics Smallpox, measles, and bubonic plague may have been the most devastating epidemics in history, but they were by no means the only ones. Typhus, cholera, typhoid, and yellow fever also took millions of lives in epidemics. Typhus, like the plague, originally arose from fleas that infect rats. One early form of typhus occasionally infected people, but it was not a serious or widespread threat. However, when people became crowded together in cities, typhus changed its form. The new form of typhus adapted to live in human head lice. Since head lice are easily transmitted from person to person, the new form of typhus became a ravaging and deadly epidemic disease. Typhus raged through ancient Greece and Rome, spread to the Near East and North Africa,

“Civilizing” Disease  21

Figure 1.5 Typhus is spread by lice infected with the bacteria Rickettsia prowazekii. The lice pick up the disease when they feed on bodies infected with the bacteria and then pass it on to people who come in contact with the infected lice’s feces.

and from there traveled to Spain and Europe. The disease’s name comes from the Greek typhos, meaning “haze” or “fog,” and it refers to the infected person’s disorientation. People with typhus also suffered high fever, rashes, swelling and darkening of the face, and then

22  Germ Theory a type of gangrene that rotted the fingers and toes of the living victim. In 1577, a single louse-ridden prisoner infected everyone in an English courtroom. They, in turn, launched a typhus epidemic that raged through the county, killing hundreds. Though it does not kill millions in one fell swoop as dramatically as bubonic plague does, typhus has killed more people than any other disease in history. Cholera is a disease that flourishes in water contaminated with sewage. Drinking, washing, or otherwise coming into contact with foul water can cause infection by cholera. Cholera’s origins are obscure. It may have been endemic to, or already existing in, India for thousands of years. Or it may have become a serious human disease only in the 1830s, when British officers in India began coming down with a strange, often fatal illness. Cholera is characterized by violent diarrhea and vomiting and severe dehydration (loss of water in the body). If not treated, it quickly leads to shock, collapse of blood circulation, and death. Between 20% and 40% of untreated victims die of the disease. Cholera pandemics traveled the world several times in the 1800s, killing millions. Typhoid is another waterborne disease transmitted to people through food. Typhoid may result when food is washed in or otherwise comes into contact with contaminated water. Yellow fever is an especially nasty illness transmitted to humans by some of the countless mites, ticks, bedbugs, and other creepy-crawlies that invite themselves into overcrowded human houses and settlements. After so many centuries of deadly epidemics, people were at their wit’s end about how to rid themselves of these lethal diseases. Unfortunately, until true scientific investigations became possible, people’s notions of what caused diseases were so off the mark that no one had a chance of curing them. People were equally clueless about how to treat disease, though they tried the best they could, given the faulty notions of disease prevalent in the centuries prior to the discovery of germs, the causes of disease.

The “Not So Good” Old Days

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oday, most people understand that disease is caused by germs. This knowledge is so basic that it seems that it must have been known for centuries. In fact, people had no knowledge of the connection between germs and disease until well into the nineteenth century. Before that time, people could only speculate about, or guess at, what caused disease. Prior to germ theory and the rise of scientific medicine, humans concocted what might seem to us today some pretty strange notions about what caused disease. Remember, though, that they developed their ideas without the benefit of scientific confirmation. They did the best they could with the limited and often faulty information they had.

The “Curse” of Ill Health For most people and for most of human history, good health was considered to be the natural order of things. So when a person became sick, it meant that the natural order was disturbed. People believed that something or someone had interfered with the natural order deliberately to make the afflicted person sick. In other words, lacking knowledge of any other way that disease might be caused, people in many societies saw disease as a kind of curse. They

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24  Germ Theory therefore tried to find out who or what had “cursed” the ill person to make him or her sick. In many preliterate societies, when a person got sick, the rest of the community attempted to find out who had put “the whammy” on that person. Sometimes a medicine man, or healer, was called in to ask the “spirits” who had done this terrible deed. The medicine man would chant and perform rituals to beg the spirits to reveal who had cursed the sick person with illness. Sometimes, the sick person would suspect that someone, an enemy, in the community had cursed him and caused his illness. Perhaps the sick person had had a fight or disagreement with another individual in the community. Perhaps the sick person knew of someone in the community who disliked him or her or who envied his or her possessions and who therefore caused the sickness as a form of revenge. Or it might be that the sick person had mistreated someone in the community, and that person placed a curse on him as punishment. Whatever the cause, the ill person and the medicine man would try to find out why the illness had occurred and who had initiated the curse. Once a culprit was identified, that person was usually asked to lift the curse so the ill person would get better. If there was a conflict between the sick person and this individual, the medicine man would negotiate with both parties to solve the problem. It was believed that once the problem was solved, the sick person would get better. Occasionally, the disease was blamed on a neighboring community, especially if the two communities did not get along or did not like each other. Then the outbreak of disease might lead to war between the communities. Blaming disease on a curse was not limited to ancient peoples. Through the seventeenth century, some Christian sects believed that witches who were in league with the devil could cause disease. Priests, monks, church officials, or other “righteous” religious folk would question—and sometimes even torture—the suspected witch. They did whatever they had to do to get the witch to admit that she was, in fact, a witch, was in contact with Satan, and had deliberately caused the illness. Too often, a woman or girl (witches were almost always female) was suspected of witchcraft simply because she was a bit rebellious or behaved slightly differently from the rest of the people in the community. Almost always, her tormentors

The “Not So Good” Old Days  25 forced a confession of witchcraft out of her, even if she was completely innocent. The confessed witch might be directed to ask Satan to leave the body of the sick person. If the person remained ill, the witch might pay with her life. Witches often met a hideous death: they were burned at the stake. If the witch was burned and the cursed person was still sick, priests might attempt to exorcise the demon inside his or her body that caused the illness. An exorcism is a ritual that is performed to force a so-called evil spirit or demon out of a sick (or “possessed”) person’s body. If that did not work, everyone simply assumed that the demon who caused the disease was just too powerful for humans to overcome.

Divine Displeasure Some societies believed that disease was the outward evidence of the anger of the gods. If a person got sick, it was because he or she had insulted a god or gods in some way. It was up to the sick individual or his or her family to figure out how the gods had been angered: What divine rule had the sick person broken? What had the ill person done that annoyed the gods? What had the sick person not done (what ritual had he or she not performed) that had made the gods want to punish him or her? Again, a medicine man or spiritual healer, often called a shaman, was called in to determine why the gods were angry and what could be done to appease them. The shaman performed rituals to contact the god or gods. Once he had made contact, he asked them to reveal what insult they had received from the sick person. Then he begged the god or gods to tell him what the sick person should do in order to get well. Sometimes the “cure” involved saying special prayers or performing certain rituals. At other times the person would not be cured until he or she had made a sacrifice of some sort to make the god or gods happy again. Whatever the cure was, in this belief system people brought on their own disease by their behavior. Disease was caused by a fault in the individual, by something the person did or did not do. In this view, a sick person was to blame for his or her own illness, which was the gods’ reminder that the person had strayed from divine will.

26  Germ Theory Blaming the victim was not an attitude held solely by ancient or preliterate people. It was, in fact, a widely held view in the Christian church through the Middle Ages. For hundreds of years, illness and epidemic swept across Christian Europe, killing hundreds of thousands of people. The church’s view was that it was usually the sinful behavior of the afflicted that caused them to become sick. Sickness was God’s punishment for wickedness. People who fell ill might

The Flagellants The Black Death was so terrifying and merciless that many medieval Christians thought it was the ultimate expression of God’s anger with the world. Many even believed that it heralded the end of days. Surely, most people believed, a scourge as horrible as the Black Death proved that humankind must be intensely wicked and sinful. What could people do to show God that they repented of their sins, that they were sorry for their wickedness and would mend their ways? During the years of the Black Death, some people banded together to wander from town to town to show citizens how they might be redeemed. The flagellants were groups of travelers who whipped themselves as they walked endlessly from place to place. The flagellants swung their knotted, leather whips over their shoulders as they walked until their backs were raw and flowing with blood. They wailed and screamed out to God to forgive their sins and take away the terrible plague. When flagellants passed through a town, the townsfolk were terrified at the sight of the half-naked religious fanatics dripping with blood. But citizens experienced other feelings, as well. Though most people were horrified at the sight of the flagellants, they also viewed them as extremely holy for the suffering they endured. Townspeople would fall to their knees and begin praying intensely to God for forgiveness whenever the flagellants passed by.

The “Not So Good” Old Days  27 be instructed to say many prayers or to cause themselves pain (by wearing a hair shirt, for example) in order to “purify” their souls. If they sincerely repented of their sins and tortured their sinful bodies into submission, then maybe God would have mercy on them and make them well. For illness was surely a visitation from God upon the wicked and upon those sinners who did not follow the rules of the Christian church.

Figure 2.1â•… This colored woodcut depicts flagellants at the time of the Black Death. Public flagellation began as a radical Christian movement, but the practice was later condemned by the Catholic Church as heretical, or a departure from accepted beliefs.

The flagellants reminded the people of their sinfulness and of the need to repent and live a more holy life. The flagellants were just one example of the Christian belief, popular at that time, that suffering brings redemption and makes one closer to God.

28  Germ Theory

Sacrifices and Herbs Treating disease was often a matter of exorcising demons, placating the gods, begging forgiveness for sins, or having a curse lifted. Sometimes, as in ancient Greece, Rome, and other ancient civilizations, animal (and occasionally human) sacrifices were prescribed to appease the gods and free the afflicted person or population from an illness. Still, there were other, more effective methods of treatment. Up until our modern era, there were many people who lived close to nature and who learned how to use native plants to treat disease. Herbal medicine was widely used in the Middle Ages and the Renaissance to treat a wide variety of diseases. Women were most often the herbalists, who would gather and prepare the necessary plants and plant parts that they used to treat various afflictions. Though the church often looked down on the practice of herbal medicine—and some women accused of witchcraft were only herbalists—knowledge of herbal medicine was fairly common among monks and in Christian monasteries. Monks recorded their knowledge in large, illustrated books called herbals. So accurate were many of these early herbal remedies that many are still used by herbal healers today. Herbal medicine has probably been practiced since early humans first walked the Earth. Studies of today’s preliterate societies from every corner of the globe have shown that all peoples have used the medicinal properties of the plants in their environment to treat and/or cure disease. For example, Native American peoples used the bark of the willow tree to treat fevers. Today we know that willow bark contains the active ingredient in aspirin. In fact, at least 25% of all the drugs that people use today have come from plants. Scientists often find out about the medicinal properties of these plants by asking native peoples about them.

The “Humourous” Theory of Disease The scientific method of experimentation did not develop until about the sixteenth century. Yet for nearly two thousand years before that, early scientists made careful observations of the human

The “Not So Good” Old Days  29

Figure 2.2â•… A page from an early British herbal medicine book depicts and names plants used for various treatments.

30  Germ Theory body in sickness and in health and attempted to formulate universal, scientific theories of disease.

Hippocrates Hippocrates was a respected physician in ancient Greece during the fifth century b.c. He carefully observed his surroundings and related them to outbreaks of disease. In his Airs, Waters, Places, Hippocrates named a whole host of environmental factors that influenced disease, including the wind and weather, the seasons, altitude, and (correctly) living in towns. He put special emphasis on the effect of swampy places and the “bad air,” or “miasmas,” they emitted as an important cause of disease. Foul, swampy water was also seen (wisely) as an agent of disease. Hippocrates formulated a theory of disease that remained the basis of medical practice for centuries. Hippocratic medicine was holistic in that it viewed health and disease in terms of the whole body. The foundation of Hippocrates’ concept is that health and disease reflect the balance among substances in the body. The substances in question were four “elements” (fire, water, air, and earth) and four fluids, or humours (blood—hot and wet; phlegm—cold and wet; yellow bile—hot and dry; and black bile—cold and dry). The “qualities” (wet, dry, hot, and cold) were added to this mix later, as were “fluxes,” or movements of humours around the body. According to Hippocrates, if the four elements and humours of the body were in balance, then a person was healthy. Any imbalance among the humours resulted in disease. Bile and phlegm were believed to be especially important in causing disease; their imbalance was believed to cause summer diarrhea and winter colds. In this view, the natural state of a human person was a fine equilibrium of all the body’s humours. Disease was the result of a disequilibrium among the humours. That is, a person became sick when the body developed too much of one particular humour, which caused an imbalance with the other humours, or when one humour became peccant, or corrupted in some way. If, for example, a physician diagnosed a patient as having an excess of phlegm, the cure involved ridding the body of this excess phlegm. If symptoms of a disease moved from one part of the body to another, physicians stated that it was because the excess phlegm (or other humour) had shifted within the body.

The “Not So Good” Old Days  31 Hippocrates’ ideas were advanced and given a more scientific veneer by the “father of medicine,” Galen of Pergamum. Galen, who lived in Greece in the first century a.d., combined the ideas of Hippocrates with the logic of the philosophers Plato and Aristotle. He wrote widely about his medical ideas, many of which were based on his own extensive experience as a healer and his skill as an acute observer and diagnoser of disease. Though Galen taught that the practice of medicine should be based on careful observation and logical reasoning, he did not question the humoural theory of disease, which guided medical practice for the next 1,700 years.

Humour Through the Ages As the humoural theory of disease was adopted by each generation of doctors, it was expanded to include more factors that affected health. Thus, between the sixteenth and the eighteenth centuries, the health of the human body was believed to rely also upon the four ages of man, the four seasons, the four mental states or temperaments (sanguine, phlegmatic, bilious, and melancholic), and other “quadrilateral” factors in addition to humours and qualities. During this period, a good physician had to take all these factors into account when making a diagnosis and deciding on a treatment. The doctor’s job was to decide which of the many factors in the body was out of balance and to prescribe a treatment that would restore balance. The humoural theory of disease reinforced the notion that there was no such thing as a single cause for a specific disease. In fact, physicians back then questioned whether specific diseases even existed. A patient’s particular complaint depended on the humours affected and where they had accumulated in the body. Doctors could, of course, tell the difference between a chest cold and bubonic plague. Yet they could not say with certainty that, as humours moved around the body, one disease would not suddenly turn into the other. With all these complicated factors to take into account, it is no wonder that doctors assigned different causes to the same disease in different people, or that they determined that the onset of different diseases arose from the same cause. For example, two individuals exposed to the same “miasma” might become ill. But one person might be diagnosed as having come down with cholera, while the other

32  Germ Theory could be diagnosed as having typhoid. The different diagnoses arose because doctors based their determination on individual history and humoural characteristics, not on the disease symptoms themselves. The emphasis doctors placed on a patient’s particular humours and other factors reinforced the class biases of the time. An instructive example of this bias is described in The Discovery of the Germ (2002). In 1774, a Dr. Buchan wrote a book on disease in which he advised his fellow physicians to diagnose and treat patients according to their station in life. In treating scurvy, for example, a poor laborer would be told that his symptoms arose from his weak and degraded humours, his poor clothing, poor diet, and overall unhygienic lifestyle. A wealthy aristocrat who had scurvy with exactly the same symptoms would be told by the physician that the symptoms arose from overly robust humours, a diet consisting of too much rich food, a lack of exercise, and sitting too long indoors on soft cushions. One’s class, not one’s symptoms, determined one’s prescription. Strong class differences also affected how physicians “examined” patients. In the seventeenth and eighteenth centuries, physicians were considered servants of the upper classes. Doctors might be respected for their skill, but they were still servants (and, thus, of a lower class) who could not take liberties with a “client,” or patient. A real physical examination of an ailing aristocrat was out of the question, as touching the high-class body would have been considered an offensive intrusion. Examinations were therefore limited to the patient’s face and pulse. Observing, smelling, and even tasting the patient’s urine and feces (as indicators of what was going on with internal humours) were a widely used and unembarrassing part of the doctor’s visit. On the opposite end of the spectrum, doctors considered themselves of a much higher class than the working poor or peasants. As such, they would not “contaminate” themselves by touching this class of patient any more than was absolutely necessary. In any case, physicians’ poor knowledge of anatomy would probably have made more intimate examinations pointless.

Cures Worse than the Disease It is only logical that if an excess of one particular humour causes an illness, then removing that humour from the body will cure the

The “Not So Good” Old Days  33 disease. And so, when the humoural theory of disease held sway, patients were routinely purged of a humour the physician thought was causing the problem.

Surgeons Versus Doctors Before the advent of modern medicine, physicians were supposedly those practitioners trained in the diagnosis and treatment of disease. As “trained” healers, doctors got some degree of respect. However, in past centuries, doctors were generally not surgeons and did not perform operations. Back then, surgery was performed by barbers. Barber-surgeons had no training in anatomy or surgery aside from their apprenticeship and experience. Despite this shortcoming, barber-surgeons pulled teeth, cut out tumors, lanced boils, removed cataracts, and generally wielded the knife whenever it was needed or requested. Barber-surgeons also used special instruments for trepanning, or drilling a hole through the skull, to let the “bad humours” that caused headaches out of the brain. Of course, in those bygone days there were no anesthetics, or painkillers, so surgery was truly an ordeal for the patient. There was also no notion of the need to use clean knives and other instruments during surgery, so infection (and death) often followed surgery as surely as night follows day. Doctors did sometimes wield the knife. When a rich woman was having difficulty delivering a baby, for example, an attending doctor might perform a cesarean section (cutting open the abdomen) to remove the infant. Both barber-surgeons and doctors were sometimes employed by the army to tend wounded soldiers. A seriously wounded limb was amputated (sawed off). Even if a lightly wounded limb was at first bandaged, it usually became infected and had to be amputated later on. Amputations, like all other procedures, were performed without benefit of anesthetics.

34  Germ Theory Purging the body of a humour took many forms. Bloodletting was a common treatment, as many doctors believed the blood caused fever and also carried the peccant humour that caused disease. The more serious the disease, the more blood was removed from the body. Bloodletting usually involved using a knife to make a cut in a vein in the arm. The blood flowed into a basin. The adult human body contains about 11 pints (5.2 liters) of blood. Doctors frequently bled half that amount from a patient. Doctors believed that the peccant blood would be replaced with healthy blood. Unsurprisingly, many patients died from weakness and blood loss. When King Louis XV of France became ill with smallpox, his physicians bled him until he lost consciousness. Four large basins of blood were removed from the royal body. The king died about a week later. Sometimes bloodletting was accomplished by applying leeches to the body. Leeches are wormlike parasites that get all their nourishment by sucking the blood of a host animal. The body of an ill person would be festooned with dangling, bloodsucking leeches. The patient was required to sit patiently watching as the leeches’ bodies became engorged with his or her own blood. When one set of leeches was “full,” they were removed and replaced with a hungrier group of parasites. Bloodletting was used to treat fevers and many other symptoms. It was also prescribed for hot-headed or bad-tempered people, who were believed to have too much hot blood in their system. Bloodletting was sometimes accompanied by a procedure called cupping, which comes from ancient Chinese medicine. In cupping, a small, bell-shaped glass was heated until it was very hot. Then the rim of the burning-hot glass was pressed into the skin. When used with bloodletting, the skin was first cut. As the air in the cup cooled, a vacuum began to form, and the blood was drawn out of the body. Cupping was also used without bloodletting to draw “bad” humours out through the skin. Cupping was usually done on the patient’s back, which retained the round, red marks of the treatment for days afterward. Of course, peccant blood was not the only humour that needed to be freed from the sick person’s body. An overabundance of phlegm was frequently identified as the cause of disease. Physicians prescribed drinking potions containing mercury, which caused the mouth and nose to stream with phlegm for hours at a time. Today

The “Not So Good” Old Days  35

Figure 2.3â•… In this image called “The Luttrell Psalter” (c. the early 1300s), a physician is shown bleeding a patient. As the physician squeezes the incision, blood spurts into a bowl held by a reluctantlooking patient.

36  Germ Theory

FIgure 2.4â•… As a leech sucks blood, it releases an anesthetic that numbs the host, so the presence of the leech is hardly felt. A leech uses both mucous and muscle-imposed suction to stay attached to a host.

we know that mercury is a poison, but back then the physician was just doing the “right thing” to help restore humoural balance. Purging commonly involved inducing vomiting or diarrhea. Here, again, what we know today to be poisonous substances were prescribed for patients. These toxic cocktails were ingested by the patient, who would then be convulsed by hours of vomiting in order to purge the ill humours from his stomach. Patients given poisonous potions suffered days of intense cramps and violent diarrhea to evacuate excess humors from the nether part of the body. Sometimes the “purifying” solution was administered through an enema. France’s King Louis XIV is reported to have suffered through more than 2,000 enemas during his life; the enemas were intended to maintain his health, not to treat any ailment. Amazingly, he lived to be 72. It is entirely likely that the father of our nation, George Washington, was killed by his physicians. In 1799, Washington came down with a sore throat and a respiratory infection. He was so highly esteemed by everyone that his physicians decided to fight his

The “Not So Good” Old Days  37 infection as aggressively as possible. As described in Killer Germs, Washington was given a poisonous compound of mercury, both by mouth and injection. He was forced to ingest a poisonous white salt that made him perspire and vomit. Caustic poultices were applied to his body that made his skin blister. He was forced to inhale vinegar vapors that burned his lungs and raised blisters in his throat, to counteract the blisters of infection. As a final affront, more than five pints of blood were drained from his body. .€.€. He died shortly afterward—perhaps as much from the cure as from the illness. It is little wonder that in centuries past, people lived in mortal terror of doctors. Many people, even the rich, preferred to be left alone to die in peace rather than be subjected to the torments of medical treatment.

A Tiny Universe Revealed

S

eventeenth-century Holland was the land of windmills, tulips, and wooden shoes that youngsters read about in children’s stories. Most people living in Holland at that time led fairly routine and ordinary lives. No one seemed more ordinary than Antony van Leeuwenhoek (LEE-ven-hook), who was born in Delft, Holland, in 1632. At 16, Leeuwenhoek left school to become an apprentice in a dry goods shop. He learned all there was to know about buying and selling fabrics and, six years later, quit to set up a dry goods shop of his own. He married, had children, and earned his living selling bolts of cloth to penny-pinching housewives. He earned extra money as a janitor, cleaning Delft’s city hall. Who could have imagined that this simple and thoroughly “ordinary” man would soon revolutionize human understanding of the world and, later, of disease. Leeuwenhoek worked long hours at his two jobs, but he still made time to pursue his hobby—actually, his obsession. Leeuwenhoek was intensely fascinated by lenses. By that time, people had created glass lenses, such as simple telescopes, that allowed people to see distant objects more clearly. Yet Leeuwenhoek was obsessed with making a lens that would let him see very small things that the unaided human eye could not see clearly. For example, he wanted to get a clear, close-up view of fleas, dog hair, skin, and the flesh from whale meat. Leeuwenhoek spent countless hours in his tiny

38

A Tiny Universe Revealed  39 workroom grinding glass into finer and finer lenses. He was nothing if not a perfectionist. Leeuwenhoek was not satisfied with making the best lenses of his time; he wanted to make lenses that were better than any that had ever been made before. He worked and worked at his glass grinding, trying to make the finest lens possible. Often, Leeuwenhoek worked half the night, patiently shaping his lenses until they were as perfect as he could make them. Neighbors who saw his workshop lights burning in the wee hours thought he was “a bit cracked.” “Who does this uneducated shopkeeper think he is, working all hours to make his tiny, newfangled lenses?” they asked themselves. Leeuwenhoek ignored them. He continued to shape and polish his perfect lenses, which were no more than one-eighth inch (3 millimeters, or mm) across. He mounted his small lenses in pieces of metal and peered through them at anything he could find worth examining. Leeuwenhoek had made the first microscope. He used that early microscope to examine the legs of a louse, the muscle of an ox, the eye of a fly, the hair of a dog, and anything else that he could get his hands on. As the amazing details of each object leaped into view under his lens, Leeuwenhoek was thrilled and astonished, like a child discovering a new toy. Leeuwenhoek continued to make finer and finer lenses. Then, in 1683, perhaps lacking anything else to look at, Leeuwenhoek took a drop of water from a rain barrel and placed it under his lens. He was struck dumb by what he saw. There, in a single drop of water, were dozens of what looked like tiny, swimming creatures. These creatures, he knew, were thousands of times smaller than even the smallest flea or louse. He wondered: What in the world could they be? If Leeuwenhoek had seemed obsessed before, now he was on fire. He put every substance he could find under his microscope. Leeuwenhoek even invented a type of dental floss, which he used to remove the “stuff” between his “usually very clean” teeth. His microscope revealed that his teeth were swarming with countless “little animals,” which Leeuwenhoek called “animalcules.” The otherwise invisible critters seemed to have all the qualities of animals: They swam and tumbled around, waved long, threadlike legs, and ate things in their environment. There were many shapes and sizes of animalcules, so there must be many different types of these “wretched beasties,” as he also called them. Leeuwenhoek soon discovered that if he let a

40  Germ Theory

Figure 3.1â•… A historical engraving shows an early microscope created by Anton van Leeuwenhoek. His microscopes used a single lens (mounted here in a flat sheet in the upper left), which he ground to nearperfection himself. A test tube rests in the middle.

dish of rainwater stand for a few days, the number of little “beasties” in the water increased dramatically. However, if he covered the dish tightly for a few days and then examined the water, it did not have lots more “beasties.” Leeuwenhoek concluded that the “beasties” could not have entered the water from the sky. So where did they come from? Leeuwenhoek’s discovery was revolutionary because it raised two very thorny and complex issues. First, Leeuwenhoek’s work showed that there were far more creatures on Earth than people had ever imagined. In fact, there were obviously far more animalcules in one person’s teeth than there were people on the planet. Second, where did these minute creatures come from? Most Europeans of that time were devout Christians who believed that God created all living things. Further, the Bible taught that every living thing was born from its two parents. How, then, could rainwater with only a few round animalcules end up a few days later having loads of little “beasties” shaped like bent twigs, rods, corkscrews, and a variety of other weird shapes?

A Tiny Universe Revealed  41

Figure 3.2â•… This engraving of animalcules, or microscopic organisms, was created after Anton van Leeuwenhoek’s death. It includes sperm (images 29 and 30) as well as magnified drawings of sperm from a warm cadaver (images 31 to 40) that were drawn by Leeuwenhoek.

Leeuwenhoek’s love of hot, strong coffee helped confirm that the “beasties” he saw under his microscope were, in fact, living animals. One day, he scraped some film from his teeth right after he had drunk a boiling hot cup of coffee. When he looked at the sample through his lens, he could not see any swimming animalcules,

42  Germ Theory but he thought he saw the bodies of dead “beasties.” Leeuwenhoek conducted an experiment. He put some rainwater under his microscope and, sure enough, he saw swarms of animalcules. Then he heated the water until it was very hot and looked at it again. His lens revealed that all the “beasties” that had been alive in the cool water were now dead. Obviously, the “beasties” had to be living animals, for only living things can die. In 1683, Leeuwenhoek wrote to the Royal Society (of science) in London, describing what he had discovered. Some members of the society ridiculed Leeuwenhoek’s notions, but others were impressed by his methods and his findings. For years afterward, Leeuwenhoek would share his discoveries with the society, and they would write to him for clarification and more information. One thing they were especially eager to learn was how he had made his wonderful lenses. Curiously, Leeuwenhoek absolutely refused to share his lens-making methods with anyone else. It was only after his death, at age 91, that other scientists had the opportunity to examine the extraordinary lenses Leeuwenhoek had made to reveal the world of animalcules, or what came to be called microbes.

Spontaneous Generation Leeuwenhoek observed many things under his microscope, including the guts of animals. Occasionally, after examining these innards, Leeuwenhoek reported suffering a bout of “looseness” (diarrhea). Yet he did not connect his illness with the microbes he was handling. Why should he? Though he had discovered microbes, he had never shown that they were agents of disease. So Leeuwenhoek’s discovery did not immediately overturn the humoural theory of disease. However, it did lead to a fierce debate about the origin of living things. For centuries, people had noticed that rotten meat soon swarmed with maggots. Not knowing any better, people believed that the maggots formed spontaneously from the meat. Similarly, they “knew” that insects were created spontaneously from standing water, that rats arose spontaneously from dirty rags or piles of rotting grain, and that frogs arose spontaneously from the mud at the bottom of a pond. Four hundred years ago, people even swapped “recipes” for making mice and other critters. Spontaneous generation refers to

A Tiny Universe Revealed  43 the belief that life can arise from nonliving material through some unexplainable change in the material. For example, if meat was left out for too long and began to rot, the material that made up the meat would “miraculously” begin to produce maggots. This concept was even supported by the vast majority of scientists. Leeuwenhoek’s “wretched beasties” were believed to arise spontaneously from the water or other material in which they occurred. There were some scientists, however, who thought this notion was totally untrue. In 1688, Francesco Redi, an Italian scientist, thought he had disproved the notion of spontaneous generation. Redi put a hunk of meat in one container and left it exposed to the air. He put another chunk of meat in another container and covered it with gauze. He left the two containers side by side for several days, until the meat began to rot. Redi watched the containers and noted that flies landed on the meat in the uncovered container. As Redi expected, the exposed meat was soon crawling with maggots. The gauze-covered meat, however, had no maggots, even though it was just as rotten. Redi announced that he had proved that maggots did not arise spontaneously from rotting meat, but instead grew from the eggs flies had laid in the meat. (Maggots are, in fact, fly larvae.) Because the gauze had kept the flies off the meat in the covered container, that meat contained no maggots. Alas, Redi’s gauze-covered container did little to prevent microbes from forming on meat. So, after Leeuwenhoek had discovered microbes, the notion of spontaneous generation gained new popularity. Some scientists may have accepted that maggots come from flies, but where did all the microbes scientists found on rotting meat come from? Using improved microscopes, scientists observed that as meat rotted, it became increasingly infested with microbes of every imaginable sort. No flies, or anything else for that matter, were observed to land on the meat—even meat that was covered with gauze. Some scientists recalled Leeuwenhoek’s experience with hot coffee and the experiment in which he heated and killed his little “beasties.” Thus, scientists began testing spontaneous generation using beef or mutton (sheep) broth, a liquid that would attract microbes (because it was made out of meat) but that also could be heated or boiled. Experimenters heated broth until they thought its microbes were killed. Then they quickly sealed the container of broth to keep air away from it. They waited several days before examining the broth to look for microbes. Time and again, no microbes were found. This,

44  Germ Theory

Figure 3.3 Francesco Redi’s experiment disproved spontaneous generation. In it, he used three different jars to show that flies could not spontaneously arise from meat. The lid on one jar prevented flies from laying their eggs on the meat, and so no maggots (which would turn into flies) appeared. The open jar and the jar with a gauze covering allowed for eggs to be laid on the meat or gauze, respectively.

they announced, was proof that spontaneous generation was a false theory. Unfortunately, supporters of spontaneous generation were not convinced. The problem was that it is very difficult, if not impossible, to prove a negative. That means that even if the scientists had seen no microbes after performing 1,000 experiments, they could not prove that microbes would not be present in the 1,001st experiment. It was a dilemma. The controversy raged for decades. In 1748, John Needham, a British priest and scientist, conducted an experiment that he thought proved the truth of spontaneous generation. Needham heated some mutton broth for a while, sealed the container with a cork plug, and waited. After a few days, Needham examined the broth under a microscope and found countless microbes swarming in it. Aha! he crowed. The container was sealed, but still microbes arose in it. This proves spontaneous generation is a fact!

A Tiny Universe Revealed  45 Needham’s triumph was short-lived. A few years later, a fiercely determined, no-nonsense Italian scientist-priest, Lazzaro Spallanzani, showed the world why Needham was wrong. Spallanzani repeated Needham’s experiment, but this time he heated the mutton broth for quite a bit longer than Needham had. He also used a much better seal on the container holding the broth. After several days, Spallanzani found zero microbes in his broth. He had shown that Needham’s findings were wrong because he had not heated his broth sufficiently to kill all the microbes; some microbes were obviously able to survive mild heating. He also proved that totally sealing the container of broth kept microbes out of it. From this latter finding, Spallanzani concluded that microbes were in the air and got into substances that were exposed to the air. Needham was not a man to give up easily. He absolutely refused to accept that microbes enter substances from the air. Instead, Needham proposed that microbes arose in substances via what he called a “vegetative force,” a type of vital life-energy that was found in every living thing. Needham claimed that the vegetative force was the origin of life on Earth. Needham claimed that Spallanzani had destroyed the vegetative force by heating his experimental broth too much.

A Problem for the Church The church taught that all life was made by the Creator. Therefore, the notion that life could arise spontaneously was a form of heresy, or serious breaking of church law. John Needham was a priest as well as a scientist. In order to reconcile spontaneous generation with divine creation, Needham stated that it was the Creator who had set down the physical laws that enable spontaneous generation to occur. Needham reinforced his argument’s acceptability to the church with his notion of the “vegetative force,” a vital life force that God put into all living things. Therefore, the Creator planned and was the driving force behind both spontaneous generation and the vegetative force. In this way, Needham helped the church accept these concepts.

46  Germ Theory Spallanzani hooted and devised an experiment to show that the vegetative force was not possible, just like spontaneous generation. Spallanzani put seeds in each of several glass flasks. To some flasks he added water, and then he boiled them for a long time. He actually baked the other flasks until the seeds were no more than lumps of soot. Spallanzani stoppered all the flasks with cork, just as Needham had done. After a few days, Spallanzani uncorked each flask and examined its contents for the presence of microbes. Each flask was swarming with “little beasties.” Spallanzani had shown that heat could not destroy the “vegetative force” because it did not exist. He also showed that there were microbes in the boiled and baked flasks because they had come from the air. The cork stoppers allowed air to enter the flasks. Air contains microbes. It was as simple as that. There was no need to believe in spontaneous generation, because these strange microscopic animalcules filled the air.

Spallanzani’s Experiment Lazzaro Spallanzani put broth in each flask he used in his experiment. Then he did what no other experimenter had done before. He held the narrow end of each flask in a flame until the glass became soft. He pressed the glass together to form a totally air-tight seal. Then he boiled some flasks for an hour and some flasks for only a few minutes. As a control, Spallanzani made a duplicate set of flasks that he plugged with corks. When he was done, he put all his flasks on a shelf and went on vacation for a few days. When he returned, Spallanzani examined the contents of each flask under a microscope. The glass-sealed flasks that had been boiled for an hour contained no microbes. Those that had been boiled for a few minutes contained a few microbes. Obviously, these microbes had been able to survive heating. All the flasks stoppered with cork were swarming with microbes, even if they had been boiled for an hour. Spallanzani was ecstatic. His experiment showed that the microbes had entered the flasks from air that seeped through the cork stoppers. So much for Needham.

A Tiny Universe Revealed  47

Figure 3.4â•… This colored transmission electron micrograph shows a microbe reproducing by splitting in two. This means of asexual reproduction that leads to the production of genetically identical offspring, or clones, is called binary fission.

Spallanzani’s experiments were impressive, but still some scientists supported Needham’s notions of spontaneous generation and the vegetative force. Yet Spallanzani had observed something about which no other scientist had speculated. During his years of peering into a microscope, Spallanzani sometimes thought he saw two microbes stuck together. In a letter to a colleague, quoted in the book The Microbe Hunters (1926), Spallanzani wrote: “When you see two individuals of any animal kind united, you naturally think they are engaged in reproducing themselves. But are they?” Spallanzani wondered if the microbes were uniting to multiply, or if, as sometimes seemed the case, they split in two in order to reproduce. Some of his colleagues thought Spallanzani was crazy, but he persisted. He decided that if he could get one microbe all by itself, he could watch it to see if it reproduced by splitting. Spallanzani put a water drop with microbes under his microscope. Then, using a brush consisting of one thin hair, he carefully coaxed a single microbe off by itself. Spallanzani peered at the single microbe until it began to split in two. The Italian scientist was the first person to witness binary fission, or the reproductive splitting of microbes.

Contagion Catapulting Corpses: The First Biological Warfare

B

y the mid-1300s, bubonic plague had spread throughout Europe and was wending its way eastward toward Asia. Within a few years, traders had brought the bubonic plague to the outskirts of Kaffa, on the shores of the Black Sea. In the Middle Ages, most cities were surrounded by high, thick walls to protect them from invaders. By 1346, Kaffa had been under siege for three years by a large army of Tatars from Central Asia. The Tatar army was unable to breach the city walls, so the soldiers began a siege of the city. They camped outside the city walls and prevented any food or other goods from entering. In this way, they hoped to break the spirit of Kaffa’s citizens and take the city. When bubonic plague struck the soldiers of the Tatar army, some citizens inside Kaffa’s walls took heart, hoping that the pestilence would destroy the army and the siege would end. In one way, the people of Kaffa got their wish. Mountains of Tatar corpses lay just outside the city’s walls. The leader of the Tatar army did plan to withdraw his troops after the majority of his soldiers died. Yet he was so angry about his failure to conquer Kaffa that he devised a terrible vengeance to punish the people of the city. Before his troops departed from the city, the Tatar leader had a catapult built. He used the catapult to hurl the corpses of his dead soldiers over the wall

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Contagion  49 and into the city. Then he and his army left. The terrified citizens of Kaffa threw all the plague-infested corpses over the wall and out of the city. But the damage was done—bubonic plague had entered Kaffa. Though the Tatar warriors had not actually conquered the city of Kaffa, they got their revenge by using the plague to kill most of its inhabitants.

Clues to Contagion It is almost certain that the Tatars, like everyone else, had no concrete notion of contagion. Contagion is the transmission of disease by direct or indirect contact with an infected person or with the microbe that causes the disease. Of course, medieval people had no idea that a microbe caused bubonic plague. However, the Tatars used their suspicion that contact with a disease-ridden corpse would transmit the plague and kill the brave citizens of Kaffa. The humoural theory of disease discouraged the notion that diseases were contagious. According to the theory, when a person became ill, it was because of an imbalance among the humours in that individual’s body. This imbalance was an internal condition that could not be passed on to someone else. Although doctors naturally noted that some diseases seemed to spread throughout a population, producing similar symptoms in everyone affected, their training and the medical theories of the time discouraged them from attributing the spread of disease to contagion. The quarantining of families whose members were suffering from bubonic plague was, however, evidence that some people recognized that diseases might be spread from one person to another via contact with an infected individual. Certainly, the explorers of the New World who witnessed the spread of European diseases among native peoples must have had an inkling that the ailments were transmitted from one person to another. From these experiences, by the eighteenth century, most physicians accepted the fact that bubonic plague, smallpox, and measles were contagious and could be transmitted from person to person. Yet until well into the nineteenth century, medical science remained highly skeptical of contagion’s role in the spread of most epidemic diseases, such as

50  Germ Theory cholera, typhus, and diphtheria. At most, physicians might admit that certain diseases might be transmitted by a mysterious “contagious effluvia” that seemed to spread via personal contact.

Cause of Death: Hospitals It was highly likely that a person who was hospitalized during the eighteenth century would end up dying of what was then called “hospitalism.” This was the term the medical profession used to describe death from infection or epidemic that swept through a hospital. Hospitals of the time had such an awful reputation that most people preferred a quiet death at home to the horrors of hospital treatment. These were the days before people understood the most basic facts about hygiene and disease. Physicians did not wash their hands after contact with dead or diseased patients or after doing surgery. Piles of infected bed linens and blood-soaked bandages lay on the floor in wards and in corridors. It was fairly common for two or three patients to lie together in the same bed, even if one or more of them

Dr. Cullen’s Conclusions In 1800, Scottish physician William Cullen wrote a book in which he classified different types of diseases. He paid special attention to those ailments thought to be transmitted by “contagious effluvia.” Cullen described these diseases in detail, but he went a step further in his analysis. Cullen wrote extensively of his observation that diseases that are transmitted by “contagious effluvia” always seem to produce the same symptoms in every person who contracts them. Though Cullen did not and could not attribute this observation to the fact that each disease is caused by a specific germ, his insightful writings provided that leap of creative thought that eventually led to germ theory—that one type of germ causes one specific disease. After Cullen, the notion that “something” was passed from person to person that always produced the same disease was more openly discussed in the medical literature.

Contagion  51

Figure 4.1â•… This image shows the poor conditions at New York City’s Bellevue Hospital in 1860. That year, The New York Times, among other publications, ran stories about the “vile, gregarious” rodents who roamed the hospital even during the day and were documented to have bitten sleeping patients.

had an infectious disease and the third suffered only from a broken bone. To say that disease was rampant in these conditions is an understatement. The hospital was a domain of death, not healing. Incredibly, despite the evidence before their eyes, doctors of the time stubbornly held on to their humoural notions of disease. They refused to consider that diseases were infectious. When large numbers of hospital patients died from a hospitalism-type infection, physicians attributed their demise to poor ventilation, or “bad air,” rather than contagion. Filth was also blamed, but how it caused disease was unknown. It was also not thought important enough to energize hospital staff to keep the place clean.

Childbed Fever The death of a mother in childbirth is a tragedy for her, for her newborn baby, and for her family. Doctors were aware of the terrible toll death from childbirth had on all concerned, but they did little to

52  Germ Theory explore why so many women died from what was then called “childbed fever.” A Scottish physician, Alexander Gordon, was one of the first doctors to suggest that childbed fever might be contagious. From 1789 to 1792, his native region of Scotland was afflicted with what seemed to him to be an epidemic of childbed fever. Gordon began to study and analyze all the cases of childbed fever he could uncover. His analysis revealed that these cases shared one thing: In virtually every case, the doctor or midwife had first attended a woman who died of childbed fever. The doctor or midwife had then immediately gone to deliver another baby. Soon, this mother died of childbed fever, too. Gordon concluded that the midwives and doctors were transmitting a contagious disease from one woman to the other. Though Gordon’s conclusions were correct, his suggestion that those attending births should wash their hands afterward fell on deaf ears. The concept of contagion was still considered too radical for doctors or midwives to take seriously. One Dr. Rutter of Philadelphia learned Gordon’s lesson the hard way. In a single year, every woman whose baby he helped deliver died of childbed fever. Rutter was smart enough to realize that this could not be a coincidence. Nor could so many cases of childbed fever be blamed on “miasmas.” Rutter admitted that something he did must have transmitted the disease from one woman to another. Rutter did everything he could think of: He changed his clothes, he quarantined himself for a while after a delivery, and he even shaved his beard. Still, his patients died. One thing Rutter did not do was wash his hands thoroughly after each delivery. Meanwhile, similar dreadful outbreaks of childbed fever were rampaging through the Vienna General Hospital in Austria. A leading doctor at the hospital, Ignaz Semmelweis, launched an investigation. As luck would have it, Vienna General had two separate maternity wards. Semmelweis’s investigations showed that one ward had a death rate from childbed fever of more than 29%. The other ward had only a 3% death rate from the disease. What accounted for the difference? Studying the procedures of the doctors and midwives in both wards led Semmelweis to the answer. In the “high-death” ward, doctors often went straight to a delivery from the hospital’s autopsy room, where they dissected the bodies of patients who had died of infection. In contrast, the midwives working in the “low-death” ward

Contagion  53

Florence Nightingale Florence Nightingale was a spirited young woman who yearned to be free from the stifling Victorian life of her well-to-do home. She decided to become a nurse, and she went to Paris to study in 1851. It seems that, at that time, nurses were taught the importance of hospital hygiene, even if physicians were not. After reading in the newspaper about the huge number of casualties among soldiers fighting the Crimean War, Nightingale and 38 fellow nurses decided to go to the war zone and set up a hospital to care for the wounded. Within six months, the nurses had built hospital barracks for treating injured soldiers. Under Nightingale’s direction, the hospital areas were kept scrupulously clean. Death from infected wounds fell from 40% to 2% in less than a year. Florence Nightingale, popularly known as “the lady with the Figure 4.2â•… Late in her life, lamp” because of her Florence Nightingale made kind and tireless tenda comprehensive statistical ing of the wounded solstudy of rural life in India and diers, became famous served as a leading figure in the push to improve public for her hygienic methhealth care there. In 1859, ods and her success. she succeeded in her call for a Soon, people were conRoyal Commission to oversee tributing large amounts public health. (continues)

54  Germ Theory (continued) of money to a fund she had set up to start nursing schools. Nightingale is credited not only with raising nursing to a respected profession but also for her courage and commitment to hospital hygiene. Though Nightingale questioned the scientific validity of contagion, her firm belief in cleanliness, in keeping wounds clean, and in disinfecting hospital wards did eventually advance the concept that some diseases are contagious.

did not do autopsies, so they did not transfer deadly germs from the dead to the living. In 1847, Semmelweis made a new rule for his hospital: Everyone must wash their hands in a chlorinated (disinfecting) solution before delivering a baby. Most doctors at the hospital were furious and fiercely resisted the new rule. Not only did they not want to wash their hands in a smelly chemical, but they were also insulted at the idea that they— the healers of the sick—could be bringers of disease and death. Yet despite initial resistance by doctors, the new rule was put in place and dramatically lowered the death rate for childbed fever. Unfortunately, the doctors still resented Semmelweis, and he was fired from his job at the hospital. The remaining doctors rejoiced. They stopped washing their hands in disinfectant. The death rate from childbed fever skyrocketed once again. News of Semmelweis’s initial success in Vienna spread throughout Europe and other parts of the world. It became increasingly clear to doctors that many diseases were contagious and that good hygiene could prevent the transfer of disease from person to person. As doctors and hospitals increasingly adopted safe and hygienic procedures, they became more open to an acceptance of the germ theory of disease that was about to revolutionize medicine.

Sour Wine

L

ouis Pasteur was, from all accounts, an unremarkable child who was merely a decent student. Nothing in his behavior either in or out of school gave any indication that he had greatness and genius in him. In fact, some villagers in his hometown thought him rather plodding and dull. This ordinary boy was born in 1822 in the French town of Dole into the humble family of a leather tanner. He grew up in Arbois, near an important wine-growing region of France. What his neighbors took for plodding turned out to be a dogged determination to work hard and succeed. Despite his mediocre school reports, Pasteur studied long and hard until he was accepted by a college in Paris. There, he studied chemistry, which he found fascinating and “marvelous.” After graduating, Pasteur married and moved to the city of Lille, where he became a college science professor. Pasteur had a good reputation as a professor and scientist. He was also known as a rather pompous, if not arrogant, egotist and was a fierce French patriot. When, in 1856, Emperor Napoleon III asked Pasteur to solve a problem plaguing one of France’s most precious industries—wine making—Pasteur was honored and took the challenge. It seems that in his home region of France, vintners (winemakers) found that their wines were continually turning sour. The vintners were desperate and could not figure out how to solve the problem and save their world-famous wines. Pasteur hurried home to Arbois, where he set up a laboratory. He visited several wineries and took samples of fermenting wine from

55

56  Germ Theory their vats. Then he examined the samples under a microscope. As he expected, Pasteur saw in the wine the yeast (minute, single-celled microbes, or fungi) that ferments grape juice and turns it into wine. Yeast is added to the juice of wine grapes because the microbes “eat” the sugar in the juice and, in the process, turn it into alcohol. This process is called fermentation. Pasteur saw lots of these beneficial yeast organisms, which have an oval shape. However, in examining the samples of sour wine, Pasteur also saw a different type of microbe, one he had never seen before in wine. After conducting several experiments, Pasteur showed that it was contamination by this other, rod-shaped type of bacteria that was making the wine sour. The first thing Pasteur did was to order the vintners to pour the spoiled wine down the drain. Then Pasteur recommended that all vintners buy a microscope and examine their wine from time to time as it fermented. Vintners were told to monitor the taste of their fermenting wine. When the wine was perfectly fermented, they had to

The Father of Bacteriology Years after Leeuwenhoek discovered his “wretched beasties,” these tiny creatures were dubbed bacteria, which comes from a Greek word meaning “little rod.” (A single one of these critters is called a bacterium.) In the mid-1800s, a German biologist named Ferdinand Julius Cohn used a greatly improved microscope to study these mysterious bacteria. Most of the microscopic creatures he looked at were less than 1/5,000 of an inch (0.005 mm) across. Yet he discovered that there was an enormous variety of bacteria. Some were larger than others and had long, whiplike tails or generated false feet that helped them “swim.” Others were shaped liked rods or spirals. Some were green and plantlike and did not move around at all. Cohn studied and made images of the bacteria for nearly two decades. In 1872, he published a book about bacteria. The book classified and described a huge variety of bacteria. Because of his comprehensive work, Cohn is known as the father of bacteriology, the study of bacteria.

Sour Wine  57

Figure 5.1â•… This photomicrograph shows yeast cells reproducing via a process called budding.

examine it under a microscope to see if it had the harmful bacteria. If the harmful microbes were present, the vintners could heat the wine gently for a little while. In his experiments, Pasteur had found that gentle heating killed the offending bacteria. The heat would kill the bad bacteria but would not affect the taste or quality of the wine. This gentle heating process, which could kill many kinds of microbes, including bacteria, came to be known as pasteurization, named after brilliant Louis Pasteur. (Pasteurization is widely used today to kill bacteria in milk.) Pasteur also recommended that everyone who worked with the wine should wash their hands after handling each vat of wine. Hand washing would prevent the workers from possibly transferring the harmful bacteria from one vat to another. Wine vats would also have to be cleaned thoroughly before they were used again to make new wine. Pasteur had saved the French wine industry! He became a national celebrity. In scientific terms, he had shown that different microbes have different effects on substances. He also thought that he had squashed the notion of spontaneous generation once and for all. After all, if spontaneous generation were true, then harmful bacteria would have reemerged spontaneously in the wine even after it had been heated. That had not happened. Pasteur’s work proved that microbes (in this case, yeast) cause fermentation and, after more time, spoilage. Pasteur showed that microbes play an important role in the natural

58  Germ Theory world by causing chemical changes to occur in a variety of substances. He also showed that yeast was a living thing, or organism. After long hours peering through his microscope, Pasteur discovered that yeast reproduces by a process called budding. Yeast must be a living thing, because only living things reproduces themselves. Scientist Rudolf Virchow had, in 1858, shown that this was true. Virchow had elaborated the theory of biogenesis (bio means “life,” and genesis means “origin”), also called “cell theory.” Cell theory states that cells are the basic units of life and that cells arise only from other cells. Pasteur’s work supported Virchow by showing that yeast cells arise only from other yeast cells.

The Last Gasp It is almost incredible to believe, but despite the work done by Spallanzani and Pasteur, quite a few scientists still refused to give up on spontaneous generation. It seemed as if spontaneous generation just kept spontaneously generating. Pasteur could hardly contain his annoyance. He decided to design and conduct experiments that would kill this foolish notion once and for all. Pasteur began by boiling a plug of cotton in water until both plug and water were completely sterile, or free from all microbes. He forced fresh air to flow through the cotton plug and then plunged it into the cooled, sterile water. He then examined the water under a microscope and, as expected, it was teeming with microbes. Pasteur concluded that there must be microbes in the air that had been trapped by the cotton plug. Yet it might be that the microbes were not in the air but had arisen spontaneously in the cotton. Then Pasteur did another experiment to show that this was not possible. Pasteur boiled a cotton plug and water as before. But this time he filtered a quantity of air by passing it through another sterile cotton plug. Then he forced this filtered air through the first cotton plug and dipped the cotton in the sterile water. Pasteur shook with excited anticipation as he peered at the water under his microscope. Success! There were no microbes in the water. Pasteur had shown that microbes do not arise spontaneously on or in any substance, but are carried instead on dust particles in the air.

Sour Wine  59

Figure 5.2â•… The brilliant design of Louis Pasteur’s experimental flask proved that spontaneous generation was false. The dust that carried airborne microbes accumulated only in the lowermost part of the curved neck. No microbes ever “arose” from the broth, even though it was exposed to the air.

60  Germ Theory To put the final nail in the coffin of spontaneous generation, Pasteur designed an experiment that improved on the ones Spallanzani had done. Pasteur revealed his genius in the way he designed the glass flasks he used in his experiment. He needed to design a flask that would let in air while keeping out microbes. Pasteur’s design was truly ingenious because air could flow into the flask and come into contact with the water, but the curved shape of the flask’s neck prevented dust from traveling up the neck and into the water. Pasteur filled his flask half full of meat broth. Then he used heat to shape the neck of the flask until it was long, narrow, and curved sharply downward from the flask, with a short up-curve at the end. Pasteur then boiled the broth in the flask until burning-hot steam flowed out of the neck, sterilizing it. At this point, everything was sterile, and

Where Do Bacteria Come From? The early Earth was mainly covered by ocean water that was a rich soup of minerals and molecules of organic matter, such as amino acids (the building blocks of proteins). As the countless zillions of molecules swarmed through the water, they occasionally bumped into each other. Now, water is a great medium for chemical reactions to occur. Scientists speculate that certain molecules sloshing about in the primeval oceans developed the ability to take in amino acids and “line them up” to make primitive proteins. This protein-making talent spread and became more sophisticated. Molecules eventually got together to become “super-molecules.” They also began to assemble material they used to build a membrane around themselves for protection. These super-molecules developed the ability to make internal “machinery” that improved their functioning (such as digesting food). These early membrane-bound creatures were the first life forms to evolve on Earth. They were single-celled bacteria that, for the next 2 billion years or so, would be the only life on the planet. Bacteria were the first life forms on Earth, and, no doubt, they will be

Sour Wine  61 there were no microbes in either the broth or the neck of the flask. Pasteur let the broth and flask cool, leaving the flask and its broth open to the air. Air flowed into and out of the flask, but dust settled out of the air in the part of the neck that was sharply curved downward. Pasteur left the flask open for several days. When he examined the broth under a microscope, it contained no microbes. But when he peered at the accumulated dust, it was teeming with microorganisms. Pasteur repeated this experiment several times, often leaving the flask sitting open for a month or more. Each time he examined the broth and the dust, he got the same results. In 1864, Pasteur made the results of his experiment public. Other scientists repeated his experiment and got the exact same results. No microbes ever arose “spontaneously” in the broth. All the microbes

Figure 5.3â•… This light micrograph shows one kind of bluegreen algae, or cyanobacterium. These simple, single-celled bacteria were the first life forms on Earth.

the last life forms left when the planet is engulfed by the Sun, billions of years from now. Bacteria are nothing if not resilient survivors.

62  Germ Theory were found attached to dust particles. Finally, spontaneous generation was dead. No one could dispute Pasteur’s findings.

Keep It Clean In the mid-nineteenth century, Scotland was the place to be if you wanted to become a first-class surgeon. Scottish medical schools had the best doctors and teachers and the most advanced courses in anatomy and dissection. Joseph Lister was a top student at the medical college in Glasgow. It was there that the forward-thinking, even radical, doctors taught the earliest form of germ theory: that microbes caused disease. Lister was convinced, and he tried to promote germ theory and the procedures that flowed from it, such as Semmelweis’s rules about hand washing, wherever he worked. Lister became a highly successful surgeon in Glasgow. He was one of the only surgeons to prevent postoperative infection by disinfecting everything used in the operating theater. Most of his colleagues ridiculed his “outlandish” procedures, but Lister was convinced that these procedures saved lives. Lister’s techniques gained popularity among patients, whose most common experience with surgery is summed up in the following quote by a surgeon cited in the book Killer Germs (2003): “I was instructed by my [senior] surgeon to obtain a woman’s permission for an operation on her daughter. The operation was one of no great magnitude. I discussed the procedure with the mother in great detail and, I trust, in a sympathetic and hopeful manner. [Then] I asked her if she consented to the performance of the operation. She replied ‘Oh! It is all very well to talk about consenting, but who is to pay for the funeral?’” Lister began using carbolic acid as an antiseptic, or germ killer, in his operating room. Surgical instruments and the surgeon’s hands were thoroughly washed in this strong chemical. Lister innovated by also soaking a sterile cloth in carbolic acid and draping the cloth around the site of the surgical incision. After one year using this technique, Lister reported that deaths from infection in his surgery had dropped to only 10%. Most other surgeons had death rates from infection of 50%. Convinced that germs entered wounds or incisions from the air, Lister invented a device that sprayed carbolic acid into the air

Sour Wine  63 of the operating room during surgery. Though the operating room stank from the chemicals, Lister persisted until he realized, sometime later, that the stinky spray did not reduce infection or death. Lister began experimenting by using different techniques to disinfect various materials in the operating room and the hospital. He came to the correct conclusion that sterilizing hands, skin, bed linens, and medical instruments was most effective in preventing infection. Lister applied the same antiseptic care to the treatment of wounds. One day in 1865, a young boy was brought into Lister’s surgery. The boy had been run over by a cart, and he had a terrible, open fracture in his leg. The compound fracture caused the bone to break through the skin, and the wound was a painful and bloody mess. For the first time in medical history, Lister not only fixed the fractured bones, but also soaked the open wound in carbolic acid. That must have been very painful, but it helped save the boy’s life. Lister then dressed the wound with material also soaked in carbolic acid. Unlike most people who suffered such accidents, the boy did not develop and die from “hospital gangrene” (sepsis, or infection of the blood). In fact, he recovered completely without his wound ever becoming infected. Lister published a paper, “On the Antiseptic Principle in the Practice of Surgery.” Within a relatively short time, his ideas were accepted by many doctors in the medical community (at least in Europe; American doctors were far more skeptical). Joseph Lister had the rare good fortune to be recognized in his own lifetime for his important achievements. He also had the humility to express his gratitude toward Louis Pasteur, whose work in germ theory had inspired him.

Silk and Chickens

B

y the late 1800s, antisepsis, the practice of using antiseptics, was generally accepted as a means to prevent infection and death from wounds and in surgery. Both before and after Lister, researchers had examined blood and tissue from wounded or diseased patients and had certainly seen bacteria that did not occur in healthy patients. Doctors accepted the fact that bacteria were implicated in infection and death from disease. Yet no one had yet proved that microbes actually caused disease. Perhaps microbes arose because the tissue or body was diseased but did not cause the condition at all. Maybe bacteria made the disease worse, but where was the proof that they caused it? Both physicians and the general public were still very skeptical of germ theory. In a way, their skepticism is understandable. Without absolute proof, the theory can sound pretty far-fetched. It is understandable that people then doubted that invisible little life forms were everywhere and could invade a body and make it sick, or even kill it. The attitude then might be likened to people’s attitude today if they were told that invisible rays from Mars caused human disease. Germ theory desperately needed uncontested proof to convince people that it was real. A germ had to be definitely and unquestionably linked to a disease to make people believe. In other words, without a cause-and-effect proof, the doubters would prevail.

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Silk and Chickens  65

Worms, Leaves, and Silk Louis Pasteur had been the savior of the French wine industry. The French practically worshipped him as a scientific genius. He was soon called upon again to rescue another French industry. A region in the south of France had been producing luxurious silk fabric for hundreds of years. The industry went into decline during and immediately after the French Revolution, when most wealthy, silk-wearing aristocrats lost their heads. By Pasteur’s time, however, wealth and silk clothes were both back in fashion. Then, in 1865, the French silk industry was struck by a devastating disease that caused millions of silkworms to shrivel up and die. The industry was on the brink of collapse when Pasteur was called in to save the day. Pasteur traveled south and set up a laboratory. He spent the next five years trying to figure out what caused this disease in silkworms, the caterpillars (larvae) that spin cocoons out of a material that people use to make silk. Pasteur first examined the leaves from the mulberry trees on which silkworms feed. Some of the mulberry leaves contained microbes, but other leaves did not. Pasteur concluded that when the silkworms ate the leaves containing microbes, the germs infected and killed the silkworms. Pasteur reported that the microbes were parasites that were living inside the silkworm’s body and eventually killing it. Pasteur and his assistants conducted more experiments to prove their ideas. The scientists speculated that the disease might be spread through silkworm feces. So they took some mulberry leaves that had no silkworm droppings on them and fed them to healthy silkworms. As expected, all these silkworms remained healthy. The researchers then ground up mulberry leaves from a tree on which diseased silkworms had fed. The paste was painted onto some healthy mulberry leaves. Then these leaves were fed to healthy silkworms. In short order, the silkworms fell ill and died. Examination showed that their bodies were full of the same microbe found in infected mulberry leaves. Pasteur and his assistants quickly discovered that the microbe also infected silkworm eggs. His assistants thought they had found the connection between the disease, called pébrine, and the microbe. However, Pasteur felt

66  Germ Theory

The Water Pump John Snow was such a respected doctor, that he was a personal physician to Britain’s Queen Victoria. In 1854, an epidemic of cholera struck a poor, overcrowded section of London called Soho. In addition to his private practice, Snow was interested in epidemiology, the study of epidemic disease. Thus, Snow visited Soho repeatedly during the epidemic. There was little he could do to treat the afflicted, but he was determined to find out what was causing the cholera outbreak. Snow’s breakthrough came when he drew a map of Soho. On the map, he marked the streets and buildings where cholera had struck. Then he thought about what these streets and houses had in common. It struck him that all the affected people obtained their drinking water from the water pump on Broad Street. Excited by this finding, Snow examined water samples from the pump under a microscope. He saw bacteria that he knew were not present in other sources of drinking water. His research revealed that the bacteria, which he named Vibrio cholera, came from infected individuals whose feces got into and contaminated the drinking water. Snow’s findings were made public, and his idea that cholera was a waterborne disease caused by this particular bacterium made quite a stir. However, Britain’s leading medical journal (both then and now), The Lancet, ridiculed Snow’s claim, accusing him of getting his ideas from “the sewer.” The Lancet refused to publish any of Snow’s scientific papers. In some ways, the journal had good reason to reject Snow’s work. Though Snow had made a connection between the water pump and cholera, he had not really proved that cholera was a waterborne disease or that it was caused by this one type of bacteria. At that time, Soho was a foul and dirty place, overcrowded and filthy, with garbage and human waste running through its streets and filling its alleys. Snow had not proved that it was not this filth that had caused the cholera epidemic. At the time, his work had too many loopholes to allow him to prove his case. Yet Snow is revered today for his hard work and his ultimately correct insight into the cause of cholera.

Silk and Chickens  67

Figure 6.1â•… Healthy silkworms feed on a mulberry leaf.

troubled. He knew something was not right. Pasteur had noticed that some of the silkworms he studied had become diseased before the pébrine bacteria had appeared in their body. How, then, could he conclude that the bacteria caused the disease? The solution to the problem came to him in a moment of insight in 1869. Pasteur suddenly realized that he had made a mistake. He had thought he was studying one disease, but in fact he had been observing two completely different illnesses. The worms that had become sick before the pébrine bacteria were present in their bodies were suffering from a completely different disease, called muscardine, which was caused by a totally different germ. When silkworms with muscardine became infected with pébrine, they were found to have both disease microbes in their bodies. Further experiments proved that each specific type of bacteria caused only one of the diseases. Finally, Pasteur had shown that one specific kind of bacteria caused one specific disease. Pasteur recommended a harsh but effective method of ridding the silk industry of these diseases. He instructed that all infected mulberry leaves and silkworms be destroyed. The silk makers gulped,

68  Germ Theory but they followed Pasteur’s advice. Soon after, the silk industry was disease-free and profitable. Pasteur, the savior, had done it again. Pasteur now knew that a particular disease was caused by a particular type of bacteria. He also knew that bacteria could be passed from one organism to another. In other words, some diseases were contagious. Silkworm disease was spread by the caterpillar’s feces. Among humans, contagious diseases were passed from person to person via coughs and sneezes or on hands and clothing that harbored the bacteria. These concepts formed the core of germ theory. Pasteur published his germ theory of disease in 1878 and changed medicine forever.

Chicken Vaccine By age 58, Louis Pasteur was one of the most famous scientists in Europe. He had saved two French industries from total ruin. He had proved the germ theory of disease. He was considered a genius by one and all. Yet Pasteur was not satisfied to sit back and bask in the adulation of others. In fact, in 1880, Pasteur was investigating a singularly unglamorous disease: chicken cholera. Though unrelated to human cholera, chicken cholera epidemics periodically devastated the French chicken and egg industries. So Pasteur was busy at work looking for the germ that caused it and a way to rid France of it. As it happened, one day Pasteur found some old broth he had made that contained chicken cholera germs. He decided to inject the broth into some chickens to see what happened. In a few days, the chickens got sick, but they did not die. In fact, they soon recovered completely. Pasteur thought it odd, but then forgot about it. He went on vacation. When he got back to his lab a few weeks later, he prepared a fresh broth of deadly chicken cholera germs. He asked an assistant to fetch some new, healthy chickens for injection. Pasteur was furious when his assistant told him that there were no new chickens at the lab. The assistant suggested that they inject the deadly broth into the chickens that had recovered several weeks before. Pasteur agreed, and the deadly microbes were injected into the chickens. Pasteur watched the birds day after day, astonished that they did not get sick and die. He had given them a powerful dose of germs. Why were they still alive?

Silk and Chickens  69

Figure 6.2â•… Although he was not the first to propose germ theory, Louis Pasteur’s successful experiments helped convince people that it was true. He is considered one of the founders of germ theory and bacteriology, along with Robert Koch, a German physician who isolated the bacteria that caused anthrax, cholera, and tuberculosis, among other diseases.

A sudden flash of insight revealed the answer. The germs that the chickens had been given before his vacation must have somehow made the birds immune to this disease. Pasteur remembered that the chickens had originally been given an old germ broth. Its age made the germs in the broth so weak that none of the birds had died.

70  Germ Theory Yet the broth’s weakened germs did give the chickens immunity to chicken cholera. By sheer luck, Pasteur had discovered a vaccine for chicken cholera. A vaccine is a medicine that contains weak germs

Cows to the Rescue Way back in the 1770s, English physician Edward Jenner became interested in a cow disease called cowpox. Jenner noticed that cowpox in cows looked very much like a mild form of smallpox, a deadly human disease. By talking to the local farm folk, Jenner learned that farmers thought it was good luck for a person to get cowpox. They thought that getting cowpox kept you from getting smallpox. Most doctors thought this idea was just ignorant superstition. But Jenner wondered if it was true and decided to conduct what might be a very dangerous experiment to find out. In 1796, Jenner met a milkmaid who had just contracted cowpox. He asked her if she would help him, and she agreed. Jenner punctured one of the milkmaid’s small cowpox blisters with a needle. The fluid from inside the blister covered the needle. Jenner then scratched the cowpox fluid into the skin of a young boy who had agreed to be part of the experiment. The boy had never had either cowpox or smallpox. The boy developed a mild case of cowpox. Other than that, he was fine. Then Jenner did the dangerous part of his experiment. When the boy was completely recovered from cowpox, Jenner scratched the boy’s skin with a needle that had fluid from a smallpox blister. Jenner was taking a terrible risk. He did not know if the boy would live or die. Jenner waited, week after week. The boy never developed smallpox. Jenner repeated his experiment two years later. The same thing happened. Jenner had discovered a vaccine for smallpox. The vaccine, which was made from the less harmful cowpox, made people immune to the far more terrible smallpox. When Jenner announced his discovery, nearly everyone wanted a vaccination against smallpox.

Silk and Chickens  71 that make the body immune to the disease they cause. After Pasteur’s discovery, French chickens were inoculated with weak cholera bacteria to make them immune to the disease.

Figure 6.3â•… Edward Jenner is shown inoculating a young boy in this image. Jenner, who pioneered the smallpox vaccine, initially tested a vaccine using cowpox on 23 people to prove it could work.

Cultural Developments Preventing Anthrax

S

everal years before Pasteur’s triumph over chicken cholera, a French scientist named Casimir-Joseph Davaine studied anthrax. Anthrax is a dreadful disease that primarily kills sheep and farm animals, though it can infect and kill people as well. Davaine noted that, mysteriously, healthy sheep that had had no contact with diseased sheep might somehow also get the disease. Davaine struggled to find out how this could happen. He had identified the “stick-shaped corpuscles,” or bacteria, that were found in the bodies of sheep that had died from anthrax. He had also caused anthrax in healthy animals by injecting them with fluids containing these bacteria. Though Davaine thought he had proved that this microbe caused anthrax, he had made a serious error. The infected fluids he injected into healthy animals contained lots of other microbes in addition to the “stick-shaped” ones. Davaine was bitterly disappointed that he had not proved that this germ caused anthrax. Pasteur, too, became interested in anthrax. In 1881, he was able to isolate the rod-shaped bacteria, or bacilli (singular, bacillus), that caused anthrax. Pasteur was interested in figuring out how to weaken the deadly bacilli enough to make them safe to use in a vaccine.

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Cultural Developments  73 For months, Pasteur developed techniques for weakening the deadly microbe. He prepared a vaccine that seemed to work in sheep, and then announced that he had created a vaccine to prevent anthrax. The medical community was skeptical. So Pasteur decided to perform a public experiment using his new vaccine. Pasteur was so famous, that crowds of people and newspaper reporters gathered at the site of the experiment to see the celebrity scientist at work. On May 5, 1881, Pasteur inoculated 24 sheep, 1 goat, and 6 cows with his anthrax vaccine. Two weeks later, he gave the same animals a somewhat stronger dose of the vaccine. As a control, Pasteur left an equal number of the same animals unvaccinated. Then, on May 31, all the animals were injected with a strong and deadly strain of real anthrax germs. Within two days, all the unvaccinated animals were dead from anthrax. All the vaccinated animals remained healthy. Pasteur had done it again! Anthrax vaccine prevented animals from succumbing to the disease.

Going Further Robert Koch studied medicine at a college in his native Germany. After graduating in 1866, Koch opened a private practice. He was a good doctor and had many patients. But Koch was not a happy man. He was frustrated because so many of his patients died and there was nothing he could do about it. Koch complained: “I hate this bluff that is my practice. Mothers come to me crying—asking me to save their babies—and what can I do?—Grope, fumble .€.€. reassure them when there is no hope. How can I cure a disease when I do not even know what causes it, when the wisest Doctor in Germany doesn’t know?” Koch’s wife decided she needed to do something to lift her husband out of his funk. So for his twentyeighth birthday, she bought him a microscope. She had no idea how important this gift was to be for science. She just wanted to cheer her husband up. And she did. Koch spent countless hours peering at microorganisms under the lens. Koch, like Pasteur, was convinced that specific germs caused specific diseases. He determined to use his new microscope to prove

74  Germ Theory

Figure 7.1 German physician Robert Koch invented methods to purify anthrax bacillus from blood samples and grow pure cultures. He found that anthrax could not live outside the host for long, but it would produce endospores (tough, non-reproductive structures) that could last a long time.

that the “one germ/one disease” theory was true. Before he could find a proof, however, Koch and his wife had to find a place where his medical practice could support them. They moved east to the

Cultural Developments  75 small town of Wollstein near the border with Poland. When he settled in and set up a practice, Koch discovered that an epidemic of anthrax was raging through the countryside. Koch decided to study this terrible disease. Perhaps researching a disease would be more satisfying than his private medical practice. Koch expanded his laboratory from a single microscope to a simple but efficient research facility. He developed new methods of preparing slides to view microbes under his microscope. He stained his samples with different types of dyes to make the microbes easier to see. These new techniques helped Koch distinguish between bacteria that otherwise looked similar. Careful examination of tissues and fluids taken from animals that had died of anthrax led Koch to identify the bacterium that caused the disease. He called the rodshaped microbe Bacillus anthracis. Despite this important achievement, Koch was not satisfied. Like most people familiar with the disease, Koch knew that anthrax could disappear and then suddenly reappear seemingly out of nowhere. Koch determined to untangle the life cycle of the anthrax bacillus in order to reveal its secrets. The problem was that it was extremely difficult to study a germ in isolation from other germs. Samples taken from diseased animals contained the anthrax bacillus, but they teemed with lots of other microbes as well. Koch had to figure out a way to “grow” Bacillus anthracis all by itself. Being able to “grow,” or culture, isolated microbes was the holy grail of bacteriologists. It would vastly increase the chances of proving that one germ caused one specific disease. For years, scientists had been inventing a whole host of weird contraptions in hopes that they could grow bacteria. None of them worked. Koch, though, was lucky as well as brilliant. One day while working in his lab, Koch noticed a leftover slice of boiled potato that he must have forgotten from a recent lunch break. Looking closely at the potato, Koch noticed that its surface contained several droplets of different colors. What could they be? Of course, the first thing Koch did was prepare a slide for each color droplet. Then he put the slide under his microscope. Eureka! Each droplet contained a pure culture of one type of microbe. The blue droplet contained only microbe X. The red droplet contained only microbe Y. Koch realized that where a microbe from dust in the air had settled on the potato, a colony of only this one type of microbe began to form. Koch had found the first pure colonies of single microbes.

76  Germ Theory The question was: Why did a pure microbe culture grow on a potato slice and not in beef broth? Koch was smart enough to realize that it was the smooth, solid surface of the potato that enabled a pure culture to grow. In liquids such as broth, all kinds of microbes get mixed up together. A microbe that lands on a solid surface stays put. It does not float around. It begins to reproduce until a pure colony forms. Of course, the solid surface on which a microbe lands also must have nutrients that the particular microbe needs to grow and multiply. Were there other solid surfaces on which microbes would grow? Koch would find out. Koch experimented by making a bacterial culture, or medium (plural, media), from different substances. He tried gelatin, but that became too runny. He tried other media, but none seemed just right. Here again, luck was on Koch’s side. One of his lab assistants liked to make homemade jams and jellies. She used an extract from seaweed to get her jellies to gel. The seaweed extract is called agar-agar. The assistant suggested that Koch try it out to see if it made a good medium on which to grow pure colonies of microbes. Koch took her advice and found that agar-agar was the ideal medium for growing microbes. It was not runny, and it did not turn into a liquid when heated or in the presence of chemicals produced by microbes. Agar (for short) is still used in laboratories around the world as the best medium for growing pure microbial cultures. Once he had found the perfect medium, Koch cultured pure colonies of anthrax bacilli. He watched them as they grew and multiplied. He carefully observed each stage in their life cycle. Koch’s painstaking work paid off. He saw that at one stage in their life cycle, anthrax bacilli form spores. He tested the spores and found that they were able to survive extreme heat and cold and exposure to the air. But when the spores came into contact with animal fluids, they immediately changed and turned into the familiar rod-shaped anthrax bacilli. Koch had shown why anthrax could disappear and reappear as if by magic. His discovery revealed that anthrax spores could survive for a long time in the soil on a farmer’s field. Only after sheep or other grazing animals have eaten them with grass do the spores change into anthrax bacilli that cause anthrax. Inside the animal, the bacilli reproduce, and the infection spreads throughout the animal’s body until eventually the animal dies. By the time the animal dies,

Cultural Developments  77

Figure 7.2â•… This lab dish contains nearly colorless agar, on which a microbe culture is growing.

the bacilli have once again changed into spores. The spores leave the dead animal’s body and fall onto the grassy field. There they wait until another hungry animal comes along to gobble them up together with the grass. Koch completed his study of anthrax by injecting its spores into animals. Each animal developed anthrax. So Koch proved that Bacillus anthracis was the one and only germ that caused anthrax. His work was a powerful argument supporting germ theory. Koch published his findings in 1876 and gained international renown. Before long, he was able to give up his private medical practice and devote himself to full-time research. In his published work, Koch outlined the basic procedure researchers should use to prove that a disease is caused by a particular microbe. These statements are known as Koch’s postulates. They are: 1. The microbe must be present in every case of the disease and must not be present in healthy animals.

78  Germ Theory

Figure 7.3 Using a setting that magnifies an image up to 12,483 times, this scanning electron micrograph shows anthrax bacillus spores. These spores can live for many years, which enables the bacteria to survive in a dormant state.

2. The microbe must be isolated from the diseased animal and must be grown in pure culture (in the lab). 3. The same disease must be produced when the microbes from the pure culture are injected into healthy, susceptible animals. 4. The same microbe must be recoverable once again from this artificially infected animal, and it must be able to be grown again in pure culture.

microbes revealed Koch’s groundbreaking work in culturing pure colonies of microbes led to the discovery of different types of germs and to the identification of many previously unseen disease-causing bacteria. Koch himself discovered the bacillus that causes tuberculosis and the bacillus that causes cholera. Between the 1870s and 1890s, researchers had identified the microbes that cause diphtheria, scarlet fever,

Cultural Developments  79 typhoid, pneumonia, leprosy, and tetanus. In the next decade, the germs that cause bubonic plague, whooping cough, and gangrene were identified. As each microbe was identified, scientists could use its pure culture to prove whether or not it was the cause of a specific disease. Koch’s work, therefore, greatly advanced germ theory and physicians’ understanding of the role of germs in causing disease.

Mad Dogs and a Frenchman When he was a child, Pasteur had been horrified when a “mad” wolf had attacked and bitten a young boy. Pasteur remembered how the blacksmith had treated the boy’s wound by burning it with a redhot poker (an early form of cauterizing, or burning, a wound to prevent infection). The young boy screamed in pain when the hot metal seared his skin. Yet this was nothing compared to what he suffered as he died from one of the most dreaded diseases of all time: rabies. Rabies is a disease that affects the brain and nervous system. Rabies disorients an afflicted animal and impairs its movement. It also constricts the throat and makes it impossible for the affected animal to drink or eat. Thus, the rabid animal drips saliva from its mouth because it cannot swallow. Crazed by thirst and by its infected brain, a rabid animal may attack and bite any living thing that comes near it. Rabies is transmitted to the victim of the attack through the disease microbes in the rabid animal’s saliva. It is possible that this early, traumatic experience led Pasteur to study rabies. Studying such an awful and highly contagious disease is very dangerous, but Pasteur was determined. He suspected that rabies was caused by a germ that was neither a fungus, like yeast, nor a bacterium, like anthrax. He believed, correctly, that rabies was caused by a mysterious kind of microbe called a virus. In beginning his study, Pasteur and his assistants trapped a mad dog. They tied it down and—very carefully—Pasteur took a sample of some of the frothy saliva dripping from the poor animal’s mouth. Then he injected the saliva into another animal. In a week or two, the animal came down with rabies. Pasteur tried to make a vaccine out of weakened, or attenuated, viruses he got from the spinal cords of infected animals. He found that allowing the infected spinal cords

80  Germ Theory

Figure 7.4 After the work of Robert Koch, scientists were able to classify different types of disease-causing bacteria, primarily by shape. These are some of the first disease-causing microbes to be cultured and identified. Today, scientists recognize 19 different classifications of bacteria.

to dry out for two weeks greatly weakened the rabies virus. Pasteur heated the virus in a solution to weaken it further. He diluted this solution several more times. Pasteur hoped he had weakened the rabies virus sufficiently to use it as a vaccine. Pasteur then followed his experimental procedure, giving animals a small dose of vaccine, and then waiting two weeks before repeating the dose. Then he gave the animal, in this case a dog, a full dose of strong, deadly rabies virus. Pasteur waited. The dog did not become ill. Pasteur put the dog in a cage with a rabid dog, which bit the experimental animal. Pasteur rescued his dog and, again, he waited. The vaccinated dog did not get rabies.

Cultural Developments  81 Now it was time for the truly risky part of the experiment. In July 1885, a young boy was bitten by a rabid dog near Pasteur’s lab. Pasteur asked the boy for permission to test his new rabies vaccine. The boy was understandably scared, but he consented. After all, he had nothing to lose, because he would soon die of rabies if he did nothing. Pasteur injected his weakest rabies germs into the boy. Two days later, he injected some more weakened germs. Each day after that, he injected stronger and stronger germs into the boy’s body. Pasteur hoped that the injections would cause the boy to become immune to full-blown rabies. On the 11th day, Pasteur injected fullstrength rabies germs into the boy. The boy never got rabies. The rabies vaccine had made him immune. Pasteur never found the microbe that caused rabies. But he had shown that there must be a particular germ that always caused this disease. Rabies did not disprove germ theory. It just showed that there are some germs that are much harder to find and to see than others.

Go-betweens In 1902, more than 200,000 Africans in the British colony of Uganda died of a mysterious and troubling illness known as sleeping sickness. A team of worried British doctors rushed to Uganda to try to halt the spread of the disease by finding out what caused it. The doctors mapped the incidence of sleeping sickness and found that it occurred mainly among people living on islands in lakes. At first, the researchers conducted many tests to see if the lake water was contaminated with a poison or with a particular microbe. They found nothing. But lacking any other explanation, they stated that sleeping sickness must come from contaminated drinking water. Various attempts to purify the drinking water did nothing to reduce the cases of sleeping sickness. This first team left Uganda shaking their heads in dismay and confusion. A year later, a second team of physicians arrived in Uganda. This team was led by Dr. David Bruce. Bruce pored over the records left by the first team. He applied what he read to his own recent experience tracking down the cause of a livestock disease. Bruce had discovered that the livestock illness was spread to the animals by the bites of a certain African fly. So Bruce concluded that sleeping sickness, too,

82  Germ Theory was not a waterborne disease. It must be a disease carried by flies that breed in lake water. Bruce did his first experiments with the tsetse fly—the insect with which he was familiar.

Viruses Viruses are germs that are thousands of times smaller than bacteria. Some scientists believe that viruses arose long ago from disintegrating bacteria. They state that certain bacteria got rid of every structure they did not need to reproduce. What was left was a virus. Other scientists believe that viruses came from tiny organs (organelles) inside cells. These organs escaped from the cells and began to live an “independent” life. In fact, no one really knows how viruses originated. A virus has a very simple structure. Basically, a virus contains genes (usually DNA) and proteins surrounded by a membrane or a protein coat that often has a structure that allows it to attach itself to the surface of a living cell. Many viruses also have a structure on their membrane that is like a hypodermic needle. The needle can break through a cell membrane and inject the virus’s genes into the cell. Scientists know that viruses are very strange beings, indeed. Viruses are not classified as living things (though they are not dead either). When they are outside a host animal, viruses lack functions (such as digestion and respiration) that living things have. In fact, a scientist could put a bottle of viruses on a shelf and leave it there for a thousand years, and the viruses would change as little as pebbles in a bottle. But once these viruses come into contact with a living host, they spring to life. A virus’s sole goal is to reproduce. This it does inside a host. A virus enters one of the host’s cells or injects the cell with its genes. Then the virus forces the cell to make copies of the virus’s genes to create many more viruses. The new

Cultural Developments  83 Bruce trapped some tsetse flies from one lake area. He examined their insides under a microscope. Sure enough, he found a protozoan parasite, which he called Trypanosoma. Bruce exposed lab animals

Figure 7.5 A transmission electron micrograph shows the smallpox virus using a negative stain technique. Viruses could be seen only after the invention of the electron microscope, which shows the virus magnified up to 370,000 times.

viruses infect more cells, which make more viruses—and the animal gets sicker and sicker. Rabies, smallpox, flu, and other diseases are caused by viruses.

84  Germ Theory to the bites of tsetse flies he knew carried this microbe. The animals all contracted sleeping sickness. The protozoan’s role in the disease was confirmed when Trypanosoma was found in the spinal fluid of several people who had sleeping sickness. The key to eradicating the disease was killing off the tsetse flies. Back then, that was easier said than done. Yet Bruce’s discovery was an important advance in the study of germs and disease. Bruce had found the vector for sleeping sickness. A vector is a go-between that has a disease-causing microbe in its body that it then transfers to another host. The tsetse fly is the disease vector for the sleeping sickness protozoan. The fleas on the Indian black rat were the disease vectors that transmitted the microbe that causes bubonic plague from rats to humans.

Yellow Fever After the Spanish-American War (1898), the United States controlled the island of Cuba. During the American invasion of Cuba, and while Americans occupied it, many soldiers and others were dying of yellow fever, an awful type of hemorrhagic (bleeding) fever that causes a victim to vomit blood just before death. In 1901, U.S.

Sleeping Sickness When sleeping sickness first strikes, the sufferer usually has constant headaches, feels depressed, and is always tired. Oddly, at this stage, the ill person may suffer from insomnia, or the inability to sleep. During this period, the affected person often has difficulty functioning and may become a burden on his or her family. This early stage of sleeping sickness may last from months to years. Then the victim enters the second stage of the disease. The person can no longer reason or think clearly and may be disoriented. Terrible pains shoot through the body, though it is at this stage that the person begins to be sleepy continuously and may sleep most of the time. Finally, the sufferer goes into a coma, from which most victims never awaken.

Cultural Developments  85

Figure 7.6â•… A tiny mosquito sucking blood can also pass on germs through its saliva.

Army surgeon Walter Reed was sent to Cuba to head a team of researchers whose task was to find out what caused yellow fever. Reed consulted with a noted Cuban doctor, Carlos Juan Finlay, who asserted that yellow fever was caused by a germ that was carried by mosquitoes. Finlay was convinced his theory was true, but he had been unable to prove it. Finlay gave Reed a bunch of eggs from the mosquito he was sure caused yellow fever, a mosquito now known as Aedes aegypti. Reed hatched the eggs in freshwater. Another doctor volunteered to be bitten by the hatched mosquitoes. In a few weeks, this doctor was dead from yellow fever. Reed designed an experiment to prove that the mosquito transmitted the yellow fever microbe in its saliva when it bit a person. He first disproved that yellow fever is transmitted by touching tainted objects. He set up a one-room barracks that was provisioned with the blood- and vomit-covered bed linens, towels, and clothing worn by soldiers who had died of yellow fever. Several healthy soldiers volunteered to stay in this rather disgusting room for a few weeks. None of them came down with yellow fever. So contact with the bodily fluids of diseased patients did not cause yellow fever. Reed then conducted

86  Germ Theory part two of his experiment. He divided a barracks room in half with a screen. He also put screens on all the windows. Some volunteers lived in the half that had no mosquitoes. They never contracted yellow fever. One volunteer lived in the half of the barracks into which Reed had released mosquitoes known to carry yellow fever. This volunteer did get yellow fever, but he survived. Reed concluded, correctly, that yellow fever was spread when the Aedes aegypti mosquito bit a person who already had yellow fever. The mosquito took in the microbe along with the person’s blood. The microbe stayed in the mosquito’s body until the bug bit another person and transferred the microbe to the healthy person via its saliva. So the Aedes aegypti mosquito was the vector for yellow fever. It was later learned that yellow fever is caused by a virus. (A vaccine for yellow fever was discovered in 1937.) Dr. Walter Reed (for whom a famous Washington, D.C., hospital is named) immediately ordered that screens be placed on all barracks’ windows. He prohibited soldiers from keeping any standing water around in buckets or other containers. All open water containers had to be emptied right away to keep the mosquitoes from breeding in the water. These simple measures significantly reduced the number of people who contracted yellow fever. Reed used the same rules during the building of the Panama Canal several years later, saving many lives. Within a few short years, researchers identified vectors for several other diseases. Flies were the culprits in spreading many diseases. Flies that came into contact with cholera-laden feces could pass the bacteria on to others when they landed on food or other things people handled. Flies could also be blamed for helping spread typhoid from feces to food. The flies in hospital tuberculosis wards were even found to pick up the disease from contaminated substances and transfer it in their bites to other people. Mosquitoes were found to transmit malaria, one of the most widespread and deadliest diseases known. Lice were discovered to carry typhus, and ticks were later found to transmit a number of diseases, including Rocky Mountain spotted fever and Lyme disease. The more doctors learned about diseases, the more insect vectors they found that transmit them.

“Magic Bullets” and Antibiotics

B

y the dawn of the twentieth century, researchers had devised a means of making vaccines to combat diseases caused by viruses. This may seem odd, as no one then had ever seen a virus. Yet the process of weakening invisible viruses was fairly straightforward. Once a solution was made that contained only very attenuated viruses, it could be injected into a person. The person would develop an immunity to the disease. Inoculation worked to prevent or treat rabies, smallpox, and other viral diseases. Pasteur had found a way to kill some disease-causing bacteria through heating or boiling. This procedure might work well for milk or wine, but boiling a person who is suffering from a bacterial disease is highly counterproductive. Another way had to be found to combat disease-causing bacteria that were already inside the human body.

The First Germ Killers Paul Ehrlich had worked in Koch’s lab. When Ehrlich got tuberculosis, he spent some time recovering in Egypt. When he was fully recovered, Ehrlich returned to Germany and set up a lab with Emil von Behring, a noted bacteriologist. Together, the researchers labored for three years to find a drug to combat diphtheria, an awful

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88  Germ Theory and often fatal childhood disease. In 1892, they announced that they had developed a cure for the dreaded disease. The scientists had created an antitoxin using blood serum, the clear part of the blood that often contains antibodies that fight a particular disease. They used serum taken from animals infected with diphtheria. When injected into a child suffering from diphtheria, the serum cured the disease. By 1901, deaths from diphtheria fell from 70% to 21%. Behring won a Nobel Prize for his work. Paul Ehrlich was not an easygoing man. He became extremely jealous of his prize-winning, now-former colleague. Ehrlich determined to make his mark on the history of medicine. He spent more than a decade searching for a “magic bullet” that would cure a bacterial disease. He was especially keen on curing sleeping sickness. During his labors, he found that a red dye, called trypan red, cured lab mice infected with sleeping sickness. Alas, it did not work on human victims of the disease. Ehrlich was not discouraged. Instead, he analyzed trypan red to find out what made it at least partly effective. Well versed in chemistry, he began replacing the nitrogen in trypan red with other elements, such as tiny amounts of arsenic. Ehrlich was the first chemist to manipulate molecules by replacing some of their components with other substances. For years, Ehrlich manipulated the trypan molecule. In 1907, during his 606th manipulation, Ehrlich found a molecular combination that seemed promising. After testing it on numerous disease-causing bacteria, Ehrlich found that “formula 606” was able to kill the spiral-shaped (spirochete) bacteria that caused syphilis, a sexually transmitted disease. Ehrlich was a bit disappointed that he had not found a cure for sleeping sickness. Still, he tested his new formula for years to make sure it was safe and effective. In 1910, he announced that he had discovered a chemical that could cure syphilis. He renamed “formula 606,” calling it salvarsan. It was the first “magic bullet” drug. Because it contained arsenic, a known poison, doses of salvarsan had to be small and carefully monitored. But the drug worked, curing a disease that affected millions of people.

Success with Sulfa German scientist Gerhard Domagk followed in Ehrlich’s footsteps, looking at different dyes as possible sources for antibacterial drugs. Domagk was intent on conquering Streptococcus, a type of bacteria

“Magic Bullets” and Antibiotics  89 that caused a variety of diseases, such as childbed fever, scarlet fever, and fatal blood poisoning. Domagk experimented with a red dye that showed promise in killing strep infections in both mice and humans. Domagk worked at the German pharmaceutical company Bayer, where an amazing and new painkiller—aspirin—had been developed and marketed since the late 1800s. Like Ehrlich before him, Domagk worked for years experimenting with different dye compounds, trying to find one that could kill the strep bacteria. A few days before Christmas in 1932, Domagk was working with an orange-colored crystal substance that had had no effect whatsoever on cultured strep bacteria. As a last resort, and just before he left for the holidays, Domagk injected the orange crystal substance into mice that had been given a fatal dose of strep bacteria. Days later, when he returned to the lab, Domagk was astounded to see that the mice—which should have been dead—showed no signs of illness. The “magic” orange crystal substance, which Domagk dubbed Prontosil, had cured the strep infections. Prontosil was one of a group of compounds called sulfonamides. Sulfonamide molecules are ring shaped and have sulfur atoms attached to the ring. This and later drugs derived from the same family are known as sulfa drugs. Domagk proceeded to find out why Prontosil had not killed the cultured bacteria. He discovered that the drug works only by damaging, not killing, the bacteria in the body. Only when the bacteria were damaged could the immune system easily finish them off. Sulfa drugs were developed to cure staph infection, gas gangrene, strep throat, and many other diseases. Prontosil had to be injected into the body to be effective. Other medical researchers made variations of Prontosil that could be taken as pills, by mouth. These new forms of sulfa drugs were called sulfanilamides. Within a few years, more than 1,300 sulfanilamide drugs were developed to destroy a whole host of infectious diseases. Domagk won the Nobel Prize for Medicine in 1939.

“Magic” Mold Alexander Fleming might have spent his entire life working as a shipping clerk if his rich uncle had not died and left him a handsome inheritance. Fleming used some of the money to pay for medical

90  Germ Theory school, which he began in 1901. After graduating, Fleming worked in the Inoculation Department of St. Mary’s Hospital, London, where he remained until his death in 1955. Fleming was interested in antibacterial substances, but he felt uncomfortable using the nonorganic, or synthetic, drugs developed by Ehrlich and Domagk. Fleming sought a more “natural” bacteria killer. As so often happens, Fleming made his momentous discovery quite by chance. Fleming’s lab at the hospital was notorious for its “casual” atmosphere. That is a polite way of saying that Fleming was not the neatest scientist in London. Often, he would leave petri dishes of bacterial cultures lying around the lab for weeks or months before an assistant found and discarded them. In the summer of 1928, Fleming took several weeks’ vacation. When he got back to his lab, he resigned himself to sorting through the stacks of abandoned petri dishes that had not been disposed of. Fleming glanced at the unremarkable agar cultures one by one and tossed them into the trash

Gram Stains In 1884, Danish doctor Hans Christian Gram developed a stain that made viewing bacteria under a microscope much easier. The Gram stain, as it is called, is based on fundamental differences in the chemicals and structures of different types of bacteria. In conducting a gram stain, bacteria are heated until they stick to the microscope slide. Then they are treated with a crystal-violet dye. This dye turns the cells purple. The slide is then washed, first with an iodine solution and then with alcohol (or a similar organic solvent). The slide is then placed back under the microscope. Gram-positive bacteria look purple because their thick cell walls hold the purple dye. Gram-negative bacteria have thinner cell walls that cannot hold the stain very well. The alcohol washes away the dye, so gram-negative bacteria have little or no color. To aid studying gram-negative bacteria, researchers stain them with a red dye that makes them easy to see.

“Magic Bullets” and Antibiotics  91 basket. He was about to throw out another one when something about it caught his eye. This neglected and long-forgotten culture of staphylococcus bacteria happened to have become contaminated with airborne microbes. The contaminant had grown well on the culture medium. The contaminated area resembled a fuzzy green blob about 1 inch (2.5 centimeters) in diameter. Fleming instantly recognized the green fuzz–blob as Penicillium notatum, or Penicillium mold. There was nothing remarkable about that. Many people knew that this mold grew on bread, for example. What struck Fleming, however, was that where the Penicillium blob had developed, all the staph bacteria had disappeared. Obviously, staph growth had been inhibited or killed in the clear area around the mold. Fleming immediately set to work to discover what other bacteria this mold might kill. He discovered that Penicillium mold produces penicillin, a molecule that could be used to effectively kill strep infections, syphilis, gangrene, and a host of other bacterial infections.

Figure 8.1â•… This photomicrograph shows multiple chains of gram-positive Peptococci bacteria.

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Figure 8.2â•… This photograph features the original culture plate of the fungus Penicillium notatum, made by Scottish bacteriologist Alexander Fleming while he worked at St. Mary’s Hospital in London.

Unfortunately, Fleming found that the mold was unstable and therefore difficult to purify. Until it was purified, penicillin could not be used to fight infection. Fleming was not a chemist, so he did not know how to proceed. Fleming’s discovery was ignored for years, until it was rediscovered by researchers Howard Florey and Ernst Chain at Britain’s Oxford University. These scientists successfully used a freezing technique to purify penicillin. The stable, purified drug turned out to be

“Magic Bullets” and Antibiotics  93 many times more effective at combating bacterial infections than the mold with which Fleming had worked. After extensive laboratory testing, the scientists published their results in 1940. Penicillin was tested successfully on human volunteers for the next few years. By the time World War II ended (1945), penicillin was being used as an antibiotic to combat a wide variety of gram-positive infections. In 1944, Fleming, Florey, and Chain received the Nobel Prize in Medicine for giving the world the first antibiotic.

Drugs from Dirt The principles of antisepsis and the revelation that anthrax spores could survive in soil led to an almost morbid fear of soil, or dirt, among a majority of people in Europe and America. Little did they know, nor could they have anticipated, that the next “wonder drug” would be derived from soil microorganisms. Selman Waksman was a soil microbiologist (a scientist who studies microbes) who emigrated to the United States from his

Wonder Drug Penicillin was hailed as the first “wonder drug” to cure many of the diseases that had plagued humankind for millennia. It is certainly true that penicillin proved to be effective at killing a whole host of disease-causing microbes. As soon as it became commercially available, laboratory researchers began testing penicillin on every microbe they could get their hands on. Penicillin is especially effective against staphylococcus infections and saved countless lives among the troops fighting in World War II. Cases of gangrene and sepsis (blood infection from wounds) fell dramatically if penicillin was given to wounded soldiers in time. Many people ecstatically proclaimed that penicillin would eradicate disease altogether. It would not be long before they learned otherwise.

94  Germ Theory native Ukraine in 1910, when he was only 22. For a while, Waksman worked on a farm in New Jersey, where his interest in soil began. In 1915, he went to college to study soil microbiology—the study of the teeming zillions of microbes that live in soil. He got a job at the U.S. Department of Agriculture but continued his education until he earned a doctorate. He then became a professor at his alma mater, Rutgers University, where he gained widespread recognition for his work identifying numerous soil microorganisms. He was particularly fascinated by a funguslike soil bacteria that he had discovered and called Actinomyces griseus. His interest in its potential as an antibiotic increased after he attended a lecture by Alexander Fleming. If Fleming’s penicillin was an effective antibiotic, maybe Actinomyces or some other soil microbe could be put to similar use. Waksman was particularly keen on finding an antibiotic that could combat gram-negative microbes—those microbes that penicillin could not kill. Gram-negative bacteria, including Salmonella, E. coli, Shigella, and V. cholerae, caused some very nasty diseases that killed millions of people. By the time Waksman began devoting himself solely to seeking his new antibiotic in 1939, he was a world-renowned expert on soil microorganisms. Rutgers University set him up in a state-of-the-art laboratory. Within a year, Waksman revealed the antibiotic properties of the Actinomyces bacteria with which he was experimenting. Waksman isolated one especially effective strain of the fuzzy, fungus-like bacteria, which he called actinomycin. The drug worked well in culture, but when Waksman tested it on infected mice, all the animals died—from the actinomycin, not the infection. Waksman’s preparation was too strong and too toxic. Undeterred, Waksman continued to experiment with substances related to actinomycin. In 1940, he isolated and cultured another substance that effectively killed microbes in a petri dish. He called the active ingredient in the new substance streptothricin. Waksman tested his new antibiotic on animals that had deadly gram-negative infections. The streptothricin cured the ailing animals. Waksman was delighted, but his elation was short lived. Only a month or so after curing the animals of infection, the streptothricin poisoned their kidneys, and the animals died. Because of this delayed toxicity, streptothricin could not be used as an antibiotic.

“Magic Bullets” and Antibiotics  95

Figure 8.3â•… Selman Waksman (left) talks to Alexander Fleming (right) and Gerhard Domagk (standing). All three men received the Nobel Prize in physiology or medicine. Fleming won in 1945 for the discovery of penicillin. Domagk won in 1939 for the discovery of prontosil rubrum as an antibiotic. Waksman won in 1952 for the discovery of streptomycin.

Shortly after this disappointment, a graduate student named Albert Schatz came to Rutgers to study with Waksman. Though at first Schatz was not that interested in antibiotics, he found Waksman’s enthusiasm contagious. Soon, Schatz was practically living at the lab because he spent so many hours looking for an Actinomyces that had antibacterial properties. After three months of exhaustive searching, Schatz found what he was looking for. Amazingly, it was the same Actinomyces griseus that Waksman had discovered 20 years before.

96  Germ Theory Schatz and Waksman found that its bacteria-killing properties were far greater than those of streptothricin. In fact, the new antibacterial substance could destroy both gram-positive and gram-negative disease bacteria. Testing on infected animals showed that the new substance quickly killed infections without any serious side effects. Waksman unveiled his new antibiotic, which he called streptomycin, in 1944. Streptomycin was the first antibiotic that could destroy tuberculosis bacteria. Because it could kill both gram-positive and gram-negative bacteria, streptomycin was hailed as the first broad-spectrum antibiotic, or one that was effective against a wide variety of bacteria and diseases. In 1952, Waksman was awarded the Nobel Prize in medicine. (Today, most scientists think it was unfair that Schatz was overlooked for his important contributions to this discovery.)

Wonders Galore After these three antibiotics were discovered and made widely available, people rejoiced that the war on illness had been won. All over the world, researchers were discovering new antibiotics to cure every imaginable infectious disease. Tetracycline (1950s), doxycyline (1966), minocycline (1972), erythromycin (1952), vancomycin (1956), methicillin (1960), oxacillin (1962), amoxicillin (1969), and other antibiotics too numerous to mention were introduced in rapid succession. By 1965, there were more than 25,000 different antibiotics available to patients. For a few years, these were indeed wonder drugs. They cured illnesses that not many years earlier would have killed millions of people. Nearly everyone was convinced that infectious diseases were under control and would no longer be a threat to humanity. Medical science had finally conquered germs and infections. Or had it?

Life in the Age of Antibiotics

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hen germ theory first began to take hold in the public mind, many people became extremely fearful of the sea of germs that surrounded them. Some fears were fed by doctors who cautioned against all types of “casual” contact that might transfer “germs.” “Experts” described germs as “murderous,” “cunning,” and “evil” creatures, unseen enemies that were everywhere waiting to strike down unwary humans. By the early twentieth century, the fear of germs affected many aspects of everyday life. The hemlines on women’s dresses got shorter to prevent them from touching the “germ-infested” sidewalk. Koch’s discovery of anthrax germs lurking in soil resulted in generations of children brought up never to get “dirty” when they play. Pasteur had shown that bacteria were carried on dust in the air. Thus began the unending war on household dust. Keeping the home clean and dust free became an obsession, a matter of life and death. Insects, especially flies, were viewed with horror by people who were certain that they brought death to anyone they touched. The recognition that germs carry disease did have some positive effects. Much-needed advances in public sanitation were implemented, such as providing clean drinking water and efficient sewer systems. Food safety measures, such as milk pasteurization, were also instituted. But the fear of germs preyed on people’s minds and

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98  Germ Theory made many, frankly, neurotic. People feared traveling on buses and trains: Who knew what germs the other passengers carried? People feared going into crowded department stores and buying things others might have touched. They were afraid to eat at restaurants, where strangers handled the food they would eat. People feared shaking hands. Some developed a phobia about using doorknobs or handling

Typhoid Mary Mary Mallon immigrated to the United States from Ireland in 1884. Between 1900 and 1907, she worked as a cook in New York City. Mallon cooked for several well-to-do families. During this time, about 24 people in the families she worked for contracted typhoid fever. Mallon was a generous and tenderhearted woman, and she tended those who fell ill. Still, some of them died. In 1906, Mallon was hired as a cook for a wealthy Long Island family. Within two weeks, 6 of the 11 family members were hospitalized with typhoid fever. Public health officials began to investigate all these cases of typhoid to see what the families had in common. They found that all the families had shared Mary Mallon’s services. One health official tracked Mallon down and asked to examine her. She refused. For months, Mallon denied that she was the cause of the typhoid outbreak. Eventually, police had to arrest her and take her to a hospital. There, tests revealed that Mary Mallon did harbor typhoid in her body. Typhoid is transmitted when a person ingests food or water contaminated by feces that contain typhoid bacteria. It seems that Mallon was not as careful as she should have been in washing her hands after using the toilet. Mary Mallon turned out to be the first person in the United States to be identified as a healthy carrier of typhoid. For some reason, the bacteria did not make her sick. However, her poor sanitary habits made others sick.

Life in the Age of Antibiotics  99 money: What germs did these things carry from others’ hands? The horror of germs carried on the human body was sometimes taken to absurd, even harmful, extremes. Until the 1950s, some mothers had their babies wear bibs that warned people not to touch them. Relatives and sometimes even the mother herself were afraid of cuddling or kissing children for fear of transferring germs to them.

Figure 9.1â•… Mary Mallon, know as “Typhoid Mary,” was the first person identified as a carrier of typhoid bacilli in the United States. She is pictured here while institutionalized on Brother Island, where she stayed from 1914 until her death in 1938.

Mallon was released from the hospital after she promised not to work as a cook ever again. She lied. After changing her name to Mary Brown, she got a job as a cook in a hospital. She infected 25 patients with typhoid. City officials had had enough. In 1915, health officials arrested Mallon and quarantined her for life in a hospital on a small island near the city.

100  Germ Theory The fear of contagion from other people also encouraged one very unwholesome attitude held by some Americans. Germs became associated with “foreigners.” Immigrants, the poor, and the working classes were all viewed with disgust and fear by people who believed them to be the carriers of disease-causing germs, especially tuberculosis. Concern for one’s health became an excuse for racial and ethnic hatred and discrimination. Between 1874 and 1914, more than 30 million immigrants were living in American cities, and contact with them was unavoidable. Germ theory became, for some, just one more weapon in their ranting war against “foreigners.” Eventually, the “universality” of germs served to improve the lives of immigrants and the poor. In his 1895 article “The Microbe as a Social Leveller,” New York City health commissioner Cyrus Edson wrote: “The microbe of disease is no respecter of persons. .€.€. It cannot be guarded against by any bank account, however large. The [wealthy] cannot afford to sit at [their] well-covered table and forget the .€.€. poor’s room. .€.€. Sooner or later, disease will break out in [that] room, and the microbes or their spores will in time pass [into] the mansion to find their prey. This is .€.€. the chain of disease which binds all the people of a community together.” The rich and middle classes took Edson’s warnings seriously. Thus began a movement to improve the living conditions of the poor. Wages were raised to help the poor afford a decent diet and warm clothing. Laws were passed to improve housing conditions and sanitation in slum buildings. Public health centers were opened to treat sick poor people who otherwise could not afford health care. People understood that the health of all depended on the health of every individual.

Commercializing Cleanliness It did not take very long for businesses and corporations to realize that there was lots of money to be made by exploiting people’s fear of germs. The age of packaging had arrived. Companies began marketing every conceivable household object as being “germfree.” To allay consumer anxiety about contamination with germs, most consumer goods were packaged in sealed wrappings of cellophane, an early type of plastic. Food, clothing, toothbrushes, toys, and just

Life in the Age of Antibiotics  101 about anything else that might come into contact with a buyer’s body was wrapped and sealed in cellophane. Companies that made personal and household hygiene products were particularly keen on advertising their wares as germfree. They developed new products to address consumers’ fears. Mouthwash, soap, toothpaste, and a host of other products were advertised as having “germ-killing” properties. One soap manufacturer’s ad contained a “Message to Good Housewives” that warned that a house might look clean, “but don’t get the idea that you can judge simply by the appearance of things.” Germs were lurking everywhere. What the good housewife needed were strong disinfectant soaps and cleansers, for “wherever there is dirt, germs can breed.” Disinfectants for cleaning the bathroom became a household requirement. Most items sold for use in kitchens, bathrooms, and laundries sported the label “sanitary” or “germ-proof.” Using a broom and dust mop for cleaning became “more and more .€.€. considered no cleaning at all” because it raised germ-ridden dust but did not get rid of it. Only vacuums would do. Ads for vacuum cleaners had testimonials from “medical experts” that this brand of vacuum did the best job of removing germ-laden dust from carpets. The fear of germs led eventually to a radical change in style that affected all aspects of life. The overstuffed living rooms of earlier days gave way to the spare, clean lines of the “streamlined” style of the 1950s. Smooth, hard surfaces were all the rage. The new “sterile” style was easier to keep clean. It was no longer fashionable for men to grow beards. Hair harbored germs, so the clean-shaven look was “in.” Women’s fashions, too, had lean and spare lines. The “sack” dress, just a tube of fabric, was the sparest of all.

Playing It Too Safe Today the intense fear of contagious diseases has lessened considerably. Most people feel confident that antibiotics will cure them of any “bug” they come down with. Yet people are still obsessed with living a germfree life. Overuse of germ killers and antibiotics has actually made us more, not less, vulnerable to infectious diseases. Except for the produce aisle, modern supermarkets are chock full of products that “kill germs,” are “antimicrobial,” or contain strong disinfectants. From floor waxes to furniture polish, from laundry

102  Germ Theory detergent to air fresheners, nearly every product boasts some germkilling or antiseptic ingredient. To make matters worse, most of the meat people eat today is “grown” in factory farms. On these farms, tens of thousands of cows, chickens, pigs, and other edible animals are raised in enormous factory-like enclosures where all the animals are crowded together. Of course, when animals live in highly crowded conditions, infectious diseases can sweep through the facility and easily kill them all. To prevent contagious diseases from spreading, meat animals are routinely injected with antibiotics or given a steady diet of antibiotics with their feed. People ingest these antibiotics when they eat meat from these animals. Another problem is people’s thoughtless demands for antibiotics even when they are unnecessary. Many people go to the doctor when they have a cold and insist on being prescribed an antibiotic to “cure” their illness. Colds are caused by viruses. Antibiotics kill bacteria and have no effect on viruses. Yet people insist on getting an antibiotic even if their ailment is caused by a virus. Doctors, too, are to blame for bowing to the demands of their patients. Instead of explaining why they will not prescribe antibiotics, many doctors find it less of a hassle to give the patient the useless antibiotic. The doctor knows it will do no good, but it is easier to provide it than to take the time to reason with a demanding patient. In short, modern life is saturated with microbe-killing substances. The average person may think this is a good thing that helps prevent disease. Experts know that just the opposite is true. Many are very worried about the effects these substances are having on disease-causing bacteria.

Drug Resistance Bacteria are single-celled organisms that reproduce by dividing in half, so one bacterium becomes two bacteria. Like all living things, when bacteria reproduce, they first make a copy of their genes. One full set of genes goes to each of the bacteria. Many bacteria reproduce very quickly, about once every 15 minutes. The more an organism reproduces, the more likely it is that an error or change will occur in its genes. An error or change in a gene is called a mutation. Rapidly reproducing bacteria generally have lots of mutations in their genes.

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Figure 9.2â•… At many factory-based poultry farms, chickens lay eggs in tightly packed coops. Such overcrowding can breed disease, so the chickens are given large doses of antibiotics in their feed to prevent the occurrence and spread of disease. People ingest these antibiotics every time they eat chicken or other factory-farmed meat.

Mutations occur randomly. Most mutations have no effect on the organism’s ability to survive. These useless mutations may or may not stay in the genes. Some mutations, however, help an organism survive, especially in an altered environment. In the case of bacteria, the altered environment has become one that is saturated with disinfectants and antibiotics. In this environment, a mutated gene that makes the bacteria immune to an antibiotic helps the bacteria survive. These hardy bacteria pass on the gene from one generation to the next. Pretty soon, all the bacteria have this antibiotic-resistant gene. For example, for years after it was discovered by Domagk, one sulfonamide drug was shown to have some effectiveness in treating tuberculosis (TB). However, it soon became clear that more than one drug had to be administered to effect a cure. Even so, after a number of years, TB bacteria mutated to become resistant to these antibiotics, and more new drugs had to be developed to treat TB.

104  Germ Theory It did not take long for the TB bacteria to develop resistance to the killing effects of each new antibiotic that was thrown at them. One common strain of tuberculosis today is resistant to every antibiotic known to medical science. Nothing can kill it. People who get this form of TB will likely die from the disease. There are now drug-resistant bacteria that cause a wide variety of diseases. People’s overuse of disinfectants and antimicrobial substances is partly to blame. But there is another reason drug resistance is on the upswing. Doctors too often give a patient an antibiotic that is too strong. For example, a simple infection may be cured with a dose of penicillin, which specifically targets the one type of bacteria that is causing the infection. However, instead of

Do Good or Do Well? Large pharmaceutical (drug) companies are businesses that need to make a profit. Many experts claim that Big Pharma (as these drug companies are called) has in recent times become far more focused on making money than on creating needed new drugs. For example, Big Pharma concentrates on research that will yield drugs for chronic (lifelong) illnesses or conditions. It is extremely profitable to make drugs to treat an illness people will have forever or to create a drug that will “cure” a condition, such as baldness, that will always be with us. It is certainly important to create drugs to treat chronic illnesses, such as diabetes. But it is far more important to create new antibiotics to combat deadly infections than it is to produce “vanity” drugs that grow hair. The problem is that there is not much profit in making antibiotics. A new antibiotic must be formulated and then tested for safety. Only then can it be sold to the public. Of course, eventually the disease-causing bacteria will become resistant to the new antibiotic. All of the drug company’s research will have been wasted. They will have to start again making another antibiotic. This process is not profitable. For this reason, very little research is being done to develop new antibiotics to kill bacteria that have become resistant to existing drugs.

Life in the Age of Antibiotics  105 prescribing a “narrow” focus antibiotic like penicillin, the physician prescribes a broad-spectrum antibiotic that is able to kill a wide variety of bacteria. When broad-spectrum antibiotics are overprescribed, many types of bacteria may develop resistance to the drug. Thus, disease-causing bacteria become resistant to both narrowfocus and broad-spectrum antibiotics. Pretty soon, there is nothing available that can kill them. Some disease-causing germs, particularly certain viruses, mutate regularly, without human interference. The influenza virus, for example, undergoes constant mutations. Every year during flu season, the flu virus is slightly different than it was before. A small mutation in the flu virus is called genetic “drift.” A slightly mutated flu virus might be suppressed by an existing vaccine that reduces the seriousness of the disease. Every few decades, however, the flu virus undergoes a dramatic mutation in its genes called genetic “shift.” A flu virus with drastically altered genes is not suppressed by any flu vaccine that was used before. When the flu virus undergoes a genetic shift, it may cause a flu pandemic. In 1918–1919, a radically altered flu virus swept around the world, killing tens of millions of people. Experts have been warning people to be ready for another genetic shift in the flu virus and for another flu pandemic. In 2009, a “swine” flu pandemic swept the globe, though there was a vaccine available that prevented or lessened the effects of the disease. Earlier, some public health officials believed that the “bird flu” that had been transmitted to people from infected fowl would cause the next flu pandemic. So far, though, bird flu has not mutated in one crucial way: Unlike the 2009 swine flu, it cannot yet be transmitted from person to person. As long as bird flu is transmitted only from bird to human, it will not cause a pandemic. It is only when it mutates so that it can be transmitted from human to human, that it is very likely that a bird flu pandemic will strike. Experts are trying to convince drug companies to begin working on a vaccine that will help protect the public against the worst effects of bird flu. Being prepared before the flu pandemic starts may save millions of lives. Many doctors and public health officials believe that we are approaching the end of the age of antibiotics. Soon, they say, all disease-causing bacteria will be resistant to drugs that once killed them. Viruses, too, will mutate to resist the vaccines that humans have concocted to kill them. What new lines of defense will people have against these resistant germs?

Looking Forward Take Action

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here are several actions people can take to help prevent the evolution of more drug-resistant, disease-causing bacteria. For example, people can use antibacterial or disinfecting products only when they are essential. Studies have found that people who use antibacterial soaps have more skin problems and get more infections. That is because the vast majority of bacteria that live on human skin are either helpful or harmless. Killing them is counterproductive, if not downright harmful. People can also recognize that viral infections, such as colds, do not respond to antibiotics, so they should not demand them from their doctors. Further, people should try to avoid eating meat or fowl that has been raised on antibiotics in factory farms. That might be difficult for an individual to do. Another approach is to contact representatives in Congress to ask them to pass laws to prohibit factory farming that requires the use of antibiotics. Or people could write letters to meat and poultry companies stating that they will not buy their products until they stop factory farming and using antibiotics.

After Antibiotics: What’s Next? Many infectious disease experts believe that we are rapidly entering the post-antibiotic age. This is a time when all germs will be drug

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Looking Forward  107 resistant and antibiotics will no longer be effective. Though this may sound scary, take heart. There is a new avenue of research that may prove to be far more effective and long lasting in combating germs than antibiotics ever were.

Infecting the Infectious As discussed earlier, every organism is vulnerable to some types of germs that can infect it. This means that even bacteria sometimes “get sick.” There are certain viruses that specialize in infecting bacteria. These viruses, called bacteriophages, kill the bacteria they infect. Medical researchers are working hard to identify bacteriophages that destroy the germs that cause human disease. Not every virus will infect every type of bacteria. So scientists must experiment to find the bacteriophage that attacks and kills a particular disease-causing bacteria. Once a useful bacteriophage is identified, researchers must figure out how to make it into a drug. The drug must be harmless to the billions of useful bacteria humans have in their bodies. The bacteriophages in the drug must also be able to find the disease-causing bacteria where they occur in the body and then destroy them. Developing bacteriophage drugs is not easy, but most experts believe that this approach is humanity’s best hope for replacing antibiotics and curing infectious diseases.

New Agents of Death Another key concern among infectious disease professionals is the rise of new diseases that have never before been known to infect humans. Many of these new diseases are caused by viruses, and most cannot be cured because there is no vaccine to combat them. (Of course, bacteriophages do not work on these germs, because they themselves are viruses.) The majority of these new viral diseases are extremely deadly. Few people who get them survive.

Where No Man Has Ever Gone Before€.€.€. Where do new viral diseases come from? Nearly all have infected people who have intruded into unspoiled natural areas where

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Figure 10.1â•… This color-enhanced transmission electron micrograph shows T2 bacteriophages invading a host.

humans did not normally go. Increasingly, people are hacking down rain forests and jungles to make money selling the wood. Or they clear the jungle in order to mine metals and other materials. Sometimes, people move deep into rain forests just to live. In some tropical countries, population growth is forcing people to find space to live where people have never lived before. When humans begin occupying deep rain forests where people have never lived, they come into contact with viruses that have never “met” humans before. The bodies of most animals, including humans, harbor bacteria or viruses with which the species has lived for hundreds or thousands of years. During this long period of time, the virus and the animal body adjust to each other. They reach a kind of truce. The virus does not sicken or kill the animal, and the animal’s immune system learns to tolerate the virus.

Looking Forward  109 When humans live or work where no human has gone before, they come into contact with wild animals that harbor these particular animal viruses. The animal viruses may then infect the intruding humans. Of course, humans do not have any immunity to these animal viruses. When the animal viruses enter the human body, they cause highly virulent diseases. Because the people that get them lack any immunity, these diseases are usually fatal.

“Bleeding” Diseases Many of these animal viruses cause hemorrhagic, or bleeding, diseases in humans. The first hemorrhagic viral diseases arose in and around the Amazon rain forest in South America in the 1950s and 1960s, when roads were first built into the forest. Some of these diseases affected relatively few people in the immediate area. The most terrifying hemorrhagic viral diseases have come from Africa, though not all of them initially affected Africans. Marburg fever was spread by the international trade in laboratory animals. A German medical research lab in Marburg, Germany, had imported some monkeys from the rain forests of Uganda. Soon the monkeys sickened and died. Then the researchers who worked with the monkeys developed a violent hemorrhagic fever. The family and friends of the lab workers also sickened, and many died. Despite a worldwide quarantine on imported African monkeys, Marburg virus still erupts from time to time. No one knows where the virus came from or how it is transmitted. In 1976, the most terrifying virus of all emerged in the African nation of Sudan. Ebola fever is the deadliest disease known to afflict humans, on par with rabies. The Sudan outbreak killed nearly half of those affected. Two months later, Ebola fever appeared in Zaire. Ninety percent of the afflicted died. Ebola fever outbreaks seem to occur randomly in Africa. They rampage through a village or region, killing hundreds, and then disappear. The virus may reappear at any time, anywhere. No one knows what causes an outbreak suddenly to begin. Ebola begins with high fever, blinding headaches, and joint and muscle pain. More horrifying symptoms quickly appear. The Ebola virus causes bleeding from most of the body’s tissues. At first, the victim suffers from internal bleeding, or hemorrhaging from internal organs. Internal organs such as the liver become rock-hard

110  Germ Theory masses of clotted blood. The kidneys fill with clotted blood, and kidney failure soon follows. Fairly soon, the body runs out of the chemical it uses to clot blood. When this chemical is gone, hemorrhaging becomes uncontrollable. Blood fills the lungs, and arteries and capillaries collapse. Blood that has accumulated under the skin begins to seep out from its pores. Bleeding from the nose, ears, and eyes is common. As the victim nears death, the virus has liquefied all the internal organs into a bloody soup. Blood in the brain often causes seizures. Mercifully, at this stage, the patient goes into shock

AIDS Acquired immune deficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV). HIV is believed to have entered the human population from chimpanzees several decades ago. It is possible that the chimps were imported into the United States from Africa for medical experiments. The virus did not harm the chimps that harbored it. But contact with the chimps transferred the virus to humans. AIDS is a very complicated disease. It is transmitted from one person to another mainly through sex and intravenous drug use. AIDS attacks cells in the human immune system, which is why it can be so deadly. Today there are drugs that help control the disease in the millions of people around the world who have contracted the virus. There is no drug to cure or prevent it. Still, the best way to avoid AIDS is through safe sex and not using injectable drugs. AIDS is caused by a special type of virus called a retrovirus. Most viruses reproduce by first making genetic material called RNA, which then makes DNA. Retroviruses add an extra step to this process. They first make DNA, which then makes RNA, which then makes more DNA. Why the extra work? Scientists believe that producing the extra DNA helps the virus become part of and hide in the cells it infects.

Looking Forward  111 (from blood loss) and soon dies, usually from heart failure. As with Marburg, no one knows where Ebola came from or how it is transmitted. It is, however, contagious via contact. Many experts contend that these and other new and deadly diseases arose from close human contact with monkeys. The trade in monkeys for medical research is a prime suspect in the development of these highly infectious diseases. Africans who supply the monkeys for medical experiments in the West travel deep into the jungle to capture the animals, which have had little or no previous contact with

Figure 10.2â•… This highly magnified transmission electron micrograph image reveals the presence of mature forms of HIV in a tissue sample.

112  Germ Theory

Figure 10.3â•… This colorized transmission electron micrograph reveals the shape of an Ebola virus.

humans. The African practice of hunting monkeys that live deep in the rain forest for food—known as bush meat—may also account for the occurrence of these diseases among Africans. In short, these new and deadly viral diseases are afflicting humans when they come into contact with wild animals. When people intrude into and/or destroy the habitats of the animals that harbor the viruses, the viruses are transmitted to humans. It is not just monkeys that have brought us new diseases. African antelopes, rodents, and squirrels also harbor viruses that are transmitted to humans via insect or rodent vectors. In an age when thousands of people jet around the globe daily, it is impossible to ensure that new viruses will not be carried throughout the world. It is too late to contain Marburg and Ebola. Yet it is not too late for people to stop intruding into unspoiled natural areas where they come into close contact with wild animals. It is also not too late to stop medical experimentation on animals taken from the wild. Scientists believe that these new viruses do not mutate before

Looking Forward  113

West nile Virus West Nile virus reached the United States in 1999. Its first victims lived in New York City, where they came down with a strange disease that affected the nervous system and also caused hemorrhaging. Soon, veterinarians at the Bronx (continues)

Figure 10.4 The transmission cycle of West Nile virus shows how it can be transferred from infected birds to humans (and horses) by infected mosquitoes.

114  Germ Theory (continued) Zoo reported that many of the zoo’s birds were dying of a similar disease. Analysis showed that both human and bird victims were infected with a new type of virus. Medical “detectives” determined that the disease was probably brought to the United States by an American who brought in an infected “exotic” tropical bird as a pet. The researchers subsequently found that a mosquito was the vector that transmitted the disease among infected birds or from birds to humans. During this first year, 66 New Yorkers were infected with West Nile virus, and 7 died. Despite efforts to deter or kill the mosquito, the virus spread quickly. By 2000, it had struck 21 people in 12 eastern states, killing 2 of them. A year later, it was found in the South and the Midwest. Within a few years, outbreaks of West Nile virus were reported throughout the nation. Most victims survive an attack of West Nile virus, but there is as yet no vaccine to fight it. Americans are advised to be on the lookout for dead birds, especially crows, during the spring and summer. Notify local health officials so the birds can be tested for West Nile virus.

infecting humans. Instead, humans contract the virus as it exists in the wild animal population. It is a change in human behavior (destroying rain forests), not a change in the virus, that has brought forth these lethal new diseases.

agarâ•… A jellylike, nearly transparent solid substance used to grow pure colonies of bacteria anatomyâ•… The internal and external physical structure of an organism anestheticâ•… A substance used to reduce pain; a painkiller antibioticâ•… A substance that disables or kills bacteria or other living disease-causing organisms antibodiesâ•… The cells produced by the immune system that specifically target one type of disease-causing organism; once the body has produced antibodies against a particular germ, that body is immune to the disease it causes antisepticâ•… A substance that kills germs on contact; a substance that prevents sepsis, or infection with germs attenuatedâ•… Weakened or reduced in force or effect bacteria (singular, bacterium)â•… Single-celled organisms that sometimes cause disease, but most of which are beneficial decomposers of dead organic matter bacteriophageâ•… A virus that infects and kills bacteria; specific bacteriophages infect specific bacteria binary fissionâ•… The process by which many single-celled organisms reproduce by dividing into two new cells; cell division biogenesis (also called cell theory)â•… The concept that all cells come only from other cells collagenâ•… A tough, structural protein used in forming bones, cartilage, muscles, and blood vessels

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116  Germ Theory contagionâ•… The spread of disease from one organism to another; also, contagious, describing a disease that can be passed from one organism to another cultureâ•… To grow a pure colony of microbes on a medium (agar); also, a culture, the pure colony of microbes growing on a medium diagnosisâ•… The identification of a disease or problem by examination of the symptoms disinfectantâ•… A substance that kills potential infectious organisms, used for cleaning in hospitals, homes, etc. endemicâ•… Naturally occurring in a particular region epidemicâ•… An outbreak of disease that afflicts many people in a given area evolveâ•… In organisms, to undergo changes resulting from gene mutations that aid in the organism’s survival fermentationâ•… The process in which yeast consumes the sugar in a liquid and turns it into alcohol, as in beer and wine; also, to ferment, to undertake this process fleaâ•… A tiny insect that is a parasite on many animals whose blood it sucks; fleas are also carriers of disease germâ•… The original, nonscientific term given to disease-causing organisms or agents hemorrhagicâ•… Referring to severe bleeding, as in hemorrhagic disease; also, to hemorrhage, or to bleed excessively either inside or outside the body herbalâ•… Relating to or made from herbs, plants, or plant parts used in foods and medicines hostâ•… The organism that is used by another organism (a parasite) for food, shelter, etc. humoursâ•… The four substances that early physicians thought were found in the human body that controlled human health; an imbalance in the humours was thought to be the cause of disease immunityâ•… The innate ability to resist disease; also, immune, not being vulnerable to a disease

Glossary  117 inoculateâ•… To introduce an infective agent into a culture medium or other organism; to treat (a person or other organism) with a vaccine to create immunity against a disease lice (singular, louse)â•… A tiny insect that lives as a parasite on warmblooded animals, particularly in the hair or fur; also a carrier of disease malariaâ•… A disease carried by mosquitoes via a protozoan parasite that invades red blood cells and causes intermittent fever; it is potentially fatal. microbeâ•… A general term referring to any microscopically small organism, but used mainly to describe those that cause disease microscopeâ•… An instrument with a lens that makes very small objects appear larger moleculesâ•… The basic units of chemical substances; in chemistry, all the atoms that make up an element or a compound mutationâ•… A random change that occurs in an organism’s (or virus’s) genes, especially when the genes are copied prior to cell division pandemicâ•… A worldwide outbreak of an infectious, contagious disease parasiteâ•… An organism that lives off another organism in such a way that the parasite benefits but the host is usually harmed; some parasites carry disease pasteurizationâ•… A process of long, gentle heating of liquids that was developed by Louis Pasteur to kill harmful microbes in the liquids quarantineâ•… The separation of diseased humans or animals from others to keep them from spreading their disease to others scurvyâ•… A disease caused by a deficiency of vitamin C, characterized by swollen, bleeding gums and opening up of old wounds spontaneous generationâ•… The disproved concept that life can arise spontaneously in substances and that living things do not necessarily come from other living things vaccineâ•… A preparation often containing weakened, or attenuated, viruses that is injected or ingested to build immunity to a particular viral disease

118  Germ Theory vectorâ•… An organism that transmits a disease-causing organism from one organism to another; for example, a mosquito that bites someone who has malaria will have the malaria parasites in its body and transfer them to the next person it bites, so the mosquito is the disease vector virulentâ•… Referring to a disease that is extremely serious, deadly, or contagious virusâ•… An agent of disease that is neither living nor dead but becomes active once inside a host, whose cells it uses to reproduce yeastâ•… A single-celled, fungus-like organism used to ferment wine and beer and also to make bread rise

DeKruif, Paul. The Microbe Hunters. New York: Harcourt, Brace, 1926. DeSalle, Rob, ed. Epidemic! New York: New Press, 1999. Karlen, Arno. Man and Microbes. New York: Putnam, 1995. Porter, Roy, ed. Cambridge Illustrated History of Medicine. Cambridge, UK: Cambridge University Press, 1996. Reh, Beth Donovan. Germs. New York: Thomson Gale, 2005. Tomes, Nancy. The Gospel of Germs. Cambridge, MA: Harvard University Press, 1998. Turkington, Carol and Bonnie Ashby. Encyclopedia of Infectious Diseases. New York: Facts On File, 1988. Waller, John. The Discovery of the Germ. New York: Columbia University Press, 2002. Zimmerman, Barry E. and David J. Zimmerman. Killer Germs. Chicago: Contemporary Books, 2003.

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Asimov, Isaac. How Did We Find Out About Germs? New York: Walker, 1974. Aymes, Sebastian. Magic Bullets, Lost Horizons: The Rise and Fall of Antibiotics. New York: Taylor and Francis, 2001. Berger, Melvin. Germs Make Me Sick. New York: HarperCollins, 1995. Biddle, Wayne. A Field Guide to Germs. New York: Henry Holt, 1995. Day, Nancy. Killer Superbugs: The Story of Drug-Resistant Diseases. Berkeley Heights, NJ: Enslow, 2001. Farrell, Jeanette. Invisible Enemies: Stories of Infectious Diseases. New York: Farrar, Straus, Giroux, 1998. Friedlander, Mark P. Outbreak: Disease Detectives at Work. Minneapolis, MN: Lerner, 2003. Nardo, Don. Germs. New York: Thomson Gale, 2003. Nikiforuk, Andrew. The Fourth Horseman. New York: M. Evans, 1991. Senior, Kathryn. You Wouldn’t Want to Be Sick in the 16th Century. New York: Franklin Watts, 2002. Yount, Lisa. Antibiotics. New York: Thomson Gale, 2005.

Web Sites Germ Theory

http://ocp.hul.harvard.edu/contagion/germtheory.html This Web site offers a complete yet easy to understand background on the development of the germ theory of disease. Cholera

http://www.nlm.nih.gov/exhibition/cholera/index.html This government Web site tells you everything you need or want to know about cholera and the researchers who worked so hard to conquer it. The site includes an introductory text and articles about

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Further Resources  121 various aspects of cholera and how it was fought, as well as interesting historical images. Contagion and Other Concepts of Disease

http://ocp.hul.harvard.edu/contagion/concepts.html This site offers an interesting overview of the discovery of contagion. It also has lots of links to other Web sites on the subject. Influenza 1918

http://www.pbs.org/wgbh/amex/influenza/ This Web site is based on the PBS American Experience program on the causes and effects of the influenza pandemic in 1918, particularly as it affected the United States. The site offers a wealth of information about influenza and the 1918 pandemic. Louis Pasteur

http://www.accessexcellence.org/RC/AB/BC/Louis_Pasteur. php This Web site provides a good and comprehensive overview of Pasteur’s life and work and explains why he was one of the great geniuses of medical science. The Plague

http://www.brown.edu/Departments/ItalianStudies/dweb/ plague/ A wealth of information about the bubonic plague, especially its effects in Italy during the fourteenth century, is found on this site. The site contains articles and images, as well as links to original documents. Reality and Politics in the War on Infectious Diseases

http://www.creatingtechnology.org/biomed/germs.htm This site presents an extensive article on the history of discoveries regarding the germ theory of disease. The article also discusses how politics affects scientific research and discoveries in this context. Yellow Fever

http://www.pbs.org/wgbh/amex/fever/filmmore/fd.html This Web site is based on the PBS American Experience program on yellow fever. It describes the disease, but concentrates mainly on Walter Reed’s brilliant efforts to find its cause and its cure. As always in this series, the site contains lots of information from many sources, including documents and images.

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11: © Borromeo/Art Resource, NY 16: U.S. Department of Health and Human Services / Centers for Disease Control and Prevention/Jean Roy 18: U.S. Library of Congress Prints and Photographs Division Washington, D.C. [LC-USZ62-12924] 19: © Infobase Publishing 21: U.S. Department of Health and Human Services/Centers for Disease Control and Prevention/Frank Collins, Ph.D. 27: © Image Select/Art Resource, NY 29: © HIP/Art Resource, NY 35: © HIP/Art Resource, NY 36: © Sergey Lukyanov/ Shutterstock 40: © SPL/Photo Researchers, Inc. 41: ©World History/Topham/ The Image Works 44: © Infobase Publishing 47: © SPL/Photo Researchers, Inc. 51: © The Granger Collection, NY 53: U.S. Library of Congress Prints and Photographs Division Washington, D.C. [LC-USZ62-5877] 57: © Andre Nantel/Shutterstock 59: © Charles O’Rear/CORBIS 61: © Michael Abbey/Photo Researchers, Inc. 67: © Zhuda/Shutterstock













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69: Hierophant Collection 71: Hierophant Collection 74: National Library of Medicine/U.S. National Institutes of Health 77: © Sven Hoppe/Shutterstock 78: U.S. Department of Health and Human Services/Centers for Disease Control and Prevention/Laura Rose 80: © Infobase Publishing 83: U.S. Department of Health and Human Services/Centers for Disease Control and Prevention/Dr. Fred Murphy 85: Yaroslav/Shutterstock 91: U.S. Department of Health and Human Services/Centers for Disease Control and Prevention/Dr. V.R. Dowell 92: © St. Mary’s Hospital Medical School/Photo Researchers, Inc. 95: © Science Source/Photo Researchers, Inc. 99: © Bettmann/CORBIS 103: © Enrico Jose/Shutterstock 108: © Lee D. Simon/Photo Researchers, Inc. 111: U.S. Department of Health and Human Services/Centers for Disease Control and Prevention 112: U.S. Department of Health and Human Services/ Centers for Disease Control and Prevention/Frederick Murphy 113: © Infobase Publishing

Page numbers in italics indicate photos or illustrations; page numbers followed by m indicate maps.

A

acquired immune deficiency syndrome (AIDS) 110, 111 Actinomyces griseus 94, 95–96 actinomycin 94 Aedes aegypti 85, 86 agar culture medium 76, 77 Agricultural Revolution 8–12, 11 AIDS (acquired immune deficiency syndrome) 110, 111 Airs, Waters, Places (Hippocrates) 30 algae, blue-green 61 amputations 33 animalcules 39–42, 41 animal hosts of disease 10–12, 109, 112, 114 animals, wild 109, 112, 114 anthrax 72–73, 75–77 anthrax bacillus spores 76–77, 78 antibiotic drug development actinomycin 94 penicillin 91–93 Prontosil 89 salvarsan 88 streptomycin 96 streptothricin 94 sulfas 88–89

antibiotic drugs current research on 104 early development of. See antibiotic drug development overuse of 101–102, 106 resistance to 102–105 antibiotics, broadspectrum 96, 105 antibodies 88 antisepsis 62–63, 64 antitoxin, for diphtheria 88 ascorbic acid (vitamin C) 9 attenuation of viruses 79

B

bacilli (bacillus) 72, 78 Bacillus anthracis 75, 77 bacteria classification of 78–79, 80 culture of 75–76, 77 drug resistance in 102–105 evolutionary origins of 60–61 gram-negative vs. grampositive 90, 91, 93, 94, 96 Gram stain for 90, 91 named 56

123

bacteriophages 107, 108 barber-surgeons 33 Behring, Emil von 87–88 Big Pharma 104 binary fission 47, 47 biogenesis 58 biological warfare, first 48–49 bird flu 105 Black Death 19–20, 19m, 26, 27 bloodletting 34, 35 blue-green algae 61 broad-spectrum antibiotics 96, 105 Bruce, David 81–84 buboes 18 bubonic plague 15–20, 18, 48–49. See also Black Death

C

carbolic acid 62–63 cell theory 58 cesarean section 33 Chain, Ernst 92–93 chicken cholera 68–71 childbed fever 51–54 China, smallpox epidemic in 13 cholera 22, 66, 78, 86 Christian church on origin of life 45 views on disease 26–27 cities, growth of 10–12

124  Germ Theory civilization, early disease emergence and 7–12 epidemics and 12–13. See also epidemics class bias 32, 100 cleanliness, commercialization of 100–102 Cohn, Julius 56 commercialization of cleanliness 100–102 contagion 17, 49–54 contagious effluvia 50 cowpox 13, 70 Crimean War 53 Cullen, William 50 culture of microbes 75– 76, 77, 78–79, 80 cupping 34 curse, disease as 23–25

D

Davaine, Casimir-Joseph 72 diagnosis, humoural theory and 31 diphtheria 87–88 diseases animal hosts of 10–12, 109, 112, 114 early treatments of 28, 29, 32–37 emerging threats 107–114 vectors of 12, 15–16, 20, 21, 84–86, 85 disease theories, early curse 23–25 divine displeasure 25–27 humours 28–32 disinfectant 54 divine displeasure, disease as 25–27 Domagk, Gerhard 88–89, 95 drug resistance 102–105

E

Ebola fever 109–111, 112

Egypt, smallpox epidemic in 13–14 Ehrlich, Paul 87–88 emerging disease threats 107–114 endemic disease 22 epidemics bubonic plague 15–20, 18, 19m cholera 22 early civilizations and 12–13 hunter-gatherers and 7 measles 13–15 smallpox 13–15, 16 typhoid 22 typhus 20–22, 21 yellow fever 22 exorcism 25

F

factory farms 102, 103, 106 fear of germs 97–100 fermentation 56 Finlay, Carlos Juan 85 flagellants 26, 27 fleas 12, 15–16, 20 Fleming, Alexander 89– 92, 94, 95 flies 43, 82–84, 86 Florey, Howard 92–93 flu virus 105 food safety 97

G

Galen 31 genetic “drift” 105 germ killers, overuse of 101–102, 106 germ phobia 97–100 germ theory Cullen and 50 Koch and 69, 77, 79 Lister and 62–63 Pasteur and 67–68, 69, 81 global travel 112 God’s punishment, disease as 26–27 Gordon, Alexander 52 Gram, Hans Christian 90

gram-negative bacteria 90, 94, 96 gram-positive bacteria 90, 91, 93, 96 Gram stains 90, 91

H

hemorrhagic fevers 84– 86, 109–114 herbal medicine 28, 29 Hippocrates 30–31 HIV (human immunodeficiency virus) 110, 111 hospitalism 50–51, 51 hosts of disease, animals as 10–12, 109, 112, 114 human immunodeficiency virus (HIV) 110, 111 humoural theory of disease 28–32 hunter-gatherer civilization 7–8 hygienic procedures 53–54

I

immigrants, discrimination against 100 India, smallpox epidemic in 13 influenza virus 105

J

Jenner, Edward 70, 71 jungles, encroachment on. See rain forest intrusions

K

Kaffa, siege of 48–49 Koch, Robert 73–78, 74 Koch’s postulates 77–78

L

leeches 34, 36 Leeuwenhoek, Antony van 38–42 lice 12, 20, 21, 86 Lister, Joseph 62–63 London cholera outbreak 66

Index  125 Louis XIV of France 36 Louis XV of France 34 Luttrell Psalter 35 Lyme disease 86

M

maggots 43 malaria 8, 11–12, 86 Mallon, Mary 98–99, 99 Marburg fever 109 measles 13–15 meat production, antibiotic use in 102, 103, 106 medicinal plants 28, 29 medicine men 24, 25 mercury 34–36, 37 microbes. See also bacteria; viruses culture of 75–76, 77 discovery of 38–42 isolation of 75–76, 78–79, 80 reproduction of 47, 47 microscope 39, 40 monkeys 109, 111–112 mosquitoes 85–86, 85 muscardine 67 mutations 103–104, 105

N

Native Americans, smallpox epidemics in 14–15 Needham, John 44–45 Nightingale, Florence 53–54, 53

P

pandemics 19, 105 parasites 8, 12, 83–84 Pasteur, Louis 69 anthrax research 72–73 rabies research 79–81 silkworm disease research 65–68 spontaneous generation disproved by 58–62, 59 vaccination for chicken cholera 68–71

wine industry work 55–58 pasteurization 57 pébrine 65 peccant humours 30, 34 penicillin 91–93 Penicillium notatum 91, 92 pharmaceutical research 104 physicians, early 33 the plague. See bubonic plague plague, defined 15 plants, medicinal 28, 29 pneumonic plague 16–17, 19 poor, discrimination against 32, 100 post-antibiotic age 106–107 Prontosil 89 public fear of germs 97–100 public sanitation 97 purging of humours 33–37

Q quarantine 17

R

rabies 79–81 rain forest intrusions 108, 109, 111–112 Redi, Francesco 43, 44 Reed, Walter 85–86 reproduction of microbes 47, 47 retroviruses 110 Rickettsia prowazekii 21 Rocky Mountain Spotted Fever (RMSF) 86 Roman Empire, smallpox epidemic in 14

S

sacrifices 28 salvarsan 88 Schatz, Albert 95–96 scurvy 9 Semmelweis, Ignaz 52, 54

shaman 25 silk industry 65–68 silkworms 67 sleeping sickness 81–84 smallpox 13–15, 16, 70 Snow, John 66 soil microorganisms 93–94 Spallanzani, Lazzaro 45–47 spontaneous generation 42–47, 58–62, 59 spores, anthrax bacillus 76–77, 78 Streptococcus 88–89 streptomycin 96 streptothricin 94 sulfa drugs 88–89 sulfanilamide drugs 89 sulfonamides 89 surgeons 33, 62 surgery, antiseptic technique for 62–63 swine flu 105 syphilis 88

T

Tatar army 48–49 ticks 86 toxic purges 35–37 trade, and disease spread 12–13 treatments, early 28, 29, 32–37 Trypanosoma 83–84 trypan red 88 tsetse fly 82–84 tuberculosis 78, 86, 103–104 typhoid 22, 86 Typhoid Mary 98–99, 99 typhus 20–22, 21, 86

V

vaccines anthrax 72–73 chicken cholera 68–71 influenza 105 Pasteur develops first 68–71 rabies 79–81 smallpox 70

126  Germ Theory vector, defined 84 vectors of disease 12, 15– 16, 20, 21, 84–86, 85 vegetative force 45–46 Vibrio cholera 66 Virchow, Rudolf 58 viruses. See also vaccines; names of specific viruses attenuation of 79 description of 82–83, 83 as emerging diseases 107–114, 112 mutations of 105 vitamin C 9

W

Waksman, Selman 93–96, 95 war, and disease spread 13 Washington, George 36–37 waterborne diseases 22, 66 West Nile virus 113–114, 113 wild animal contact 109, 112, 114 wine making 55–58

witches 24–25 World War II 93

Y

yeast 56, 57, 58 yellow fever 22, 84–86

Natalie Goldstein has been an educational writer for 20 years.

She has written Chelsea House books on the subjects of vaccines, Parkinson’s disease, and animal behavior. Goldstein has master’s degrees in education and environmental science from the City College of New York and environmental science from the SUNY College of Environmental Science and Forestry.

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