CONTENTS
Volume 331 Issue 6019
EDITORIAL 821 Why Bother?
Engage Students in Education Reform
M. Torchia
Response
Alice S. Huang
R. Losick and D. O’Dowd
NEWS OF THE WEEK 829
A roundup of the week’s top stories
NEWS & ANALYSIS 832
Obama’s 2012 Vision Clashes With House Cuts in 2011
834
High-Priced Recruiting of Talent Abroad Raises Hackles
835 836
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BOOKS ET AL. 859 Conservation Science
P. Kareiva and M. Marvier, reviewed by J. Fanshawe
860
Science in Ivins Case Not Ironclad, NRC Says A Quake May Have Hinted That It Was on the Way
Deflating the Genomic Bubble
J. P. Evans et al. >> Genome Anniversary Essays p. 872
Growth Defect Blocks Cancer and Diabetes
PERSPECTIVES 863 A Hand to Support the Implantation Window
Emerging Forensics Field May Hit Legal, Ethical Obstacles >> Genome Anniversary Essays p. 872; Science Podcast
S. C. Hewitt and K. S. Korach >> Report p. 912
864
865
Europe’s Eager Reformer Takes on Framework Funding Goliath
866
SPECIAL FEATURE 847 2010 VISUALIZATION CHALLENGE
868
LETTERS 857 Amazon Science Needs Brazilian Leadership A. C. M. Malhado
Unlocking the Door to Invasion
A. Kereszt and E. Kondorosi >> Report p. 909
A Windfall for Defenders of the Planet
>> For related online content, go to www.sciencemag.org/special/vis2010/; Science Podcast
A New Twist on Spintronics
G. L. J. A. Rikken >> Report p. 894
NASA Weighs Asteroids: Cheaper Than Moon, But Still Not Easy
844
Life on Low Flame in Hibernation
G. Heldmaier >> Report p. 906
Controlling the Flow of Suspensions
H.-J. Butt >> Report p. 897 869
Creating Stable Memories
pages 864 & 894
J. D. Sweatt >> Report p. 924 870
Hitting a Tiny Target in the Dark
Boosting CITES Through Research
R. S. Hawley >> Report p. 916
Response
CONTENTS continued >>
M. J. Smith et al.
page 841
POLICY FORUM 861
NEWS FOCUS 838 Can This DNA Sleuth Help Catch Criminals?
841
Visceral
O. Catts and I. Zurr, curators, reviewed by D. Dixon et al.
>> Research Article p. 877
837
CORRECTIONS AND CLARIFICATIONS
D. Bickford et al.
COVER False-colored atomic force micrograph of two types of molecules forming a mixed self-assembled monolayer on a gold surface. The two molecules differ in height by 0.2 nanometers, giving the appearance of ripples. This image was awarded first place in the photography category in the 2010 Science/NSF International Science & Engineering Visualization Challenge. The winning entries are featured in a special section starting on page 847 and at www.sciencemag.org/special/vis2010/.
DEPARTMENTS 817 823 826 956 957
This Week in Science Editors’ Choice Science Staff New Products Science Careers
Image: Seth B. Darling, Argonne National Laboratory; and Steven J. Sibener, University of Chicago
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ESSAYS 872 Genome-Sequencing Anniversary: A Celebration of the Genome, Part III A Living Constitution
892
B. S. Zhao et al. The helium molecule can interact at large distances with the evanescent repulsion potential of the surface.
S. Jasanoff
What Does a “Normal” Human Genome Look Like?
894
M. V. Olson
Of Mice and Humans Human Genome Sequencing: Celebrating 10 Years L. Al-Gazali
Gene Patents: The Shadow of Uncertainty
897
R. Cook-Deegan
The Genomic Foundation Is Shifting J. S. Mattick
Famine in the Presence of the Genomic Data Feast
900
E. Hoal >> News story p. 838; Policy Forum p. 861
Synthetic Clonal Reproduction Through Seeds
903
M. P. A. Marimuthu et al. Clonal reproduction is engineered in a sexual plant by manipulating conserved genes controlling meiosis.
881
906
Extended Nucleation of the 1999 Mw 7.6 Izmit Earthquake
909
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Time-Reversed Lasing and Interferometric Control of Absorption W. Wan et al. Tuning the amplitude and phase of incident light can induce an enhancement of the optical absorption process.
Hibernation in Black Bears: Independence of Metabolic Suppression from Body Temperature
LysM-Type Mycorrhizal Receptor Recruited for Rhizobium Symbiosis in Nonlegume Parasponia
The Antiproliferative Action of Progesterone in Uterine Epithelium Is Mediated by Hand2
page 928
920
916
Distinct Properties of the XY Pseudoautosomal Region Crucial for Male Meiosis
924
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Early Tagging of Cortical Networks Is Required for the Formation of Enduring Associative Memory
E. Lesburguères et al. Tagging of cortical networks at the time of encoding is crucial for long-lasting associative memories. >> Perspective p. 869 928
L. Kauppi et al. Recombination between the sex chromosomes during sperm formation is controlled by a splicing isoform of the SPO11 protein. >> Perspective p. 870
Classic Selective Sweeps Were Rare in Recent Human Evolution
R. D. Hernandez et al. Much human genetic variation is likely due to purifying selection against deleterious mutations.
Q. Li et al. A progesterone-regulated transcription factor regulates stromal-epithelial communication in early pregnancy. >> Perspective p. 863
Metallic and Insulating Oxide Interfaces Controlled by Electronic Correlations
H. W. Jang et al. The strength of electronic correlations dictates the transport properties of oxide interfaces.
The Magnitude and Duration of Late Ordovician–Early Silurian Glaciation
R. Op den Camp et al. Parasponia uses a mycorrhizal signaling receptor essential for arbuscle formation to control rhizobium nodule symbiosis. >> Perspective p. 865
REPORTS 886
Steric Control of the Reaction of CH Stretch–Excited CHD3 with Chlorine Atom
Ø. Tøien et al. Hibernating black bears suppress their metabolic rate to 25% of normal, but only slightly reduce their body temperature. >> Perspective p. 866
The Crystal Structure of the Signal Recognition Particle in Complex with Its Receptor
S. F. Ataide et al. Guanine triphosphate controls changes in the signal recognition particle that facilitate transfer of the signal sequence to the translocon.
pages 868 & 897
S. Finnegan et al. Carbonate isotopes reveal a link between past ocean temperatures and mass extinction.
RESEARCH ARTICLES
M. Bouchon et al. Low-frequency seismic events may have been part of slip accumulation before a large earthquake. >> News & Analysis p. 836
Capillary Forces in Suspension Rheology
E. Koos and N. Willenbacher The addition of a small amount of a nonwetting immiscible fluid to a suspension can drastically alter its rheological properties. >> Perspective p. 868
F. Wang et al. Spectroscopy elucidates the complex interplay between orientational and vibrational effects in a simple chemical reaction.
BREVIA
877
Spin Selectivity in Electron Transmission Through Self-Assembled Monolayers of Double-Stranded DNA
B. Göhler et al. Photoelectrons emitted from a DNA-covered gold surface can have an unbalanced spin population of up to 60%. >> Perspective p. 864
S. Yamanaka
876
Quantum Reflection of He2 Several Nanometers Above a Grating Surface
Microtubule Stabilization Reduces Scarring and Causes Axon Regeneration After Spinal Cord Injury
F. Hellal et al. Taxol stimulates the capacity of axons to grow after spinal cord injury.
CONTENTS continued >>
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SCIENCEONLINE SCIENCESIGNALING SPECIAL FEATURE
Slideshow: 2010 Visualization Challenge Browse the striking sights, sounds, and motion that represent the contest’s winning entries and honorable mentions. www.sciencemag.org/special/vis2010/
SCIENCEXPRESS
www.sciencexpress.org
Crystal Structure of the Dynein Motor Domain A. P. Carter et al. The structure reveals the functional elements of the dynein motor and suggests how they change conformation during motility. 10.1126/science.1202393
Mechanistic Basis of Resistance to PCBs in Atlantic Tomcod from the Hudson River
I. Wirgin et al. Chronic pollution of the Hudson River, New York, results in rapid evolution of resistance to the pollutants. 10.1126/science.1197296 >> Science Podcast
The Biodiversity and Ecosystem Services Science-Policy Interface C. Perrings et al. 10.1126/science.1202400
Atmospheric pCO2 Perturbations Associated with the Central Atlantic Magmatic Province
M. F. Schaller et al. Emplacement of the Central Atlantic Magmatic Province 200 million years ago greatly elevated atmospheric CO2 concentrations. 10.1126/science.1199011
Revealing Extraordinary Intrinsic Tensile Plasticity in Gradient Nano-Grained Copper
www.sciencesignaling.org The Signal Transduction Knowledge Environment 15 February issue: http://scim.ag/ss15Feb11
COMMENTARY: Thinking Outside the Box— Fostering Innovation and Non–Hypothesis-Driven Research at NIH
EDITORIAL GUIDE: Focus Issue— Conquering the Data Mountain
RESEARCH ARTICLE: Growth Hormone Receptor Deficiency Is Associated with a Major Reduction in Pro-Aging Signaling, Cancer, and Diabetes in Humans
R. Ahmad et al. An inflammatory response of epithelial cells may be co-opted to promote cancer cell survival.
N. R. Gough and M. B. Yaffe Massive data sets create challenges for annotation, sharing, and presentation.
PERSPECTIVE: Effective Representation and Storage of Mass Spectrometry–Based Proteomic Data Sets for the Scientific Community
PERSPECTIVE: The Potential Cost of High-Throughput Proteomics
PERSPECTIVE: For Placebo Effects in Medicine, Seeing Is Believing
PERSPECTIVE: Integrating Multiple Types of Data for Signaling Research—Challenges and Opportunities
SCIENCEPODCAST
H. S. Wiley Easy integration of biological data has enormous potential to drive advances in biology and medicine.
On the 18 February Science Podcast: pollutant-resistant fish, forensic genetics, the 2010 Visualization Challenge, and more.
PERSPECTIVE: Setting the Standards for Signal Transduction Research
SCIENCEINSIDER
F. M. White The production of false leads by automated curation of high-throughput proteomic data sets exerts a toll on biological research and advancement.
J. Saez-Rodriguez et al. Standardized methods to link large, complex data sets to models are needed.
SCIENCECAREERS
Do Vibrating Molecules Give Us Our Sense of Smell?
A controversial new study flies in the face of a century of physiological research. http://scim.ag/sense-smell
The Mystery of the Stone Scorpion
Chemical bonds hold clues to how flexible arthropod exoskeletons can turn into fossils. http://scim.ag/stone-scorpion
J. Guevara-Aguirre et al. Ecuadorians who have a genetic mutation in the growth hormone receptor almost never die of cancer or diabetes complications.
RESEARCH ARTICLE: The Effect of Treatment Expectation on Drug Efficacy—Imaging the Analgesic Benefit of the Opioid Remifentanil
SCIENCENOW
Geothermal activity may sustain hidden oceans on worlds ejected from their planetary systems. http://scim.ag/loneplanet
R. Aragon NIH programs that fund the development of high-risk technologies contribute to translational research.
J. V. Olsen and M. Mann Proteomics data need a “reliability” tag to allow scientists to discriminate among data sets in public repositories.
PRESENTATION: Visual Representation of Scientific Information
Outcast Planets Could Support Life
www.sciencetranslationalmedicine.org Integrating Medicine and Science 16 February issue: http://scim.ag/stm021611
RESEARCH ARTICLE: MUC1-C Onocoprotein Promotes STAT3 Activation in an Auto-Inductive Regulatory Loop
T. H. Fang et al. Nanometer-sized grain copper confined by a graded substrate leads to a material with both high strength and high ductility. 10.1126/science.1200177 www.sciencenow.org Highlights From Our Daily News Coverage
SCIENCETRANSLATIONAL MEDICINE
B. Wong Judicious choice of graphical representations can improve visual communication. www.sciencecareers.org/career_magazine Free Career Resources for Scientists
Tooling Up: Playing the Name Game
D. Jensen Need to find out who’s who inside a company? Here’s how the pros do it. http://scim.ag/fhopnC
Seeing Is Believing
J. Carpenter Trained as a chemical engineer, Jon Heras has moved on to become a professional science illustrator and animator. http://scim.ag/i06erj
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U. Bingel et al.
R. L. Gollub and J. Kong Non-invasive whole-brain imaging can enhance our understanding of brain-based placebo effects. www.sciencemag.org/multimedia/podcast Free Weekly Show
news.sciencemag.org/scienceinsider Science Policy News and Analysis
SPECIAL SERIES
http://scim.ag/genome10 Human Genome 10th Anniversary A special month-long series explores the impacts of the genomics revolution on science and society. SCIENCE (ISSN 0036-8075) is published weekly on Friday, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue, NW, Washington, DC 20005. Periodicals Mail postage (publication No. 484460) paid at Washington, DC, and additional mailing offices. Copyright © 2011 by the American Association for the Advancement of Science. The title SCIENCE is a registered trademark of the AAAS. Domestic individual membership and subscription (51 issues): $149 ($74 allocated to subscription). Domestic institutional subscription (51 issues): $990; Foreign postage extra: Mexico, Caribbean (surface mail) $55; other countries (air assist delivery) $85. First class, airmail, student, and emeritus rates on request. Canadian rates with GST available upon request, GST #1254 88122. Publications Mail Agreement Number 1069624. Printed in the U.S.A. Change of address: Allow 4 weeks, giving old and new addresses and 8-digit account number. Postmaster: Send change of address to AAAS, P.O. Box 96178, Washington, DC 20090–6178. Single-copy sales: $10.00 current issue, $15.00 back issue prepaid includes surface postage; bulk rates on request. Authorization to photocopy material for internal or personal use under circumstances not falling within the fair use provisions of the Copyright Act is granted by AAAS to libraries and other users registered with the Copyright Clearance Center (CCC) Transactional Reporting Service, provided that $25.00 per article is paid directly to CCC, 222 Rosewood Drive, Danvers, MA 01923. The identification code for Science is 0036-8075. Science is indexed in the Reader’s Guide to Periodical Literature and in several specialized indexes.
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Membrane-Docking Complex
CREDITS (TOP TO BOTTOM): ØIVIND TØIEN/INSTITUTE OF ARCTIC BIOLOGY, UNIVERSITY OF ALASKA, FAIRBANKS; BOUCHON ET AL.
Don’t Wake the Bears
In hibernating mammals, temperature and metabolic rate decrease, allowing survival over long winter periods of starvation and cold. In small hibernators, such as hamsters, decreases in metabolic rate and temperature are linked; temperature decreases follow a physiological reduction in metabolic rate. In bears, body temperature remains relatively high during hibernation, which has been assumed to be owing to their large size. Tøien et al. (p. 906; see the Perspective by Heldmaier) undertook the challenging task of maintaining hibernating bears in artificial conditions and found, surprisingly, that metabolic rate and body temperature were completely unlinked. Instead, the bears cycled through elevated temperatures (between 30° to 36°C) over multiday cycles throughout hibernation, while undergoing a fourfold reduction in heart rate and maintaining a metabolic rate at 25% of normal. Despite a return to active body temperatures, metabolic rate remained depressed for several weeks post-hibernation.
Mixing Sand and Water The flow properties of a suspension of sand in water will be controlled by how much sand is added and will change over time as the sand sediments out. Koos and Willenbacher (p. 897; see the Perspective by Butt) studied the agglomeration of particles suspended in a liquid under the influence of a small amount of a secondary, immiscible liquid. For the case where
Correct targeting of membrane and secretory proteins involves the binding of the signal recognition particle (SRP), a ribonucleoprotein complex, to the ribosome nascent chain (RNC) complex. This joint complex then binds to a receptor (SR) in the target membrane and delivers the protein cargo to the protein translocation machinery, the translocon, in a guanosine triphosphate (GTP)–dependent process. Ataide et al. (p. 881) now describe the structure of the eubacterial SRP:SR complex bound to a nonhydrolysable GTP analog. The structure shows the arrangement of the SRP proteins relative to the RNA in a conformation that is likely to represent the cargo release state, and gives insight into how GTP hydrolysis may be coupled to conformational changes that facilitate transfer of the signal sequence to the translocon.
Lasing in Reverse Recent theoretical work has shown that the time-reversal symmetry of electromagnetism allows a lasing process to be run backwards, so that photons of the correct amplitude and phase incident on a cavity medium can be coherently absorbed. Wan et al. (p. 889) experimentally demonstrate that such carefully tuned beams incident from either side on a silicon wafer multiply scatter within the wafer so that the total transmitted and reflected beams destructively interfere, leading to the predicted enhanced absorption within the silicon cavity. The effect provides a route to control absorption through coherent illumination, with numerous potential applications in optical circuitry.
Turned Away at a Distance When a gas-phase molecule scatters off a solid surface, the interaction potential attracts at a distance because of favorable alignment of dipoles in the molecule and the surface. At a certain point, the molecule gets close enough to the surface so that electron repulsions dominate and the molecule is repelled. In many ways, the scattering of molecules can largely be described as classical scattering off these potential surfaces. Zhao et al. (p. 892) now show that the
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helium dimer, an extremely weak molecule, can scatter off a grating intact, but does so several nanometers above the surface, when it is still in the attractive part of the interaction potential. The scattering is quantum mechanical in nature, with the wave functions of the repulsive potential and the dimer extending evanescently and interacting at a distance.
Spin Filtering with DNA Monolayers Spin filters can create an excess of one electron spin population over another with applications in spin-based electronics. Typically, such devices use magnetic materials. Göhler et al. (p. 894; see the Perspective by Rikken) measured the spin distribution of photoelectrons emitted from layers of double-stranded DNA (up to 80 base pairs in length) adsorbed on gold. Excitation with unpolarized ultraviolet light at room temperature led to a 60% increase in spin polarization.
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the second liquid preferentially wets the solid particles, one would expect the flow properties to change, but significant changes were also observed even when a small amount of a nonwetting fluid was added to the mix.
Prelude to an Earthquake? To improve warning systems and minimize damage, it is important to understand the moments leading up to large earthquakes. Bouchon et al. (p. 877) observed a persistent and repeating low-frequency seismic signal in the hour before the 1999 magnitude 7.6 Izmit earthquake in Turkey that may have been the beginning stages of the major slip along the fault. The signal originated from the base of the brittle crust near the hypocenter, suggesting that slip accumulated leading up to the earthquake. The increase of seismic noise over this time frame indicates possible movement along the fault before the main quake. It is not yet clear whether similar patterns are likely to have occurred before other large ruptures, or whether such patterns occur in the absence of any subsequent rupture.
Frozen to Death Global biodiversity throughout geologic time has been punctuated by mass extinction events, the causes of which are often controversial. Major swings in climate are often accompanied by variations in temperature, sea level, and glacial coverage. Finnegan et al. (p. 903, published
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online 27 January) used an isotope-based paleothermometry technique to tease out ocean temperatures during one of the most devastating losses of marine life around 440 to 450 million years ago. Ocean temperatures cooled by up to 5°C in the tropics at the same time that the mass extinction was in full swing, which also coincides with a disruption of the marine carbon cycle.
Many plants form symbiotic relationships with mycorrhizal fungi. A much smaller group of plants, mostly the legumes, form symbiotic relationships with rhizobial bacteria. Op den Camp et al. (p. 909, published online 23 December; see the Perspective by Kereszt and Kondorosi) analyzed the molecular pathways underlying the early stages of mycorrhizal and rhizobial symbioses. The nonleguminous small tree Parasponia can form symbiotic relationships with rhizobia. Comparisons of the nodulation pathways in legumes with that in Parasponia suggest that the rhizobial pathway is derived from the mycorrhizal pathway.
Progesterone-Estrogen Antagonism In reproductive biology, the steroid hormone progesterone counteracts estrogen-induced uterine growth. The antiproliferative action of progesterone in the uterus relates to female infertility as well as to estrogen-driven hyperplasia and endometrial cancer. Using targeted genetic mutation in mice, Li et al. (p. 912; see the Perspective by Hewitt and Korach) demonstrate that the transcription factor Hand2 is a target of progesterone regulation in the uterine stroma and that Hand2 controls estrogen-induced epithelial proliferation via a paracrine mechanism involving fibroblast growth factors.
Minding Your Xs and Ys The double (or “reduction”) division of meiosis generates haploid gametes from diploid cells. Meiotic recombination is required for pairing of homologous chromosomes, which ensures correct segregation of the chromosomes. The X and Y chromosomes of mammals have only a small segment of homology, the pseudoautosomal region, where recombination must take place to hold the chromosomes together. Although sex chromosomes missegregate more frequently than autosomes, X-Y nondisjunction is rare, which suggests that mechanisms exist to ensure X-Y recombination. Kauppi et al. (p. 916; see the Perspective by Hawley) show that, in mice, a distinct chromosome structure renders the PAR more conducive to recombination-initiating double-strand break formation, which occur at a 10- to-20-fold higher frequency than the genome average.
Mastering Memory Maintenance The mechanisms involved in the formation of enduring memories are still largely unknown. Lesburguères et al. (p. 924; see the Perspective by Sweatt) investigated the hippocampal-cortical dialogue during memory consolidation. Neurons in the rat orbitofrontal cortex appeared to be “tagged” at the time of initial encoding, even though the initial learning was hippocampal. Inactivating the orbitofrontal cortex at the time of encoding affected late memory while not affecting memory during the period when it was still supported by the hippocampus.
CREDIT: OP DEN CAMP ET AL.
Taxol and Spinal Cord Repair Because neuron-intrinsic factors and the lesion site itself impose obstacles to axon regeneration, a combination of therapeutic approaches is required to promote axonal regeneration after spinal injury. Hellal et al. (p. 928, published online 27 January) now provide evidence from spinal cord injury experiments on rats that the licensed anticancer drug Taxol can induce axon regeneration by altering microtubule dynamics. Moderate microtubule stabilization reduced scarring and decreased the deposition of factors that prevent axonal regeneration after spinal cord injury so that axons could regenerate through the Taxol-treated lesion site. www.sciencemag.org SCIENCE VOL 331
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Two Ways to Plant Symbiosis
EDITORIAL
Why Bother?
CREDITS: (TOP) AAAS; (RIGHT) ROBERT LEHMANN/GETTY IMAGES
WHEN WE MENTION WOMEN IN SCIENCE AND ENGINEERING, IT IS OFTEN ABOUT THE DIMINISHING
numbers, the lower pay, the many difficulties for women, and the personal sacrifices that women necessarily make. Perhaps, by focusing on the negatives, we are unwittingly persuading young women that science and engineering may not be the right careers for them. Why bother to join this profession? There are many rewards. The wealthy parents of John Enders, a Nobel Laureate of the 1950s, could not believe that he was being paid to play in the laboratory. He had the freedom to be curious. Carol Reiss, a New York University professor, described this freedom to me: “It is the ability to ask questions and develop experiments to answer them, learning something new which no one else has previously found. Yes, I would definitely do it again. Science is a very rewarding and gratifying profession, not a job.” Moreover, scientific work contributes to furthering our understanding of the universe and our place in it. Scientists feel uniquely relevant. In the past, women often received friendly advice to accept less demanding positions, such as research assistant or associate rather than that of professor. It was argued that taking such positions would give women the flexibility for domestic responsibilities and childbirth. Also, there would be no need to search for funding. However, many professors and directors set their own schedule for getting the job done. Financial responsibility may indeed be a hassle, especially now, but having that responsibility also means deciding how that money is spent. Assistants and technicians can be assigned the routine functions, giving additional flexibility to the laboratory chief. Except for teaching, academic scientists and engineers have great flexibility in scheduling, although this might mean working well into the evening hours and weekends. Few other jobs provide such flexibility. Although time-consuming, teaching has special rewards. Another professor (Amy Cheng Vollmer, Swarthmore College) remarked to me: “Being a mentor—in the classroom [or] laboratory . . . has been the most rewarding—seeing former students become successful . . . and developing balance in their professional and personal lives.” Not often mentioned but taken for granted, scientists and engineers mainly interact with smart, capable individuals, making it a pleasure to work together. Sometimes achieving “balance” is elusive for women. Many women feel they have to decide between a career and family. Rosalind Franklin and Barbara McClintock chose not to have children in favor of science. However, for women who can juggle the demands of a profession and a family, there are special rewards of motherhood. As a young investigator (Theresa Chang, Public Health Research Institute, University of Medicine and Dentistry, New Jersey) told me, “many female colleagues . . . chose not to have children to be competitive. Having children is the best thing that I have done. I am more effective at work and integrate my skill and knowledge into the society through my involvement in the school.” To be a mother and a scientist is well worth the effort. And should it be that after training, a woman decides that academic life is not for her, that training provides an open door to a wide variety of options. Scientists are prepared to solve problems, almost any kind. She can analyze new situations and immerse herself in learning about them. She is able to provide solutions and leadership. There are jobs in industry, on Wall Street, in government, in philanthropy, in administration, in national parks, in advocacy, in defense, and numerous others areas. There is nothing to lose and everything to gain. Yes, it is worth the bother!
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Alice S. Huang is the president of AAAS, Senior Faculty Associate at the California Institute of Technology, former Dean for Science at New York University, and former professor of Microbiology and Molecular Genetics at Harvard Medical School. E-mail: alice.
[email protected].
– Alice S. Huang
10.1126/science.1203124
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ENGINEERING
The Pros (and Cons) of Plugging In
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The adage out of sight, out of mind has some resonance as the first big crop of plug-in hybrid cars hits the road in the United States. People see and sometimes smell gasoline; plugging a car into a socket may make it seem like the energy is conjured from the ether. Of course, power plants actually bear the burden, and Peterson et al. are among the growing number of researchers gauging the implications. They have examined the net effect on carbon, nitrogen, and sulfur emissions of replacing a fraction of the cars in a number of Eastern and Midwestern U.S. states with plug-in hybrids. They modeled several different scenarios, such as when cars were charged and whether carbon dioxide emissions were priced or captured and sequestered. For a 10% hybrid fleet scenario, they found significant reductions in CO2 emissions across the board, and NOx reductions in most cases. The principal drawback was an increase in sulfur dioxide emissions as demand for coal combustion rose. — JSY Environ. Sci. Technol. 45, 10.1021/es102464y (2011).
APPLIED PHYSICS
CREDITS (TOP TO BOTTOM):RAMIN TALAIE/CORBIS; DAVID LINDENMAYER
A Sharper Focus Imaging techniques are rarely applied in ideal environments. Ultrasound imaging, for instance, is hindered by scattering from tissue, bone, and other surrounding organs, which often blur the images. The same is true for terahertz body scanners, wherein scattering from clothing or designed concealers may obscure detection. Scattering from random scatterers creates speckle noise in the backscattered signal that results in an overall deterioration in image quality. Montaldo et al. show that this speckle noise can be controlled and mitigated by a time-reversed scattering process using a time-domain array of transmitters and receivers. By sending in pulses of ultrasound from the array and tweaking the timing at each array element, the signals at the receivers are fed back to the transmitters, and the timing is iteratively adjusted to effectively steer the pulses to focus on a desired point. The improved imaging capability is demonstrated in a phantom for ultrasound but should be extendable to other frequency regimes for radar and communication applications. — ISO Phys. Rev. Lett. 106, 54301 (2011). ECOLOGY
Brother, Can You Share a Hollow? Tree hollows are a key resource for numerous forest-dwelling species. Hollow reductions that result from forest harvest and management
practices are a significant threat to forest species worldwide. Although the reduction of hollows has generally been followed by a decline in dependent species, two species of Australian possum (Gymnobelidus leadbeateri and Trichosurus cunninghami) have not followed this trend. By tracking the denning behavior of individuals of known genetic relatedness, Banks et al. show that this resilience is largely due to a change in social behavior. When hollows are plentiful, possums use a large number of dens, have overlapping home ranges, and prefer to share hollows with unrelated individuals. When hollows are scarce, the animals show increased aggression and defense of hollows and instead prefer to nest with relatives. Thus, when resources are scarce, animals obtain an inclusive fitness benefit of sharing with relatives and excluding nonrelatives, whereas when resources are plentiful, inclusive fitness is less important than other considerations, such as inbreeding or pathogen avoidance. — SNV
CHEMISTRY
Happy Couple In principle, dimeric molecules may seem easier to synthesize than lower-symmetry compounds of comparable size. After all, both halves can be generated together and then conveniently coupled at the end. In practice, the coupling step often poses a tremendous challenge—all the more frustrating because it comes after long and meticulous preparation of the penultimate monomer. Such was the case with the polycyclic core of lomaiviticin, an organic natural product of exploratory pharmaceutical interest. The compound comprises two identical tetracyclic frameworks linked by a C-C bond and two C-O bonds; an especially unusual feature is the presence in each half of a diazo group, ordinarily a highly reactive substituent. Herzon et al. have now succeeded in assembling the lomaiviticin framework (without the pendant sugars in the natural product) using 11 steps, perhaps the hardest of which proved to be the formation of that central C-C bond. After an extensive search, the authors discovered that a trivalent manganese complex bearing three fluorinated acetylacetonate ligands was a uniquely selec-
Proc. R. Soc. London Ser. B 278, 10.1098/ rspb.2010.2657 (2011).
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J. Am. Chem. Soc. 133, 10.1021/ja200034b (2011). PLANT SCIENCES
Food Fight During reproduction, some genes in the offspring are “imprinted”: They contain inherited epigenetic markings that promote specific expression of either the maternal or paternal allele. Genetic imprinting can be viewed within the parental conflict theory, which postulates that females allocate resources equally to all offspring, whereas males favor the expression of genes that maximize resource use by individual offspring. In Arabidopsis, a few imprinted genes are known to be expressed in the endoderm, which is the portion of the seed that will nourish the growing embryo. Hsieh et al. have now surveyed the gene expression landscape of the Arabidopsis endoderm and found 43 imprinted genes in the endoderm, 34 maternally expressed and 9 paternally expressed. The genes that maternal and paternal sources disagreed over encode transcription factors, hormone signaling components, and regulators of chromatin modification and small RNA pathways. The Arabidopsis embryo, on the other hand, reflected an inner peace, with no imprinted genes identified. — PJH Proc. Natl. Acad. Sci. U.S.A. 108, 1755 (2011). DEVELOPMENT
CREDIT: STSCI
No Damaged Daddies Cells have evolved mechanisms to protect against damaged DNA, including the induction of apoptotic cell death. Such protection is especially important in germline cells in order to ensure the evolutionary stability of a species. The p53 homolog, p63, functions to protect the female germ line by promoting apoptosis of oocytes with damaged DNA. Beyer et al. sought to determine whether p63 also functions in the male germ line and identified p63 isoforms that are expressed in the human testis. Male germ cell–associated transcriptionally active p63 (GTAp63) is encoded by the p63 gene with a long terminal repeat (LTR), the result of an integration event of the endogenous retrovirus ERV9 LTR, inserted upstream. Spermatogenic precursors, but not mature spermatozoa, expressed GTAp63, which induced www.sciencemag.org
the expression of proapoptotic genes upon DNA damage. Analysis of primate DNA showed conservation of the LTR insertion in great apes and humans, which suggests that the insertion occurred recently in evolution. Besides ensuring germline genomic integrity, p63 may also act as a tumor suppressor: Examination of tissue from human testicular cancers revealed a loss of p63 expression. — BAP Proc. Natl. Acad. Sci. U.S.A. 108, 10.1073/ pnas.1016201108 (2011). ASTROPHYSICS
Pulsing Once Again Just as seismic waves allow scientists to study Earth’s interior, stellar oscillations can tell us about the interior of stars. Cataclysmic variables are binary systems in which an extremely dense star, or white dwarf, accretes material from
another star; in a dozen such cases so far, the white dwarf is known to pulsate. As their name suggests, cataclysmic variables can experience sudden outbursts—with the brightness of the entire system sometimes increasing by several orders of magnitude—when the accreted material undergoes thermonuclear fusion on the white dwarf’s surface. The extent to which these events affect the white dwarf’s interior is not completely understood. The white dwarf in the cataclysmic variable SDSS J074531.92+453829.6 was shown to have stopped pulsating 1 year after its first recorded outburst, suggesting that it was heated to temperatures beyond those at which pulsations can occur. Now, 3 years after the outburst, Mukadam et al. show that the pulsations have resumed and that their properties, which depend on fundamental parameters such as the density, pressure, and temperature in the stellar interior, are similar to those of the pre-outburst pulsations. This white dwarf has thus cooled down to its previous state, with no signs of its interior having been perturbed by the outburst. — MJC
SCIENCE
Astrophys. J. 728, L33 (2011).
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tive oxidant for the coupling reaction (though the bacterial solution to the same challenge remains somewhat mysterious). — JSY
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NEWS OF THE WEEK AROUND THE WORLD 3
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Dhaka, Bangladesh 4 Washington, D.C. 1
CREDITS (TOP TO BOTTOM): FRITZ GELLER-GRIMM/WIKIMEDIA COMMONS; ASOCIACIÓN ANDES
Dueling Science Budgets President Barack Obama sent the U.S. science community a valentine this week, submitting a 2012 budget request to Congress that would increase federal support for basic and applied research by 11% over current spending levels, to $66 billion. It fleshes out his promise in last month’s State of the Union speech to “out-innovate, out-educate, and out-build” the rest of the world. The plan is a long way from becoming reality, however. In addition to the usual hurdles facing any presidential budget, there’s a new wrinkle this year: Congress has yet to finish work on a 2011 budget for the fiscal year that ends in September. Toward that end, Republicans in the House of Representatives have proposed cutting $3.3 billion in research from current spending at various federal agencies, including $1.6 billion from the National Institutes of Health, nearly $900 million from the Department of Energy’s Office of Science, and $388 million from the National Science Foundation. Those cuts are part of a campaign to shrink the federal deficit, which both political parties agree is a necessity. But they disagree strongly on how to do it. For details, see page 832. Bilaspur, Chhattisgarh, India 2
Court Ignores Nobelists’ Plea to Release Physician-Activist
An appeal by 45 of the world’s top scientists to release an Indian doctor accused of helping Maoist insurgents has failed to sway the High Court in India’s central state of Chhattisgarh. Binayak Sen, the vice president of India’s People’s Union for Civil Liberties, was arrested in 2007 and accused of aiding
local Maoist rebels, including smuggling notes from one of them who was held in jail. He was initially released but was convicted of sedition and sentenced to life in prison on 24 December 2010. In a petition authored by chemistry Nobel laureate and Rice University professor emeritus Robert Curl and released to Indian media, the Nobelists ask that Sen be released on bail, stating that he is an “exceptional, courageous, and selfless colleague, dedicated to helping those in India who are least able to help themselves.” Sen’s lawyers have said that they will appeal to India’s Supreme Court. http://scim.ag/sen-appeal Cusco, Peru, and Svalbard, Norway 3
Tubers to Seek Safety on Ice “Potato preservationists” with the Global Crop Diversity Trust plan to send seeds of more than 1500 types of Andean potato to the Svalbard Global Seed Vault, 1300 kilometers north of the Arctic Circle. The seeds come from Potato Park, a 10,000-hectare reserve in Peru established by indigenous groups to preserve potatoes and their role in local culture. In the Andes, potatoes are a cultural symbol and dietary staple that come in thousands of varieties, including the red moro boli (pictured) and the “bride’s potato,” which is so bumpy it’s considered a test of a newlywed’s peeling skills. But global warming and a declining number of varieties under cultivation may threaten the tuber’s diversity. “Sending this collection to Svalbard is like sending our family members to a distant place for safekeeping, in case the rest of us need to be rescued by them in the future,” Potato Park agronomist Alejandro Argumedo said in a statement.
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Emerging Virus Strikes Again A killer is back with a vengeance in South Asia. Over the past 10 years, Nipah virus has haunted villages in western Bangladesh almost every winter and early spring, killing approximately 70% of the people it infects. The virus doesn’t seem to spread easily to humans, so the toll has been low—usually less than a dozen deaths each year nationwide. But this season is shaping up to be bad: So far, Bangladesh health authorities have attributed 24 deaths to the virus, whose hallmark symptoms are fever and encephalitis. Fruit bats are thought to be the viral reservoir, and in Bangladesh authorities suspect that the virus is transmitted mainly when people drink raw date palm sap tainted with bat saliva or feces. There is no vaccine against the virus. Cusco, Peru 5
Yale to Return Machu Picchu Artifacts
Ending a bitter dispute, Yale University will return to Peru thousands of items excavated from Machu Picchu by 20th century explorer Hiram Bingham. In an agreement signed 11 February, Yale and the Universidad Nacional de San Antonio Abad del Cusco said they would create a new museum and research center in an Inca palace in Cusco, Peru, to display and house thousands of artifacts, including pottery, stone tools, and human bones. Peru had sued the university, and last November Peruvian President Alan Garcia called Yale’s refusal to return the artifacts a “global crime.” “Yale has done the right thing probably if they want a quiet life,” said archaeologist Colin Renfrew of the University of Cambridge in the United Kingdom. http://scim.ag/yale-peru
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NEWS OF THE WEEK FINDINGS
Fetal Surgery Success Fetal surgery can help unborn babies with spina bifida—but at a price. Although most fetal surgeries focus on fatal malformations, spina bifida is an exception: Children with it often have trouble walking and controlling bladder and bowel functions, but they rarely die. Because of the risks to mother and baby, surgeons felt it was especially important to test spina bifida fetal surgery in a big clinical trial. Last week, a team led by N. Scott Adzick of Children’s Hospital of Philadelphia reported online in The New England Journal of Medicine that among 158 moth-
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New Stem Cell Lab Designed to Inspire A stem cell research building opened 9 February at the University of California, San Francisco (UCSF), is generating oohs and ahhs from scientists and architecture buffs alike. The $123 million Ray and Dagmar Dolby Regeneration Medicine Building, which will headquarter the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, snakes along a 65˚ slope and features four split-level floors with terraced roofs planted with native grasses. Labs with open floor plans, interspersed with offices and lounge areas, are meant to foster interaction among its 300 researchers. It seems to be working, says the center’s director, Arnold Kriegstein: “People are already congregating in the lunchrooms and in the hallways and striking up collaborations.” ers and their babies, those who were operated on before birth fared better than those who got surgery immediately after. Forty percent of the fetal surgery group received shunts to drain fluid from the brain, and 42% could walk without help from devices. That compared with 82% in the control group who got shunts, and 21% who could walk without assistance. But nearly half of the babies who experienced fetal surgery were born quite prematurely, and there were other risks to mom and baby, too. Some say it may take years, tracking the children as they grow, to really understand when and whether the surgery is worth it. http://scim.ag/fetal-surgery
Probing the Secrets of Prostate Tumors A group of researchers has unveiled the first whole genome sequences of prostate tumors. Their results, published online last week in Nature, may lead to the development of more efficient, less invasive ways to diagnose and treat this cancer.
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Sequencing the whole genome of a prostate tumor, says co-author Levi Garraway of Harvard Medical School in Boston, allowed the researchers to see “biology that would have been invisible with any other method.” Most genetic analyses of tumors have focused on figuring out which mutations turn normal cells cancerous and how these “spelling errors” foster tumor growth. But by sequencing the entire genomes of seven prostate tumors and comparing them with genomes from the patients’
NOTED >>The U.S. Department of Health and
Human Services’ Office of Research Integrity has produced an interactive online movie called The Lab. The chooseyour-own-adventure-style film allows viewers to play as one of four characters, including an insecure postdoc and a promising young graduate student, to avert a case of scientific misconduct. http://scim.ag/labmovie
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The century-old surgical practice of removing lymph nodes from breast cancer patients is likely unnecessary, says a new study in the 9 February issue of The Journal of the American Medical Association. Conventional wisdom has been that after a biopsy from a sentinel lymph node finds cancer, removal of all the armpit lymph nodes before they can spread the disease throughout the body would increase survival. But researchers at John Wayne Cancer Institute in Santa Monica, California, and other institutions found no difference in survival or clinical outcomes in a randomized trial of 891 women with early-stage breast cancer who were undergoing chemotherapy or radiation. Half of the women had only the sentinel node removed, whereas the others had all their lymph nodes removed. The authors credit the results to aggressive therapy that wiped out the cancer before it could spread from the lymph nodes. They recommend that physicians reconsider the need for the painful surgery, which can have complications such as swelling and infection—although persuading the field to change could be tough because the practice is so ingrained. Even so, several cancer clinics such as Memorial Sloan-Kettering, where some of the trials took place, have already started to implement the new standard.
CREDITS (TOP TO BOTTOM): © BRUCE DAMONTE/UCSF; ILLUSTRATION COURTESY OF THE CENTER FOR FETAL DIAGNOSIS AND TREATMENT AT THE CHILDREN’S HOSPITAL OF PHILADELPHIA
Lymph Node Surgery Unnecessary for Early Breast Cancer
NEWS planet between 1/10 and 10 times the size of Earth. They calculated that a planet with Earth’s composition of rock and water but three times as big would, in spite of losing heat through its icy shell, generate enough warmth to maintain a hidden ocean. A planet with much more water, they say, would only need to be one-third Earth’s size. David Ehrenreich, a planetary scientist at the Joseph Fourier University in Grenoble, France, calls the study interesting but notes that life buried under an ice sheet would be hard to detect. So would the planet itself, admits Switzer: Rogue planets are currently visible only within about 100 billion miles of Earth, where the probability of one existing is just one in a billion. http://scim.ag/lone-planet
Outcast Planets Could Support Life
Computer scientist Geoffrey Hinton of the University of Toronto has carried off Canada’s most prestigious science prize—along with a $1 million grant to support his research over the next 5 years. Hinton was awarded the Gerhard Herzberg Canada Gold Medal for Science and Engineering on 14 February for his work on machine learning. British-born Hinton works
CREDITS (TOP TO BOTTOM): (SOURCE) AAAS R&D BUDGET AND POLICY PROGRAM; NSERC; ANDREW ELLISON/BUMC
http://scim.ag/tumor-genes
Many astronomers assume a planet that harbors life would have to be warm and wet like Earth. Now, in a paper submitted to The Astrophysical Journal Letters, Dorian Abbot and Eric Switzer of the University of Chicago in Illinois suggest that a planet that has been slingshotted into the cold of outer space could also support life—in a hidden ocean under a blanket of ice, kept warm by geothermal activity. Abbot and Switzer simulated a lone
NEWSMAKER
Machine Learning Nets Canada’s Top Science Prize
BY THE NUMBERS
The budget for U.S. science got more complicated this week when President Barack Obama submitted his 2012 spending plan. Here are three starting points for the coming debate over how much the country should invest in nondefense research:
$66.8 billion The amount
President Barack Obama has requested for 2012, a 6.5% increase over current spending levels.
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normal cells, the researchers discovered an unexpected phenomenon. Rather than single spelling errors, the tumors had long “paragraphs” of DNA that seem to have broken off and moved to another part of the genome. The chunks of DNA that broke off all contained genes that help drive cancer progression, and they moved to prime locations in the genome where they would be most active. The authors note that they need to sequence more prostate tumors to learn how frequently different mutations occur and which of the rearranged genes drive cancer. Once researchers learn which genes may be markers for cancer, says co-author Mark Rubin, a pathologist at Weill Cornell Medical College in New York City, sequencing technology might be able to detect them in a blood or urine test, replacing an invasive prostate exam or biopsy.
$62.7 billion Current spend-
ing under a so-called continuing resolution for 2011 that expires on 4 March.
$58.3 billion The amount
Republicans have budgeted in 2011 as part of a government-wide spending plan being debated this week by the House of Representatives. on neural networks and their application to processes such as monitoring industrial plants for improved safety and systems for voice recognition. The prize, named after the Nobel Prize-winning chemist, is awarded by the Natural Sciences and Engineering Research Council of Canada.
Random Sample
Art From Produce Using the same MRI machines with which he conducts brain scans by day, Andrew Ellison, a technologist at Boston University School of Medicine, spends his evenings scanning fruit and vegetables. The resulting ethereal videos are produced as the scanner passes through the skin, pith, and flesh of everyday edibles. Ellison initially used an orange as a quality control. “A problem with the scanner would show itself with most fruits and veggies,” he explains. But, fascinated by the orange’s fleshy insides, Ellison began to scour the markets for other fruit and vegetables to scan. Encouraged by his colleagues’ enthusiasm for his new art form, he started to post his videos to a blog (http://insideinsides.blogspot.com) that has received more than 500,000 hits since July 2010. Ellison has now racked up 36 different scans and is looking for more-exotic produce. “No one seems to be as amazed and moved by the artichoke as I am,” he says, “but everyone has a favorite.” (See also the Visualization section of this special issue on p. 848.)
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MRI scans of peapods, a watermelon, black raspberries, and a persimmon (clockwise, from top left).
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NEWS OF THE WEEK FINDINGS
Fetal Surgery Success Fetal surgery can help unborn babies with spina bifida—but at a price. Although most fetal surgeries focus on fatal malformations, spina bifida is an exception: Children with it often have trouble walking and controlling bladder and bowel functions, but they rarely die. Because of the risks to mother and baby, surgeons felt it was especially important to test spina bifida fetal surgery in a big clinical trial. Last week, a team led by N. Scott Adzick of Children’s Hospital of Philadelphia reported online in The New England Journal of Medicine that among 158 moth-
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New Stem Cell Lab Designed to Inspire A stem cell research building opened 9 February at the University of California, San Francisco (UCSF), is generating oohs and ahhs from scientists and architecture buffs alike. The $123 million Ray and Dagmar Dolby Regeneration Medicine Building, which will headquarter the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, snakes along a 65˚ slope and features four split-level floors with terraced roofs planted with native grasses. Labs with open floor plans, interspersed with offices and lounge areas, are meant to foster interaction among its 300 researchers. It seems to be working, says the center’s director, Arnold Kriegstein: “People are already congregating in the lunchrooms and in the hallways and striking up collaborations.” ers and their babies, those who were operated on before birth fared better than those who got surgery immediately after. Forty percent of the fetal surgery group received shunts to drain fluid from the brain, and 42% could walk without help from devices. That compared with 82% in the control group who got shunts, and 21% who could walk without assistance. But nearly half of the babies who experienced fetal surgery were born quite prematurely, and there were other risks to mom and baby, too. Some say it may take years, tracking the children as they grow, to really understand when and whether the surgery is worth it. http://scim.ag/fetal-surgery
Probing the Secrets of Prostate Tumors A group of researchers has unveiled the first whole genome sequences of prostate tumors. Their results, published online last week in Nature, may lead to the development of more efficient, less invasive ways to diagnose and treat this cancer.
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Sequencing the whole genome of a prostate tumor, says co-author Levi Garraway of Harvard Medical School in Boston, allowed the researchers to see “biology that would have been invisible with any other method.” Most genetic analyses of tumors have focused on figuring out which mutations turn normal cells cancerous and how these “spelling errors” foster tumor growth. But by sequencing the entire genomes of seven prostate tumors and comparing them with genomes from the patients’
NOTED >>The U.S. Department of Health and
Human Services’ Office of Research Integrity has produced an interactive online movie called The Lab. The chooseyour-own-adventure-style film allows viewers to play as one of four characters, including an insecure postdoc and a promising young graduate student, to avert a case of scientific misconduct. http://scim.ag/labmovie
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The century-old surgical practice of removing lymph nodes from breast cancer patients is likely unnecessary, says a new study in the 9 February issue of The Journal of the American Medical Association. Conventional wisdom has been that after a biopsy from a sentinel lymph node finds cancer, removal of all the armpit lymph nodes before they can spread the disease throughout the body would increase survival. But researchers at John Wayne Cancer Institute in Santa Monica, California, and other institutions found no difference in survival or clinical outcomes in a randomized trial of 891 women with early-stage breast cancer who were undergoing chemotherapy or radiation. Half of the women had only the sentinel node removed, whereas the others had all their lymph nodes removed. The authors credit the results to aggressive therapy that wiped out the cancer before it could spread from the lymph nodes. They recommend that physicians reconsider the need for the painful surgery, which can have complications such as swelling and infection—although persuading the field to change could be tough because the practice is so ingrained. Even so, several cancer clinics such as Memorial Sloan-Kettering, where some of the trials took place, have already started to implement the new standard.
CREDITS (TOP TO BOTTOM): © BRUCE DAMONTE/UCSF; ILLUSTRATION COURTESY OF THE CENTER FOR FETAL DIAGNOSIS AND TREATMENT AT THE CHILDREN’S HOSPITAL OF PHILADELPHIA
Lymph Node Surgery Unnecessary for Early Breast Cancer
Obama’s 2012 Vision Clashes With House Cuts in 2011 It’s a tale of two budgets, and the U.S. science community is applauding one while deploring the other. The twin story lines involve the president’s vision for 2012, submitted to Congress on Valentine’s Day, along with a spending plan by House Republicans for the rest of this fiscal year. The latter is needed because Congress still hasn’t finished work on the budget for the 2011 fiscal year that began last October. And while budgets are always political statements, this pair goes further by painting starkly contrasting visions of where the country should be headed—and the role of research in helping it to get there. All this is a recipe for confusion and uncertainty. The first order of business is the 2011 budget. Three days before the president unveiled his 2012 budget, Republicans in the House of Representatives offered a plan to cut $62 billion in current spending as a first step in erasing the nation’s $1.5 trillion budget deficit. They argue that a bankrupt government can’t fund any type of research, and that what’s needed now is fiscal belt-tightening. Representative Harold Rogers (R–KY), chair of the House appropriations committee, acknowledges that his panel has crafted a 2011 spending plan with cuts that “will affect every community in the nation. I know many people will not be happy with everything we’ve proposed in this package.” Republicans have proposed reductions of more than $3.3 billion in current research
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spending by various federal agencies. The list is long and the cuts are deep, including an $893 million reduction below current spending at the Department of Energy’s (DOE’s) Office of Science, to $4.1 billion, and a cutback of $1.6 billion at the National Institutes of Health (NIH), to $29.5 billion, bringing both agencies to 2008 spending levels. The National Science Foundation (NSF), one of the favored children of the Obama Administration, would see its current budget pared by $388 million to a level—$6.57 billion—that would be more than $1 billion below the president’s request of $7.77 billion in 2012. The new Republican majority in the House was given the chance to craft a 2011 budget after Democrats gave up trying to pass a spending bill in the lame-duck session after the November elections. Debate was expected this week on the so-called continuing resolution (CR) to finish out the fiscal year, which ends on 30 September. The plan, once passed by the House, would then go to the Democrat-controlled Senate, which is expected to oppose many of the cuts with backing from the White House. The CR expires on 4 March, so Congress must reach a compromise by that date or extend the CR to avoid a government shutdown. With the 2011 budget still up in the air, Obama’s 2012 budget request appears to be more a statement of principle than a blueprint for what might actually be spent. The $3.73 trillion in planned spending for all fed-
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eral agencies fleshes out his promise in last month’s State of the Union speech to “outinnovate, out-educate, and out-build” the rest of the world by providing healthy increases for research and education. Among other things, it keeps his promise for a 10-year budget doubling at three important research agencies, proposes a significant expansion of clean-energy and climate research, including $550 million for a fledgling blue-sky energy research agency, and offers a slew of initiatives to improve U.S. science education by training more and better teachers and helping those already in the classroom. The growth would occur despite a promised 5-year freeze in overall domestic discretionary spending that would put the squeeze on a vast array of government programs, including some research efforts that the Administration likes but says the country can’t afford. “This is a budget that the nation can be proud of,” says the president’s science adviser, John Holdren, speaking about the R&D portfolio. But Holdren said the proposed 11% growth in basic and applied research (all comparisons are with 2010 spending levels since there is no 2011 budget) also exemplifies “tough love,” with sharp cuts to environmental programs at the Environmental Protection Agency and within the “development” portfolio of defense research. Officials at NASA, which would face a stagnant budget under Obama’s plan, said that the agency will kill plans for a space telescope to explore dark energy, the top priority of a recent decadal survey by the astrophysics community, in the hope that it can collaborate more cheaply with the European Space Agency on a similar mission. NSF Director Subra Suresh says he sees “a lot of love” in the president’s pro-
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NEWS
SOURCE: OMB, CONGRESS
posal for a 13% increase for NSF, and he hopes that Congress reciprocates. Even biomedical researchers, reacting to a 2.4% boost for NIH that would fall short of what the Administration requested last year in its 2011 budget, say they are grateful for any increase at a time when so many federal agencies are looking at reductions. Not surprisingly, Republicans have little love for Obama’s Valentine’s Day budget. “The president’s budget will destroy jobs by spending too much, taxing too much, and borrowing too much,” declared House Speaker John Boehner (R–OH). Rogers expressed his disdain for the 2012 proposal by saying that the country “must go much further than this anemic effort of symbolic reductions and additional spending proposed under the guise of funding ‘freezes’ if we are truly to get our nation’s finances on a sustainable course.” And Representative John Kline (R–MN), chair of the Education and the Workforce Committee that will pass judgment on many of the education initiatives, declared that “the president’s budget denies the reality of the fiscal crisis we face.” What’s at stake The dueling budgets offer a sampler of sweets and sourballs for the palates of scientists of various stripes. Obama’s 2012 proposals include: • Interdisciplinary research at NSF would flourish, reflecting Suresh’s effort to break down disciplinary walls. He’s proposed a $30 million National Robotics Initiative in collaboration with other federal agencies, for example, as well as a solicitation for a new program supporting all manner of interdisciplinary proposals that he promises “will change the way NSF does business.” • A 24% boost for competitive research within the Department of Agriculture, to $325 million, for grants ranging from improving food safety to mitigating the impact of climate change on agriculture. Obama had requested $104 million more than that for the program in 2011, while the Republican proposal would result in a cut of 13% from 2010 levels. • Climate change research across the government would rise by 20%, to $2.6 billion, including a 25% boost for earth sciences at NASA. A related collection of programs that NSF began in 2010, called
Science, Engineering, and Education for Sustainability, would jump by nearly onethird, to $998 million. • The Advanced Research Projects Agency–Energy, which Energy Secretary Steven Chu sees as the flagship for the Administration’s push to discover, scale up, and disseminate clean-energy technologies, would receive $550 million in 2012. It would be the first annual budget for the 2-year-old agency that was launched with money from the 2009 stimulus act. On the other hand,
NIH
$31.8 billion • $ 31.1 billion • $29.5 billion •
Obama’s 2012 request Current funding House plan for 2011 CR
NSF
$7.8 billion • Obama’s 2012 request $ 6.9 billion • Current funding $ 6.5 billion • House plan for 2011 CR DOE Science
$5.4 billion • Obama’s 2012 request $ 4.9 billion • Current funding $ 4.0 billion • House plan for 2011 CR House Republicans would keep it on a starvation diet, with $50 million in 2011. • A new National Center for Advancing Translational Sciences (NCATS) at NIH to “reengineer” the drug-development pipeline. NCATS would include a $100 million Cures Acceleration Network, created by last year’s health care law. Although creating NCATS would entail abolishing the National Center for Research Resources, NCRR remains in the 2012 budget and NCATS does not appear because NIH is still trying to assign various pieces of NCRR.
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• DOE science programs would pony up $15 million to keep alive a project to turn an abandoned gold mine in South Dakota into a vast Deep Underground Science and Engineering Laboratory (DUSEL). NSF’s oversight board decided recently that the proposed $875 million lab didn’t fit its mission, and the agency zeroed out funding for DUSEL in its 2012 request. • A 32% increase in funding for the in-house laboratories and other research initiatives at the National Institute of Standards and Technology, to $679 million, would expand efforts in nanoscale manufacturing, advanced energy materials, and novel time and electrical measurement capabilities. • Research on solar photovoltaics would grow from $126 million to $337 million at DOE as part of Chu’s SunShot Initiative to spur commercial use of the renewable energy source by lowering its cost. In contrast, House Republicans would prefer that private industry take on the task. • Termination of two NSF programs to strengthen precollege science education, one for graduate students to spend time in the classroom and another to support research on the science of learning. They would be replaced by more targeted efforts to improve the teacher workforce through improved training and research on best practices. The fate of these and other budget proposals hinges on whether the White House and Congress can find common ground. Senate Democrats, who have so far kept their powder dry, cobbled together a plan last December that would have provided increases for many science agencies while still coming in under the president’s 2011 request. But it was withdrawn after failing to win enough support from Republicans. In the meantime, the science community has lined up behind Obama’s version of the future. “His budget, while freezing discretionary spending and taking other steps to reduce deficits, invests in research that will help us grow our economy, conquer disease, achieve greater energy independence, and strengthen our national security,” says Robert Berdahl, president of the Association of American Universities in Washington, D.C. The House CR, he notes, “would truly harm this nation’s capacity for innovation by slashing research spending for nearly every agency that sponsors scientific research.” The fate of many research projects—for this year and well beyond—hinges on which vision prevails. –JEFFREY MERVIS
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Presidential vision. Science adviser John Holdren is flanked by the president’s numbers and words as he rolls out the 2012 science budget.
With reporting by the Science News staff.
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NEWS&ANALYSIS CHINA
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“[The current policy tells] the best and the brightest to spend their most productive years abroad.” —MU-MING POO, INSTITUTE OF NEUROSCIENCE, CHINESE ACADEMY OF SCIENCES
“It is better to invest in a whole new generation of talent than to buy reputation.” —DAVID HO, ADARC
p. 1732), a phenomenon that many scientists dismiss out of hand. University President Zhang Jie and Montagnier did not respond to messages before Science went to press. In the original Qianren Jihua, the program’s sponsor, the Organization Department of the Chinese Communist Party’s Central Committee (Zhongzubu), provides each recruit with a $150,000 tax-free relocation allowance. Beyond this subsidy, awardees must negotiate salaries and start-up packages with recruiters. Eager to please Zhongzubu, university and institute officials routinely dangle start-up funds of $1.5 million or more
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to entice candidates—then fail to deliver, says Xu Ruiming, a structural biologist at CAS’s Institute of Biophysics in Beijing. Xiao-Fan Wang, a cancer researcher at Duke University in Durham, North Carolina, says some Qianren recipients “sincerely wanted to go back but have to reconsider when they see no research funding.” However, the $150,000 incentive, sometimes doubled or tripled by local governments, entices opportunists, Wang and others say. Problems that dogged previous recruitment programs have tainted Qianren Jihua as well, such as recruits padding their resumés and professors with full-time jobs overseas double-dipping in China. Some Qianren recruits, Science has learned, are postdocs masquerading as faculty members or are not full professors as the program announcement requires. That doesn’t appear to perturb Zhongzubu. “Coming from overseas is the most important qualification of Qianren Jihua. All other factors, such as age, degree, or one’s professional title, are not that important,” says Zhongzubu official Zhang Dong. The perception that a tide of opportunists is cashing in and that many Qianren awardees are holding out for even bigger carrots riles many Chinese scientists. In recent years, CAS has established a merit-based promotion and compensation system, but “now you suddenly have people coming from the outside getting paid four to five times more,” says Poo, who also holds a full-time faculty position at the University of California, Berkeley, and does not receive a salary from CAS. Qianren packages make “people really jealous,” says Poo. Qianren may also inadvertently worsen a long-standing problem faced by Chinese science: the paucity of talented young researchers. It is difficult to recruit good assistant professors in China already, says Poo, and Qianren Jihua, by requiring recipients to be tenured full professors or the equivalent at an overseas institution, essentially tells “the best and the brightest to spend their most productive years abroad.” Buffeted by complaints and misinformation, Zhongzubu has chosen to keep the names of most awardees under wraps. The agency “does not want recipients subjected to criticism before they even begin working” in China, says Zhang. But Internet users have collected some 450 Qianren names gleaned from Chinese university announcements. Of known awardees, more than 300 have full-
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CREDITS (TOP TO BOTTOM): COURTESY OF MU-MING POO; ADARC
How much would it take to get you to relocate to China? Would 150 million yuan ($23 million) do the trick? If so, pack your bags—if you are a Nobel laureate, that is. Science has learned that the Chinese government will soon announce a new initiative to lure up to 10 winners of prestigious international science prizes—including the Nobel Prize—to China each year by offering what may be the heftiest reward ever paid to individual researchers. Some prizewinners may be salivating, but at least one prominent Chinese-American scientist aware of the new program blasts it as a massive waste of resources. “It is better to invest in a whole new generation of talent than to buy reputation,” says David Ho, director of the Aaron Diamond AIDS Research Center (ADARC) in New York City. “Someone should step up and put an end to this folly.” The initiative will be a new component of the Chinese government’s Recruitment Program of Global Experts, commonly known as Qianren Jihua. Launched in 2008 with the goal of recruiting up to 2000 experts from abroad over 5 to 10 years (Science, 31 July 2009, p. 534), the program so far has tallied 1143 recipients, including 880 “innovative talents” to work at universities and research institutes. The rest are “entrepreneurial talents” recruited to run high-tech companies. Despite Qianren Jihua’s impressive numbers, many observers say the program is foundering. Initially, it mandated that awardees spend 6 to 9 months a year in China for a minimum of 3 years. Most recruits, however, have not signed contracts or moved to China, says Li Ning, a public policy researcher at the University of Guam. The main reason awardees give for not having signed contracts is that they haven’t received start-up funds. Qianren Jihua “is a huge disaster right now,” claims Mu-ming Poo, part-time director of the Institute of Neuroscience of the Chinese Academy of Sciences (CAS) in Shanghai. That sentiment is shared by many contributors to blog sites on Chinese science. The new component dubbed “Top Qianren” is likely to make the program even more controversial. Its first catch, sources say, is 78-year-old French virologist Luc Montagnier, who won the 2008 Nobel Prize in physiology or medicine for co-discovering HIV. Shanghai Jiaotong University recruited Montagnier, who intends to lead research into electromagnetic radiation from highly diluted pathogen DNA (Science, 24 December 2010,
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High-Priced Recruiting of Talent Abroad Raises Hackles
NEWS&ANALYSIS time faculty positions outside China, judging by information on their employers’ Web sites. More than 100 have research projects sponsored by the U.S. National Institutes of Health or the National Science Foundation, with funding for several years down the line. Most of these awardees cannot spend six or more months in China, as the program envisioned, without reducing the commitment to their current employers. To accommodate them, Zhongzubu created a Qianren
category last year that allows recipients to spend as little as 2 months a year in China. The government expects fewer than 100 awardees each year to choose the short-term category, says Zhang. The failure to land many big fish has prompted Zhongzubu to cast for small fry. Last month, the government launched Young Qianren Jihua, which over the next 5 years aims to recruit from overseas 2000 researchers under age 40. The government will pro-
vide young recipients with a relocation allowance of about $75,000 and research funds ranging from $152,000 to $456,000 over 3 years. Requirements include Ph.D.s obtained from foreign universities and overseas work experience of 3 years or more. At 1000 or so pay grades higher will be the Nobel laureates and other elites who accept a Top Qianren award. They’ll never have to worry about funding again.
–HAO XIN
A N T H R A X I N V E S T I G AT I O N
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Science in Ivins Case Not Ironclad, NRC Says The scientific evidence behind the U.S. The FBI, working with scientists inside and logical weapon. U.S. intelligence officials colgovernment’s implication of U.S. Army outside the bureau, used assays to screen lected environmental samples from this undisresearcher Bruce Ivins as the perpetrator of anthrax samples at labs around the United closed site in May 2004 as part of the anthrax the 2001 anthrax letter attacks is not as strong States and overseas for the presence of four investigation, swabbing “the outside of an as claimed by the Federal Bureau of Inves- morphological types of the Ames strain of unopened medicine dropper package, a sink tigation (FBI), according to a long-awaited Bacillus anthracis that were present in the and a sink drain hose.” The swabs tested posreview by the National Research Council attack material. The results of this analysis itive for anthrax and contained certain DNA (NRC) released this week. Although the led the FBI to conclude that the spores were sequences of the Ames strain. However, when report agrees with the FBI on most of the con- derived from flask RMR-1029, to which Ivins the paraphernalia from this site was brought to clusions drawn from the analysis of anthrax had access. the United States in November 2004, no traces spores used in the mailings, it cautions that Although the review panel agreed that of anthrax could be found. “The committee the science by itself does not definitively link the spores could have originated from believes that the complete set of data and conthe attack material to a flask under Ivins’s RMR-1029, it did not agree with the inves- clusions concerning these samples, including control at the U.S. Army Medical Research tigative claim that the spores could only all relevant classified documents, deserves a Institute for Infectious Diseases more thorough scientific review,” in Frederick, Maryland, as the the report says. FBI asserted. The panel also suggests that the The FBI asked NRC to conFBI could have made use of more duct the review in September advanced tools for genetic analy2008, weeks after the FBI and sis that became available as the the Department of Justice (DOJ) investigation progressed. “Using claimed Ivins was behind the tools such as high-throughput, deadly mailings that killed five ‘next generation’ DNA sequencpeople and terrorized the nation. ing could have strengthened or Ivins committed suicide just days weakened the association between before the FBI went public with spores found in the mailed letters the charges, so the case never and spores from RMR-1029,” went to trial. Many of Ivins’s col- Inconclusive science. The methods the FBI used to investigate the anthrax let- says Stanford University microleagues alleged that the FBI had ters were sound, says a new report, but not sufficient to establish their source. biologist David Relman, vice chair hounded an innocent man to of the committee. death, whereas the FBI and DOJ laid out their have come from RMR-1029. “Some of the The review is bound to stir up controversy case against Ivins at press conferences and mutations identified in the spores of the and provide fodder for critics of the FBI investhrough the release of hundreds of pages from attack letters … might have arisen by paral- tigation. However, Paul Keim, an anthrax the case files. A cornerstone of the investiga- lel evolution rather than by derivation from researcher at Northern Arizona University in tion, FBI officials said, was the use of genetic RMR-1029,” the review concludes. “This Flagstaff who helped the FBI conduct some analysis to trace the source of the anthrax. possible explanation of genetic similarity of the analysis, says the flaws pointed out by Although not intended to be a proxy trial, between spores in the letters and in RMR- the NRC panel do not undermine the evidence NRC’s review of the FBI’s scientific evidence 1029 was not rigorously explored during in any significant way. That said, he agrees in the case has been the closest thing to an the course of the investigation.” that studies of how the Ames strain evolves independent assessment of the investigation. The review also questions whether inves- in the lab would have strengthened the forenThe review found that the methods used tigators had sufficient evidence to rule out sic side of the investigation, and such studies for the genetic and chemical analyses were the possibility, however remote, that the are now under way, he says, but overall “the generally sound but that the FBI and DOJ had spores originated at an overseas site where review seems like a cautious endorsement of overstated the scientific case against Ivins. Al Qaeda might have been developing a bio- the investigation.” –YUDHIJIT BHATTACHARJEE www.sciencemag.org
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NEWS&ANALYSIS time faculty positions outside China, judging by information on their employers’ Web sites. More than 100 have research projects sponsored by the U.S. National Institutes of Health or the National Science Foundation, with funding for several years down the line. Most of these awardees cannot spend six or more months in China, as the program envisioned, without reducing the commitment to their current employers. To accommodate them, Zhongzubu created a Qianren
category last year that allows recipients to spend as little as 2 months a year in China. The government expects fewer than 100 awardees each year to choose the short-term category, says Zhang. The failure to land many big fish has prompted Zhongzubu to cast for small fry. Last month, the government launched Young Qianren Jihua, which over the next 5 years aims to recruit from overseas 2000 researchers under age 40. The government will pro-
vide young recipients with a relocation allowance of about $75,000 and research funds ranging from $152,000 to $456,000 over 3 years. Requirements include Ph.D.s obtained from foreign universities and overseas work experience of 3 years or more. At 1000 or so pay grades higher will be the Nobel laureates and other elites who accept a Top Qianren award. They’ll never have to worry about funding again.
–HAO XIN
A N T H R A X I N V E S T I G AT I O N
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Science in Ivins Case Not Ironclad, NRC Says The scientific evidence behind the U.S. The FBI, working with scientists inside and logical weapon. U.S. intelligence officials colgovernment’s implication of U.S. Army outside the bureau, used assays to screen lected environmental samples from this undisresearcher Bruce Ivins as the perpetrator of anthrax samples at labs around the United closed site in May 2004 as part of the anthrax the 2001 anthrax letter attacks is not as strong States and overseas for the presence of four investigation, swabbing “the outside of an as claimed by the Federal Bureau of Inves- morphological types of the Ames strain of unopened medicine dropper package, a sink tigation (FBI), according to a long-awaited Bacillus anthracis that were present in the and a sink drain hose.” The swabs tested posreview by the National Research Council attack material. The results of this analysis itive for anthrax and contained certain DNA (NRC) released this week. Although the led the FBI to conclude that the spores were sequences of the Ames strain. However, when report agrees with the FBI on most of the con- derived from flask RMR-1029, to which Ivins the paraphernalia from this site was brought to clusions drawn from the analysis of anthrax had access. the United States in November 2004, no traces spores used in the mailings, it cautions that Although the review panel agreed that of anthrax could be found. “The committee the science by itself does not definitively link the spores could have originated from believes that the complete set of data and conthe attack material to a flask under Ivins’s RMR-1029, it did not agree with the inves- clusions concerning these samples, including control at the U.S. Army Medical Research tigative claim that the spores could only all relevant classified documents, deserves a Institute for Infectious Diseases more thorough scientific review,” in Frederick, Maryland, as the the report says. FBI asserted. The panel also suggests that the The FBI asked NRC to conFBI could have made use of more duct the review in September advanced tools for genetic analy2008, weeks after the FBI and sis that became available as the the Department of Justice (DOJ) investigation progressed. “Using claimed Ivins was behind the tools such as high-throughput, deadly mailings that killed five ‘next generation’ DNA sequencpeople and terrorized the nation. ing could have strengthened or Ivins committed suicide just days weakened the association between before the FBI went public with spores found in the mailed letters the charges, so the case never and spores from RMR-1029,” went to trial. Many of Ivins’s col- Inconclusive science. The methods the FBI used to investigate the anthrax let- says Stanford University microleagues alleged that the FBI had ters were sound, says a new report, but not sufficient to establish their source. biologist David Relman, vice chair hounded an innocent man to of the committee. death, whereas the FBI and DOJ laid out their have come from RMR-1029. “Some of the The review is bound to stir up controversy case against Ivins at press conferences and mutations identified in the spores of the and provide fodder for critics of the FBI investhrough the release of hundreds of pages from attack letters … might have arisen by paral- tigation. However, Paul Keim, an anthrax the case files. A cornerstone of the investiga- lel evolution rather than by derivation from researcher at Northern Arizona University in tion, FBI officials said, was the use of genetic RMR-1029,” the review concludes. “This Flagstaff who helped the FBI conduct some analysis to trace the source of the anthrax. possible explanation of genetic similarity of the analysis, says the flaws pointed out by Although not intended to be a proxy trial, between spores in the letters and in RMR- the NRC panel do not undermine the evidence NRC’s review of the FBI’s scientific evidence 1029 was not rigorously explored during in any significant way. That said, he agrees in the case has been the closest thing to an the course of the investigation.” that studies of how the Ames strain evolves independent assessment of the investigation. The review also questions whether inves- in the lab would have strengthened the forenThe review found that the methods used tigators had sufficient evidence to rule out sic side of the investigation, and such studies for the genetic and chemical analyses were the possibility, however remote, that the are now under way, he says, but overall “the generally sound but that the FBI and DOJ had spores originated at an overseas site where review seems like a cautious endorsement of overstated the scientific case against Ivins. Al Qaeda might have been developing a bio- the investigation.” –YUDHIJIT BHATTACHARJEE www.sciencemag.org
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A Quake May Have Hinted That It Was on the Way All this discouraged seismologists, including Michel Bouchon of Joseph Fourier University in Grenoble, France, who had intensively studied the Izmit quake and its aftershocks. But about a year ago, Bouchon and five Turkish and French colleagues got around to analyzing the skimpy foreshock record using new techniques for extracting information from seismic recordings that look like mostly noise. The methods were developed in the past 10 years to understand seismic tremor, the newly recognized continuous seismic “hum” that strikes some faults. Using these and other techniques, the group found some 22 foreshocks in addition to the 18 obvious ones, all of them impercep-
Earthquake
Storms at sea gave sailors of old fair warning: a falling barometer, a shift in the wind, ominous harbingers in the sky. Seismologists have not been so lucky. Decades of monitoring have failed to turn up any warning sign of an imminent quake, and most seismologists have moved on to other problems. Now, however, a new analysis of decadeold, low-quality data from a large Turkish earthquake has revealed tantalizing signs of a quake precursor. “The jury’s out, but we should be in court,” says seismologist Ross Stein of the U.S. Geological Survey (USGS) in Menlo Park, California, who was not involved in the new study. “This is too important to dismiss. It’s what we should be doing.”
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Harbingers? Tiny earthquakes uncovered in a decade-old seismic record (labeled spikes, right) may have signaled slow fault slip that triggered the 1999 quake near Izmit, Turkey.
The encouraging development, reported on page 877, comes from records of the magnitude-7.6 Izmit earthquake that struck just 100 km from Istanbul in 1999. Having ruptured 150 km of the well-studied North Anatolian fault and killed about 17,000 people, the quake got seismologists’ attention. The tiny foreshocks that ticked off in the minutes leading up to it garnered far less notice, for good reason: Only one seismometer near the quake’s starting point recorded more than one foreshock. (Complete records from multiple instrument sites enable seismologists in effect to triangulate quakes and multiply the information that can be extracted about them.) And even the single seismograph was in the geometrically least helpful location, directly opposite the spot on the fault where the large quake got started.
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tible at the surface. In some cases, the foreshocks’ squiggly seismogram traces showed a striking similarity, which suggested that most or all of the foreshocks resulted from the rupture of the same patch of fault. From tiny differences in how long different sorts of seismic waves took to reach the seismograph, Bouchon and colleagues concluded that the foreshock ruptures were striking the same spot on the fault where the main shock would get started. And they found that the whole process was accelerating, from the time of the first foreshock to one 44 minutes later, just 0.07 second before the main shock. To Bouchon and his colleagues, the Izmit foreshocks signify far more than a run-ofthe-mill swarm of microearthquakes. They are a clear sign that the fault was slipping— not just feeling the increasing strain—during
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a buildup to the magnitude-7.6 shock. In the group’s interpretation, a patch of the fault a few hundred meters across located about 15 km beneath the eventual epicenter repeatedly ruptured, letting the fault patch slip 1 millimeter to 1 centimeter each time. Bouchon thinks the fault slipped at the same spot where the big quake eventually started. So it was the accelerating slow slip that led to the runaway rupture of the big quake. “Izmit is the first time we see the fault slipping at depth before the earthquake,” says Bouchon. And, he says, the distinctive nature of the first couple of foreshocks tells a seismologist—or a computer program monitoring a fault—that “there’s a probability that something big is coming.” Researchers are impressed, up to a point. Bouchon “has wrung as much as anyone possibly could out of such crappy data,” says Stein. And, says seismologist William Ellsworth of the USGS in Menlo Park, “there is a very clear sequence of some foreshocks from a small region that leads to eventual initiation” of the large quake. But the view from the single seismic record is still fuzzy, Ellsworth says. All the foreshocks “may be at the same spot, maybe not.” More fundamentally, seismologists wonder how far the Izmit sequence of accelerating foreshocks can be generalized. “We know there’s a range of behavior” among large quakes, says Ellsworth. More than half of large earthquakes have no foreshocks at all. “Many earthquakes simply come out of the blue,” he notes. Researchers were able to take particularly close looks at the starting points on the San Andreas fault of both the 2004 magnitude-6.0 Parkfield earthquake and the 1989 magnitude-6.9 Loma Prieta earthquake. “We simply did not see anything,” says Ellsworth. And for all researchers know, says seismologist David Shelly of the USGS in Menlo Park, fault slip before a quake may “happen relatively frequently and then may or may not trigger an earthquake.” The Izmit observations are both tantalizing and frustrating, says seismologist Gregory Beroza of Stanford University in Palo Alto, California. Tantalizing, he says, because “this is the sort of thing you’d expect to see” based on theory. “The frustrating part is they don’t have enough data to show exactly what’s going on. But this is going to cause people to redouble their efforts to closely examine the beginning of other earthquakes.” The problem with that, he notes, will be snaring big quakes in dense nets of geophysical monitors, because “we don’t know where earthquakes are going to start.”
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–RICHARD A. KERR
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EARTHQUAKE PREDICTION
CREDITS (TOP TO BOTTOM): NEWSCOM; ADAPTED FROM M. BOUCHON ET AL., SCIENCE 331, 6019 (18 FEBRUARY 2011)
NEWS&ANALYSIS
NEWS&ANALYSIS GENETICS AND DISEASE
Life can be treacherous for Ecuadorians with Laron syndrome, a rare type of dwarfism. As children, they are vulnerable to infectious diseases. As adults, they are prone to fatal accidents, such as falls on stairs that aren’t sized for their short legs. But a new study shows that these people, who carry a genetic defect that prevents them from responding to growth hormone (GH), are almost exempt from cancer and diabetes. The paper solidifies a link researchers have long suspected from animal studies and suggests that dialing down the growth-controlling molecular pathways might protect healthy adults from these diseases. “The strength [of this paper] is that finally someone has made this connection in humans,” says physiologist Holly BrownBorg of the University of North Dakota School of Medicine and Health Sciences in Grand Forks. “The fact that they found such a striking absence of cancer and diabetes in such a large cohort makes it a very valuable study,” says mammalian endocrinologist Andrzej Bartke of the Southern Illinois University School of Medicine in Springfield. Numerous studies show that mice gain from short circuits in the GH pathways. Minimice that can’t make GH or lack the receptor that relays its message are less susceptible to cancer than are their huskier counterparts. They also have low quantities of blood insulin, and their cells are sensitive to the hormone—high insulin levels and insulin resistance can be harbingers of diabetes. Although some data support the notion that GH-deficient people derive similar benefits, the evidence has been “anecdotal,” says Brown-Borg. Enter diabetologist Jaime GuevaraAguirre of the Institute of Endocrinology, Metabolism and Reproduction in Quito, Ecuador. In the late 1980s, he was studying body composition when he chanced on several people with Laron syndrome who lived in small, isolated villages in Ecuador. He has been tracking the group—which now numbers almost 100 people—ever since. They carry mutations that cripple the GH receptor and stunt growth. The tallest men top out at about 140 centimeters (4.5 feet), the tallest women at about 124 centimeters (4 feet). In 1994, Guevara-Aguirre noticed that none of the subjects had cancer. To investi-
gate, he and his colleagues teamed up with researchers led by molecular geneticist Valter Longo of the University of Southern California in Los Angeles. The scientists analyzed medical information for the 99 subjects Guevara-Aguirre has been tracking, for another 53 Laron patients who died before 1988, and for more than 1600 relatives who didn’t have the condition. Only one of the Laron subjects developed cancer, an ovarian tumor that didn’t
Cancer free. Jaime Guevara-Aguirre with several of his Laron syndrome subjects in 1988 (top) and in 2009 (bottom).
recur after chemotherapy. By contrast, cancer killed 20% of the normal-sized relatives. The Laron syndrome individuals were also free of type 2 diabetes, the cause of death for 5% of their taller kin, the team reported in the 16 February issue of Science Translational Medicine. The diabetes result was surprising because Laron syndrome often causes obesity, a risk factor for diabetes. But the researchers found that the subjects, like the minimice, had lower blood insulin levels and much higher sensitivity to the hormone than did controls.
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Scientists haven’t worked out exactly how GH prompts diabetes. But Longo and colleagues did identify a possible mechanism for the Laron subjects’ cancer resistance. They immersed human cells in blood serum from either the Laron subjects or the control group and added DNA-breaking hydrogen peroxide. Cells basting in the control serum accumulated more DNA breaks that can spur tumors and were less likely to commit suicide, a mechanism for weeding out potentially cancerous cells. GH rouses another hormone, insulin-like growth factor-1 (IGF-1), and researchers think that both molecules promote cancer. Adding IGF-1 to the serum from the Laron group cut the amount of cell suicide to control levels, possibly increasing cancer susceptibility. Unlike the dwarf mice with similar genetic defects, the Laron subjects didn’t live longer than normal, despite their lack of mortality from cancer and diabetes. Along with higher death rates from accidents, they also fell victim to epilepsy and similar conditions and to other causes. The study shows that “two major diseases are prevented by a single point mutation in the GH receptor,” says Longo. Does that mean that comparable changes in healthy people could prevent cancer and diabetes? It’s possible, Longo says. In the future, doctors might prescribe drugs that interfere with the GH pathways for adults who have abovenormal levels of IGF-1, much like they currently prescribe statins for people who have high cholesterol, he says. Other researchers suggest that we should be cautious about intervening in the growthcontrolling pathways to forestall disease. “Manipulating this in a healthy person as prevention is a very delicate issue and very complicated,” says Bartke. Although it’s not necessary for growth in adults, GH might still perform important functions, such as preventing obesity, he says. Reducing insulin levels throughout the body might have a downside, adds geriatrician William Banks of the University of Washington School of Medicine in Seattle. “There could be unexpected consequences on the central nervous system” because insulin in the brain improves mental acuity.
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Growth Defect Blocks Cancer and Diabetes
–MITCH LESLIE
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Forensic geneticist Manfred Kayser is exploring whether DNA found at a crime scene can predict what a suspect looks like 838
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Can This DNA Sleuth Help Catch Criminals?
ROTTERDAM, THE NETHERLANDS—The murder was heinous, there were no witnesses, and the police had few clues—except for some skin found under the fingernails of the victim that might belong to the killer. And that was all it took. From a few nanograms of DNA in the skin cells, a police lab determined that the murderer was a man of European origin with brown eyes and straight, dark-brown hair, approximately 45 years old and balding, and likely 1.90 meters in height. Within a few more hours, a police computer spewed out a sketch of the man’s face seen from three different angles, which was all over the evening news. Soon, calls started pouring in from people who recognized the suspect. Sure, that’s science fiction. But according to German gene sleuth Manfred Kayser, the scenario might come true one day. Kayser, who leads the forensic molecular biology department at Erasmus University Medical Center here, is at the forefront of an emerging research area that seeks to predict people’s looks, age, and geographic ancestry from their DNA. If successful, the endeavor, sped along by the genomic revolution, could provide crime fighters with a powerful new toolbox. Kayser’s group made headlines around the world last year with a paper showing how the DNA in a blood sample can give away someone’s age—albeit with a margin of error of at least 9 years. His group has developed a DNA test to predict someone’s eye color; work on hair color, skin color, and other traits is in progress. Kayser is “an upcoming star” in forensic DNA phenotyping, as the field is called, says Bruce Budowle, a geneticist with 40 years of experience with the FBI who is now at the University of North Texas Health Science Center in Fort Worth. He’s “a clear leader,” adds Christopher Phillips, a forensic geneticist at the University of Santiago de Compostela in Spain. The genetic clues that Kayser and others are trying to glean from minuscule amounts of blood, semen, saliva, and hair are unlikely to be introduced as evidence in a courtroom. After all, when someone is suspected of a crime, or charged, a conventional DNA fingerprinting test can determine if his or her DNA matches traces found at the crime scene. Instead, forensic DNA phenotyping could be useful during an investigation, when predicting a criminal’s looks can help the police focus their search. Forensic DNA phenotyping raises new ethical and legal issues, and the Netherlands is the only country so far to regulate the practice in a new law (see sidebar, p. 840). But Kayser doesn’t anticipate that the concerns will stop
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NEWSFOCUS
HUMAN GENOME 10TH ANNIVERSARY | NEWSFOCUS and stayed in his old college town until he was offered the leadership of a new forensics department at Erasmus University Medical Center in 2004. In an unusual arrangement, his department is co-funded by the NetherMusic and animals lands Forensic Institute (NFI), a governmenKayser, 43, isn’t fascinated by crime. He tal lab in The Hague. NFI management recdoesn’t read John Grisham novels or watch ognized that an academic setting would be CSI, the sleek TV hit show centered on foren- a more fertile place to invest in science and sic research. His lab looks as unexciting as development than a lab that’s loaded with any other molecular biology casework, according to Kayser. lab in the world. In fact, Kayser “When I saw the business entered the entire field more or plan, I realized this departless by chance. ment was really going to He was born and raised in be a unique place,” he says, East Berlin in the communist because it would run “the full era. As a teenager, he developed monty” from basic science passions for both music and the to developing and validating animal world, neither of which tests. Kayser works closely Find a podcast on this topic were particularly appreciated with NFI researchers and and other genome stories at in the German Democratic with Peter de Knijff, who runs http://scim.ag/genome10. Republic, he says. After high a well-established forensic school, he worked in the frog genetics lab at Leiden Univercollection of the Natural History Museum in sity Medical Center where Kayser did part Berlin; he was accepted as an accordion stu- of his Ph.D. work. The three groups have dent at the Weimar conservatory but eventu- formed a consortium that in 2008 bagged ally chose to study biology at the University of a €6.5 million grant from the Netherlands Leipzig in 1989. Two months later, the Berlin Organisation for Scientific Research. Wall came down. Kayser said it was relatively easy to setHis first experiences with forensic sci- tle in Holland—although he misses sourence left him frustrated. Between 1994 and dough bread and other things German. From 1998, at Humboldt University in Berlin, Kay- his 10th-floor office, he has a view of Rotser studied microsatellites—short, repetitive terdam’s ultramodern skyline. And although DNA sequences—on the human Y chromo- he would have preferred a city with more hissome. The work, carried out mostly at the uni- toric character, he feels he can’t complain: versity’s Institute of Legal Medicine’s genetic After all, the Germans flattened Rotterdam’s research lab, had obvious forensic applica- ancient center in 1940. tions; in rape cases, for instance, evidence often comes from vaginal swabs that contain Eyes, hair, and skin a mix of DNA from perpetrator and victim. The division of labor within Kayser’s Zooming in on the Y chromosome ensures 15-person lab reflects the stages within the that you’re looking at the rapist’s DNA. full monty. Some researchers are primarKayser’s work helped lay the groundwork ily focused on finding the genes and genetic for male identification using the Y chromo- markers that underlie phenotypic differences, some, a now widespread method. But Kayser utilizing so-called genome-wide association says it took a long time for the technique to studies, for instance. Others are working on become accepted in forensics. “Forensic sci- turning what’s found into actual forensics entists aren’t the most open-minded people tests and validating them—a laborious prowhen it comes to innovative science,” he says. cess governed by international standards. “It was discouraging.” He decided to join Eye color was low-hanging fruit. Over the anthropological geneticist Mark Stoneking’s past 2 years, his group has developed a test, lab at Pennsylvania State University, Univer- called Irisplex, based on the identity of just six sity Park. Stoneking was piecing together the so-called single-nucleotide polymorphisms. human history of Polynesia with mitochon- It can now predict with over 90% accuracy drial DNA, which is inherited via the maternal whether someone has blue or brown eyes— line. Kayser’s expertise with the Y chromo- not perfect, says Kayser, but a lot better than some—which tells the male story—complemented this work perfectly, Stoneking says. Predictable? Many visible traits are at least in part Less than a year later, Stoneking moved genetically determined and may be predictable to the Max Planck Institute for Evolutionary from a person’s DNA—but the only validated test Anthropology in Leipzig. Kayser joined him so far is for eye color. www.sciencemag.org SCIENCE VOL 331 Published by AAAS
eyewitness testimony, which research has shown to be off the mark at alarming rates. Last month, Kayser’s team published a paper in Human Genetics that indicated hair color, too, can be predicted fairly accurately, at roughly 90% for red or black hair and 80% for blond or brown. Those findings are now being translated in a test kit too—most likely combined with eye color, so as to save precious DNA. Skin color is the next candidate. Although his team and others have identified some of the genes involved—they overlap with those for eye and hair color—the picture isn’t complete yet. Beyond that, forensic DNA phenotyping quickly gets complicated. Height, for
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the field. “We are not doing anything else than what police are doing with eyewitnesses,” he says. Except for one thing, he asserts: DNA will prove a more reliable witness.
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instance, is known to have a high degree of heritability: Although diet plays a role in how fast and tall people grow, much of the variation between people is caused by genes. Indeed, a genome-wide association study among 180,000 people published last year revealed more than 180 genetic loci that appear to influence adult height—but together, they account for only 10% of the variation between individuals. De Knijff believes height to be so complex that a useful DNA test is “a bridge too far.” The age test offered a different challenge, as it’s not something one can easily read in a person’s genome. People have tried to predict age by counting the number of mutations in a person’s mitochondria, or measuring the length of their telomeres— the protective caps on the ends of chromosomes, which fray as we age—but both pose practical problems. Kayser’s method instead relies on circles of leftover DNA stored in T cells whose amount decreases as people get older. The field could also target traits like hair structure, baldness, handedness, and earlobe attachment. Its greatest triumph, however, would be that computer-generated, DNA-based facial sketch. Kayser’s group is working on it as part of a consortium of labs
called VisiGen that Kayser founded with Tim Spector of King’s College London. Fan Liu, a genetic epidemiologist in Kayser’s lab, is trying to link genome data to key facial morphology traits, such as facial width or nose size. Kayser is cautious about the prospects. “On paper, it’s possible,” he says. The extreme resemblance between monozygotic twins suggests that facial features are mostly genetic. “But we have no idea yet what genes they are or how complex it is.” Ingrained racism Kayser’s department is also working on tests that can determine someone’s biogeographical ancestry. The technique appears to have been used in hundreds of crime investigations in the United States, but modesty is still in order, says Kayser. Although several companies offer detailed ancestry tests to the public, scientists don’t have a strong basis to go much beyond the continental level—that is, predicting whether someone is, say, European, sub-Saharan African, East Asian, or Native American. Distinguishing a Norwegian from a Swede, for example, is not usually possible, and Kayser rejects as “totally baseless” a controversial U.K. program to use DNA to determine asylum seekers’ nationality (Science, 2 October 2009, p. 30).
This application of forensic DNA phenotyping is an area filled with explosive issues about race and crime about which the debate hasn’t fully begun. Most forensic DNA phenotyping predictions will likely come with a significant level of uncertainty, as opposed to conventional DNA fingerprinting matches, and police officers may have trouble interpreting them. Moreover, genetic ancestry does not equal race, a concept that most scientists shun because it has no well-defined meaning, and does not necessarily predict someone’s appearance. “Ancestry and appearance overlap, but they’re not the same,” Kayser says. Just how important caution is was driven home to Kayser by a series of psychology studies, published in 2004, that showed how deeply ingrained stereotypes about black men and crime are among U.S. law enforcement officers. “It was an eye-opener to me,” he says. It will be important for scientists like him to explain the uncertainties in DNA-based phenotyping carefully, he stresses. Fortunately, says Budowle, Kayser is unlikely to oversell his science to overzealous cops. “Manfred knows the molecular biology but also the population genetics and the statistics,” he says. “He won’t overstate the evidence, and he’ll make clear what the limitations are.” –MARTIN ENSERINK
Emerging Forensics Field May Hit Legal, Ethical Obstacles A year after a 16-year-old girl was brutally raped and murdered in the Netherlands in 1999, forensic geneticist Peter de Knijff broke the law himself. At the police’s request, he set out to determine the geographic ancestry of the murderer from DNA in his semen. That was, he later admitted, “completely illegal” under Dutch law, which at the time allowed using DNA for traditional DNA identification but not for determining race, looks, or disease risk. De Knijff has no remorse. The police were unable to solve the case, and tensions were escalating in the rural community where the girl lived. Many pointed fingers at a nearby hostel for Kurdish, Iraqi, and Afghan asylum seekers. De Knijff’s analysis showed that the killer was most likely from northwest Europe, which helped cooler heads prevail. His dilemma could arise any day in many countries. In the wake of the murder—still unsolved today—the Dutch parliament adopted a law in 2003 regulating forensic DNA phenotyping, the use of DNA samples to predict a suspect’s ancestry or physical characteristics (see main text). But the Netherlands is still the only country to have done so. Countries such as Belgium and Germany—and the U.S. states of Indiana, Rhode Island, and Wyoming—explicitly ban the practice, says BertJaap Koops, a professor at Tilburg University Law School who studies the issue. In the United Kingdom and most U.S. states, forensic DNA pheno-typing isn’t explicitly regulated but is allowed under existing laws for forensic DNA. Geographical ancestry tests appear to have been used in several hundred U.S. investigations, says Pamela Sankar, a bioethicist at the University of Pennsylvania. Most were done by a company called DNAPrint Genomics, she says, which ceased operations in 2009. Sankar, who is tracking the field with funding from the U.S. National
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Human Genome Research Institute, says forensic DNA phenotyping raises ethical and legal issues that need more debate. Her own research, for instance, suggests that police officers may not realize that—as opposed to the high degree of certainty in DNA fingerprinting—phenotyping is probabilistic in nature. Cops could also use ancestry predictions, however imprecise, as an excuse to target minority populations, she says. Other dilemmas loom. In theory, knowing that a criminal is, say, a hemophiliac or a diabetic could help nab him. But the 2003 Dutch law categorically bans looking for disease-related genes because it would violate a suspect’s privacy and the “right not to know,” a basic tenet of medical ethics. (The law allows only the prediction of visible traits and “race.”) Koops argues that these restrictions are overly protective; if genetic sleuthing can reveal that a killer has a very mild or curable disease, or is likely to be a chain smoker, solving the crime might well trump individual rights, he says. The distinction between visible traits and disease is not always tenable anyway, says forensic geneticist Christopher Phillips of the University of Santiago de Compostela in Spain. A mutation in a gene called MC1R can cause pale skin, for instance—which increases the risk of melanoma. “Predictive tests should confine themselves to the visible,” he says, “but sometimes this encroaches on the private at the same time.” The paradox is that conventional DNA fingerprinting has been introduced with the reassurance that it can never reveal any personal information—but now, it’s personal information that forensic geneticists are after. That’s why caution is important, says Phillips. “If we move too quickly, the whole edifice of public confidence in DNA profiling could erode.” –M.E.
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NEWSFOCUS
NASA Weighs Asteroids: Cheaper Than Moon, But Still Not Easy
CREDITS (TOP TO BOTTOM): ©DANIEL DURDA/FIAAA; NASA/JHUAPL/ISAS/JAXA/EMILY LAKDAWALLA
Budgetary realities are driving U.S. astronauts away from the moon toward near-Earth asteroids, but the new goal on the way to Mars should prove uniquely challenging
gravity-free asteroid would be like taking a spacewalk rather than landing on the moon, but without a space station’s handholds.
knows of even one NEA that would clearly serve as a practical first target for astronauts. And no one knows what the first visitors will find at a tiny, nearly gravity-free body, except that it could be both bizarre and dangerous. From what they do know, planetary scientists say, meeting the president’s 2025 schedule would be a heck of a rush requiring considerable investment.
Asteroids are about to get a new reputation. appointed lunar scientists, naturally enough, For decades, those that pass near Earth on but planetary scientists who study the small their circuits about the sun—the so-called bodies of the solar system are delighted. For near-Earth asteroids (NEAs)—have played them, the redirection promises a bonanza of the heavy. A huge NEA 10 kilometers across new data that had seemed beyond their reach killed off the dinosaurs, after all. And there for decades to come. And astronomers look- A bridge too costly was that tiny, perhaps 40-meter-diameter ing for that next catastrophic impacter would Mars has long been the ultimate goal of NEA that leveled 2000 square kilometers of get a boost just as their ongoing search gets a U.S. space exploration. Presidents George Siberian forest in 1908. Earth will inevitably lot harder (see sidebar, p. 843). H. W. Bush and George W. Bush promulcollide with more, both huge and small. But the same planetary scientists who gated national space policies that would But NEAs could soon be redeemed. would most benefit from an NEA-studded have humans setting foot on Mars in the They recently became the next prized des- “flexible path” to Mars are warning that coming decades. In the past decade, NASA tination in the U.S. human exploration of the new route looks bumpy. So far, no one took up George W. Bush’s plan, spending space. President Barack $9.1 billion on the developObama has declared that the ment of a giant rocket that path to landing astronauts on could get astronauts to the Mars is dotted with NEAs. moon by 2020, paving the Rather than f irst returnway for a permanent base. ing astronauts to the moon Only then would NASA turn before heading off to Mars, toward Mars. NASA will be aiming for But this moon-first stratasteroids as steppingstones egy wasn’t going to fly, in the human exploration of according to a committee set deep space. Smaller still. Spacecraft have visited two near-Earth asteroids, big Eros (left) and up by Obama and headed by The new approach has dis- little Itokawa. The first target for astronauts would likely be just 100 meters across. Norman Augustine, former www.sciencemag.org SCIENCE VOL 331 Published by AAAS
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Where do I stand? Visiting a small, nearly
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But wait Extending humans’ reach into deep space within 15 years is all well and good, NEA researchers say, but there are some costly and time-consuming hurdles to be cleared. First, someone needs to find a suitable asteroid. “There just aren’t very many targets out there,” says NEA researcher Alan Harris of the Space Science Institute in La Cañada, California. “Even though there are thousands and thousands of objects out there, there are only a few tens that will ever fit the bill.” Some NEAs are too small, little larger than the craft that would carry astronauts to them. Some spin so fast—with a “day” of minutes or an hour or two—that they couldn’t be approached and would fling away any astronaut touching down on them. The toughest requirement is finding an asteroid with an orbit enough like Earth’s that astronauts could catch up with it using a practical amount of fuel and get back to Earth in a reasonable amount of time—say, 6 months. On to an asteroid A NASA study of possible The Obama Administration asteroid targets conducted last went for the flexible path, aimfall came up empty-handed. ing at visiting an asteroid, which “We’ve found only a handcan have nearly no gravity well ful of objects accessible in the at all. Going to an asteroid 2025 to 2030 time frame,” says would not require any construcLindley Johnson, NASA protion on the surface, but NASA gram executive for near-Earth would acquire experience in object observations, “all of long-duration, deep-space operthem quite small and not parations needed for the trip from ticularly attractive targets.” All Earth to Mars. By 2025, “we’ll were smaller than 50 meters start by sending astronauts to an in diameter; objects about the asteroid for the first time in his- A matter of scale. Asteroid Itokawa dwarfs the international space station (lower length of a football field or tory,” Obama told an audience right) and the Orion crew exploration vehicle (upper right). The 50-meter-long pitch are thought more desirat Kennedy Space Center last boulder Yoshinodai on Itokawa is about the size object astronauts would visit. able. So right now, Johnson April. As for the moon, he said, says, there’s no steppingstone “I just have to say pretty bluntly here: We’ve NASA headquarters. The notional schedule known on the way to Mars around the presibeen there before.” through 2018 has major missions to an NEA dent’s target date. Those were harsh words for lunar sci- launching in 2014 and 2017 that would cost They’re out there, everyone agrees; it’s entists, or “lunatics,” as some call them- $640 million to $840 million each and a third just a matter of looking harder. In a report selves. In the past few years, lunar science NEA mission launching 2014 that would run in October on the threat of impacts on Earth, has experienced a renaissance as the Euro- $100 million to $200 million. a National Research Council committee pean Union, Japan, China, India, and the These missions would check out poten- looked at two ways of searching for small United States sent robotic missions into tial targets for human exploration, but NEAs. The cheaper way of finding 90% of lunar orbit. Sending humans to the moon Jenkins did note the “tremendous poten- objects 140 meters in diameter and larger motivated both U.S. and Chinese efforts, tial for collateral benefit” for NEA science. passing near Earth is using a telescope on the which included NASA’s $504 million Lunar Lunar science would not fare so well. Only ground, the committee concluded. But even Reconnaissance Orbiter (LRO) still orbit- one mission would target the moon, sending for these larger objects, the survey would ing the moon as well as the LCROSS mis- a tiny rover to the surface in 2015 to verify not be completed until late in the 2020s, far sion that “bombed” the moon for water ice some of LRO’s observations. Laurie Leshin, too late for Obama’s goal. A telescope with of potential use to astronauts. NASA deputy associate administrator in the a better vantage point, one orbiting the sun Whatever the motivation, the rush to the Exploration Systems Mission Directorate, inward of Earth’s orbit, would cost more moon has revitalized lunar studies. At the says that even then, most funding early on than a ground-based telescope—perhaps Lunar and Planetary Science Conference would go to developing NEA missions, put- half a billion dollars—and involve greater held each March in Houston, Texas, the num- ting the modest lunar rover mission on the risk, but it could complete the survey faster, ber of moon sessions has more than doubled back burner for the moment. “perhaps as early as 2022.” Given the need
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since 2007 to five times the number of asteroid sessions and equal to the number of sessions on perennial favorite Mars. Researchers’ attachment to our nearest neighbor is stronger than ever. “It’s not just any moon, it’s our moon, with a shared history with Earth,” notes planetary scientist David Morrison of NASA’s Ames Research Center in Mountain View, California, who has been involved on both the lunar and asteroid sides. Now, in the wake of Obama’s speech, “small NEAs are it,” says Morrison, at least in the United States. The president’s fiscal year 2011 budget request (yet to be taken up by Congress) more than triples NASA’s budget for the search for NEAs to $20.3 million. Any newly discovered NEAs could be the targets for a series of robotic missions called for in the budget request, as outlined last September at a NASA meeting in Washington, D.C., by Jason Jenkins of
CREDIT: P. ABELL ET AL., METEORITICS & PLANETARY SCIENCE 44, 12 (DECEMBER 2009)
CEO of Lockheed Martin. “The U.S. human spaceflight program appears to be on an unsustainable trajectory,” its September 2009 report found. The Augustine committee did see options for returning to the moon under increased NASA budgets, but its novel contribution was the “Flexible Path.” This is an approach that leads—at least for years if not decades to come—anywhere but to the moon’s surface: to lunar orbit, to gravitationally balanced holding patterns near Earth called Lagrange points, to NEAs, and to the tiny moons of Mars. The strategy would be to put off the considerable expense of a vehicle able to ease astronauts onto the lunar surface and lift them off again against the moon’s pull, not to mention the cost of building an outpost on the surface. The idea, says Augustine committee member Christopher Chyba of Princeton University, was “let’s avoid going into gravity wells as long as we can.”
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A Windfall for Defenders of the Planet
CREDIT: ©DANIEL DURDA/FIAAA
for robotic scouting missions in the 20-teens and a likely requirement for backup targets, says Morrison, “we really need to get cracking. We all have 2025 looming.” Another challenge unique to the asteroidfirst approach is tiny NEAs themselves. On a 100-meter NEA, an astronaut would weigh something like 10 grams, Harris notes, space suit included. Operating around such an object would be like a spacewalk around the international space station, says Morrison, but without the built-in handholds. And making handholds or installing instrumentation on the surface could be a dicey business, says planetary dynamicist Daniel Scheeres of the University of Colorado, Boulder. Hundred-meter NEAs could be “rubble piles” of boulders, cobbles, and pebbles held together, barely, by their own microgravity. Stepping onto the surface could be “like jumping into a pit of Styrofoam ‘peanuts,’ ” he says. Once kicked up, dust and pebbles could take hours or days to settle out. Even NEAs of equal size could
Inbound. Asteroids will pass
near Earth this century, but none are known that will hit. targets before 2020. And the asteroids easiest for astronauts to reach happen to be the ones most likely to strike Earth. So human exploration could pick up the half-billion-dollar-or-more tab for an NEA search that the NASA task force recommended. In addition, the precursor robotic missions needed to inspect potential targets for later astronaut visits would provide information on the physical makeup of NEAs crucial to deciding how to nudge a threatening NEA off its collision course with Earth. Human space exploration could also benefit planetary defense by prodding governments to prepare for the inevitable. “Increasing [NEA] surveys are going to create many worrisome situations” that no one is yet ready for, says asteroid researcher Richard Binzel of the Massachusetts Institute of Technology in Cambridge. A newly discovered NEA may have a small but significant chance of hitting Earth that will take years to evaluate. “We should be ready,” says Binzel. There are early signs that we could be. In October, at the direction of Congress, the president’s science adviser, John Holdren, outlined a plan to notify federal agencies and emergency response organizations in case of an impending threat and recommended that NASA be the agency responsible for protecting the United States from a specific threat. –R.A.K.
have different reactions to the tread of astronauts because NEAs come in rocky, metallic, and crumbly carbonaceous versions. Is the moon in the stars after all? Although Obama’s vision for space exploration has often been said to “bypass the moon,” it may not happen that way. “I still don’t think a rational person would try to go to Mars without going to the moon first,” says geochemist David Kring of the Lunar and Planetary Institute in Houston, principal investigator of the institute’s Center for Lunar Science and Exploration. Actually, the Augustine report leaves that possibility wide open. “When we said ‘flexible path,’ we meant it,” says committee member Chyba. The moon “is not the near-term objective,” but a decision to return humans to the moon could be made further down the road, he says. Moon advocates argue that the return should come soon. The moon is, after all, our nearest near-Earth object, they note. It’s easier to get to than an NEA whizzing
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If U.S. astronauts hopscotch from one near-Earth asteroid practicing for their trip to Mars (see main text), it will be a big help to astronomers campaigning to find and fend off the rare NEAs that threaten to collide with Earth. With a nudge from Congress, NASA-led astronomers have now reached a major milestone in their search for threatening NEAs. After a decade-long concerted hunt, they have found enough of the largest NEAs to reduce their estimate of the potential hazard by about 90%. That’s because they have now found about 90% of the estimated 1000 NEAs a kilometer across and larger that could have been on a collision course with Earth. It turns out that none actually are, so the risk in this century of a civilization-ending impact is essentially gone. But that leaves the other part of the threat, the one from objects 140 meters in diameter and larger—so-called city killers. Only about 5% of them have been found under NASA’s search program. In 2005, Congress directed NASA to identify 90% of city killers by 2020, but so far, Congress has provided no additional funds for its mandated search. Funding has been about $4 million a year recently, raised to $6.5 million last year. But at current discovery rates, most of the city killers would remain undetected for many decades. In October, an ad hoc task force on planetary defense recommended to the NASA Advisory Council that NASA should meet the 2020 congressional target date using a space-based telescope rather than the slower ground-based option. And the president’s fiscal year 2011 budget request for NASA (not yet acted on by Congress) includes a boost in search funding from $6.2 million to $20.3 million. Planetary defense may be in line for a boost, but the present Congress is in a serious budget-cutting mood. That’s where the human exploration of space could come in. If NASA hopes to meet the president’s goal of sending humans to an NEA by 2025, the search for small NEAs will have to be at least as fast as that required to meet the 2020 planetary defense goal. That’s because NASA would need to identify potential exploration
by on its way around the sun. It offers a far more complex setting befitting the problemsolving skills of on-scene astronauts. Much more remains to be learned about the moon chemically, mineralogically, and geologically than about asteroids, they say; samples from asteroids—meteorites picked up on Earth— number over 50,000, whereas there are little more than 2000 samples with which to unravel the moon’s more complex history. The strongest argument, moon advocates say, is gravity: The moon has it and NEAs don’t. Most crucially, the safe landing and return of astronauts could be demonstrated only on the moon, not to mention astronaut activities on a solid surface. But that may not help. The president’s own National Space Policy, released in June after his asteroidfirst speech, directs that the NASA administrator shall “by the mid-2030s, send humans to orbit Mars and return them safely to Earth.” His policy for the next 30 years says nothing about landing on Mars.
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Europe’s Eager Reformer Takes on Framework Funding Goliath An outsider to the scientific community, the E.U.’s new research commissioner promises to cut red tape, champion basic research, and fight to save ITER For Irish teacher-turned-politician Máire Geogheghan-Quinn, landing one of Europe’s top political jobs in charge of research has meant a steep learning curve. Having served her country in ministerial roles covering Gaelic culture, justice, and European affairs, she then spent 10 years overseeing European Union finances. But in her first year as E.U. commissioner for research, innovation, and science, she has had to come up with plans to reengineer the European Union’s huge €54 billion research-funding program, prepare for a battle over budgets, find extra funding for the troubled ITER fusion reactor project, and has managed to raise the profile of science policy at the European Union’s highest levels. She spoke with Science last week in her Brussels office. Her remarks have been edited for clarity and brevity. (You can read more of this interview at http://scim.ag/MGQ.)
–GRETCHEN VOGEL
Q: You weren’t known for much involvement with science before taking this job. What’s the most provocative or most interesting bit of science you’ve come across in your first year?
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M.G.-Q.: Oh, there have been lots of things, but I suppose at the very beginning when I went to one of my first meetings at the ERC [European Research Council], there was a professor from Italy who was getting a large grant to get this driverless truck to go from Europe to Shanghai. And that was just mindboggling. I said to myself, “It’s not going to happen.” And yet it did. Later, I told everybody about it: “I was there when he was telling us about this, and I had a doubt in my mind!” To me it proves that the ERC is about championing researchers with good ideas who would never get that kind of substantial money from a member state. So there are fantastic possibilities in what they do. And it has made me ever since a real strong supporter and probably the ERC’s greatest fan. Q: If that’s the case, ERC leaders are hoping for a big boost in funding … M.G.-Q.: Aren’t we all! Q: They’re hoping for as much as €24 billion between 2013 and 2020. What’s your reaction? M.G.-Q.: My reaction is that we’ve only just
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N E W S M A K E R I NT E RV I E W: M Á I R E G E O G H EG H A N - QU I N N
Q: The green paper you issued last week on future E.U. research funding included few concrete proposals, which disappointed some observers. What do you say to them? M.G.-Q.: The green paper is the start of the conversation. I don’t think you should ever start a conversation by laying down in black and white the answers you want. So instead you pose questions, you put it out there. We are very anxious to encourage the scientific community and the other stakeholders to really get involved and engaged in this conversation, because this is an opportunity to really change the whole landscape of the way we fund research and innovation. I want to help the people who have said to me, “Look, we’re overloaded with the E.U. administrative burden. The bureaucracy has gone mad. There’s so much red tape that if we could find the money elsewhere, we wouldn’t come to the European Union.” And to me that’s a tragedy. In looking at all of this, we looked at what does a small research center have to do when they come for the funding? If they’re going to the Framework Programme, they go to one postbox. If they are going to the CIP [Competitiveness and Innovation Framework Programme], they go to another. If it’s contributions to the EIT [European Institute of Innovation and Technology], then it’s another. So let’s bring it all together, under one framework so that there is one postbox: one simple, unique set of rules so that it cuts out all the extra paperwork that people have to go to— and the expense that they have to go to—to put together an application. For the moment we’re calling it the Common Strategic Framework, but that’s not going to be the name.
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started the budget question. No figures are on the table, and no figures will be on the table for quite some time. First of all, I have to make a pitch for my two directorates general. And depending on what we get out of that, I hope to be in a position to be able to strengthen the ERC. Unfortunately, we’re in the hands of two other institutions—the Council [of Ministers] and the [European] Parliament—who decide whether or not to give us an increased budget and what that increase might be. I think it will be one of the most difficult budgetary discussions that the E.U. has ever had, mainly because of the financial crisis. I think you’ll find that a lot of those member states who have had to take deep cuts in their own budgets will try and curtail any increases in the E.U. budget. But within all of those possibilities, the ERC has a very strong supporter in myself.
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Q: Some worry that the new funding program will focus on “innovation” and that basic science will be squeezed. What do you see as a proper balance between the two? M.G.-Q.: You can’t have innovation, as I keep saying, unless you have really excellent basic research and unless you give support to excellent basic research. My problem is that we have had this wonderful, excellent research here. We have delivered the goods, as it were, on the research side. But we have failed to bring that research all the way to the marketplace. It has been brought to the marketplace elsewhere, outside the E.U. And I want to see the excellent research that we do here brought to the market here. But we can’t have innovation of any kind unless you have basic research. So my commitment is total when it comes to basic research. It is so vital and so important.
CREDITS (TOP TO BOTTOM): F4E/ITER; VIAC/VISLAB
Who’s paying and who’s driving? The ITER fusion reactor project under construction in France (top). ERCfunded driverless solar-powered trucks (bottom) at the Shanghai Expo.
Q: Under your proposal, EIT would become part of the new, expanded program. The scientific community has viewed EIT with a healthy dose of skepticism. What value do you think it will really add to European research? M.G.-Q.: I think it’s very, very early to be judging something that has just been set up. [European Commission] President [José Manuel] Barroso, as I understand it, went to MIT [the Massachusetts Institute of Technology] and was very impressed with what he saw. Now MIT has taken quite some time to become as successful and well-known as it has become. [The EIT] needed to have security, and I think the EIT is very happy to be within the Common Strategic Framework now. I think it sees it has a home. It’s like a sapling; we have to help it to grow and nourish it. I really do believe that once it is up and running, it’s going to be a very, very positive element within the E.U. Q: How is the commission intending to cover the €1.4 billion shortfall in ITER funding for 2012 and 2013, and how will further cost increases be contained in the Common Strategic Framework? M.G.-Q.: ITER. [Laughs] Wonderful. When I came into this office almost a year ago now, one of the first files that was put on my
desk was the ITER file, and I wanted to run out the door and go home. This project was badly managed. There were issues not just in relation to the financing of it, there were also issues of governance that needed to be tackled. Those were resolved, at both the European and international level. Then we sat down to discuss with the budget commissioner and the commission as a whole how we might fill this [laughs] “hole,” as it were, for 2012 and 2013. And we agreed that two-thirds of the money would come from unspent funds and one-third from the Framework Programme. We had that package put together, and we went to the parliament and the council. And suddenly you had the commission caught in a row between the parliament and the council. That row had nothing to do with ITER. [The ITER package was cut out of the budget deal.] As a result, we now have to restart the whole thing again. We still have the two-thirds/one-third on the table. [Budget] Commissioner Lewandowski has been strongly supporting that and pushing that. And we have to live in hope and watch what happens with the parliament and the council. It’s very hard for our international partners to understand. When the U.S. government makes a decision, it’s implemented.
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Q: Will there be a European chief science adviser? M.G.-Q.: It will absolutely happen. President Barroso is very committed to a chief scientific adviser. I know he is looking at a list of people that’s been drawn up and trying to decide what the best solution would be. I’m very anxious for it to happen. I think it strengthens the whole area of research and science, which is what I’m interested in doing. You know, for us to have a European Council meeting just last week that discussed energy and research and innovation was almost a miracle when you consider everything else that was going on. And I think discussing research and innovation proved that the European heads of government realize that it’s an economic policy. And it’s the policy that will bring us the growth, the competitiveness, and the jobs. That shows the tremendous importance that is now attached to the whole area of research and innovation. When [U.S.] President [Barack] Obama gave his State of the Union address, I thought it was fantastic. It happened just before the European Council, and it reinforced once again how important research and innovation is on a world scale. It shows that on both sides of the Atlantic we’re competitors, but there are lots of things I believe we should cooperate on in order to compete with the rest of the world. There are lots of ways that we do cooperate, but we should even intensify our cooperation.
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The E.U. works in a different way. The commission makes a proposal, but then it’s in the hands of the parliament and the council to decide, and they have to agree to do it.
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VISUALIZATION CHALLENGE AN “OCEAN” COMPOSED OF A SINGLE LAYER OF MOLECULES; AN INTRICATE depiction of an HIV particle as a study in orange and gray; a phantasmagoria of fungi; a video tracing the long-distance travels of items dumped in the trash in Seattle: The four first-place winners in this year’s International Science & Engineering Visualization Challenge grab your attention and draw you into unseen worlds in very different ways. Researchers are generating mind-boggling volumes of data at exponentially increasing rates. The ability to process that information and display it in ways that enhance understanding is an increasingly important aspect of the way scientists communicate with each other and—especially—with students and the general public. That’s why, for the past 8 years, Science and the U.S. National Science Foundation (NSF) have co-sponsored annual challenges to promote cutting-edge efforts to visualize scientific data, principles, and ideas. This year’s awardees span scales from nanoparticles to colliding galaxies, and from microseconds to millennia. We received 111 entries from 63 countries (U.S. entries came from 24 states). A committee of staff members from Science and NSF screened the entries, and an outside panel of experts in scientific visualization reviewed the finalists and selected the winners. The winning entries are featured on the following pages, in a slideshow at www.sciencemag.org/special/vis2010/, and at www.nsf.gov/ news/scivis. Some entries were put together by large teams, not all of whose members could be listed in print; the online presentations provide full details. Tarri Joyner of NSF and Esther Chon of Crabtree + Company organized this year’s challenge. Kristen Minogue of Science’s News staff wrote the text that accompanies the images in this special section. We encourage you to submit applications for next year’s challenge, details of which will be available on NSF’s Web site, and to join us in celebrating this year’s winners.
Patrice Legro Marian Koshland Science Museum Washington, DC Thomas Lucas Thomas Lucas Productions Ossining, NY Alisa Zapp Machalek National Institute of General Medical Sciences Bethesda, MD Corinne Sandone The Johns Hopkins School of Medicine Baltimore, MD Tom Wagner NASA Headquarters Washington, DC
–JEFF NESBIT, DIRECTOR, OFFICE OF LEGISLATIVE AND PUBLIC AFFAIRS, NSF COLIN NORMAN, NEWS EDITOR, SCIENCE
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PLACE: Ivan Konstantinov Yury Stefanov Aleksander Kovalevsky Yegor Voronin Visual Science Company
At first glance, it could pass for a piece of crochet, a fluffy gray and orange ball. But its real-world counterpart is far more destructive: It claims an estimated 2 million lives a year and has wreaked more global havoc than some wars. Ivan Konstantinov’s winning illustration reduces HIV to unnerving simplicity. His team at the Visual Science Company in Moscow spent months combing through the latest research, compiling data from more than 100 papers and assembling the information into a coherent image of a 100-nanometer HIV particle. They depicted the proteins in just two basic colors: Gray equals host, orange equals virus. HIV breaks into immune cells and hijacks their genes. The orange proteins on the outside bind to the immune cell, letting the viral core slip inside. Once in, it fuses with the cell
membrane (gray shell), turns its viral RNA into DNA, and integrates into the cell nucleus. The host cell then starts making viral proteins, turning into a virus factory. The restrained, two-color system worked for the judges. “It uses material from the host to sort of wrap itself in this membrane,” says panel of judges member Corinne Sandone. “That point is brought home much clearer than another example of that same model that might be coded with eight to 10 different colors.” In addition to the stark color scheme, the image of the particle split open to reveal its viral core itself deeply shook the panel, says panel of judges member Tom Wagner: “You have this gaping mouth that almost looks like it’s ready to eat you the way AIDS is eating away at society.”
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(3-way tie)
AraNet: A Genome-wide Gene Function Association Network for Insuk Lee Michael Ahn Edward Marcotte Seung Yon Rhee Carnegie Institution for Science
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Picture DNA on Facebook. The image to the right is a map of links between the genes of the mustard plant Arabidopsis thaliana. Genes involved in the same biological process are connected by lines: red for more certain links, blue for less certain links. “It’s not unlike a social network,” says biologist Seung Yon Rhee.
Enterobacteria Phage T4 Jonathan Heras Equinox Graphics Ltd. One judge compared this illustration of a virus attacking an Escherichia coli bacterium to something out of a 1950s science-fiction film. That’s not too far from the creator’s view, either. Before creating it, chemical engineer Jonathan Heras says he knew almost nothing about viruses. When he first saw a depiction of one in a textbook, he admits not believing it, until he looked at microscopic images: “It really did have these spindly legs and this really alien, weird appearance.”
Proposed Structure of Yeast Mitotic Spindle The Mitotic Spindle Group* University of North Carolina, Chapel Hill This is a depiction of a yeast cell about to divide, a stage biologists call metaphase. Green microtubules prepare to pull apart 16 pairs of chromosomes (yellow) in a process scientists still don’t fully understand. It’s the product of 2 years of collaboration among biologists, physicists, computer scientists, and artists, but it’s still a work in progress. “This is our version 20 of probably 50 we’re going to end up doing,” says computer scientist Russell Taylor. *www.cismm.org/research-collaborations/cell-mechanicscluster/mitotic-spindle
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PLACE: Kandis Elliot Mo Fayyaz University of Wisconsin, Madison
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For senior artist Kandis Elliot, postermaking is one of the best tasks of the job. Her series of educational posters started 4 years ago, when greenhouse and garden director Mo Fayyaz of the University of Wisconsin (UW), Madison, asked for a fruit poster. Introduction to Fungi is just the latest—and one of the hardest, because the botany department lacks a mycologist. And Elliot didn’t want to settle for a simple mushroom poster. “There’s a gazillion of those things,” Elliot says. “We wanted something that shows fungi as mushrooms but something more than mushrooms. Your beer, your wine, and your bread. The stuff on the back of your fridge.” The beer and wine are easy enough to spot in the center of this poster. Other specimens include gourmet delicacies, such as truffles and the mold on bleu cheese, and the less savory stinkhorns, whose stench attracts carrion beetles to disperse their spores. It also features some unfriendly fungi, such as the culprit behind white-nose syndrome, a mysterious white fungus that grows on hibernating bats and seems to kill them by leading to starvation. “The fungi poster was a clear winner. That was just amazing,” says panel of judges member Alisa Zapp Machalek. Besides the imagery, the fact that it was about fungi had an appeal of its own. “There’s sort of an innate intrigue factor. If it was different kinds of apples, even though I love apples, I don’t know that it would hold our attention as much.” “It’s very appealing to the layperson,” says panel of judges member Corinne Sandone. “There’s nothing that hard. It’s very accessible.” That’s valuable praise for Elliot, who says squeezing all the information in was one of the hardest parts. “There’s like 25 pounds of information on a 5-pound poster, and you want to put it in some kind of logical order,” she says. “There is order in there, but you kind of have to search for it.”
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HONORABLE MENTION Everyone Ever in the World Peter Crnokrak The Luxury of Protest
The poster represents roughly what the title says: every person who lived and died on the planet, from 3200 B.C.E. to 2009 C.E. The total paper area represents the 78 billion people who lived over the past 5000 years. The gaping hole in the center represents every person who died in a major war, genocide, or massacre: approximately 969 million people, or 1.25% of the total number of people who have ever lived on the planet. Text is printed in transparent ink on plastic (shown as white on black, right). The circles at
the top represent the number of conflicts per millennium with more than 1000 deaths, and the circle of text lists them by name. The bottom circle represents the expected number of conflicts in the next millennium if the escalating pattern continues. Human life is one of the few values that’s almost always given as an absolute (1100 died in a flood in Pakistan; 20 million Russians died in World War II), says Peter Crnokrak of The Luxury of Protest design studio in London. Framing deaths as a percent of those who ever lived, he says, might risk degrading the value of individual life. But he says he wanted to create something thought-provoking, and the judges say he succeeded. “People have made the case that we need to bring more artists and poets into the science process to explain the results,” says panel of judges member Tom Wagner. “And I think a poster like that achieves that goal.
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PLACE: Seth B. Darling Argonne National Laboratory Steven J. Sibener University of Chicago
Don’t take the title literally. The ripples Seth Darling of Argonne National Laboratory and Steven Sibener of the University of Chicago, both in Illinois, captured with an atomic force microscope may look like the surface of an ocean, but they are a mere nanometer deep, and there’s not a drop of water in sight. The rich shades of turquoise and indigo are artificial, but the choppy waves are real. They are formed by millions of molecules arranging themselves on a gold surface. These “self-assembled monolayers” come with a head that clings to the surface and a tail that sticks out into the environment. Darling compares it to dumping a bowl of wet spaghetti on the floor and “all of a sudden it stands up as if it were uncooked spaghetti on end. That’s kind of a weird thing to happen.”
The ripple effect in the image is caused by two similar molecules, synthesized by Dong-Chan Lee and Luping Yu of the University of Chicago. Each molecule has sulfur at the head, but one has carbon and hydrogen at the tail whereas the other has carbon and fluorine, which leads to their heights differing by about 0.2 nanometers. Darling captured them at the moment they began separating. He hopes to find out if surfaces like these will form larger “islands” of short and tall molecules or if they will remain blended together. Eventually, Darling says, scientists hope to use such monolayers to adjust the properties of a surface. Winning entries need good art and good science, says panel of judges member Alisa Zapp Machalek, and this photo had both. “The science was amazing, and the image was—wow.”
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HONORABLE MENTION (tie) TRICHOMES (Hairs) on the Seed of the Common Tomato Robert Rock Belliveau Downloaded from www.sciencemag.org on February 17, 2011
Tomato seeds have hair. Not the ordinary, dead protein that hangs limply off human scalps. These trichomes secrete an insect-repelling, flavor-inducing mucus that helps give tomatoes their signature taste while acting as a natural bug spray. Robert Rock Belliveau took this photo of a 2-mm × 3-mm tomato seed last April. The color contrast comes from the polarizing microscope he uses, which has both transmitted and reflected light capabilities. The thinner parts at the edge of the seed (purple) are viewed with transmitted light while the trichomes on the top of the seed (red) are viewed with reflected light. The pathologist has been taking microscopic photos of plants ever since he retired 10 years ago. He started with desert wildflowers, but when a drought in Las Vegas temporarily wiped out his subjects, he switched to vegetables. Anything, from ovaries to leaves to pulp, is fair game. “Every once in a while,” he says, “you see something that’s so bizarre, it is startling!”
Centipede Millirobot Katie L. Hoffman Robert J. Wood Harvard University Imitating insects is all the rage in robotics right now. Graduate student Katie Hoffman based this 12-legged, segmented robot on the body morphology of a centipede. The top view shows the actuators that control each leg, the reflection shows the flexible connections between the segments, and the penny gives a sense of the robot’s size. Hoffman says most robots that size mimic cockroaches, which have only six legs and much more rigid bodies. By modeling a centipede, she hopes to study how flexibility and body undulations enhance locomotion. www.sciencemag.org SCIENCE VOL 331 18 FEBRUARY 2011 Published by AAAS
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PLACE: SENSEable City Lab Massachusetts Institute of Technology
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Many people know about the supply chain. They care about whether their fruit is organic, whether their chickens are freerange, whether the products they buy are domestically manufactured or imported. But the other end of the consumer chain—where all the used products go after they’re dumped in the trash—is murkier. Dietmar Offenhuber and his colleagues at the SENSEable City Laboratory at the Massachusetts Institute of Technology in Cambridge wanted to bring that side of consumerism to light. So they stuck location sensors onto 3000 pieces of trash to see where the garbage ended up months later. They recruited households in Seattle and gave them wish lists of items they wanted to track: cell phones, fluorescent light bulbs, and other “household hazardous waste” that’s difficult to regulate. The sensors were shielded by an insulating foam to protect them from being crushed. Over the next 2 months, they kept tabs on their garbage and plotted its journey on a U.S. map. While most of it remained in Washington state, after a week some had seeped into Oregon and Idaho. In 2 weeks, some of the cell phones had gone as far as Florida. The end of the 2 months found fluorescent light bulbs in the Midwest, batteries in Michigan, and printer cartridges in Mexico. “It’s one of those knowledge is power things,” says panel of judges member Tom Wagner. “Hey, guess what, if you have complex packaging, this is what’s going to happen to it when it goes in our refuse system.” 18 FEBRUARY 2011 VOL 331 SCIENCE www.sciencemag.org Published by AAAS
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GPS and Relativity Damian Pope Greg Dick Sean Bradley Steve Kelley Perimeter Institute for Theoretical Physics
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Damian Pope made this video for any nonscientists who think relativity matters only to theoretical physicists and Star Trek fans who want to know how many laws of physics the series has broken. Millions of people use relativity every day—in their GPS receivers. GPS satellites orbit at an altitude of 20,000 kilometers. The problem: Time moves 38 microseconds a day faster at that altitude than on Earth’s surface. That may not seem like much, but after a month, it could throw the GPS system off by more than 300 kilometers. The solution: Slow down the satellite clocks so they tick 38 microseconds less every day. Just one more reason to thank Einstein.
GlyphSea Amit Chourasia Emmett Mcquinn Bernard Minster Jurgen Schulze San Diego Supercomputer Center, UCSD For earthquake scientists, predicting when the next “big one” will strike is the million-dollar question. But predicting how much damage it will do is just as important—and almost as uncertain. Knowing exactly how seismic waves transform the landscape could offer clues. Seismologists have made numerous attempts to model seismic waves passing through Earth. But depicting their direction is difficult. Arrows or cones are ambiguous because viewed from the very front or the very back, they have the same shape: a circle. Amit Chourasia and his team at the University of California, San Diego, devised a straightforward solution: Use simple glyph shapes, such as spheres or ellipsoids, with a white dot on the end moving toward the observer and a black dot on the end moving away. By varying size and color to show magnitude, the method can display any kind of motion intuitively, from a major earthquake on the San Andreas fault to magnetic turbulence in stars millions of light-years from Earth. “How’s [an earthquake] going to affect people 30 miles away?” asks panel of judges member Tom Wagner. The new model offers an answer. “There has not been a way to do that before that was nearly as sophisticated.” www.sciencemag.org SCIENCE VOL 331 18 FEBRUARY 2011 Published by AAAS
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Thomas J. Cox Carnegie Institution for Science Galaxy mergers rank among the most violent and spectacular events in the cosmos. In a dance that can last billions of years, spiral arms of stars are thrown out into sweeping tails, and clouds of dust and gas are shoved into the center where, according to the prevailing theory, a supermassive black hole waits to consume them. Most astronomers think that all the gas pouring in will excite the black holes into quasars, the brightest objects in the universe, and that many merging galaxies will evolve into “binary quasars,” two quasars circling each other until their host galaxies unite. The Sloan Digital Sky Survey observed a binary quasar, SDSS J1254+0846, 4.6 billion light-years away. In 2009, deep imaging
at the Carnegie Observatories’ Magellan Telescope confirmed that this binary quasar was indeed a pair of interacting spiral galaxies 70,000 light-years apart, one of the first clear sightings of a binary quasar being triggered by a galaxy interaction. Thomas Cox modeled the galactic pas de deux over 3.6 billion years; the two partners arrived at a stage similar to that of the SDSS J1254+0846 image after 2.33 billion years. There was no narration and no audio except for background music. But that simplicity made it easy to follow, according to panel of judges member Corinne Sandone: “It was very visual. … You don’t need much narration to understand what you’re viewing.”
Visualization of the Whole Brain Catalog Drew Berry Mark Ellisman François Tétaz The Walter and Eliza Hall Institute of Medical Research
VISUALIZATION CHALLENGE 2010
Animator Drew Berry and his neurobiologist colleagues take you on a journey deep inside the mouse brain. The video brings to life data from the Whole Brain Catalog, a massive database of microscopy and other data sets on the mouse brain, under development at the University of California, San Diego. It opens with a mouse sniffing a camera—a fitting image, says Berry, because the part of the brain that stores memory also controls the sense of smell. The video then zooms in on the mouse brain, focusing on the hippocampus, the headquarters of scent and memory. From there it isolates the dentate gyrus (upper right), the region that recognizes smells and creates new memories. Individual brain cells then start to appear. Finally, a new connection forms between two neurons, representing the creation of a new memory. “For a memory, you’d have many, many neurons forming, or connections being broken and new patterns being made,” says Berry. Even so, he hopes this video will inspire a sense of wonder at how the brain works.
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Noninteractive Media cont.
Computer Simulation of a Binary Quasar
COMMENTARY Facing up to vexing problems
A nod to nodules
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LETTERS I BOOKS I POLICY FORUM I EDUCATION FORUM I PERSPECTIVES
LETTERS edited by Jennifer Sills
A. REGALADO’S NEWS FOCUS STORY “BRAZILIAN SCIENCE: RIDING A GUSHER” (3 DECEMBER 2010, p. 1306) rightly highlights the “dearth of Brazilian-led science” in the Amazon and the “very delicate question” of Brazil’s dependence on foreign knowledge production. However, based on my experience and publication statistics from the Large-Scale Biosphere-Atmosphere experiment in Amazonia (1), I would challenge the statement that the “majority of publications on the Amazon don’t have a Brazilian author.” In fact, many papers have Brazilian co-authors. Brazilians (and Amazonian researchers) are involved in the majority of Amazonian research projects, but often in a subsidiary role as data providers and field workers rather than leading the research and developing the scientific arguments. Clearly, foreign researchers, resources, technology, and expertise have been instrumental in developing Amazonian science and raising Brazilian capacity in this biologically unique and important part of world. However, Brazilian researchers need to stop gratefully receiving fish and quickly learn how to use the rod and the line.
ANA C. M. MALHADO
Laboratory of Analysis and Processing of Imaging Satellites, LAPIS, Federal University of Alagoas, Maceió, Alagoas, Brazil. E-mail:
[email protected]
Reference
Research in Brazil. Many Amazon projects are led by foreign researchers.
CREDIT: DEVA RODRIGUES/EMBRAPA
Boosting CITES Through Research IN THEIR POLICY FORUM “BOOSTING CITES” (24 December 2010, p. 1752), J. Phelps et al. propose improvements to the implementation of the Convention on International Trade in Endangered Species of Wild Flora and Fauna (CITES). Most of their recommendations would involve the negotiation of cross-Party agreements and procurement of additional financial resources, both of which are likely to delay or prevent their implementation. We suggest a more straightforward improvement to CITES implementation: Scientists should consider choosing CITES-listed taxa as model taxa for their research. At a workshop in 2008, more than 100
1. Ministério de Ciência e Tecnologia, Programa de Grande Escala da Biosfera-Atmosfera na Amazônia (http://lba.inpa.gov.br/lba/) [in Portuguese].
scientists and regulators compiled 60 case studies covering a wide range of CITESlisted taxa. The group outlined how information on the biology, harvesting, and management could be used to determine whether international trade in CITES-listed taxa is detrimental to their survival in the wild. Most of those case studies (78%) mentioned that more basic information on the biology of the taxa in the wild (including taxonomy, biology, and ecology) would improve their ability to make this determination (1). A lot of scientific research is done on species that are chosen out of convenience. We recommend that, all else being equal, scientists coordinate with national scientific authorities, local communities, and commercial traders to work on CITES-listed taxa instead. Such research could directly address
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Amazon Science Needs Brazilian Leadership
sustainable exploitation practices or could simply aim to generate relevant information as a by-product (for example, by generating additional information on the basic taxonomy, biology, and ecology of taxa). Either way, those implementing CITES would benefit from the additional information and scientists would achieve additional impact from their research.
MATTHEW J. SMITH,* RICHARD J. WILLIAMS, DREW W. PURVES
Computational Science Laboratory, Microsoft Research, 7 J J Thompson Avenue, Cambridge, CB3 0FB, UK. *To whom correspondence should be addressed. E-mail:
[email protected]
Reference
1. M. J. Smith et al., Biol. Conserv. 144, 82 (2011).
Response
WE AGREE WITH SMITH ET AL. THAT BASIC BIOlogical information is the cornerstone of CITES effectiveness and sustainable resource management, and that scientists should be encouraged to select CITES-listed species as research taxa. However, many of the most important and delicate issues for CITES go far beyond biology of species under threat. Biological data provide a critical, lowest common denominator for CITES decisionmaking, but strengthening CITES funding, checks and balances, analyses, and accompanying human institutions and capacities are equally critical to conservation. Smith et al. suggest that collecting biological research would be a more straightforward approach to improving CITES implementation than our solutions, many of which would require substantial financial support and political will. In fact, even issues of basic biological research on vulnerable species are about Party funding, negotiations, safeguards, and collaboration. Bridging the logistical, financial, political, and permit-laden gulf to attract significantly more researchers to study these vulnerable species is not a simple process. For example, obtaining research permits for work on CITES-listed or locally threatened (e.g., Red List) species is time-
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LETTERS
DAVID BICKFORD,1* JACOB PHELPS,1 EDWARD L. WEBB,1 VINCENT NIJMAN,2 NAVJOT S. SODHI1
Department of Biological Sciences, National University of Singapore, Singapore, 117543, Singapore. 2School of Social Sciences and Law, Oxford Brookes University, Oxford, OX3 0BP, UK. 1
*To whom correspondence should be addressed. E-mail:
[email protected]
Engage Students in Education Reform
the authors’ seven initiatives. Students— the largest stakeholders in the current landscape of science education reform— should be added to the list of chairs, deans, and presidents as parties to engage in the policy debate (initiative 7). Such an addition would add a fresh perspective on the issue, open valuable communication pipelines between students and policy-makers, and provide opportunities for students interested in educational policy to gain experience in the field. Restructuring the culture of education at research universities will require a new paradigm: Students should be considered not as passive consumers but as active participants in their education.
MIKE TORCHIA
University of Minnesota, Minneapolis, MN 55455, USA. E-mail:
[email protected]
WE AGREE THAT STUDENTS SHOULD BE ACTIVE participants in their own education, and we have indeed made changes to programs at both of our own institutions based on student feedback from anonymous course evaluations. For example, several years ago one of us (D.O.) began experimenting with in-class demonstrations using large objects to illustrate dynamic microscopic biological processes. Feedback indicated that students felt demonstrations were more useful than any other tools we used, including iClickers and animations, for understanding the course material. Guided by student feedback, we refined existing demonstrations and continue to develop new demonstrations each year (1). We maintain a Web site with video clips of demonstrations, some with additional instructions for faculty, to promote the use of this type of teaching tool both at our own institutions and more broadly (2). We thank Torchia for calling attention to this important aspect of the educational policy debate.
RICHARD LOSICK1 AND DIANE O’DOWD2
Harvard University, Cambridge, MA 02138, USA. E-mail:
[email protected] 2University of California, Irvine, Irvine, CA 92697, USA. E-mail:
[email protected] 1
References
1. D. K. O’Dowd, N. Aguilar-Roca, CBE-Life Sci. Educ. 8, 118 (2009). 2. Bridging the Divide Between Research and Teaching, Biological Demonstrations (www.researchandteaching. bio.uci.edu/lecture_demo.html).
CORRECTIONS AND CLARIFICATIONS
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Letters (~300 words) discuss material published in Science in the past 3 months or matters of general interest. Letters are not acknowledged upon receipt. Whether published in full or in part, Letters are subject to editing for clarity and space. Letters submitted, published, or posted elsewhere, in print or online, will be disqualified. To submit a Letter, go to www.submit2science.org.
Training the Next Generation
1984
Letters to the Editor
News and Analysis: “NIH report urges greater emphasis on training for all graduate students” by J. Mervis (4 February, p. 525). Two bars were mislabeled in the graph showing modes of support for graduate students. The labels for fellowships and research assistantships were reversed. The correctly labeled graph appears here. Also, the comments attributed to Carolyn Bertozzi regarding the pressures on today’s graduate students actually were expressed by another council member and HHMI investigator, Karolin Luger of Colorado State University. Luger was speaking about high-performing students who are repelled by the cut-throat atmosphere within a laboratory and choose to leave research altogether.
Number of graduate students
AS A SENIOR UNDERGRADUATE STUDENT AT a large public research university, I agree with W. A. Anderson et al. that excellent teaching and research are not mutually exclusive pursuits (“Changing the culture of science education at research universities,” Education Forum, 14 January, p. 152). However, engagement with the students themselves is nowhere to be found in
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consuming and expensive. A streamlined research permit process could facilitate this type of research. Furthermore, studying species with cross-border distributions and trade requires inter-Party collaboration and support; only with this coordination can researchers make efficient use of limited financial resources. Whereas many policymakers seek quality data to support sustainable harvests, those research findings that could lead to increased regulations, monitoring, and management requirements may be viewed as increasing burdens on Party governments. Furthermore, improving wildlife harvest and trade data, a necessary supplement to data on sustainable use, will rely on increased Party funding, strengthened institutions, improved capacity, and greater collaboration. Increasing biological research cannot take place without these related changes. Perhaps one of the best ways to help researchers, CITES policy-makers, and customs agents to increase research collaborations would be to identify the needs of all stakeholders and improve communication among them.
BOOKS ET AL. ENVIRONMENT
of contemporary conservation. The authors confront readers with the reality that conservation raises uncomfortable truths, such as the valuation of endangered species. They also demonstrate that the roles of Conservation Science conservation scientists demand Balancing the Needs ence, Kareiva and Marvier interdisciplinary skills rooted in of People and Nature are, at the very least, putting diverse disciplines ranging across the tools of argument into the ecology, economics, and ethics. by Peter Kareiva and hands of the next generation To satisfy an unashamedly Michelle Marvier of conservation scientists and biocentric readership, the authors Roberts, Greenwood on-the-ground practitioners. have drawn on a diverse range of Village, CO, 2011. 573 pp. $90, £50, €60. The book is aimed at taxa to illustrate their arguments: ISBN 9781936221066. undergraduates and earlyfrom African wild dog (Lycaon career graduates, but the pictus) to wood frog (Rana sylauthors entreat those of us with established vatica), chanterelle mushroom (Cantharelconservation careers to confront our out- lus cibarius) to eelgrass (Zostera marina), of-date learning and assumptions and to and monarch butterfly (Danaus plexippus) explore new ideas and analyses. We should. to zebra mussel (Dreissena polymorpha), One of the book’s strengths lies in its mix of as well as, of course, that iconic symbol of scholarship and practice—Kareiva is chief extinction, Raphus cucullatus (which they scientist for The Nature Conservancy—and charmingly index as “dodo bird”). the book’s acknowledgments list a stellar Each chapter concludes with a potentially cast of, albeit U.S.-centric, reviewers from polarizing short essay. These “consider this” both lab and field. pieces raise such questions as: What are the Neatly designed—with boxed texts, ques- risks of relying on the economic valuation of tions for discussion, suggestions for group ecosystem services? Who benefits from proprojects, and examples of case studies and tected areas? Does habitat restoration work? sound practice—the book is divided into four Are carbon markets a silver bullet? Are popbroad sections. These cover the need for con- ulation viability assessments useful? When servation; the roles of policy, protected areas, do we give up? Clearly, Kareiva and Marand planning; how science informs conserva- vier do not balk at tough debate, and their tion strategy; and how we face the challenge concluding chapter, “Making conservation a success story,” even opens with a substantial nod to the pundits who have “bemoaned the failure of the environmental and conservation movements.” If the decline of public empathy for environmentalism is to be reversed, the authors argue that, as Nurse proposed, we must all broaden the appeal of conservation science. A failure to do so, as Dowling despairs, renders any scientist-versus-skeptic debate “a mere distraction ... destined to be overtaken by events.” In Conservation Science, Kareiva and Marvier have definitely crafted a book that combines sound argument with practical examples. While being entirely frank about the complex challenges ahead, their efforts must effectively arm a new wave of environmentalists with the skills needed to face those.
John Fanshawe
CREDIT: AMI VITALE/WWW.AMIVITALE.COM
A
mong many great images in Peter Kareiva and Michelle Marvier’s robust and elegant Conservation Science is a striking 1947 advertisement for pesticides from the company Killing Salt Chemicals. In it, a happy chorus of dog, tomato, milkmaid, cow, potato, and hen sing out, “DDT is good for me-e-e!” Fifteen years later, Rachel Carson published Silent Spring (1), so often cited as the dawning inspiration for the modern environment movement. For lifelong conservation scientists and practitioners, the depredations of DDT, and Carson’s response, represent a seminal evidence-based legacy that is characterized by many of the examples that fill Kareiva and Marvier’s book. As indicated by the subtitle Balancing the Needs of People and Nature, the authors have shaped a textbook that makes a robust case for balance and for the role conservation science must play in achieving it. The book is timely, especially at this moment when science faces a regular media siege. In his recent, brilliantly calm Horizon program on BBC2, “Science under attack” (2), Paul Nurse, president of the Royal Society, made a seemingly irrefutable case for rational, evidence-driven decision-making. By challenging several high-profile skeptics—most notably over Climategate—Nurse made, at least to any reasonable observer, a clear case for science. Indeed, Tim Dowling, the Guardian’s critic, lamented in his paper the following day that it was only a television show and not “a fouryear degree course in climatology” (3). This apparent high ground is natural territory for Science’s readership, but it remains the case that the public at large, whose support for conservation (as Kareiva and Marvier acknowledge) is often lacking, is losing faith in science. When combined with a growing disconnect from natural environments— more than half the world’s population now live in urban areas, and the figure is likely to reach 70% by 2050 (4)—the case for a global strategy that really does balance the needs of people and nature is paramount. As Dowling explained in his review, “Nurse issued a call to scientists to be more politically savvy … and to make more of an effort to put data in the public domain.” With Conservation SciThe reviewer is at BirdLife International, Wellbrook Court, Girton Road, Cambridge CB3 0NA, UK. E-mail: john.
[email protected]
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Facing Up to Vexing Choices
References
Humans are the crucial factor. Home to more than three million people, China’s northwest Yunnan Province retains diverse habitats that harbor numerous endangered animals.
1. R. Carson, Silent Spring (Houghton Mifflin, Boston, 1962). 2. P. Nurse, on Horizon, BBC 2, 24 January 2011. 3. T. Dowling, review of “Science under attack” (BBC 2), Guardian (London), 25 January 2011, p. G2. 4. U.N. Habitat [United Nations Human Settlements Programme], State of the World’s Cities 2010/11: Cities for All: Bridging the Urban Divide (Earthscan, London, 2010).
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BOOKS ET AL. art-science collaborations. In the wet lab at ise of a more open, inclusive world for others. the University of Western Australia, artists Several exhibits—including Paul Vanouse’s are fully implicated in the biological world Latent Figure Protocol (2008), which uses that they comment on and from which they DNA samples from an industrially produced draw inspiration. Indeed, the organism to create an image in immediate focal point upon reactive gel; Andre Brodyk’s Visceral entering the Dublin gallery Proto-Animate20 (2009–), in Deborah Dixon, Elizabeth Straughan, The Living Art Experiment is a working biosafety level which Escherichia coli and the Harriet Hawkins* Oron Catts and Ionat Zurr, 2 laboratory, in which the artgene APOE (associated with Curators Alzheimer’s disease) are used en years ago SymbioticA, an art- ists grow and maintain their Science Gallery, Trinity as creative agents; and Nigel science collective based within the artworks. All 15 pieces in the College, Dublin, Ireland. Helyer’s Host (2003), which School of Anatomy and Human exhibition deploy “living” Through 25 February 2011. presents 200 live crickets with Biology, University of Western Australia, biomaterials as an expreshttp://sciencegallery.com/ a video presentation on the sex embarked on an ambitious program wherein sive medium. Tissue Culture visceral life of insects—explore quesartists would be invited to enter scientific lab- and Art Project’s now-iconic tions of how we are to consider oratories as “residents.” There they would Semi-Living Worry Dolls learn various biological techniques and proto- (2000) was crafted from degradable poly- and negotiate both life and agency in a postcols and would be mentored by both scientists mers and surgical sutures and seeded with Darwinian world. The significance of the exhibition’s title and other artists as they produced “bioart.” A living cells that are nurtured within the surretrospective of some of the resulting work is rogate body of a microgravity bioreactor. In thus seems to ensue not so much from the Neurotica’s Silent Barrage (2009), a gory spectacle of experimentally manipuset of robotic relays, responding to lated viscera but from the desire to seek audience movement, amplifies neu- within these tissues a vision of things to ral activity in distantly located, cul- come. Collaborators such as Paul Thomas tured nerve cells. Boo Chapple’s and Kevin Raxworthy do not seek to presTransjuicer (2010) takes advantage ent the “truth” of science but rather to place of the piezoelectric nature of bone particular scientific endeavors and techmatrix to make cow-bone audio niques within a format and setting that allows speakers that emit nanosonic vibra- them to be experienced via the senses, thus tions. Elsewhere in the exhibition, encouraging the emergence of a complex works—such as Alicia King’s The set of feelings and thoughts toward them. In Vision Splendid (2009), Svenja Thomas and Raxworthy’s immersive installaKratz’s Afterlife: Immortalisation of tion Midas, this is accomplished by realizing Kira and Rama (2011), and Tagny touch at the nanoscale (otherwise indiscernSemi-Living Worry Dolls. Tissue Culture and Arts Project Duff’s Cryobook Archives (2010)— ible) as a series of atomic vibrations recorded (Oron Catts and Ionat Zurr) (2000). examine technological and ethical via an atomic force microscope. This sonic issues involved in the storage of tis- representation is played back by touching a currently on display in Visceral (curated by sue-based bioart as well as more philosoph- gold-coated model of a skin cell connected to SymbioticA cofounder Oron Catts and mem- ical issues involved in thinking of cells and a digital projection of a cell. A work created especially for the exhibiber Ionat Zurr), at the Science Gallery, Trin- living systems as reservoirs for inheritance tion, Perdita Phillips’s The Summer Flurries ity College, Dublin. The show’s three-day and memory. The embeddedness of the artist within (2011), collapses both scale and space. Wearopening (“birth”) included a symposium that drew together the curators, former residents, the laboratory undercuts any easy reading ing headphones and using a Global Positionother bioartists, and scholars working in the of these works as critical of the “monstrous” ing System receiver, visitors walk the streets humanities and social sciences (1), as well capacity of the biological sciences to reor- of Dublin while listening to the sounds of an as a seminar by students in the SymbioticA der and reform living material. Certainly, Australian wetland. The waves of sound dismasters program. The exhibition will close such works as Abhishek Hazra’s Let a Thou- locate one’s sense of place but also allow for with a “death” ritual, during which the equip- sand Proteins Bloom (2011), which attempts connections to emerge between the human ment nurturing the living tissues that form an to produce ammonium nitrate from human and nonhuman, the city and the environment. Although encompassing a wide range of essential part of several installations will be breast milk, speak to an underlying philosoturned off; essential nutrient solutions will phy of science that privileges utilitarianism. practices and materials, the works appearnot be renewed, and samples will be contami- And the exhibition’s guidebook points out ing in Visceral are drawn together by a sense the squeamishness invoked by the chimeri- of ongoing experimentalism and a delight in nated by exposure to air. It is this emphasis on working with living cal, semi-living creatures on show elsewhere exploring what contemporary experimental tissue (from animals, plants, fungi, protists, within the gallery. But, taken as a collection, systems make possible. Such bioart is at once archaea, and bacteria), as well as viruses, these works harken not to a Faustianism but wondrous and unsettling, spectacular and that marks SymbioticA’s key contribution to to the classical monster (from the Latin mon- deeply felt. stratum, to point to that which is worthy of The reviewers are at the Institute of Geography and Earth References and Notes warning). These singular wonders portend Sciences, Llandinam Building, Aberystwyth University, 1. Deborah Dixon was an invited speaker at this symposium. a radical shift in the social order, prompting Penglais Campus, Aberystwyth SY23 3DB, UK. *Author for correspondence. E-mail:
[email protected] 10.1126/science.1203549 horror and anxiety in some but also the promEXHIBITION
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POLICYFORUM P
Deflating the Genomic Bubble James P. Evans,1* Eric M. Meslin,2 Theresa M. Marteau,3 Timothy Caulfield4
“S
CREDIT: P. HUEY/SCIENCE
occer is the sport of the future in America … and it always will be.” This oft-quoted epithet poking fun at the promise of the “beautiful game” in the United States can seem uncomfortably apt when applied to genomic medicine. It’s now been 10 years since humans deciphered the digital code that defines us as a species. Although it may be hard to overestimate the significance of that achievement, it is easy to misconstrue its meaning and promise. People argue about whether mapping the human genome was worth the investment (1–3). With global funding for genomics approaching $3 billion/year (4), some wonder what became of all the genomic medicine we were promised (5). It thus seems an appropriate time to take stock of whence the real benefits from genomic research may come and how best to attain a future in which genomics improves human health. Recent methodological progress in genomics has been breathtaking. We now regularly assay genomes at millions of loci (6), and routine whole-genome sequencing may soon be a reality (7). If this trajectory continues, genomic research will illuminate fundamental mechanisms of human disease with a reasonable expectation of practical results (8). But claims of near-term applications are too often unrealistic and ultimately counterproductive. From the South Sea and dot-com “bubbles” to the ongoing housing market crisis, the world has seen its share of inflated expectations and attendant dangers. Science is immune to neither. If we fail to evaluate the considerable promise of genomics through a realistic lens, exaggerated expectations will undermine its legitimacy (9), threaten its sustainability, and result in misallocation of resources. Fueling unrealistic expectations for predictive genetic testing and uncritical translation of discoveries may also distract our gaze from other promising approaches to preventing disease and improving health. 1 Departments of Genetics and Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. 2 Center for Bioethics, Indiana University, Indianapolis, IN 46202, USA. 3Health Psychology Section, King’s College London, London SE1 9RT, UK. 4Faculty of Law and School of Public Health, Health Law Institute, University of Alberta, Edmonton, Alberta T6G 2H5, Canada.
*Author for correspondence. E-mail:
[email protected]
Impediments and Hyperbole
Substantial impediments to realizing many of the claims most frequently heard include the following: The problem of clinical utility and relative risk. The numerous genetic variants that mediate disease risk typically confer woefully low relative risks (i.e., compared with the much more meaningful absolute risk) and are thus meager in their predictive power (10). Their applicability to patient care shows little promise; studies (11–14) demonstrate that even combining dozens of risk markers provides little clinically meaningful information. In the public health realm, the prospect of effectively stratifying populations as high or low risk, thereby guiding screening, is equally dismal. Given the multifactorial nature of common diseases and the weak predictive properties of genetic-risk alleles, the probability of misclassifying individuals as high or low risk is likely too great to make such an approach feasible in the general population for guiding such things as mammography or colorectal cancer screening (15). The illusion of parsing risk. For common diseases, by definition, we are all at high levels of absolute risk. In this setting, defining precise relative risk on the basis of individuals’ genetic information is less meaningful; interventions that lower risk will be useful to everyone, regardless of their relative risk. And for rare diseases, shifting an individual’s risk from an already low level may not be very clinically meaningful. For example, the lifetime risk for an individual in the United States to develop Crohn’s disease is about 1/1000. How helpful is it for clinicians and patients if that risk shifts to 1/500 or 1/2000?
Unrealistic expectations and uncritical translation of genetic discoveries may undermine other promising approaches to preventing disease and improving health.
The difficulty of changing behaviors. The idea that genetic information will promote a healthy life-style has emerged as a dominant claim by those who promote genomic medicine (16, 17). However, there is little evidence that simply telling someone they are at a genetically increased risk for heart disease or diabetes, for example, leads to lasting beneficial changes in diet or exercise habits (18, 19). Altering environments is increasingly recognized as a more effective way of changing those counterproductive behaviors that contribute most to poor health in high-income countries—namely, diet, sedentary behavior, smoking, and alcohol use (20). The paradox of risk information. Even if, despite evidence to the contrary, knowledge of one’s genetic status drives behavior change, another problem emerges: for everyone identified at increased risk of a malady, there will be an equal number at decreased risk. Thus, if genetic information were actually found to be uniquely powerful in changing behavior, it could well promote counterproductive behaviors. The translation of science into the clinic is inherently messy. The public, researchers, and clinicians frequently fail to appreciate that the history of medicine is strewn with ideas once thought promising that did not pan out when scrutinized through the lens of evidencebased medicine (21). Hormone replacement therapy, prostate-specific antigen screening, peri–myocardial infarction lidocaine, and many other good ideas, when prematurely implemented, created bubbles of expectation and investment, leaving sponsors disappointed and patients ill-served when reality did not live up to theoretical promise. Given these hurdles to practical application, why has genomics been the recipient of such hyperbole? Impatience for practical applications from genetic advances is understandable. To be sure, there is much room for improvement in modern medicine: Screening programs
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GENOMICS
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POLICYFORUM
Realistic Promises
Harold Varmus observed that the full potential of a DNA-based transformation of medicine will be realized only over the course of decades (8). We agree; the true promise of genomics is to help lay bare the mechanisms of human disease. Genes responsible for most Mendelian disorders will soon be identified. Genome-wide association studies are illuminating loci that contribute to common disease, and novel drug targets are being identified that will ultimately lead to new therapies. But the timeline for translation of such discoveries will be long. Pharmacogenomics (PGx; the study of influence of genetic variation on drug response) may represent a near-term payoff of genomic research for carefully selected treatments and could enhance the safety and utility of treatments used for serious disorders (26, 27). But it is unrealistic to expect PGx to revolutionize the use of all (or perhaps even most) drugs, given that much variability in efficacy is not genetically determined (28). Indeed, the most powerful predictor of drug efficacy is whether a patient takes the drug, highlighting the importance of human behavior in health outcomes. If properly harnessed and based on evidence, appropriate risk assessment could aid in clinical decision-making (29). The ability to make diagnoses, especially for disorders that result from disruption of a single gene, will provide tangible benefit in the near term. Enhanced diagnostic capacity promises to spare both anxiety and money, ending the cruel “diagnostic odyssey” of families who
862
go for years without a definitive diagnosis. But we should not overestimate the value of diagnosis or risk stratification. Without effective interventions, a diagnosis is only a dimly realized, partially fulfilled hope. Couples will be empowered to make informed reproductive decisions, as preconceptual screening, augmented by robust genomic analysis, allows them to learn whether they are carriers of disease-related genes. Newborn screening will also benefit as medically actionable conditions are identified. Such advances hold great promise if the information so gathered is useful, costeffective, and welcome (since not all parents may welcome such information). So how do we avoid inflating an unsustainable genomic bubble but still realize the true—and considerable—promise of the “genomic revolution”? Solutions range from the political to the personal, from short term to long term. We offer a short list of recommendations as a starting point for debate, aimed at deflating the genomic bubble and realizing the field’s long-term promise: 1. Reevaluate funding priorities. A sober assessment of disease etiology suggests that funding priorities may be mismatched to the potential for practical benefit. Much morbidity and premature mortality in high-income countries results from smoking, sedentary behavior, and excessive food and alcohol consumption (30, 31). It is likely that common diseases arising from these behaviors can be reduced by behavioral change (32, 33), but our knowledge of how to effect such change across populations is limited. Yet, U.S. National Institutes of Health and Department of Energy spending on genomics vastly exceeds the budget for behavioral and social science research (4, 34). Given that even a small improvement in our ability to alter behaviors could yield major benefits, we suggest a reappraisal of the apportioning of funds to promote the promise of improved human health. 2. Foster a realistic understanding among the scientific community, the media, and the public of the incremental nature of science and need for statistical rigor. Scientists can start this process by making responsible claims and by advocating that reporters and editors do the same. 3. Maintain focus on developing highquality evidence before integrating good ideas into medical practice. Develop novel ways of assessing evidence so as not to delay implementing promising modalities. We believe that genomic discovery and resultant applications will provide great benefits to human health. Ours is not a call
to gut existing research or too rigidly tie funding to the degree of disease burden. Indeed, the nature of scientific progress is arguably not optimized by a rigid allocation of resources to purely practical need. But failing a (desirable but unlikely) massive expansion of total funding for all types of research, a realistic view of the promise of genomics and an appropriate prioritization of research funding are vital to realizing that future. The pursuit of our common goal—improved human health—demands that we take a hard look at disease causation and order our priorities accordingly. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34.
35.
References and Notes
A. Pollack, New York Times, 14 June 2010, p. B5. P. Kraft, D. J. Hunter, N. Engl. J. Med. 360, 1701 (2009). J. N. Hirschhorn, N. Engl. J. Med. 360, 1699 (2009). J. R. Pohlhaus, R. M. Cook-Deegan, BMC Genomics 9, 472 (2008). F. S. Collins, N. Engl. J. Med. 341, 28 (1999). Editors, Nature 464, 649 (2010). E. Pettersson, J. Lundeberg, A. Ahmadian, Genomics 93, 105 (2009). H. Varmus, The Art and Politics of Science (Norton, New York, 2009). A. Petersen, Monash Bioeth. Rev. 28, 5.1 (2009). L. A. Hindorff et al., Proc. Natl. Acad. Sci. U.S.A. 106, 9362 (2009). S. Wacholder et al., N. Engl. J. Med. 362, 986 (2010). S. Kathiresan et al., N. Engl. J. Med. 358, 1240 (2008). V. Lyssenko et al., N. Engl. J. Med. 359, 2220 (2008). N. L. Pedersen, JAMA 303, 1864 (2010). M. S. Pepe, H. Janes, G. Longton, W. Leisenring, P. Newcomb, Am. J. Epidemiol. 159, 882 (2004). F. Collins, Nature 464, 674 (2010). Navigenics Inc., Genetics and health; http://www. navigenics.com/visitor/genetics_and_health/taking_ action/personalized_health/. J. B. McClure, Am. J. Prev. Med. 22, 200 (2002). T. M. Marteau et al., Cochrane Database Syst. Rev. 10, CD007275 (2010). WHO Regional Committee for Europe, “Resolution: Behaviour change strategies & health: The role of health systems” (World Health Organization, Geneva, 2008). K. Goodman, Ethics and Evidence-Based Medicine: Fallibility and Responsibility in Clinical Science (Cambridge Univ. Press, Cambridge, UK, 2003). J. Kimmelman, Gene Transfer and the Ethics of First-inHuman Research: Lost in Translation (Cambridge Univ. Press, Cambridge, UK, 2009). L. P. Garrison Jr. et al., Drug Metab. Rev. 40, 377 (2008). T. Caulfield, PLoS. Med. 1, e38 (2004). B. Carlsson, Z. J. Acs, D. B. Audretsch, P. Braunerhjelm, Ind. Corp. Change 18, 1193 (2009). S. Mallal et al., N. Engl. J. Med. 358, 568 (2008). M. P. Goetz et al., Breast Cancer Res. Treat. 101, 113 (2007). G. Tucker, BMJ 329, 4 (2004). A. J. Vickers, E. Basch, M. W. Kattan, Ann. Intern. Med. 149, 200 (2008). R. L. Keeney, Oper. Res. 56, 1335 (2008). W. C. Willett, Science 296, 695 (2002). W. C. Knowler et al., Lancet 374, 1677 (2009). R. Doll, R. Peto, J. Boreham, I. Sutherland, BMJ 328, 1519 (2004). H. J. Silver, A. L. Sharpe, H. Kelly, P. Kobor, G. Sroufe, in AAAS Report 33: Research and Development 2009 (AAAS, Washington, DC, 2008), chap. 19; www.aaas.org/ spp/rd/09pch19.htm. The authors thank R. Whiting and Genome Alberta.
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are inherently inefficient given the need to test entire populations, drugs have widely variable efficacy, and diseases strike capriciously. But there are other drivers of inflated expectations (22). Researchers gain funding, jobs, and fame, while pressure to commercialize their work adds fuel to the tendency to oversell (23, 24). In a distressing way, biomedical research is often viewed by governments as primarily an engine of economic growth (25) and, only secondarily, as an engine of scientific and medical progress. Further pressure results from retail marketing of genomic information, such as directto-consumer genetic testing. As boundaries between private and public efforts erode, academic endeavors are increasingly subject to market forces that demand quick payoffs. Finally, the press plays an obvious role in creating unrealistic hopes (24). Collectively, these factors contribute to heightened expectations; left unchallenged, they take on a momentum that is hard to unseat.
PERSPECTIVES CELL BIOLOGY
A Hand to Support the Implantation Window
A signaling pathway connects ovarian hormones to preparation of the mammalian uterus for pregnancy.
Sylvia C. Hewitt and Kenneth S. Korach
CREDIT: Y. HAMMOND/SCIENCE
R
National Institute of Environmental Health Science, National Institutes of Health, Research Triangle Park, NC 27709, USA. E-mail:
[email protected]
Fallopian tube
Epithelium Endometrium (epithelium, stroma)
Uterus lumen
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eproduction in mammals is coordinated by an intricate sequence of events and signals that culminate in implantation of the embryo in the uterus (1–3). To succeed, these signals must be produced at the correct time, in the proper place, and in the amounts needed, and must be received by the appropriate targets. Perturbation of any of these factors can prevent establishment of pregnancy, resulting in infertility. On page 912 of this issue, Li et al. (4) show that the transcription factor Hand2 regulates signals that establish conditions in the mammalian uterus to support pregnancy. Uterine tissue (see the figure) consists of an outer muscle layer (myometrium) which contracts during labor to facilitate delivery. The inner lumen is lined by an epithelial cell layer from which emanate glandular structures, also lined by epithelial cells. The embryo must attach to, and then invade through, the epithelial layer to establish a pregnancy, and the glands secrete factors essential to the process. Stromal cells between the outer and inner layers expand and differentiate into decidual cells to support fetal and placental development. The ovarian hormones estrogen and progesterone have relatively complementary roles, reflecting their temporal and cyclical fluctuations. Estrogen production surges just before ovulation, and induces growth of the uterine epithelial cells that will come into contact with a developing embryo. Progesterone increases after ovulation and further prepares the endometrial tissue (the stromal and epithelial cells) for pregnancy by both dampening the proliferative effect of estrogen on the epithelial cells, and acting with estrogen to stimulate proliferation of stromal decidual tissues. This convergence of hormonal and other signals with the arrival of the embryo at the proper time is called the “implantation window.” The responses of uterine cells to estrogen and progesterone are mediated in part by receptors that are transcription factors. The estrogen receptor (ER) is found in all uter-
Myometrium (muscle) Lumen
Stroma
Cervix Vagina Signaling Epithelium Ovulation
Progesterone
Hand2 (Transcription factor)
Blocks FGF production and secretion
Prevents ERα activation in epithelium
Blocks epithelium growth
Allows embryo implantation
Implantation signals. Stromal cells respond to progesterone during pregnancy by activating the transcription factor Hand2. This triggers a signaling cascade that blocks estrogen receptor (ERα) signaling in uterine epithelial cells, thereby creating an epithelium that is receptive for embryo implantation.
ine cell types, whereas progesterone receptor (PR) expression varies depending on the cell type and phase of the ovarian cycle. As in earlier studies with PR-deficient mice (1, 3), Li et al. show that when progesterone is unable to decrease estrogen’s proliferative effect on the endometrial epithelium, pregnancy cannot be established. Disrupting this effect of progesterone is the basis for the estrogen-containing “morning after pill.” In certain clinical conditions, estrogen in the absence of progesterone (“unopposed estrogen”) may damage the endometrium. Hormone-replacement therapies that lack progesterone, or anovulatory conditions (such as polycystic ovarian syndrome) that lengthen the estrogenic portion of the menstrual cycle, are associated with increased incidence of endometrial cancers (5). However, the signaling pathways by which estrogen and progesterone successfully establish uterine receptivity have not been fully elucidated. Estrogen, acting through ERα in the stromal cells, increases the production of paracrine factors, including insulin-like growth factor 1 (IGF-1), which then trigger the proliferation of epithelial cells (6, 7). Estrogen also maintains the epithelia by preventing
programmed cell death of epithelial cells (8). These mechanisms have been established through numerous approaches including ablation of certain progesterone target genes (Ihh, Couptf2, Fkbp4, and Errfi1), leading to loss of uterine receptivity (3, 9, 10). Overall, these findings emphasize that proper progesterone-mediated regulation of multiple uterine stromal signals is critical for controlling the epithelial estrogenic responses that allow embryo implantation. To identify the progesterone-regulated signaling pathways that underlie implantation, Li et al. used microarray gene profiling analysis of progesterone-responsive transcription at the implantation window in the mouse. Comparison of mRNA in receptive uterine tissue to that in tissue treated with the PR antagonist RU486 revealed altered expression of Hand2. Selective ablation of the Hand2 gene in uterine cells showed that the transcription factor plays a key role in establishing a receptive endometrium. Microarray analysis also revealed misregulation of signaling by fibroblast growth factor (FGF) in the uterine tissue of Hand2-deficient mice compared to that in normal mice. Previous studies had indicated a role for FGF signaling in ovine implanta-
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PERSPECTIVES an FGF receptor (FGFR2) are associated with endometrial cancer (12, 13). Whether mutations in the Hand2 gene can explain clinical dysfunction also will require further research. Reproduction and endometrial function involve intricate interplay between different cell types that are too complex to adequately study with cell culture approaches. The findings of Li et al. relied on the development of elaborate in vivo models. Such approaches promise to open important new avenues of investigation into this critical window of receptivity.
2. F. W. Bazer, T. E. Spencer, G. A. Johnson, R. C. Burghardt, G. Wu, Reproduction 138, 195 (2009). 3. H. J. Lim, H. Wang, J. Clin. Invest. 120, 1004 (2010). 4. Q. Li et al., Science 331, 912 (2011). 5. A. E. Schindler, Maturitas 62, 334 (2009). 6. G. R. Cunha, P. S. Cooke, T. Kurita, Arch. Histol. Cytol. 67, 417 (2004). 7. L. J. Murphy, A. Ghahary, Endocr. Rev. 11, 443 (1990). 8. W. Winuthayanon, S. C. Hewitt, G. D. Orvis, R. R. Behringer, K. S. Korach, Proc. Natl. Acad. Sci. U.S.A. 107, 19272 (2010). 9. D.-K. Lee et al., Mol. Endocrinol. 24, 930 (2010). 10. T. H. Kim, D. K. Lee, H. L. Franco, J. P. Lydon, J. W. Jeong, Biol. Reprod. 82, 706 (2010). 11. B. C. Paria et al., Proc. Natl. Acad. Sci. U.S.A. 98, 1047 (2001). 12. P. M. Pollock et al., Oncogene 26, 7158 (2007). 13. P. Krejci, J. Prochazkova, V. Bryja, A. Kozubik, W. R. Wilcox, Hum. Mutat. 30, 1245 (2009).
References
Downloaded from www.sciencemag.org on February 17, 2011
tion (2), indicating that the mechanism may have broader application to other mammals. Additionally, expression of Fgf2 transcript in the stroma surrounding an implanting blastocyst was previously reported in mice (11). However, Li et al. link regulation of the FGF signals to progesterone regulation of Hand2, which helps to explain how progesterone establishes uterine receptivity. Whether there is a general role for Hand2 and FGF signaling in establishing receptive endometria of other mammals remains to be determined. It will be important to evaluate whether perturbing this pathway might lead to adverse clinical outcomes, such as infertility, endometriosis, or malignancy. Indeed, mutations in the genes encoding FGF9 and
10.1126/science.1202372
1. H. Wang, S. K. Dey, Nat. Rev. Genet. 7, 185 (2006).
PHYSICS
A New Twist on Spintronics
A thin layer of ordered DNA acts as an efficient spin filter for photoemitted electrons from a gold surface.
Geert L. J. A. Rikken
G
Laboratoire National des Champs Magnétiques Intenses, CNRS/INSA/UJF/UPS, 143 Avenue de Rangueil, 31400 Toulouse and 25 Avenue de Martyrs, 38042 Grenoble, France. E-mail:
[email protected]
864
Twist and spin. Illustrating the spin-filtering effect. Electrons with their spin parallel to their velocity (here represented as rightrotating) are mostly transmitted through an ordered layer of DNA helices, whereas electrons with their spin antiparallel to their velocity (represented as left-rotating) are mostly reflected by it.
ily, meaning that this layer acts as a spin filter, strongly hindering the passage of the other spin type. This filter effect is observed only if the DNA is assembled on the gold surface as a closely packed ordered array of helices, and is stronger if the helices are longer, reaching selectivities of 60%. For chaotic assemblies of floppy DNA chains on the gold surface, the spin filter effect was not observed.
These findings reveal a fascinating and promising link between chirality and spintronics, which at first sight seem unlikely bedfellows. Objects are chiral (from the Greek “cheir,” meaning “hand”) if they exist in two nonsuperimposable forms that are each other’s mirror image, like our hands. Chirality is essential in stereochemistry and plays a vital role in biochemistry, as natural sugars are all righthanded and natural proteins are all left-handed. DNA chains are made of chiral building blocks, and can assemble into helical (chiral) superstructures, like the helices used by Göhler et al. Spin, on the other hand, has nothing to do with spatial symmetries, but is a quantum-mechanical property that is related to rotation, i.e., an absence of timereversal invariance. However, if the spincarrying particle has a velocity along its spin axis, it is chiral, as the combination of velocity and rotation results in a screwlike motion. Spin-polarized currents therefore are chiral, and their handedness depends on
18 FEBRUARY 2011 VOL 331 SCIENCE www.sciencemag.org Published by AAAS
CREDIT: P. HUEY/SCIENCE
reat hopes exist for improving the storage and processing of information by using not only the charge of electrons, as is done in everyday electronics, but by also exploiting a quantum mechanical property of electrons known as spin. In the rapidly growing field of spintronics (1), the electron spin is essentially a minute magnet that can be pointing either “up” or “down.” The most efficient way to manipulate spins is by means of a magnetic field, either externally applied or existing inside a ferromagnetic material. By sending electrons through ferromagnetic materials, scientists have achieved spin-filtering effects, discriminating between electrons with “up” and “down” spins, with selectivity up to 25% (2). On page 894 of this issue, Göhler et al. (3) describe a surprisingly efficient method for electronic spin filtering. They have studied how electrons emitted by a gold substrate, upon absorption of light, pass through a self-assembled DNA monolayer on the gold surface. In particular, they have studied the spin of the electrons after their passage through the DNA layer and have found that one spin type passes through much more eas-
PERSPECTIVES an FGF receptor (FGFR2) are associated with endometrial cancer (12, 13). Whether mutations in the Hand2 gene can explain clinical dysfunction also will require further research. Reproduction and endometrial function involve intricate interplay between different cell types that are too complex to adequately study with cell culture approaches. The findings of Li et al. relied on the development of elaborate in vivo models. Such approaches promise to open important new avenues of investigation into this critical window of receptivity.
2. F. W. Bazer, T. E. Spencer, G. A. Johnson, R. C. Burghardt, G. Wu, Reproduction 138, 195 (2009). 3. H. J. Lim, H. Wang, J. Clin. Invest. 120, 1004 (2010). 4. Q. Li et al., Science 331, 912 (2011). 5. A. E. Schindler, Maturitas 62, 334 (2009). 6. G. R. Cunha, P. S. Cooke, T. Kurita, Arch. Histol. Cytol. 67, 417 (2004). 7. L. J. Murphy, A. Ghahary, Endocr. Rev. 11, 443 (1990). 8. W. Winuthayanon, S. C. Hewitt, G. D. Orvis, R. R. Behringer, K. S. Korach, Proc. Natl. Acad. Sci. U.S.A. 107, 19272 (2010). 9. D.-K. Lee et al., Mol. Endocrinol. 24, 930 (2010). 10. T. H. Kim, D. K. Lee, H. L. Franco, J. P. Lydon, J. W. Jeong, Biol. Reprod. 82, 706 (2010). 11. B. C. Paria et al., Proc. Natl. Acad. Sci. U.S.A. 98, 1047 (2001). 12. P. M. Pollock et al., Oncogene 26, 7158 (2007). 13. P. Krejci, J. Prochazkova, V. Bryja, A. Kozubik, W. R. Wilcox, Hum. Mutat. 30, 1245 (2009).
References
Downloaded from www.sciencemag.org on February 17, 2011
tion (2), indicating that the mechanism may have broader application to other mammals. Additionally, expression of Fgf2 transcript in the stroma surrounding an implanting blastocyst was previously reported in mice (11). However, Li et al. link regulation of the FGF signals to progesterone regulation of Hand2, which helps to explain how progesterone establishes uterine receptivity. Whether there is a general role for Hand2 and FGF signaling in establishing receptive endometria of other mammals remains to be determined. It will be important to evaluate whether perturbing this pathway might lead to adverse clinical outcomes, such as infertility, endometriosis, or malignancy. Indeed, mutations in the genes encoding FGF9 and
10.1126/science.1202372
1. H. Wang, S. K. Dey, Nat. Rev. Genet. 7, 185 (2006).
PHYSICS
A New Twist on Spintronics
A thin layer of ordered DNA acts as an efficient spin filter for photoemitted electrons from a gold surface.
Geert L. J. A. Rikken
G
Laboratoire National des Champs Magnétiques Intenses, CNRS/INSA/UJF/UPS, 143 Avenue de Rangueil, 31400 Toulouse and 25 Avenue de Martyrs, 38042 Grenoble, France. E-mail:
[email protected]
864
Twist and spin. Illustrating the spin-filtering effect. Electrons with their spin parallel to their velocity (here represented as rightrotating) are mostly transmitted through an ordered layer of DNA helices, whereas electrons with their spin antiparallel to their velocity (represented as left-rotating) are mostly reflected by it.
ily, meaning that this layer acts as a spin filter, strongly hindering the passage of the other spin type. This filter effect is observed only if the DNA is assembled on the gold surface as a closely packed ordered array of helices, and is stronger if the helices are longer, reaching selectivities of 60%. For chaotic assemblies of floppy DNA chains on the gold surface, the spin filter effect was not observed.
These findings reveal a fascinating and promising link between chirality and spintronics, which at first sight seem unlikely bedfellows. Objects are chiral (from the Greek “cheir,” meaning “hand”) if they exist in two nonsuperimposable forms that are each other’s mirror image, like our hands. Chirality is essential in stereochemistry and plays a vital role in biochemistry, as natural sugars are all righthanded and natural proteins are all left-handed. DNA chains are made of chiral building blocks, and can assemble into helical (chiral) superstructures, like the helices used by Göhler et al. Spin, on the other hand, has nothing to do with spatial symmetries, but is a quantum-mechanical property that is related to rotation, i.e., an absence of timereversal invariance. However, if the spincarrying particle has a velocity along its spin axis, it is chiral, as the combination of velocity and rotation results in a screwlike motion. Spin-polarized currents therefore are chiral, and their handedness depends on
18 FEBRUARY 2011 VOL 331 SCIENCE www.sciencemag.org Published by AAAS
CREDIT: P. HUEY/SCIENCE
reat hopes exist for improving the storage and processing of information by using not only the charge of electrons, as is done in everyday electronics, but by also exploiting a quantum mechanical property of electrons known as spin. In the rapidly growing field of spintronics (1), the electron spin is essentially a minute magnet that can be pointing either “up” or “down.” The most efficient way to manipulate spins is by means of a magnetic field, either externally applied or existing inside a ferromagnetic material. By sending electrons through ferromagnetic materials, scientists have achieved spin-filtering effects, discriminating between electrons with “up” and “down” spins, with selectivity up to 25% (2). On page 894 of this issue, Göhler et al. (3) describe a surprisingly efficient method for electronic spin filtering. They have studied how electrons emitted by a gold substrate, upon absorption of light, pass through a self-assembled DNA monolayer on the gold surface. In particular, they have studied the spin of the electrons after their passage through the DNA layer and have found that one spin type passes through much more eas-
PERSPECTIVES Mayer et al. (4) observed spin selectivity only if a heavy atom, in their case ytterbium, was incorporated in the chiral molecule. They did not observe any selectivity for molecules consisting only of light atoms, like carbon, oxygen, or hydrogen. Other experiments studying the transmission of electrons polarized by an external magnetic field through chiral conductors also showed only very small spinfiltering effects (5). The spin filter effect reported by Göhler et al. is almost four orders of magnitude stronger than the one observed by Mayer et al. As there are no heavy atoms in the DNA molecule, spin-orbit coupling alone cannot explain it. The fact that only well-ordered long DNA helices show a strong effect suggests that the supramolecular periodic character of the helices somehow greatly enhances the spin filtering, but more work is needed to understand the phenomenon. The high efficiency of the filtering action observed by Göhler et al. makes supramolecular chiral materials very
interesting for spintronics. The richness of supramolecular chiral organic synthesis (6) holds great promise for detailed studies and fine-tuning of this new effect, which may one day find application in spintronics devices. Periodic chiral structures created by other methods, like glancing angle deposition (7), may also prove to be efficient spin filters. In any case, Göhler et al. have definitely given a new twist to spintronics. References
1. S. D. Bader, S. S. P. Parkin, Annu. Rev. Cond. Mat. Phys 1, 71 (2010). 2. Y. Lassailly, H.-J. Drouhin, A. van der Sluijs, G. Lampel, C. Marlière, Phys. Rev. B 50, 13054 (1994). 3. B. Göhler et al., Science 331, 894 (2011). 4. S. Mayer, J. Kessler, Phys. Rev. Lett. 74, 4803 (1995). 5. G. L. J. A. Rikken, J. Fölling, P. Wyder, Phys. Rev. Lett. 87, 236602 (2001). 6. Y. Furusho, E. Yashima, J. Polym. Sci. A Polym. Chem. 47, 5195 (2009). 7. K. Robbie, M. J. Brett, A. Lakhtakia, Nature 384, 616 (1996).
Downloaded from www.sciencemag.org on February 17, 2011
whether the spin direction is parallel or antiparallel to the current (see the figure). The everyday frustration of putting your left hand in your right-hand glove immediately illustrates that the interaction between objects of opposite handedness is not the same as that between objects of the same handedness. It came therefore as no surprise that the transmission of spin-polarized electron beams through a vapor of chiral molecules was reported by Mayer et al. in 1995 to depend on the relative handedness of the spin-polarized electron current and the molecular chirality (4). This effect was, however, found to be quite small (~10−4), as predicted by theory. The mechanism behind this selectivity is the spin-orbit coupling; an electron moving through the electric field of the atomic nucleus experiences effectively also a magnetic field (a weak, relativistic effect), which acts on the electron spin. This coupling is stronger if the nucleus carries more charge, that is, it is stronger for heavier elements.
10.1126/science.1201663
PLANT SCIENCE
Unlocking the Door to Invasion
A single plant receptor recognizes related bacterial and fungal signals to initiate symbiosis.
Attila Kereszt1,2 and Eva Kondorosi1,3
CREDIT: S. SCHAARSCHMIDT AND B. HORVATH
T
o increase crop yields, farmers use inorganic fertilizers that provide plants with usable forms of nitrogen and phosphorus. The production and application of fertilizers, however, requires huge amounts of fossil energy and causes pollution. To reduce these problems and support the growing human population, sustainable agriculture will require new plant varieties capable of supplying themselves with these elements. On page 909 of this issue, Op den Camp et al. (1) take a step toward this goal by describing a cell surface receptor that enables a plant to establish symbiotic relationships with both the bacteria and fungi that help it to fix nitrogen from the atmosphere and take up phosphorus. Most land plants, including the major crops, are able to establish endosymbiotic “partnerships” with arbuscular mycorrhizal (AM) fungi that enhance uptake of phosphate (2). More recently in evolutionary Institute for Plant Genomics, Human Biotechnology and Bioenergy, Bay Zoltan Foundation for Applied Research, Derkovits fasor 2, Szeged, Hungary. 2Karoly Robert College, Matrai ut 36, Gyöngyös, Hungary. 3Institut des Sciences du Végétal, Centre National de la Recherche Scientifique, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France. E-mail:
[email protected];
[email protected]
terms, a small group of plants belonging to certain orders of the eurosid I group of eudicots gained the ability to develop novel symbiotic organs called nodules to accommodate nitrogen-fixing (NF) bacteria. These include Gram-negative (rhizobia) and Gram-positive A
(Frankia) species. Most past studies of symbiotic nitrogen fixation have focused on rhizobial symbiosis with commercially valuable and model legume plants such as soybean and alfalfa. Genetic analysis of mutant plants have revealed that the development of B
1
Root symbioses. (A) Mycorrhizal hyphae, arbuscules, and vesicules of AM fungi stained with ink. (B) Rhizobial root nodules.
www.sciencemag.org SCIENCE VOL 331 18 FEBRUARY 2011 Published by AAAS
865
PERSPECTIVES Mayer et al. (4) observed spin selectivity only if a heavy atom, in their case ytterbium, was incorporated in the chiral molecule. They did not observe any selectivity for molecules consisting only of light atoms, like carbon, oxygen, or hydrogen. Other experiments studying the transmission of electrons polarized by an external magnetic field through chiral conductors also showed only very small spinfiltering effects (5). The spin filter effect reported by Göhler et al. is almost four orders of magnitude stronger than the one observed by Mayer et al. As there are no heavy atoms in the DNA molecule, spin-orbit coupling alone cannot explain it. The fact that only well-ordered long DNA helices show a strong effect suggests that the supramolecular periodic character of the helices somehow greatly enhances the spin filtering, but more work is needed to understand the phenomenon. The high efficiency of the filtering action observed by Göhler et al. makes supramolecular chiral materials very
interesting for spintronics. The richness of supramolecular chiral organic synthesis (6) holds great promise for detailed studies and fine-tuning of this new effect, which may one day find application in spintronics devices. Periodic chiral structures created by other methods, like glancing angle deposition (7), may also prove to be efficient spin filters. In any case, Göhler et al. have definitely given a new twist to spintronics. References
1. S. D. Bader, S. S. P. Parkin, Annu. Rev. Cond. Mat. Phys 1, 71 (2010). 2. Y. Lassailly, H.-J. Drouhin, A. van der Sluijs, G. Lampel, C. Marlière, Phys. Rev. B 50, 13054 (1994). 3. B. Göhler et al., Science 331, 894 (2011). 4. S. Mayer, J. Kessler, Phys. Rev. Lett. 74, 4803 (1995). 5. G. L. J. A. Rikken, J. Fölling, P. Wyder, Phys. Rev. Lett. 87, 236602 (2001). 6. Y. Furusho, E. Yashima, J. Polym. Sci. A Polym. Chem. 47, 5195 (2009). 7. K. Robbie, M. J. Brett, A. Lakhtakia, Nature 384, 616 (1996).
Downloaded from www.sciencemag.org on February 17, 2011
whether the spin direction is parallel or antiparallel to the current (see the figure). The everyday frustration of putting your left hand in your right-hand glove immediately illustrates that the interaction between objects of opposite handedness is not the same as that between objects of the same handedness. It came therefore as no surprise that the transmission of spin-polarized electron beams through a vapor of chiral molecules was reported by Mayer et al. in 1995 to depend on the relative handedness of the spin-polarized electron current and the molecular chirality (4). This effect was, however, found to be quite small (~10−4), as predicted by theory. The mechanism behind this selectivity is the spin-orbit coupling; an electron moving through the electric field of the atomic nucleus experiences effectively also a magnetic field (a weak, relativistic effect), which acts on the electron spin. This coupling is stronger if the nucleus carries more charge, that is, it is stronger for heavier elements.
10.1126/science.1201663
PLANT SCIENCE
Unlocking the Door to Invasion
A single plant receptor recognizes related bacterial and fungal signals to initiate symbiosis.
Attila Kereszt1,2 and Eva Kondorosi1,3
CREDIT: S. SCHAARSCHMIDT AND B. HORVATH
T
o increase crop yields, farmers use inorganic fertilizers that provide plants with usable forms of nitrogen and phosphorus. The production and application of fertilizers, however, requires huge amounts of fossil energy and causes pollution. To reduce these problems and support the growing human population, sustainable agriculture will require new plant varieties capable of supplying themselves with these elements. On page 909 of this issue, Op den Camp et al. (1) take a step toward this goal by describing a cell surface receptor that enables a plant to establish symbiotic relationships with both the bacteria and fungi that help it to fix nitrogen from the atmosphere and take up phosphorus. Most land plants, including the major crops, are able to establish endosymbiotic “partnerships” with arbuscular mycorrhizal (AM) fungi that enhance uptake of phosphate (2). More recently in evolutionary Institute for Plant Genomics, Human Biotechnology and Bioenergy, Bay Zoltan Foundation for Applied Research, Derkovits fasor 2, Szeged, Hungary. 2Karoly Robert College, Matrai ut 36, Gyöngyös, Hungary. 3Institut des Sciences du Végétal, Centre National de la Recherche Scientifique, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France. E-mail:
[email protected];
[email protected]
terms, a small group of plants belonging to certain orders of the eurosid I group of eudicots gained the ability to develop novel symbiotic organs called nodules to accommodate nitrogen-fixing (NF) bacteria. These include Gram-negative (rhizobia) and Gram-positive A
(Frankia) species. Most past studies of symbiotic nitrogen fixation have focused on rhizobial symbiosis with commercially valuable and model legume plants such as soybean and alfalfa. Genetic analysis of mutant plants have revealed that the development of B
1
Root symbioses. (A) Mycorrhizal hyphae, arbuscules, and vesicules of AM fungi stained with ink. (B) Rhizobial root nodules.
www.sciencemag.org SCIENCE VOL 331 18 FEBRUARY 2011 Published by AAAS
865
both the AM and the NF symbioses are based on the shared activity of a set of plant genes, SYM genes (3–5). This indicates that bacteria hijacked the signal transduction pathway that fungi had used to gain entry into plant tissues and cells. Op den Camp et al. provide evidence that in Parasponia, the only nonlegume partner of rhizobia, a single receptor can recognize both the fungal and bacterial signals and induce the common SYM pathway to promote the intracellular accommodation of the partner microorganisms. Op den Camp et al. used Rhizobium strains, some of which were able to form nodules, and some of which were unable to form nodules, to prove that both Parasponia and legumes use lipochito-oligosaccharides called Nod factors to induce nodule development. They also showed that Nod factors act similarly in both symbioses via a common signaling cascade; in Parasponia, the introduction of a dominant active form of calcium/ calmodulin-dependent kinase (CCaMK), a key element of this pathway, resulted in spontaneous nodulation, as in legumes. Op den Camp et al. also provide insight into how bacterial Nod factor receptors (NFRs) evolved from receptors involved in plant-fungi partnerships. The most-studied legumes recognize rhizobia—or, more accurately, the bacterial Nod factors—via a pair of LysM-type receptor-like kinases, NFR1/ LYK3 and NFR5/NFP (6, 7). Because these NFRs are specific to bacterial symbiosis, investigators had hypothesized that they evolved either by duplication of the mycorrhiza-specific receptors, which then gained new functions, or by the recruitment of new
receptors that turned on the common signaling pathway. Op den Camp et al.’s analysis indicates that receptor duplication was not essential for plants to acquire the ability to form a symbiotic relationship with NF bacteria. Instead, the presence of a single NFR5like receptor in Parasponia, and its indispensable role in both symbioses, strongly suggests that rhizobia entered symbiotic interactions with plants through the same entrance used by mycorrhizal fungi. It also means that the molecular “keycard” that opens the door to plant partnerships for both bacteria and fungi—the bacterial Nod factor and mycorrhizal (Myc) factor—must be very similar. Indeed, Maillet et al. (8) recently described the Myc factors of AM fungi as lipochito-oligosaccharide molecules that are very similar to Nod factors. These results raise several questions: Why is the appearance of nitrogen-fixing nodules, especially rhizobial ones, restricted to a small fraction of mycorrhizal plants? How do plants discriminate between symbiotic fungi and bacteria? Was it necessary for host plants to distinguish between the microbes to create different niches? Studies of genes from related plants suggest that plant families establishing rhizobial or actinorhizal (Frankia) symbioses belong to the same large lineage. This raises the possibility that, during the evolution of flowering plants, a predisposition for symbiotic nodule formation originated only once (9). Did this predisposition occur by changing the activity of one or more component(s) of the common symbiotic pathway, for example, by enabling it to provide different outputs?
Both bacteria and mycorrhizal fungi induce changes in intracellular calcium (Ca2+-) concentrations (termed calcium spiking). However, the frequency and duration of the oscillations, as well as the speed of Ca movement, are different in the two symbioses (10). Early elements of the common SYM pathway, such as the LysM-type receptors and another receptor protein, the symbiosis receptor kinase (SYMRK), are required for the induction of the calcium spiking, which is then deciphered by CCaMK. It will be interesting to compare calcium spiking upon rhizobial and fungal inoculations in species that possess dual-functioning receptors. There is not yet enough systematic data from different plant lineages to determine exactly how molecules like SYMRK and CCaMK contributed to the evolution of a predisposition to nodule formation. The real challenge is to find out why lineages with predisposition for nodulation (for example, certain legumes) are unable to establish NF symbiosis. References
1. R. Op den Camp et al., Science 331, 90
