7 April 2006 | $10 www.sciencemag.org SCIENCE VOL 312 7 APRIL 2006 7 CONTENTS CONTENTS continued >> NEWS OF THE WEEK Premier Science University Ousts Unpopular President 32 Revised NASA Media Rules Promise Greater Openness 32 Fossil Shows an Early Fish (Almost) out of Water 33 With Friends Like CAESAR’s, Who Needs Brutus? 34 Major Fisheries Bill Introduced in House 34 New Polymer May Rev Up the Output of Fuel Cells 35 Used to Power Cars SCIENCESCOPE 35 Villagers Drafted Into China’s Model of ‘Sustainability’ 36 Old Drug, New Hope for Marfan Syndrome 36 >> Report p. 117 NEWS FOCUS Cleaning Up the Paper Trail 38 Even Retracted Papers Endure NSF Board Wades Into Swirling Debate on School Reform 45 Qatar Taps Wells of Knowledge 46 Technique From Outer Space Takes On Earth Observation 48 DEPARTMENTS 13 Science Online 15 This Week in Science 21 Editors’ Choice 26 Contact Science 29 NetWatch 31 Random Samples 51 Newsmakers 122 New Products 123 Science Careers COVER An ant of genus Ectatomma foraging at the Project Amazonas field station in Peru at sunset. An analysis of molecular data and fossils indicates that most subfamilies of extant ants originated 75 to 120 million years ago and diversified by about 60 million years ago. See page 101. Photo: Corrie S. Moreau EDITORIAL 19 FDA Centennial by Donald Kennedy 38 LETTERS The Burden of Brain Disorders M. Cruz, 53 R. Jenkins, D. Silberberg Evolution of Metazoa and Fungi D. Redecker Response A. Rokas and S. B. Carroll Evaluating Education Effectiveness B. Alberts; M. J. Feuer and J. Confrey BOOKS ET AL. Ecological Consequences of Artificial Night Lighting 56 C. Rich and T. Longcore, Eds., reviewed by D. Hill The Sauropods Evolution and Paleobiology 57 K. A. Curry Rogers and J. A. Wilson, Eds., reviewed by D. Norman POLICY FORUM “Knowledge Innovation” and the Chinese Academy 58 of Sciences R. P. Suttmeier, C. Cao, D. F. Simon PERSPECTIVES Cooperation, Punishment, and the Evolution of 60 Human Institutions J. Henrich >> Report p. 108 Reducible Complexity 61 C. Adami >> Report p. 97 New Additions to the Schrödinger Cat Family 63 N. Gisin >> Report p. 83 Chemistry in a Computer: Advancing the in Silico Dream 64 A. M. Wodtke >> Report p. 86 Mixed Messages in Early Development 65 S. M. Cohen and J. Brennecke >> Research Article p. 75 Volume 312, Issue 5770 60 & 108 www.sciencemag.org SCIENCE VOL 312 7 APRIL 2006 9 CONTENTS continued >> CONTENTS TECHNICAL COMMENT ABSTRACTS CELL SIGNALING Comment on “PDK1 Nucleates T Cell Receptor–Induced 55 Signaling Complex for NF-κB Activation” T. Gruber et al. full text at www.sciencemag.org/content/full/312/5770/55a Response to Comment on “PDK1 Nucleates T Cell Receptor–Induced Signaling Complex for NF-κB Activation” K. Lee, J H. Shim, M. S. Hayden, J S. Luehrmann, S. Ghosh full text at www.sciencemag.org/content/full/312/5770/55b REVIEW CHEMISTRY C–H Bond Functionalization in Complex 67 Organic Synthesis K. Godula and D. Sames BREVIA EVOLUTION Sexual Conflict via Maternal-Effect Genes in 73 ZW Species P. M. Miller, S. Gavrilets, W. R. Rice In species with Z and W sex chromosomes (such as birds and butterflies), a model predicts that genes with negative maternal effects on daughters accumulate on the Z chromosome. RESEARCH ARTICLES DEVELOPMENTAL BIOLOGY Zebrafish MiR-430 Promotes Deadenylation and 75 Clearance of Maternal mRNAs A. J. Giraldez et al. A small regulatory RNA promotes the degradation of the maternal messenger RNAs that are packaged into the oocyte to guide the first steps of animal development. >> Perspective p. 65 OCEANS Evolution of the Eastern Tropical Pacific 79 Through Plio-Pleistocene Glaciation K. T. Lawrence, Z. Liu, T. D. Herbert Five million years of sea surface temperature data from the eastern equatorial Pacific point to the southern ocean as the source of the observed variations over long time scales. REPORTS PHYSICS Generating Optical Schrödinger Kittens for 83 Quantum Information Processing A. Ourjoumtsev, R. Tualle-Brouri, J. Laurat, P. Grangier Subtraction of a photon from a squeezed coherent light pulse produces a small flying Schrödinger cat state (with an unbound photon), an essential element for quantum communication. >> Perspective p. 63 SCIENCE EXPRESS www.sciencexpress.org MATERIALS SCIENCE Virus-Enabled Synthesis and Assembly of Nanowires for Lithium Ion Battery Electrodes K. T. Nam et al. Viruses provide a template for growing cobalt oxide nanowires that can be used as battery electrodes, and cobalt oxide–gold hybrid wires that enhance the capacity of nanobatteries. 10.1126/science.1122716 STRUCTURAL BIOLOGY Recognition of Histone H3 Lysine-4 Methylation by the Double Tudor Domain of JMJD2A Y. Huang, J. Fang, M. T. Bedford, Y. Zhang, R M. Xu Tandem domains form an interdigitated structure that is required to recognize and demethylate methylated histone tails, a reaction important for gene regulation. 10.1126/science.1125162 APPLIED PHYSICS Quantum-Dot Spin-State Preparation with Near-Unity Fidelity M. Atatüre, J. Dreiser, A. Badolato, A. Högele, K. Karrai, A. Imamo˘glu Laser cooling can reduce the temperature of a single electron trapped in a quantum dot to 0.02 kelvin, which locks in its spin state with high fidelity. 10.1126/science.1126074 PLANT SCIENCE PIN Proteins Perform a Rate-Limiting Function in Cellular Auxin Efflux J. Petrá˘sek et al. Inserting a specific plant protein and its regulated hormone auxin into nonplant cells shows that the protein can move auxin out of cells on its own. >> Science Express Brevia by J. Wi´sniewska etal. 10.1126/science.1123542 PLANT SCIENCE BREVIA: Polar PIN Localization Directs Auxin Flow in Plants J. Wi´sniewska etal. The polarity of a specific protein controls the flow direction of the hormone auxin in plants, producing a gradient that guides development. >> Science Express Report by J. Petrá˘sek et al. 10.1126/science.1121356 NAM et al. www.sciencemag.org SCIENCE VOL 312 7 APRIL 2006 11 CONTENTS continued >> REPORTS CONTINUED CHEMISTRY Reactive and Nonreactive Scattering of H 2 from a 86 Metal Surface Is Electronically Adiabatic P. Nieto et al. The interaction of H 2 with a platinum surface can be accurately modeled by treating electronic and nuclear motion as separate, confirming a basic approximation in chemical modeling. >> Perspective p. 64 MATERIALS SCIENCE Cobalt-Base High-Temperature Alloys 90 J. Sato et al. Alloys based on cobalt maintain their strength at temperatures close to the melting point better than conventional alloys based on nickel or other metals. PLANETARY SCIENCE New Dust Belts of Uranus: One Ring, Two Ring, 92 Red Ring, Blue Ring I. de Pater, H. B. Hammel, S. G. Gibbard, M. R. Showalter The broad inner ring of Uranus is unusually blue, like Saturn’s E ring at the same relative distance, and also has an embedded moon; the outer ring is red like Saturn’s G ring. ATMOSPHERIC SCIENCE Deconvolution of the Factors Contributing to the 94 Increase in Global Hurricane Intensity C. D. Hoyos, P. A. Agudelo, P. J. Webster, J. A. Curry Higher sea surface temperature was the only statistically significant controlling variable related to the upward trend in global hurricane strength since 1970. EVOLUTION Evolution of Hormone-Receptor Complexity by 97 Molecular Exploitation J. T. Bridgham, S. M. Carroll, J. W. Thornton A steroid receptor developed its modern specificity by changes in two amino acids, followed by modification of a steroid biosynthetic enzyme to make its ligand. >> Perspective p. 61 EVOLUTION Phylogeny of the Ants: Diversification in the 101 Age of Angiosperms C. S. Moreau, C. D. Bell, R. Vila, S. B. Archibald, N. E. Pierce A phylogeny constructed with DNA sequence data from 139 of the 288 extant ant genera indicates that modern ants arose 140 to 170 million years ago but diversified much later. 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 © 2006 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): $139 ($74 allocated to subscription). Domestic institutional subscription (51 issues): $650; Foreign postage extra: Mexico, Caribbean (surface mail) $55; other countries (air assist delivery) $85. First class, airmail, student, and emeritus rates on request. 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Science is indexed in the Reader’s Guide to Periodical Literature and in several specialized indexes. 36 & 117 DEVELOPMENTAL BIOLOGY Platelet-Derived Serotonin Mediates 104 Liver Regeneration M. Lesurtel et al. In mice, regeneration of damaged liver tissue unexpectedly requires the neurotransmitter serotonin carried by circulating blood platelets. PSYCHOLOGY The Competitive Advantage of Sanctioning Institutions 108 Ö. Gürerk, B. Irlenbusch, B. Rockenbach People choosing between two artificial societies initially pick one that tolerates free-loaders, but ultimately prefer the greater rewards of the other, in which free-loaders are punished. >> Perspective p. 60 EVOLUTION Darwinian Evolution Can Follow Only Very Few 111 Mutational Paths to Fitter Proteins D. M. Weinreich, N. F. Delaney, M. A. DePristo, D. L. Hartl Of 120 ways in which an enzyme can sequentially acquire five mutations that together confer drug resistance, 102 fail because the intermediate combinations decrease fitness. IMMUNOLOGY Naïve and Memory CD 4+ T Cell Survival 114 Controlled by Clonal Abundance J. Hataye, J. J. Moon, A. Khoruts, C. Reilly, M. K. Jenkins Clonal subpopulations of immune T cells—each of which binds to a different antigen—are more stable if they contain smaller numbers of cells. MEDICINE Losartan, an AT1 Antagonist, Prevents Aortic Aneurysm 117 in a Mouse Model of Marfan Syndrome J. P. Habashi et al. A mouse study suggests that life-threatening heart defects in patients with Marfan syndrome may be preventable by losartan, a drug widely given for high blood pressure. >> News story p. 36 CONTENTS www.sciencemag.org SCIENCE VOL 312 7 APRIL 2006 13 ONLINE SCIENCENOW www.sciencenow.org DAILY NEWS COVERAGE Climate Change on the Flip Side Falling temperatures are delaying seabird arrival and egg-laying in Antarctica. Bye Bye Bifocals Electronic lens that switches focus could someday replace bifocal lenses . More Telly, More Belly Study links excess TV exposure to weight gain in preschoolers. SCIENCE’S STKE www.stke.org SIGNAL TRANSDUCTION KNOWLEDGE ENVIRONMENT PERSPECTIVE: What’s Ub Chain Linkage Got to Do With It? I. Kim and H. Rao Ubiquitin binding proteins may hold the key to substrate fate. EVENTS Plan to attend meetings, conferences, or workshops for cell signaling researchers. SCIENCE CAREERS www.sciencecareers.org CAREER RESOURCES FOR SCIENTISTS GLOBAL: Pregnancy and the Lab—Feature Index E. Pain Next Wave talks to women who have combined pregnancy and scientific work. US: Two Problems in Search of One Solution B. Benderly Can new incentives lure postdocs into the pre-college classroom? US: Alone in the Lab J. Kling Most U.S. institutions lack guidelines for pregnant lab workers, leaving women to identify hazards and solutions on their own. UK: Managing Your Career Through a Pregnancy A. Forde Next Wave investigates the experiences of U.K based expectant mothers in the lab. MISCINET: The Wild World of Doctoral Funding C. Parks Doctoral students pay for graduate school in a variety of ways. GRANTSNET: April 2006 Funding News J. Fernandez Get the latest index of research funding, scholarships, fellowships, and U.S. government opportunities. Selective protein recycling keeps cells alive. Combining pregnancy and science. SCIENCE’S SAGE KE www.sageke.org SCIENCE OF AGING KNOWLEDGE ENVIRONMENT PERSPECTIVE: SENS and the Polarization of Aging-Related Research D. A. Gray and A. Bürkle Controversy surrounds the “strategies for engineered negligible senescence” concept and conference. NEWS FOCUS: Tag-Team Recycling M. Leslie Mechanisms for protein disposal interact. Separate individual or institutional subscriptions to these products may be required for full-text access. www.sciencemag.org Interacting with the Ub-binding protein p62. Listen to the 7 April edition of the Science Podcast to hear about a potential new therapy for Marfan syndrome, insights into the roots of human cooperation, efforts by journals to “clean up the literature” in the wake of recent scientific scandals, and other stories. SCIENCEPODCAST are prone to creep and oxidation. Through the addition of solutes like aluminum or titanium, or both, a two-phase equilibrium microstructure forms that consists of γ and γ’ phases; the latter phase is largely responsible for the elevated-tem- perature strength of the material and its incredi- ble resistance to creep. Cobalt superalloys typi- cally have lower strengths than those based on nickel, which is why the latter has dominated in applications. However, Sato et al. (p. 90) now show than a ternary cobalt alloy based on the addition of aluminum and tungsten has properties that compete with those of the nickel superalloys. H 2 Leaves Pt Unexcited The Born-Oppenheimer (B-O) approximation, which treats nuclear and electronic motion inde- pendently during chemical interactions, is a cor- nerstone of computational modeling. Without it, theoretical analysis of even small molecule reac- tions in the gas phase would prove dauntingly complex. However, the ease with which electrons can be excited at metal surfaces has cast doubt on the valid- ity of the approxima- tion for simu- lating molecule- surface collisions, which play a major role in industrial catalysis. Nieto et al. (p. 86, published online 9 February; see the Perspective by Wodtke) show that data for scattering and dissociative adsorption of H 2 at a platinum surface are well predicted with a den- sity functional theory approach with the B-O cri- teria intact. The absence of Pt electronic excita- tion during the H 2 interaction suggests that Beginning with C−H Bonds Carbon-hydrogen bonds in organic molecules and biopolymers are among the least reactive chemical groups, and in chemical synthesis, a C−H bond is first activated by oxygenation or halogenation reactions that can be unselective or difficult to control. Godula and Sames (p. 67) review recent progress in transition metal cataly- sis that has allowed direct, selective formation of carbon-carbon bonds from isolated C−H bonds. These synthetic routes offer great potential for increased synthetic efficiency in preparing com- plex molecules such as drug precursors. From Quantum Kittens to Flying Cats Quantum information processing will require the reliable preparation of quantum states of matter. While these are easy to specify theoretically, experimental realization of such states has been difficult, especially the type of “flying” states that are expected to be useful for quantum com- munication purposes. By subtracting a single photon from a squeezed coherent optical pulse, Ourjoumtsev et al. (p. 83, published online 9 March; see the Perspective by Gisin) report on the production of small Schrödinger cat states, or Schrödinger kittens, and show that these kittens can be grown into cats through a suitable amplification and distillation process. Superalloying Cobalt Superalloys, which are based on iron, cobalt, or most commonly nickel, can be safely used at tem- peratures in excess of 0.7 of the absolute melting temperature, unlike conventional alloys, which accurate modeling of a wide range of heteroge- neous reactions should be feasible. Hunting Hurricane Causes A number of different factors can affect the for- mation and development of hurricanes, including sea surface temperature (SST), lower tropospheric humidity, vertical wind shear, and large-scale atmospheric circulation patterns. Which of these factors are most important and which are respon- sible for the increase in global hurricane intensity observed since 1970? Hoyos et al. (p. 94, pub- lished online 16 March) use a method based on Bayesian statistics and information theory to iso- late the causes of the trend from short-term vari- ability, for all of the major ocean basins where these storms occur. They conclude that only rising tropical SSTs have had a significant influence on the recent multi-decadal trend. No Pain, No Gain Societal behavior is complex and multifaceted. One complicated question is the conditions under which we cooperate with others for mutual gain. Experimental results using a public goods game suggest that the threat of costly punishment of free-riders by altruistically minded souls suffices to maintain groupwide compliance. Gürerk et al. (p. 108; see the Perspective by Henrich) show that if allowed to choose freely, individuals first elect to join a sanction-free game where punish- ment is not permitted. As successive rounds are played, they come to appreciate that cooperation yields greater rewards, so they switch to the sanc- tioning regime where punishment (which makes free-riding costly) is allowed and themselves become active monitors of compliance. EDITED BY STELLA HURTLEY AND PHIL SZUROMI www.sciencemag.org SCIENCE VOL 312 7 APRIL 2006 15 CREDITS (TOP TO BOTTOM): M. SHOWALTER, I. DE PATER, H. HAMMEL, AND S. GIBBARD; NIETO ET AL. Repeating Ring Properties Two new outer rings and moons were recently discovered around Uranus. Using the infrared Keck adaptive optics system, de Pater et al. (p. 92) show that the rings are blue and red like Saturn’s E and G rings. Blue ring R1 is associated with moon Mab, and Saturn’s E ring hosts the active moon Enceladus. This correspondence suggests that Mab may be the source of ring material and the blue color, because only small grains survive gravitational forces, solar radiation pressure, and electromagnetic forces. Ring R2 is as red as Saturn’s G ring and shows the same forward- and back-scattered light ratios. Both the uranian and saturnian rings are also at similar locations in planetary radii. Continued on page 17 EDITED BY STELLA HURTLEY AND PHIL SZUROMI www.sciencemag.org SCIENCE VOL 312 7 APRIL 2006 CREDIT: ANTONIO J. GIRALDEZ This Week in Science Ant Family Tree Ants are a dominant feature of terrestrial ecosystems and yet we know surprisingly little about their evolutionary history. Moreau et al. (p. 101; see the cover) sequenced DNA from multiple genes for a representative sample of ant species from around the world to reconstruct an ant family tree. A single group, the Leptanillinae, lies at the base of the tree, while all the other groups fall into two major clusters. By using fossils to calibrate the rates of DNA evolution in ants, they con- clude that present-day ants arose approximately 140 to 168 million years ago. However, ant diversification only took off ~100 million years ago, immediately after the rise of flowering plants, the angiosperms. MicroRNAs in Embryogenesis Early in animal development, the embryo switches from using maternally provided messenger RNA (mRNA) transcripts to expressing mostly zygotic genes. Dur- ing this maternal-to-zygotic transition, a large number of maternal mRNAs are somehow eliminated. Giraldez et al. (p. 75, published online 16 February; see the Perspective by Cohen and Brennecke) examined possible microRNA (miRNA)-based mechanisms and identified 203 putative tar- gets for the zebrafish miRNA miR-430, which is specifically expressed at the maternal-to-zygotic transition. Hundreds of miR-430 target mRNAs are maternally expressed during early development, and miR-430 can promote their deacetylation and decay. Thus, during the maternal-to-zygotic transition in zebrafish embryogenesis, miR-430 plays a critical role. Serotonin and Liver Regeneration The liver can regenerate after severe injury or surgery, even when up to 70% of the tissue has been removed. Lesurtel et al. (p. 104) report that in a mouse model, serotonin carried by platelets circulating in the blood plays a role in the regenerative process. Liver was found to express serotonin receptors. Mice with impaired platelet function had a reduced regenerative response, but when treated with a serotonin receptor agonist, hepatocyte proliferation was restored. Liver regeneration in mice lacking peripheral serotonin was also restored when their platelets were reloaded with serotonin. Therapeutic treatment with serotonin receptor agonists may thus be useful in tissue recovery. Limits to Evolutionary Flexibility Genetic mutations are the substrate for evolution. Genes conferring fitness can accumulate multiple mutations during a period of selection. There are, of course, many potential evolutionary trajectories for the appearance of these mutations. However, it is likely that not all trajectories are available because the fitness of individual mutations may depend on the genetic background in which they appear. Weinreich et al. (p. 111) chart the available evolutionary trajectories for five mutations in β-lactamase in Escherichia coli, which together confer a 100,000-fold increased resistance to the antibiotic cefotaxime. Only 18 of a potential 120 routes to high fitness are accessible to selection, due to pleiotropic effects of the mutations on the enzyme. Therapy for Marfan Syndrome Marfan syndrome (MFS) is a hereditary disorder characterized by systemwide defects in connec- tive tissue. People with MFS have a greatly increased risk of developing an aortic aneurysm, a bulge in the wall of the aorta that can rupture and cause life-threatening internal bleeding. Studying a mouse model of MFS, Habashi et al. (p. 117; see the news story by Travis) found that aneurysm formation is accompanied by activation of the transforming growth factor–β (TGF-β) signaling pathway in the aortic wall. Treatment of the MFS mice with losartan, a drug recently shown to antagonize TGF-β signaling in other disease states, almost completely normal- ized the aortic phenotype in the MFS mice, even after an aneurysm had formed. Losartan is already widely used to control high blood pressure, and the authors suggest that a prospective clinical trial in MFS patients is warranted. Continued from page 15 Untreated (-) and ExoSAP-IT treated (+) PCR products were analyzed by gel electrophoresis. A variety of PCR products of different lengths may be treated with ExoSAP-IT, with no sample loss. 125 bp 455 bp 1.55 kb 4.6 kb HES-1 numb NRAGE numb M- + - + - + -+ No Sample Loss with ExoSAP-IT ® For more information on ExoSAP-IT ® call 800.321.9322 or visit www.usbweb.com/exosapit At USB, we know the pursuit of discovery can be a time- consuming proposition. For PCR clean up, speeding up the process means ExoSAP-IT. ® This unique reagent can treat PCR products in a single step, enzymatically, to remove excess primers and nucleotides. And it does it without columns. Without expensive purification plates. And most importantly, without sample loss. ExoSAP-IT is perfect for working with small sample quantities by hand or high-throughput quantities with robotics. And it can be customized to meet your precise automated specs. All to give you 100% recovery, 100% of the time.With ExoSAP-IT, you’ll agree that eliminating a step is a huge step in the right direction. ExoSAP-IT: 1 less step in PCR clean up. 1 step closer to discovery. FDA Centennial THE U.S. FOOD AND DRUG ADMINISTRATION (FDA) IS TURNING 100. ITS LONGEVITY IS IN MANY ways a political miracle. Originally a chemistry unit in the Department of Agriculture, it was founded soon after Upton Sinclair’s scary portrait of turn-of-the-century meat production in The Jungle. Several metamorphoses followed over the next half-century: drugs were added; food laws were amended; and the agency moved to the Department of Health, Education and Welfare after World War II. It still bears remnants of that history: the FDA gets its appropriation from Agriculture committees in Congress and its oversight from Health and Commerce committees. What that meant, as I discovered when I became FDA commissioner in 1977, was that you go to rural conservatives for your money and to consumer-friendly urbanites for punishment or occasional praise. Somehow the FDA has managed to retain a fairly respectable image with U.S. citizens while holding some regulatory responsibility for about 25 cents out of every dollar they spend. Food safety is a serious public concern, and most people like the fact that the FDA protects them from things such as bad seafood and aflatoxin in corn. The approval process for drugs and medical devices is trickier. Industry argues that FDA regulation keeps valuable therapies away from us, whereas consumers claim that it approves too many drugs with harmful side effects. Yet most Americans think the agency is staffed by seasoned professionals who have the public interest at heart and do their jobs with professional skill. What I’d tell the few old friends left at the FDA is that you deserve better than you’re getting. Many of the current problems aren’t your fault, beginning with the alarming fact that in the past 6 years, the agency has had a confirmed commissioner for less than 20 months. That’s a clear signal that the FDA doesn’t matter much to the folks in the White House, and it won’t elevate agency morale. Acting FDA Commissioner Andrew von Eschenbach, also Director of the National Cancer Institute (NCI), has now been nominated for the top job, but the Senate may ask why he’s been allowed to develop drugs at NCI and then approve them at the FDA. After he explains that, his next challenge will be to deal with the Plan B contraceptive, which remains unavailable despite an advisory committee recommendation and is now hung up pending a long public comment period to evaluate whether it should available over the counter to women over the age of 17. Those imposed burdens accompany other issues falling into the FDA’s responsibilities. Drug safety questions arose over the use of antidepressants by adolescents. Then came Vioxx and other COX-2 inhibitors and concerns about cardiovascular side effects. In the medical devices area, problems surfaced regarding the initial approval and postmarketing safety surveillance of certain pacemakers produced by the Guidant Corporation. Finally, there is the ethical controversy about patient protection in the clinical trial for a blood substitute called PolyHeme. Northfield Laboratories seeks approval for its use in treating hemorrhagic blood loss after trauma. In the trial, one group of patients will get PolyHeme while a control group gets saline along with blood transfusions. How do you get informed consent from a trauma victim? You waive the requirement for it! The Office of Human Research Protections objected vainly to that for over 2 years, and the FDA has been dressed down by a furious Senator Charles Grassley over its prolonged unresponsiveness. The plan is that the trial sites will deliver “community briefings” to help citizens decide whether to be subjects. To opt out, you call the company, request a blue hospital-style bracelet, and then wear it to warn paramedics that you’re not part of the experiment! If this is an adequate proxy for informed consent, I am a coloratura soprano. Back in defense of the FDA, it’s not their fault that they have been chronically underfunded. Despite the recent requirement that pediatric drugs be approved and the need to monitor increasingly international drug production, appropriations have not accompanied the new mandates, and earmarks have cut the budget further. The White House seems to have forgotten who’s in charge there, and Congress is considering a new statute that lets patients who have run out of treatment options get new drugs that have not been fully tested (remember Laetrile?). It’s really too bad that we can’t find a few friends in high places for the FDA. After all, it’s their birthday; how about a little love? Or maybe money? – Donald Kennedy 10.1126/science.1127486 Donald Kennedy is Editor-in-Chief of Science. www.sciencemag.org SCIENCE VOL 312 7 APRIL 2006 19 CREDIT: PAT N. LEWIS EDITORIAL . Observation 48 DEPARTMENTS 13 Science Online 15 This Week in Science 21 Editors’ Choice 26 Contact Science 29 NetWatch 31 Random Samples 51 Newsmakers 122 New Products 123 Science Careers COVER An. a gradient that guides development. >> Science Express Report by J. Petrá˘sek et al. 10.1126 /science. 1121356 NAM et al. www.sciencemag.org SCIENCE VOL 312 7 APRIL 2006 11 CONTENTS continued. for high blood pressure. >> News story p. 36 CONTENTS www.sciencemag.org SCIENCE VOL 312 7 APRIL 2006 13 ONLINE SCIENCENOW www.sciencenow.org DAILY NEWS COVERAGE Climate Change on the Flip