[Scientific journal] Science -.. May.4.2012

CONTENTS Volume 336 Issue 6081 BOOKS ET AL. EDITORIAL Empowering Science Teachers 542 The Bioregional Imagination 519 Sheila Tobias and Anne Baffert T. Lynch et al., Eds., reviewed by C. Cokinos >> Science Podcast 543 The Republic of Nature M. Fiege, reviewed by J. R. McNeill NEWS OF THE WEEK 524 A roundup of the week’s top stories POLICY FORUM 544 Rethinking Research Ethics: NEWS & ANALYSIS The Case of Postmarketing Trials 528 Budget Cap Could Gut Next Big A. J. London et al. Fermilab Project 529 One H5N1 Paper Finally Goes to Press; PERSPECTIVES Second Greenlighted 546 Superresolution Subspace Signaling >> See all H5N1 coverage online at W. J. Lederer et al. http://scim.ag/_h5n1 >> Report p. 597 530 New Light on Revolutions That Weren’t 547 The Impact of Ionic Frustration 533 First Spinoff of African Math Institute on Electronic Order page 534 Takes Root in Senegal L. Balents >> Report p. 559 548 A Dynamic Twist in the Tail NEWS FOCUS 534 Search for Pore-fection J. A. Slavin Going Solid-State >> Report p. 567 >> Science Podcast 550 Regional Sea-Level Projection 538 American Association of Physical J. K. WIllis and J. A. Church Anthropologists Meeting 551 Modeling Ice-Sheet Flow For Early Hominins, Many Ways To Take a Walk R. B. Alley and I. Joughin How the Modern Body Shaped Up 552 Impacts of Biodiversity Loss Older Dads Have Healthier Kids Than You Think B. Cardinale >> Report p. 589 LETTERS 540 Food Price Complexities Require Nuance BREVIA G. Kripke 554 Melanesian Blond Hair Is Caused Response by an Amino Acid Change in TYRP1 J. Swinnen and P. Squicciarini E. E. Kenny et al. A Step Backward for Italy’s Meritocracy Naturally blond hair in Solomon Islanders maps to a missense mutation in a gene I. R. Marino associated with pigmentation. 541 CORRECTIONS AND CLARIFICATIONS page 543 541 TECHNICAL COMMENT ABSTRACTS CONTENTS continued >> COVER DEPARTMENTS A jumble of icebergs forms in front of the heavily crevassed 517 This Week in Science calving front of Jakobshavn Isbræ, one of the fastest outlet 520 Editors’ Choice glaciers draining the Greenland Ice Sheet. The ~5-kilometer-wide 522 Science Staff ice front rises ~80 meters out of the water and extends more 615 New Products than 600 meters underwater. Recent research shows that the 616 Science Careers speeds of Greenland glaciers are increasing. See page 576. Photo: Ian Joughin www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 513 Published by AAAS

CONTENTS 585 Function, Developmental Genetics, RESEARCH ARTICLE and Fitness Consequences of a Sexually 555 Spin-Torque Switching with the Giant Spin Hall Effect of Tantalum Antagonistic Trait L. Liu et al. A. Khila et al. Sex-specifi c modifi cations of male water Tantalum is found to generate strong spin strider antennae that are important for currents that can induce switching of mating require distal-less gene expression. ferromagnets effi ciently and reliably. 589 Impacts of Biodiversity Loss Escalate Through Time as Redundancy Fades REPORTS P. B. Reich et al. 559 Spin-Orbital Short-Range Order Long-term grassland experiments show that on a Honeycomb-Based Lattice high-diversity species combinations become S. Nakatsuji et al. more functionally diverse with time. pages 546 & 597 Magnetic measurements indicate that a >> Perspective p. 552 material remains disordered to millikelvin temperatures, thanks to its unusual lattice 593 Removal of Shelterin Reveals the Telomere End-Protection Problem structure. A. Sfeir and T. de Lange >> Perspective p. 547 “Naked” chromosome ends are mistakenly 563 Anisotropic Energy Gaps of Iron-Based targeted by six different DNA repair–related Superconductivity from Intraband systems in the cell. Quasiparticle Interference in LiFeAs 2+ M. P. Allan et al. 597 Elementary Ca Signals Through The energy needed to break up electron pairs Endothelial TRPV4 Channels Regulate in a pnictide superconductor depends on Vascular Function position on the Fermi surface. S. K. Sonkusare et al. Imaging reveals single-channel openings of 567 Magnetic Reconnection in the Near cation channels at the heart of endothelial Venusian Magnetotail cell–mediated blood pressure control. T. L. Zhang et al. >> Perspective p. 546 Venus Express observations show that magnetic reconnection occurs in the 601 Multidimensional Optimality of magnetotail of an unmagnetized planet. Microbial Metabolism >> Perspective p. 548 R. Schuetz et al. A key design principle of bacterial metabolic 570 Ancient Impact and Aqueous Processes networks is optimal performance, but not at at Endeavour Crater, Mars the expense of adaptability. S. W. Squyres et al. Analysis of data from the Mars Exploration 604 Radio-Wave Heating of Iron Oxide Rover Opportunity provides evidence for Nanoparticles Can Regulate Plasma past water fl ow near an ancient crater. Glucose in Mice page 570 >> Science Podcast S. A. Stanley et al. Gene expression in mice can be activated CREDITS: (MIDDLE) NASA/JPL/CORNELL/ASU; (BOTTOM) ANDRES GARELLI, ALISSON GONTIJO, MARIA DOMINGUEZ 576 21st-Century Evolution of Greenland remotely and noninvasively by radio-wave Outlet Glacier Velocities heating of nanoparticles. T. Moon et al. >> Science Podcast A decade-long compilation of velocity data for Greenland’s outlet glaciers shows complex 608 Substrate-Controlled Succession of Marine spatial and temporal variability. Bacterioplankton Populations Induced by 579 Imaginal Discs Secrete Insulin-Like Peptide a Phytoplankton Bloom 8 to Mediate Plasticity of Growth and H. Teeling et al. Seasonal diatom growth in the North Sea Maturation results in a temporal succession of A. Garelli et al. metabolically specialized bacteria. An insulin/relaxin-like peptide coordinates fi nal organ size in response to fl y injury and 612 Don’t Look Back in Anger! tumors. Responsiveness to Missed Chances in 582 Secreted Peptide Dilp8 Coordinates Successful and Nonsuccessful Aging S. Brassen et al. Drosophila Tissue Growth with Emotionally healthy older adults show Developmental Timing a reduced responsiveness to regret when J. Colombani et al. performing a sequential decision task. In fruit fl ies, growing tissues send signals to the endocrine system to coordinate growth pages 579 & 582 and metamorphosis. CONTENTS continued >> www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 515 Published by AAAS

CONTENTS SCIENCEONLINE COMMENTARY: Learning from Hackers— SCIENCESIGNALING SCIENCEXPRESS www.sciencexpress.org www.sciencesignaling.org Open-Source Clinical Trials Interglacial Hydroclimate in the Tropical West The Signal Transduction Knowledge Environment A. G. Dunn et al. The open-source software movement can serve Pacifi c Through the Late Pleistocene 1 May issue: http://scim.ag/ss050112 as a model for a similar initiative in the clinical A. N. Meckler et al. RESEARCH ARTICLE: TACE Activation by trial community. Precipitation in Borneo, largely invariant during MAPK-Mediated Regulation of Cell Surface the last four interglacial periods, decreased during Dimerization and TIMP3 Association glacial terminations. SCIENCECAREERS P. Xu et al. www.sciencecareers.org/career_magazine 10.1126/science.1218340 A metalloproteinase implicated in infl ammation and Free Career Resources for Scientists B Cell Receptor Signal Transduction in the GC cancer is inactive as a dimer and active as a monomer. Is Short-Circuited by High Phosphatase Activity RESEARCH ARTICLE: Genomic Survey of Taken for Granted: Two Reports and the Worlds A. M. Khalil et al. Premetazoans Shows Deep Conservation of They Made Restricted B cell signaling in the areas responsible Cytoplasmic Tyrosine Kinases and Multiple B. L. Benderly for immune memory cell production promotes Radiations of Receptor Tyrosine Kinases Why do clinical medicine and academic science— affi nity maturation. both expert labor markets—offer such different H. Suga et al. 10.1126/science.1213368 career outlooks? PODCAST http://scim.ag/TFG_Flexner Awake Hippocampal Sharp-Wave Ripples H. Suga and A. M. VanHook Support Spatial Memory A genomic survey suggests that cytoplasmic tyrosine Translational Volcanology S. P. Jadhav et al. kinases diversifi ed before the establishment of R. Berkowitz The neuronal “replay” of past experience may allow multicellular organisms. Volcanologists have a range of opportunities animals to retrieve specifi c memories and use them to help predict eruptions and limit damage to guide behavior. PERSPECTIVE: Phosphoinositides as Regulators to people and places. 10.1126/science.1217230 of Protein-Chromatin Interactions http://scim.ag/TransVolcanology K. Viiri et al. MORC Family ATPases Required for Phosphoinositides can promote or reduce the binding Volcanologists for Public Safety Heterochromatin Condensation and of proteins with roles in transcription to chromatin. R. Berkowitz Three volcanologists tell Science Careers how Gene Silencing their work enhances public health and safety G. Moissiard et al. SCIENCETRANSLATIONAL MEDICINE for communities at risk from volcanoes. A conserved family of adenosine triphosphatases www.sciencetranslationalmedicine.org http://scim.ag/SafetyVolcanologists predicted to catalyze alterations in chromosome Integrating Medicine and Science superstructure is required for gene silencing. 10.1126/science.1221472 2 May issue: http://scim.ag/stm050212 SCIENCEPODCAST RESEARCH ARTICLE: Temporal Dynamics www.sciencemag.org/multimedia/podcast of the Human Vaginal Microbiota Free Weekly Show TECHNICALCOMMENTS P. Gajer et al. On the 4 May Science Podcast: remotely controlled Comment on “Global Resilience of Tropical gene expression, evidence for water on ancient Mars, Forest and Savanna to Critical Transitions” FOCUS: Complexities of the Uniquely nanopore sequencing advances, and more. Z. Ratajczak and J. B. Nippert Human Vagina Full text at www.sciencemag.org/cgi/content/ S. S. Witkin and W. J. Ledger full/336/6081/541-c The vaginal microbiome is dynamic, varying over SCIENCEINSIDER time in composition and function with implications news.sciencemag.org/scienceinsider Response to Comment on “Global Resilience for women’s health. Science Policy News and Analysis of Tropical Forest and Savanna to Critical Transitions” RESEARCH ARTICLE: Decade-Long Safety E. H. Van Nes et al. and Function of Retroviral-Modifi ed Full text at www.sciencemag.org/cgi/content/ Chimeric Antigen Receptor T Cells full/336/6081/541-d J. Scholler et al. Adoptively transferred chimeric antigen receptor T cells have stable stem cell–like persistence for SCIENCE (ISSN 0036-8075) is published weekly on Friday, except the last SCIENCENOW week in December, by the American Association for the Advancement of at least a decade and more than 500 years of www.sciencenow.org Science, 1200 New York Avenue, NW, Washington, DC 20005. Periodicals Mail patient safety. postage (publication No. 484460) paid at Washington, DC, and additional mailing Highlights From Our Daily News Coverage offi ces. Copyright © 2012 by the American Association for the Advancement of RESEARCH ARTICLE: Vascular COX-2 Modulates Science. The title SCIENCE is a registered trademark of the AAAS. Domestic individual Natural Selection Is Still With Us membership and subscription (51 issues): $149 ($74 allocated to subscription). Church records confi rm that 18th and 19th century Blood Pressure and Thrombosis in Mice Domestic institutional subscription (51 issues): $990; Foreign postage extra: Mexico, Caribbean (surface mail) $55; other countries (air assist delivery) $85. First class, people still followed Darwin’s rules. Y. Yu et al. airmail, student, and emeritus rates on request. Canadian rates with GST available http://scim.ag/Natural-Selection Deletion of vascular COX-2 predisposes mice to upon request, GST #1254 88122. Publications Mail Agreement Number 1069624. thrombosis and hypertension. Printed in the U.S.A. Effective Ad? Ask Your Brain Change of address: Allow 4 weeks, giving old and new addresses and 8-digit account Neural activity predicts which antismoking ad RESEARCH ARTICLE: Human Mesenchymal 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 will elicit the greatest public response. Stem Cell–Derived Matrices for Enhanced includes surface postage; bulk rates on request. Authorization to photocopy http://scim.ag/Neural_Activity Osteoregeneration 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 S. Zeitouni et al. registered with the Copyright Clearance Center (CCC) Transactional Reporting Service, Mapping China’s Ancient Name Game provided that $30.00 per article is paid directly to CCC, 222 Rosewood Drive, Danvers, Geographic patterns of the country’s surnames Stem cell–generated matrices provide optimal MA 01923. The identifi cation code for Science is 0036-8075. Science is indexed in the match historic migrations. environment for bone regeneration in mice. Reader’s Guide to Periodical Literature and in several specialized indexes. http://scim.ag/Geographic_Patterns 4 MAY 2012 VOL 336 SCIENCE www.sciencemag.org 516 Published by AAAS

EDITED BY STELLA HURTLEY bounds that have been proposed on the basis of a few rapidly accelerating locations, implying that sea level rise over the next century may be less than the 2 meters that have been suggested. Magnetic Reconnection Magnetic reconnection (MR) has been observed in the magnetospheres of planets with an intrinsic magnetic fi eld, such as Earth, Mercury, Jupiter, and Saturn. MR is a universal plasma process that occurs in regions of strong magnetic shear and converts magnetic energy into kinetic energy. On Earth, MR is responsible for magnetic storms and auroral events. Using data from the European Space Agency Venus Express spacecraft, Zhang et al. (p. 567, published online 5 April; see the Perspective by Slavin) present surprising evidence for MR in the magnetosphere of Venus, on May 3, 2012 Hooking Up in Water Striders which is a nonmagnetized body. The male water strider Rheumatobates rileyi has an extensively modifi ed antenna that is used Going to Ground for forced copulations with females. Khila et al. (p. 585) describe several microscopic antenna attributes that make the antenna fi t perfectly with the female head when the male grasps the Frustrated systems, in which the geometry of the female. The features depend upon the expression of the gene distal-less (dll) during antenna crystal lattice stands in the way of achieving an development. Reducing the expression of dll compromised male grasping traits, while female energetic minimum on all lattice sites simultane- antennae were unaffected. ously, have the potential to remain disordered www.sciencemag.org down to the lowest temperatures. Numerous experimental efforts to fi nd a material with a Giant Spin Hall certain points. What happens in the pnictide truly fl uctuating ground state have failed because superconductors is still a subject of debate, not ordering often sets in at a fi nite temperature One of the primary challenges in the fi eld of least because there appear to be differences owing to symmetry breaking. Nakatsuji et al. spin-electronics, which exploits the electron’s spin between the different pnictide families. Allan (p. 559; see the Perspective by Balents) identify rather than its charge, is to create strong currents et al. (p. 563) used scanning tunneling spec- the compound Ba 3 CuSb 2 O 9 as a promising can- Downloaded from of electrons with polarized spins. One way to do troscopy to study the compound LiFeAs. The gap didate for this state; the Cu-Sb dipoles reside this is to use a ferromagnet as a polarizer, a prin- was mapped on three of the fi ve bands on which on a hexagonal structure, forming ciple used in magnetic tunnel junctions; however, the Fermi surface resides and was found to be fl uctuating spin singlets. Multiple these devices suffer from reliability problems. An anisotropic in momentum space. lines of evidence suggest that alternative is the spin Hall effect, where running the material does not order a charge current through a material generates a Not So Fast down to the millikelvin spin current in the transverse direction, but the temperature range, remaining effi ciency of this process tends to be small. Liu Recent observations of some of Greenland’s out- magnetically isotropic. et al. (p. 555) now show that the spin Hall ef- let glaciers have shown large and rapid increas- Martian Veins fect in Tantalum in its high-resistance β phase es in the speeds at which their ice has streamed CREDITS (TOP TO BOTTOM): ABDERRAHMAN KHILA; NAKATSUJI ET AL. energy dissipation in the ferromagnet. These prop- great public concern. In order to provide a more Exploration rover Opportunity reached the generates spin currents strong enough to induce to the sea. Simple projections of ice loss and sea After more than 7 years of traveling across the switching of the magnetization of an adjacent level rise, based only on these increases, result Meridiani Planum region of Mars, the Mars ferromagnet; at the same time, Ta does not cause in alarmingly high values and correspondingly erties allowed effi cient and reliable operation of a Endeavour Crater, a 22-km-impact crater made of comprehensive and detailed picture of this type materials older than those previously investigated of ice sheet mass loss, Moon et al. (p. 576; see prototype three-terminal device. the cover) compiled a decade-long record of ice by the rover. Squyres et al. (p. 570) present a stream velocity measurements for nearly all of comprehensive analysis of the rim of this crater. Uneven Gap Greenland’s major outlet glaciers. The pattern Localized zinc enrichments that provide evidence Electron pairs that are responsible for the for hydrothermal alteration and gypsum-rich of fl ow variability around the ice sheet was both phenomenon of superconductivity can only be spatially and temporally complex, with clear dif- veins that were precipitated from liquid water at broken by investing a fi nite amount of energy, ferences between marine- and land-terminating a relatively low temperature provide a compelling case for aqueous alteration processes in this area types, as well as between regions. Furthermore, called the energy gap. The size of the gap may at ancient times. the integrated velocity of all of the outlet glaciers depend on the position on the Fermi surface; measured was considerably less than the upper in cuprates, the gap completely disappears at www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 Continued on page 518 517 Published by AAAS

Submityour This Week in Science research Continued from page 517 Small But Perfectly Formed The imaginal discs of Drosophila represent defi ned larval tissues that give rise to the subsequent adult appendages. These tissues regenerate in response to damage. When the imaginal discs are injured or show tumor growth, they signal to the rest of the larval animal to slow down growth and delay morphogenesis. Garelli et al. (p. 579) and Colombani et al. (p. 582) now show that an insulin-like peptide, termed Dilp8, is secreted into the hemolymph (insect “blood”) and participates Science in the communication between growing organs and the endocrine system to adjust the growth program and maturation time. This collaboration ensures that adults attain the normal size and Signaling maintain appropriate proportions and symmetry. The Leading Journal for Cell Signaling Not Broken Until Repaired Humans, and indeed most eukaryotes, have linear chromo- A weekly, peer-reviewed somes with two DNA ends, known as telomeres. Cells have research journal committed evolved sophisticated systems to repair broken chromosomes, to publishing key research of which specifi cally recognize DNA ends as damage. Telomeres broad relevance in the field are protected from these repair systems, which would otherwise of cell signal transduction. wreak havoc in the cell, causing genome aberrations that, ironically, can lead to cancer. To under- on May 3, 2012 • Biochemistry stand all the possible threats to telomeres Sfeir and de Lange (p. 593) mutated components of the • Cell Biology mouse shelterin protein complex, which forms a protective cap over the telomere ends, rendering • Computational Biology telomeres completely devoid of the complex (and packaged only in nucleosomal chromatin). These “naked” telomeres were vulnerable to six DNA repair–related pathways: classical and alternative • Developmental Biology nonhomologous end joining; ATM and ATR signaling pathways; homology directed recombination; • Immunology and unmitigated DNA resection. • Microbiology • Molecular Biology Blood Pressure Gauge www.sciencemag.org • Neuroscience • Pharmacology Endothelial cells line blood vessels and, by interacting with smooth muscle, can help to control blood • Physiology and Medicine fl ow. Sonkusare et al. (p. 597; see the Perspective by Lederer et al.) describe how signaling in endo- • Plant Biology thelial cells controls contraction of surrounding smooth muscle cells, which provides an important mecha- • Systems Biology nism for control of blood pressure. A calcium-sensitive fl uorescent protein was expressed in endothelial cells of mouse arteries to image small changes in calcium concentration that appear to represent opening of single TRPV4 ion channels and consequent infl ux of calcium into the cell. Clustering of the channels Downloaded from Submit your research at: allowed cooperative activation of a handful of channels, which appeared to produce a suffi cient calcium www.sciencesignaling.org/ signal to open another set of calcium-sensitive potassium channels. The resulting depolarization of the about/help/research.dtl endothelial cells then passes an electrical connection to smooth muscle cells through gap junctions. Gene Expression by Remote Control Techniques that allow remote, noninvasive activation of specifi c genes in specifi c tissues could one day be applied to regulate expression of therapeutic proteins in a clinical setting. In a proof-of- concept study, Stanley et al. (p. 604) showed that heating of iron oxide nanoparticles by radiowaves can remotely activate insulin gene expression in cultured cells and in a mouse model. Heating of membrane-targeted nanoparticles induced opening of a temperature-sensitive membrane channel in the cells and triggered calcium entry. The intracellular calcium signal in turn stimulated expression of an engineered insulin gene, leading to the synthesis and release of insulin. In experiments with mice bearing tumors that expressed the engineered insulin gene, exposure to radiowaves promoted secretion of insulin from the tumors and lowered blood glucose levels in the animals. No Regrets As people grow older, the possibility to think about “missed chances” increases. When we are young, thinking about missed opportunities may help to optimize future behavior. However, the older we get the probability of “second chances” decreases and thus the benefi t of ruminating upon them disappears. Brassen et al. (p. 612, published online 19 April) studied the behavioral and neural response to missed CREDIT: SFEIR AND DE LANGE chances in young adults, the healthy elderly subjects and late-life depressed volunteers. Compared with young and depressed subjects, the healthy elderly subjects showed a reduced sensitivity to missed oppor- tunities. The fi ndings suggest a potential mechanism for preserved emotional health in older age. ScienceSignaling.org 4 MAY 2012 VOL 336 SCIENCE www.sciencemag.org Published by AAAS

EDITORIAL Empowering Science Teachers Sheila Tobias writes AT ANY ONE TIME, THERE ARE THOUSANDS OF U.S. GRADUATE STUDENTS WITH STRONG SCIENCE about math and science expertise and an interest in education who would be more than qualifi ed to stem the critical education. E-mail: shortage of secondary chemistry, physics, earth sciences, and biology teachers, but who will sheilax@sheilatobias. most likely never set foot in a high-school (precollege) classroom. Instead, nearly all of them com. are choosing to pursue research rather than to teach the science that fascinates them to young people. To change this situation, and the widespread lack of understanding and appreciation for science in the United States, it is critical to pinpoint the major source of the problem. A look at teaching in Finland is a useful place to start. Finland attracts and retains the best and the brightest to precollege teaching careers. There are 10 applicants for every teaching post in that country, corresponding to a 1-in-10 acceptance rate into teacher training programs.* In 1994, Finland established a Teacher Researcher Network to connect college education research faculty and precollege teachers, and to involve classroom teachers directly in education research. Finnish precollege teachers thereby on May 3, 2012 become equipped to formulate changes in curricula. This not only empowers classroom teachers but also appropriately treats them as edu- cation experts, further raising their social status. Unfortunately, the United States is headed in the opposite direction. Too many precollege teachers work in a “command-and-control” envi- ronment, managed by those who lack any real understanding of how to Anne Baffert is a improve the system. Yet the teachers who know how to make improve- chemistry teacher at ments are rarely empowered to do so. It is not surprising that an annual www.sciencemag.org Salpointe Catholic High poll of U.S. teachers found that only 44% were “very satisfi ed” with School, Tucson, AZ. their jobs in 2011, the lowest level recorded in the survey’s 28-year his- E-mail: azchemmom@ tory.‡ Science teachers rarely become superintendents in the nation’s yahoo.com. 14,000 school districts. In one state, only 6 of 189 district superinten- dents had ever taught science in the classroom.§ And yet science teach- ers have expertise that is important for wise system governance. We recommend that school districts select outstanding teachers to serve on a Science Teacher Council. This council should Downloaded from CREDITS: (TOP LEFT) CODY CONRAD; (BOTTOM LEFT) STUDIO Z IN TUCSON ARIZONA; (RIGHT) ISTOCKPHOTO.COM set criteria for hiring new precollege science teachers, assessing and promoting such teachers, achieving state science standards, and properly assessing student achievement. Science teachers’ professionalism also rests on their continual active involvement in science through structured collaborations with scientists. There are successful model programs in the United States (but far too few), such as the Partners in Science Program Online of the M.J. Murdoch Charitable Trust, California State University’s Sci- sciencemag.org ence Teacher and Researcher Program, and Columbia University’s Sum- mer Research Program for Science Teachers, where teachers partner Podcast interview (http://scim.ag/ with researchers in academic or industrial settings. Teachers often coau- ed_6081) with author thor papers with their research colleagues and present fi ndings at scien- Sheila Tobias. tifi c meetings. And as local science faculty and researchers in industry become aware of the circumstances in which precollege science teachers work, many become active supporters of the teachers in their community. This support is crucial when rewards for teaching and broader school funding issues are at stake. It will take time to reverse the diminishing professional status of precollege science educa- tors in the United States, but surveys of the current generation of young people new to the work- force reveal that they are looking for challenges, problems to solve, and most importantly, a pro- fession in which they can make an impact early on in their careers. Education would certainly fi t the bill if the United States, like Finland, treated teachers as real professionals. – Sheila Tobias and Anne Baffert 10.1126/science.1223116 *J. Burris, Science 335, 146 (2012). https://www.jyu.fi /edu/laitokset/okl/tutkivaopettaja/teacherresearcher. ‡www.metlife.com/ about/corporate-profi le/citizenship/metlife-foundation/metlife-survey-of-the-american-teacher.html. §S. Tobias, A. Baffert, Sci- ence Teaching as a Profession: Why It Isn’t. How It Could Be. (National Science Teachers Association Press, Arlington, VA, 2010). www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 519 Published by AAAS

EDITORS’CHOICE EDITED BY KRISTEN MUELLER AND JAKE YESTON ASTROPHYSICS Planetary Confi nement Located 25 light-years away, the star Fomalhaut is surrounded by a away from their birth region, show that the disk is both narrower and spectacular eccentric disk of dust and debris somewhat similar to the thinner than previously thought and has very sharp inner and outer Kuiper Belt in our solar system. Boley et al. traced the parent body edges. N-body simulations suggest that the disk is being confi ned by population for this debris disk using observations of millimeter-sized two planets with masses around that of Earth, one orbiting between the grains obtained with the Atacama Large Millimeter Array, an observa- star and the disk and the other outside the disk. This is analogous to the tory under construction on the Chajnantor plateau, 5000 m altitude confi nement of Saturn’s F ring by the moons Pandora and Prometheus on May 3, 2012 in northern Chile. The 350-GHz images, which trace grains that do not and that of Uranus’s ε ring by Cordelia and Ophelia. — MJC respond to stellar radiation and hence manifest orbits that do not move Astrophys. J. 750, L21 (2012). C MOLECUL AR BIOL OGY PrP may do this through subcellular traffi cking, combination of iron and copper additives to the Prions: A New Part to Play as it seems to increase the interaction between zeolites offered >90% methanol selectivity at MVBs and AGO-rich structures, such ~10% methane conversion. Although hydrogen MicroRNAs (miRNAs) are small as P or GW bodies, thence promoting peroxide is currently an expensive oxidant to www.sciencemag.org noncoding RNAs that, when part shuttling of AGO between the RISC- apply to commodity-scale methanol synthesis, of a miRNA-induced silencing loading complex and the miRNA- the selectivity principles uncovered in the study complex (miRISC), repress the induced silencing complex. — GR may enhance selective hydrocarbon oxidation expression of fully or partially Nat. Struct. Mol. Biol. 19, 10.1038/ processes more broadly. — JSY complementary mRNAs. Argonaute nsmb.2273 (2012). Angew. Chem. Int. Ed. 51, 10.1002/ (Ago) proteins bind miRNAs and CHEMISTRY anie.201108706 (2012). form the heart of the silencing Making Methanol Downloaded from machinery. Intriguingly, plasma GENETICS membrane–associated forms of If chemistry worked like Tinkertoys, Isoform Identifi cation C the human prion protein (PrP ), it would be rather straightforward which is associated with neurode- to make methanol from methane: The differential reconnection of transcribed generative diseases in humans, You’d simply pull off a hydrogen atom exons, termed alternative splicing, has the po- also interact with components of and stick on an OH group. Alas, it’s tential to result in one gene encoding multiple the miRNA pathway. not that simple, and most scalable protein isoforms. The degree to which alterna- Gibbings et al. show that a implementations of this reaction tend tively spliced transcripts are translated into func- C transmembrane form of PrP ex- toward overoxidation; the primary tional proteins, however, is not well understood. poses an AGO anchor sequence in industrial route circuitously oxidizes Ezkurdia et al. used data across multiple mass the cytoplasm and that this repeat the carbon to CO before reducing it spectrometry experiments to investigate the de- CREDITS (TOP TO BOTTOM): ALMA (ESO/NAOJ/NRAO); GIBBINGS ET AL., NAT. STRUCT. MOL. BIOL.19, 10.1038/NSMB.2273 (2012) binds AGO1 and AGO2. These back down to the alcohol. Hammond gree to which genes with alternative transcripts PrPC-AGO complexes are found et al. explored one means of taming gave rise to protein isoforms. Comparison of the on vesicles in cells that resemble the direct oxidation, so as to stop at predicted proteins from the gene and genetic multivesicular bodies (MVBs). the desired product. Specifi cally, they variant database of ENCODE (GENCODE) to the During miRNA maturation, AGO sought to optimize zeolite-catalyzed Swiss-Prot database allowed for the identifi ca- protein bound to miRNA must be oxidation of methane by hydrogen tion of 150 human genes that encoded at least transferred from the RISC-loading peroxide. They fi rst discovered that one protein isoform and 13 with three or more, complex (RLC) to the miRISC silencing complex. trace iron is essential to the catalytic activity and with the caveat that identifi cation was biased C PrP binds components of both the RLC and the went on to map out a preliminary diiron-centered toward those most likely to be detected. Het- miRISC but seems to do so in distinct cellular mechanism using a combination of spectroscopic erogeneous nuclear ribonucleoproteins, which C locations. PrP promotes the association of probes and density functional theory simulations. are involved in the regulation of alternative AGO with the miRISC and/or the stability of this Next, the authors observed that OH radicals splicing, showed enrichment in alternative iso- C complex. Indeed, PrP is required for effective underlie overoxidation processes and that the forms. Furthermore, the majority of differences miRNA silencing of a number of target mRNAs. introduction of copper ions stems this activity. A detected among all predicted isoforms differed 4 MAY 2012 VOL 336 SCIENCE www.sciencemag.org 520 Published by AAAS

EDITORS’CHOICE in sequence by the insertion/deletion of a single eggs had disrupted development and were less amino acid. Investigations into the Drosophila likely to prevent proper development of the and mouse proteomes revealed similar patterns. fl y larvae. Furthermore, the fl ies seem to know Together, these results suggest that alternative what’s good for them. When given a choice of splicing is under selective constraint. — LMZ food with or without alcohol, fl ies that were Mol. Biol. Evol. 29, 10.1093/ infected were more likely than control fl ies to molbev/mss100 (2012). seek out and consume the ethanol-spiked food. Whether humans might derive benefi ts from BIOMEDICINE such a defense against parasites remains to be Aiming Even Lower determined. — LBR Curr. Biol. 22, 488 (2012). The use of statins to lower plasma levels of LDL (low-density lipoprotein) cholesterol can reduce ECOL OGY * the risk of cardiovascular disease by an estimat- Fluctuating Forests $14,626.79 ed 30 to 40%. Yet some experts have argued that lowering LDL cholesterol to levels below In the current era of rapidly changing climate, current recommendations—by coadministering the past can provide useful lessons about the in savings. drugs that act by a complementary mechanism, responses of ecological communities to climate for example—may confer even more health fl uctuations. Increased or repeated drought is Onemoredatapoint on benefi ts than statins alone. PCSK9 (proprotein a plausible scenario in some currently humid why it’s worth investing on May 3, 2012 convertase subtilisin/kexin type 9) is an ap- environments under climate change, although pealing new drug target because where and when this inamembershipat it keeps plasma cholesterol levels might occur is still membercentral.aaas.org. high by promoting degradation hard to predict. The Thereyou canenjoy videos, of the receptor on liver cells that kinds of ecological removes cholesterol from the blood. change that might be webinars, blogs and Interestingly, a small percentage of expected, however, are downloads while you humans carry mutations in PCSK9 illustrated in a study calculate the potential www.sciencemag.org that reduce its activity and these in- of historical ecological dividuals have a lower risk of heart change in the humid members-only savings disease, suggesting that thera- western Great Lakes from all our Apple hardware peutic inhibition of PCSK9 will be area of North America safe. Stein et al. conducted small in response to the Me- and software discounts phase-1 trials of a human PCSK9 dieval Climate Anomaly combined. monoclonal antibody (REGN727) (MCA). The MCA began given to healthy volunteers and approximately 1050 Downloaded from to individuals with familial and years ago, lasted for nonfamilial hypercholesterolemia. 450 years, and was Injection of REGN727 induced no characterized by a serious adverse effects in these warmer climate in north short-duration trials, and in all temperate regions and groups the antibody signifi cantly a series of droughts in reduced LDL cholesterol levels as the Great Lakes region. compared with placebo. — PAK Booth et al. used pollen N. Engl. J. Med. 366, 1108 (2012). analyses and subfossil testate amoebae (which ENT OMOL OGY are sensitive indicators A Toast to Fruitfl y Health of water table depth in peatlands) to trace the A propensity for rotting fruit puts the fruit population changes in drought-sensitive beech *The combined member discount when purchasing fl y Drosophila melanogaster in contact with trees during this period. They show that beech one of each item at the Apple Store. fermented material that can contain substantial declined in abundance sharply wherever drought amounts of alcohol. Milan et al. tested whether and increased moisture fl uctuations occurred, with associated effects on fi re incidence and alcohol consumption by fl y larvae might actually CREDIT: ISTOCKPHOTO.COM attack and lay their eggs in the fruit fl y larvae. other components of the ecological community. serve to protect them from nasty wasps that These fi ndings illustrate how currently moist regions could experience rapid ecological change Indeed, the wasps appeared to be more sensitive to the toxic effects of alcohol than were the fl ies. as a result of increased climatic fl uctuations in a The wasps laid fewer eggs on fl ies that were warming world. — AMS consuming ethanol and when they did, those Ecology 93, 219 (2012). membercentral.aaas.org www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 Published by AAAS

NEWS OF THE WEEK AROUND THE WORLD 2 1 4 3 Sado Island, Japan 1 Washington, D.C. 2 Back From the Brink Research Agencies Hear About on May 3, 2012 Japan went gaga last week when three The Possibility of More crested ibis chicks pecked through their Research increases weren’t supposed to shells in a nest on Sado Island and became be an option for next year because the U.S. the fi rst of their species born in the wild in government was tightening its belt. But the country in 36 years. the Obama Administration is facing the Abrolhos Shelf, Brazil 3 Scientists were equally thrilled. “We’ve un expected—and not entirely unpleasant— Massive Coral Beds learned a lot about captive breeding, prepar- job of deciding how to respond to pre- ing birds for release, and how to monitor liminary steps by Congress to give some Charted off Brazil www.sciencemag.org them,” says Satoshi Yamagishi, an ornitholo- research programs more money in 2013 The Abrolhos Shelf of Brazil boasts the gist at Niigata University in Japan who heads than the White House had requested. world’s largest expanse of rhodoliths, a a Ministry of the Environment task force A House of Representatives spending spherical type of coralline algae, according panel last week voted to add to a survey published last month in PLoS $76 million to the president’s ONE. The beds cover a total area the size request for fusion research of El Salvador and produce an estimated at the Department of Energy, 25 million metric tons of calcium carbonate reversing cuts for domestic pro- a year, but face several threats. The slow- Downloaded from grams and coming closer to the growing rhodoliths are made of magnesium- promised U.S. contribution to rich calcite, which is particularly vulnerable the ITER fusion reactor being to ocean acidifi cation. In addition, river sedi- built in France. Within NASA, ments from deforestation may be harming the panel had previously added the beds. Southern portions are also dredged $150 million to the Adminis- as a source of lime for use as an additive to tration’s request for continued agricultural soils. work on a Mars sample return on reestablishing the birds in the wild. He mission, and $115 million for two pro- expects their experience to benefi t breeding- grams supporting planetary missions. NOTED and-release programs for other species. While Congress is months away from >Alvin Ailey, Duke Ellington, and yes, Nipponia nippon once fl ew over much of a fi nal decision on spending for next year, Dr. Seuss—oh, the places you’ve gone! Japan and northeastern Asia, but overhunting these initial moves raise a new issue for the The International Astronomical Union (for their feathers) and habitat loss devastated White House: Is more money for research (IAU) has approved a proposal by the sci- CREDITS (TOP TO BOTTOM): © RODRIGO L. DE MOURA; MINISTRY OF THE ENVIRONMENT, JAPAN their numbers. In 1981, the environment min- always a good thing? “Yes, as a general ence team of NASA’s MESSENGER mis- istry captured Japan’s last fi ve wild birds for matter, increases [in research budgets] are sion to assign new names to 23 impact breeding, but the last of those birds died in good,” presidential science adviser John craters on Mercury—including Ailey, 2003. Efforts continued with birds donated Holdren said after a speech last week at Ellington, and Seuss. by China, where a small wild population the AAAS annual policy forum. “But, of Those will join 53 previously named survives. Since 2008, Japan has released 78 course, under overall caps, whether par- craters since the MESSENGER spacecraft birds; 45 are known to remain in the wild. ticular increases are good depends on what fi rst fl ew by Mercury in January 2008— Before claiming success, “we would like to they come out of. That’s why we need to all honoring deceased artists, musicians, see a second generation born in the wild and study the House proposals before offering and authors. a stable population,” Yamagishi says. an opinion.” http://scim.ag/budget_2013 4 MAY 2012 VOL 336 SCIENCE www.sciencemag.org 524 Published by AAAS

NEWS Researchers have known about the rho- dolith beds since the 1970s, but they had never been mapped in detail. So marine bio- logist Rodrigo Moura of Rio de Janeiro Fed- eral University, along with colleagues from Brazil and Conservation International, spent 2 years surveying the beds with remotely operated vehicles, sonar, and SCUBA div- ers. The tennis ball–size rhodoliths cover 20,902 square kilometers. “It was very surprising to fi nd beds these big,” Moura says, adding that the rhodolith beds need to be protected in part because they may be important migration routes for species that live on coral reefs. Oshika Peninsula, Japan 4 A New Deep-Sea Drilling Record on May 3, 2012 The deep-sea drilling vessel Chikyu, oper- ated by the Japan Agency for Marine-Earth Psyched About STEM Science and Technology, has set the record for the deepest undersea research borehole, Sumo-wrestling LEGO robots (pictured), jumbo squid dissections, and virtual helicop- extending to a total depth of 7740 meters ter rides were just a few of the attractions at the second USA Science & Engineering below sea level (856 meters of which are Festival held in Washington, D.C., last weekend. The festival included more than 3000 exhibits, as well as appearances by science celebrities such as Bill Nye the Science Guy, neuroscientist and TV actor Mayim Bialik (of Blossom and The Big Bang Theory), and www.sciencemag.org the MythBusters team. Designed to get kids interested in science, technology, math, and engineering (STEM), the festival’s Finale Expo was packed with thousands of young attendees eager to build robots, test out fi ghter jet simulators, and play 3D videogames. It seems to Downloaded from be working, if the opinion of attendee 8-year-old Jacob Morey is any indication. “I like talking to the experts because I get responses and I can ask questions,” Morey says. “I think science is the greatest invention since the Internet!” NEWSMAKERS THEY SAID IT Steven Koonin is preparing for a home- coming of sorts: The Brooklyn-born physi- “ You have the right to prepare CREDITS (TOP TO BOTTOM): MEGHNA SACHDEV/SCIENCE; KYODO/LANDOV; FNAL.GOV cist has been named director of New York for interesting work and University’s new Center for Urban Science economic independence.” and Progress (CUSP), which will study how to make cities work better. Koonin, —Shorma Bianca Bailey, president once provost of the of the Howard University Chapter of California Institute of Engineers Without Borders, at a 24 April Technology in Pasa- White House panel offering advice to below the sea fl oor) in waters off the coast dena, stepped down last young women entering science, technol- of Oshika Peninsula, the agency announced fall as under secretary ogy, engineering, or mathematics fi elds. 27 April. The previous record was set in for science at the U.S. 1978, when the U.S. vessel Glomar Chal- Department of Energy. lenger drilled to a total of 7049.5 meters Last year, New York Koonin 60, thinks that CUSP, supported by a consor- below sea level in the Mariana Trench— City Mayor Michael tium of universities and high-tech compa- although only about 15.5 meters of that was Bloomberg invited proposals to raise the nies, can also make a big splash. below the sea fl oor. city’s academic applied science and engi- Chikyu has been probing into the fault neering IQ. The winner, and recipient of Q: How will CUSP differ from other research zone around the Japan Trench, where the $100 million in city funding, was a team led programs on sustainable cities? 11 March 2011 Tohoku earthquake and tsu- by Cornell University and the Technion– We have the city and its agencies as a deeply nami were generated. Israel Institute of Technology. But Koonin, engaged partner. That means work- >> www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 525 Published by AAAS

NEWS OF THE WEEK NEWS OF THE WEEK zation rates in the developing world, and served as executive director of The Carter Center in Atlanta. More recently, as a senior fellow at the Bill & Melinda Gates Foundation, he has helped shape the orga- nization’s global health efforts. Foege is among 13 people recognized by President Barack Obama for their contribu- tions to the United States or to the world who will receive the medal at the White House later this spring. FINDINGS Wind Farms Warm the Night Large wind farms can boost nighttime tem- peratures, according to a study that ana- lyzed satellite images of a 10,000-square- kilometer area of west-central Texas. More on May 3, 2012 than 95% of the turbines in the area were Part Real, Part Fantasy: Disney’s Chimpanzee erected between 2003 and 2011. And, dur- ing those 9 years, the areas where the wind The Disney fi lm Chimpanzee tells the story of Oscar, an orphan chimp in Ivory farms were located warmed up on summer Coast’s Taï Forest that was adopted by one of his troop’s males. The movie tells a nights by, on average, 0.65°C more than scientifi cally accurate story—in fact, “the main plot was decided by the chimps,” nearby areas without wind turbines. says primatologist Christophe Boesch of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. Boesch and his colleagues described the real-life www.sciencemag.org adoption of another young orphan chimp named Victor by an older male in his troop in a 2010 PLoS ONE paper. (The movie blends Victor’s story with Oscar’s.) However, the story is also fi ctionalized in that it was pieced together from 3 years’ worth of footage fi lmed not only in Taï but also among chimpanzee troops in Ngogo, Uganda—and, to Boesch’s disappointment, the movie might not directly benefi t its stars. Disney is donating some proceeds to the Jane Goodall Institute’s sanctuary for orphaned chimps in the Republic of Congo. But Boesch says he’d Downloaded from hoped proceeds would also go to the Wild Chimpanzee Foundation, which works to protect the chimpanzees in Taï, and the Ngogo Chimpanzee Project, which supports conservation in Uganda. Both populations are severely threatened, he says. “They need support to have them survive.” >>NEWSMAKERS Epidemiologist Among Medal ing with the people who actually run the sub- ways and write the building codes. We have Of Freedom Winners been promised the data and the opportunity William Foege, a leader of the global At night, the air at ground level is cooler to use the city as a living laboratory. campaign that wiped out smallpox, has than the air a few dozen meters up; turbu- been named a recipient of the Presidential lence generated by individual wind turbines Q: What will industry contribute? Medal of Freedom, the brings warm air downward to heat the sur- I know academics, and I love the free- nation’s highest civil- face, the team reported online 29 April in CREDITS (TOP TO BOTTOM): © DISNEY; WIKIMEDIA COMMONS; PHOTO BY EMORY PHOTO/VIDEO wheeling, curiosity-driven atmosphere of ian honor. Nature Climate Change. The warming rates a university. But CUSP is meant to have an Foege, 76, is a phy- measured in this study—the fi rst to show impact. That comes through demonstra- sician and epidemi- temperature increases based on satellite tion projects and deployment, and industry ologist who helped data rather than computer simulations, the knows how to do that. spearhead the massive researchers note—are high simply because Foege immunization effort the region has experienced a rapid growth Q: Any downsides to returning to New York? that eradicated small- in wind farm development. The warming I’m long enough out of California that I pox in the 1970s. He directed the Centers effect for any given wind farm will likely don’t miss the sunshine. No, I can only for Disease Control and Prevention from level off if no more turbines are added, the think of upsides. 1977 to 1983, worked to boost immuni- researchers report. 4 MAY 2012 VOL 336 SCIENCE www.sciencemag.org 526 Published by AAAS

NEWS BY THE NUMBERS Random Sample 12% Percentage of clinical drug trials that are pediatric trials, although children bear nearly 60% of the disease burden for high- priority conditions such as malaria and HIV/AIDS, according to a study presented 28 April at the Pediatric Academic Societies’ annual meet- ing in Boston. 7327 Number of family names among a population of 1.28 billion Chinese recorded in a study appearing in an up coming issue of the American on May 3, 2012 Journal of Physical Anthropology. By contrast, a study of 18 million Understanding the Lords of Time people in the United States found The putative end of the Maya Long Count calendar on 21 December 2012 has unleashed a cot- tage industry of doomsaying. Books, articles, TV shows, and movies portray myriad cataclysmic nearly 900,000 last names. events that the Maya are said to have foreseen. This can be a frustrating exercise for scientists; Maya scholars tend to think the end of the calendar is merely the end of a cycle—hardly the www.sciencemag.org Plants More Sensitive to Global end of the world or of time itself. But Simon Martin, a noted Maya epigrapher and associate curator at the University of Pennsylvania’s Museum of Archaeology and Anthropology, sees an Warming Than Tests Suggest upside to the doom and gloom. This, he says, is a “once-in-a-lifetime opportunity, when the Ecologists trying to anticipate the effects world is focused on the ancient Maya,” to inform people about the true role time played in the of climate change often set up “warming” Maya’s lives. experiments in which they artifi cially heat Martin is the co-curator of Maya 2012: Lords of Time, an exhibit opening 5 May at the up an environment and monitor plants’ museum. Despite the forecasts of doom, experts note there is only one reference to the por- reactions. But those results are falling tentous date in all of the Maya glyphs; that reference was found at Tortuguero, a small site in short of reality, says Elizabeth Wolkovich, southern Mexico. And although the 2012 date itself is discernible, the inscription that follows Downloaded from an ecologist at the University of British is diffi cult to decipher because of its poor condition. Columbia, Vancouver. “Even in damaged form, (what comes after the date) doesn’t appear to refer to 2012,” The timing of plants leafi ng out or said Martin. The syntax and structure of this glyph suggest the damaged script would refer to a blooming—part of a fi eld called phenol- much earlier event. There’s also a reference to a much later date, 4772 C.E., in an inscription at ogy—is a sensitive indicator of how eco- Palenque, which indicates the Maya thought life would continue beyond 2012. CREDITS (TOP TO BOTTOM): ALEXANDRA FLEISCHMAN FOR PENN MUSEUM; DAREN EIRI systems respond to climate change. Aside from using warming experiments, ecologists track phenology through long-term moni- toring of plant populations. Wolkovich and ies and in 14 long-term data sets. The team problems to scientists who use warming her colleagues compared phenology data on determined how much sooner each species experiment data in modeling studies. “If the 1643 different species in 36 warming stud- fl owered or leafed out per degree of tempera- warming experiments are not providing an ture rise. Plants in accurate prediction, then you can’t predict the longterm studies how ecosystem services will respond,” says leafed out four times Johanna Schmitt, a plant ecologist at Brown sooner and fl owered University, who was not involved with the eight times sooner work. http://scim.ag/PlantsWarm than the warming experiments pre- dicted, Wolkovich and her colleagues Join us Thursday, 10 May, at 3 p.m. EDT reported this week for a live chat on how conservatives and in Nature. liberals view science differently. That discrep- http://scim.ag/science-live ancy could present www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 527 Published by AAAS

NEWS Researchers have known about the rho- dolith beds since the 1970s, but they had never been mapped in detail. So marine bio- logist Rodrigo Moura of Rio de Janeiro Fed- eral University, along with colleagues from Brazil and Conservation International, spent 2 years surveying the beds with remotely operated vehicles, sonar, and SCUBA div- ers. The tennis ball–size rhodoliths cover 20,902 square kilometers. “It was very surprising to fi nd beds these big,” Moura says, adding that the rhodolith beds need to be protected in part because they may be important migration routes for species that live on coral reefs. Oshika Peninsula, Japan 4 A New Deep-Sea Drilling Record on May 3, 2012 The deep-sea drilling vessel Chikyu, oper- ated by the Japan Agency for Marine-Earth Psyched About STEM Science and Technology, has set the record for the deepest undersea research borehole, Sumo-wrestling LEGO robots (pictured), jumbo squid dissections, and virtual helicop- extending to a total depth of 7740 meters ter rides were just a few of the attractions at the second USA Science & Engineering below sea level (856 meters of which are Festival held in Washington, D.C., last weekend. The festival included more than 3000 exhibits, as well as appearances by science celebrities such as Bill Nye the Science Guy, neuroscientist and TV actor Mayim Bialik (of Blossom and The Big Bang Theory), and www.sciencemag.org the MythBusters team. Designed to get kids interested in science, technology, math, and engineering (STEM), the festival’s Finale Expo was packed with thousands of young attendees eager to build robots, test out fi ghter jet simulators, and play 3D videogames. It seems to Downloaded from be working, if the opinion of attendee 8-year-old Jacob Morey is any indication. “I like talking to the experts because I get responses and I can ask questions,” Morey says. “I think science is the greatest invention since the Internet!” NEWSMAKERS THEY SAID IT Steven Koonin is preparing for a home- coming of sorts: The Brooklyn-born physi- “ You have the right to prepare CREDITS (TOP TO BOTTOM): MEGHNA SACHDEV/SCIENCE; KYODO/LANDOV; FNAL.GOV cist has been named director of New York for interesting work and University’s new Center for Urban Science economic independence.” and Progress (CUSP), which will study how to make cities work better. Koonin, —Shorma Bianca Bailey, president once provost of the of the Howard University Chapter of California Institute of Engineers Without Borders, at a 24 April Technology in Pasa- White House panel offering advice to below the sea fl oor) in waters off the coast dena, stepped down last young women entering science, technol- of Oshika Peninsula, the agency announced fall as under secretary ogy, engineering, or mathematics fi elds. 27 April. The previous record was set in for science at the U.S. 1978, when the U.S. vessel Glomar Chal- Department of Energy. lenger drilled to a total of 7049.5 meters Last year, New York Koonin 60, thinks that CUSP, supported by a consor- below sea level in the Mariana Trench— City Mayor Michael tium of universities and high-tech compa- although only about 15.5 meters of that was Bloomberg invited proposals to raise the nies, can also make a big splash. below the sea fl oor. city’s academic applied science and engi- Chikyu has been probing into the fault neering IQ. The winner, and recipient of Q: How will CUSP differ from other research zone around the Japan Trench, where the $100 million in city funding, was a team led programs on sustainable cities? 11 March 2011 Tohoku earthquake and tsu- by Cornell University and the Technion– We have the city and its agencies as a deeply nami were generated. Israel Institute of Technology. But Koonin, engaged partner. That means work- >> www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 525 Published by AAAS

NEWS OF THE WEEK NEWS OF THE WEEK zation rates in the developing world, and served as executive director of The Carter Center in Atlanta. More recently, as a senior fellow at the Bill & Melinda Gates Foundation, he has helped shape the orga- nization’s global health efforts. Foege is among 13 people recognized by President Barack Obama for their contribu- tions to the United States or to the world who will receive the medal at the White House later this spring. FINDINGS Wind Farms Warm the Night Large wind farms can boost nighttime tem- peratures, according to a study that ana- lyzed satellite images of a 10,000-square- kilometer area of west-central Texas. More on May 3, 2012 than 95% of the turbines in the area were Part Real, Part Fantasy: Disney’s Chimpanzee erected between 2003 and 2011. And, dur- ing those 9 years, the areas where the wind The Disney fi lm Chimpanzee tells the story of Oscar, an orphan chimp in Ivory farms were located warmed up on summer Coast’s Taï Forest that was adopted by one of his troop’s males. The movie tells a nights by, on average, 0.65°C more than scientifi cally accurate story—in fact, “the main plot was decided by the chimps,” nearby areas without wind turbines. says primatologist Christophe Boesch of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. Boesch and his colleagues described the real-life www.sciencemag.org adoption of another young orphan chimp named Victor by an older male in his troop in a 2010 PLoS ONE paper. (The movie blends Victor’s story with Oscar’s.) However, the story is also fi ctionalized in that it was pieced together from 3 years’ worth of footage fi lmed not only in Taï but also among chimpanzee troops in Ngogo, Uganda—and, to Boesch’s disappointment, the movie might not directly benefi t its stars. Disney is donating some proceeds to the Jane Goodall Institute’s sanctuary for orphaned chimps in the Republic of Congo. But Boesch says he’d Downloaded from hoped proceeds would also go to the Wild Chimpanzee Foundation, which works to protect the chimpanzees in Taï, and the Ngogo Chimpanzee Project, which supports conservation in Uganda. Both populations are severely threatened, he says. “They need support to have them survive.” >>NEWSMAKERS Epidemiologist Among Medal ing with the people who actually run the sub- ways and write the building codes. We have Of Freedom Winners been promised the data and the opportunity William Foege, a leader of the global At night, the air at ground level is cooler to use the city as a living laboratory. campaign that wiped out smallpox, has than the air a few dozen meters up; turbu- been named a recipient of the Presidential lence generated by individual wind turbines Q: What will industry contribute? Medal of Freedom, the brings warm air downward to heat the sur- I know academics, and I love the free- nation’s highest civil- face, the team reported online 29 April in CREDITS (TOP TO BOTTOM): © DISNEY; WIKIMEDIA COMMONS; PHOTO BY EMORY PHOTO/VIDEO wheeling, curiosity-driven atmosphere of ian honor. Nature Climate Change. The warming rates a university. But CUSP is meant to have an Foege, 76, is a phy- measured in this study—the fi rst to show impact. That comes through demonstra- sician and epidemi- temperature increases based on satellite tion projects and deployment, and industry ologist who helped data rather than computer simulations, the knows how to do that. spearhead the massive researchers note—are high simply because Foege immunization effort the region has experienced a rapid growth Q: Any downsides to returning to New York? that eradicated small- in wind farm development. The warming I’m long enough out of California that I pox in the 1970s. He directed the Centers effect for any given wind farm will likely don’t miss the sunshine. No, I can only for Disease Control and Prevention from level off if no more turbines are added, the think of upsides. 1977 to 1983, worked to boost immuni- researchers report. 4 MAY 2012 VOL 336 SCIENCE www.sciencemag.org 526 Published by AAAS

NEWS OF THE WEEK NEWS OF THE WEEK zation rates in the developing world, and served as executive director of The Carter Center in Atlanta. More recently, as a senior fellow at the Bill & Melinda Gates Foundation, he has helped shape the orga- nization’s global health efforts. Foege is among 13 people recognized by President Barack Obama for their contribu- tions to the United States or to the world who will receive the medal at the White House later this spring. FINDINGS Wind Farms Warm the Night Large wind farms can boost nighttime tem- peratures, according to a study that ana- lyzed satellite images of a 10,000-square- kilometer area of west-central Texas. More on May 3, 2012 than 95% of the turbines in the area were Part Real, Part Fantasy: Disney’s Chimpanzee erected between 2003 and 2011. And, dur- ing those 9 years, the areas where the wind The Disney fi lm Chimpanzee tells the story of Oscar, an orphan chimp in Ivory farms were located warmed up on summer Coast’s Taï Forest that was adopted by one of his troop’s males. The movie tells a nights by, on average, 0.65°C more than scientifi cally accurate story—in fact, “the main plot was decided by the chimps,” nearby areas without wind turbines. says primatologist Christophe Boesch of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. Boesch and his colleagues described the real-life www.sciencemag.org adoption of another young orphan chimp named Victor by an older male in his troop in a 2010 PLoS ONE paper. (The movie blends Victor’s story with Oscar’s.) However, the story is also fi ctionalized in that it was pieced together from 3 years’ worth of footage fi lmed not only in Taï but also among chimpanzee troops in Ngogo, Uganda—and, to Boesch’s disappointment, the movie might not directly benefi t its stars. Disney is donating some proceeds to the Jane Goodall Institute’s sanctuary for orphaned chimps in the Republic of Congo. But Boesch says he’d Downloaded from hoped proceeds would also go to the Wild Chimpanzee Foundation, which works to protect the chimpanzees in Taï, and the Ngogo Chimpanzee Project, which supports conservation in Uganda. Both populations are severely threatened, he says. “They need support to have them survive.” >>NEWSMAKERS Epidemiologist Among Medal ing with the people who actually run the sub- ways and write the building codes. We have Of Freedom Winners been promised the data and the opportunity William Foege, a leader of the global At night, the air at ground level is cooler to use the city as a living laboratory. campaign that wiped out smallpox, has than the air a few dozen meters up; turbu- been named a recipient of the Presidential lence generated by individual wind turbines Q: What will industry contribute? Medal of Freedom, the brings warm air downward to heat the sur- I know academics, and I love the free- nation’s highest civil- face, the team reported online 29 April in CREDITS (TOP TO BOTTOM): © DISNEY; WIKIMEDIA COMMONS; PHOTO BY EMORY PHOTO/VIDEO wheeling, curiosity-driven atmosphere of ian honor. Nature Climate Change. The warming rates a university. But CUSP is meant to have an Foege, 76, is a phy- measured in this study—the fi rst to show impact. That comes through demonstra- sician and epidemi- temperature increases based on satellite tion projects and deployment, and industry ologist who helped data rather than computer simulations, the knows how to do that. spearhead the massive researchers note—are high simply because Foege immunization effort the region has experienced a rapid growth Q: Any downsides to returning to New York? that eradicated small- in wind farm development. The warming I’m long enough out of California that I pox in the 1970s. He directed the Centers effect for any given wind farm will likely don’t miss the sunshine. No, I can only for Disease Control and Prevention from level off if no more turbines are added, the think of upsides. 1977 to 1983, worked to boost immuni- researchers report. 4 MAY 2012 VOL 336 SCIENCE www.sciencemag.org 526 Published by AAAS

NEWS BY THE NUMBERS Random Sample 12% Percentage of clinical drug trials that are pediatric trials, although children bear nearly 60% of the disease burden for high- priority conditions such as malaria and HIV/AIDS, according to a study presented 28 April at the Pediatric Academic Societies’ annual meet- ing in Boston. 7327 Number of family names among a population of 1.28 billion Chinese recorded in a study appearing in an up coming issue of the American on May 3, 2012 Journal of Physical Anthropology. By contrast, a study of 18 million Understanding the Lords of Time people in the United States found The putative end of the Maya Long Count calendar on 21 December 2012 has unleashed a cot- tage industry of doomsaying. Books, articles, TV shows, and movies portray myriad cataclysmic nearly 900,000 last names. events that the Maya are said to have foreseen. This can be a frustrating exercise for scientists; Maya scholars tend to think the end of the calendar is merely the end of a cycle—hardly the www.sciencemag.org Plants More Sensitive to Global end of the world or of time itself. But Simon Martin, a noted Maya epigrapher and associate curator at the University of Pennsylvania’s Museum of Archaeology and Anthropology, sees an Warming Than Tests Suggest upside to the doom and gloom. This, he says, is a “once-in-a-lifetime opportunity, when the Ecologists trying to anticipate the effects world is focused on the ancient Maya,” to inform people about the true role time played in the of climate change often set up “warming” Maya’s lives. experiments in which they artifi cially heat Martin is the co-curator of Maya 2012: Lords of Time, an exhibit opening 5 May at the up an environment and monitor plants’ museum. Despite the forecasts of doom, experts note there is only one reference to the por- reactions. But those results are falling tentous date in all of the Maya glyphs; that reference was found at Tortuguero, a small site in short of reality, says Elizabeth Wolkovich, southern Mexico. And although the 2012 date itself is discernible, the inscription that follows Downloaded from an ecologist at the University of British is diffi cult to decipher because of its poor condition. Columbia, Vancouver. “Even in damaged form, (what comes after the date) doesn’t appear to refer to 2012,” The timing of plants leafi ng out or said Martin. The syntax and structure of this glyph suggest the damaged script would refer to a blooming—part of a fi eld called phenol- much earlier event. There’s also a reference to a much later date, 4772 C.E., in an inscription at ogy—is a sensitive indicator of how eco- Palenque, which indicates the Maya thought life would continue beyond 2012. CREDITS (TOP TO BOTTOM): ALEXANDRA FLEISCHMAN FOR PENN MUSEUM; DAREN EIRI systems respond to climate change. Aside from using warming experiments, ecologists track phenology through long-term moni- toring of plant populations. Wolkovich and ies and in 14 long-term data sets. The team problems to scientists who use warming her colleagues compared phenology data on determined how much sooner each species experiment data in modeling studies. “If the 1643 different species in 36 warming stud- fl owered or leafed out per degree of tempera- warming experiments are not providing an ture rise. Plants in accurate prediction, then you can’t predict the longterm studies how ecosystem services will respond,” says leafed out four times Johanna Schmitt, a plant ecologist at Brown sooner and fl owered University, who was not involved with the eight times sooner work. http://scim.ag/PlantsWarm than the warming experiments pre- dicted, Wolkovich and her colleagues Join us Thursday, 10 May, at 3 p.m. EDT reported this week for a live chat on how conservatives and in Nature. liberals view science differently. That discrep- http://scim.ag/science-live ancy could present www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 527 Published by AAAS

NEWS & ANALYSIS PA RTICLE PHYSICS But facing stiff competition from DOE’s other priorities, DOE’s high-energy physics Budget Cap Could Gut program cannot afford such a grand exper- iment. The program’s annual budget, now $792 million, is unlikely to grow anytime Next Big Fermilab Project soon. That means DOE can spend roughly $150 million a year on LBNE, DOE project manager Eli Rosenberg said at the workshop. BATAVIA, ILLINOIS—How do you chop down metry in the way neutrinos and antineutri- However, LBNE’s projected 10-year con- the budget of a major experiment by two- nos oscillate that could help explain how struction budget would have peaked at $280 thirds and still leave something that’s worth the universe generated so much more mat- million per year. In addition, Rosenberg said, doing? That’s the riddle physicists here at ter than antimatter. DOE has capped the cost of the first 5 to Fermi National Accelerator Laboratory The original plan for the LBNE detector 6 years of the project at $600 million to (Fermilab) are struggling to solve as they would have been a multipurpose laboratory in $700 million, including infl ation. chart the lab’s long-term future. itself. Located 2250 meters below the surface But whittling down LBNE to that level Last month, offi cials with the Department and shielded from interference from cosmic won’t be easy. The project consists of several of Energy (DOE) told Fermilab that its pro- rays, it would perform a type of astronomy by pieces, each costing hundreds of millions of posed $1.9 billion fl agship experiment for detecting bursts of neutrinos from supernova dollars. The huge detector alone is projected the next decade costs too much to construct explosions. It would also search for signs to cost $399 million. Excavation of a cav- on May 3, 2012 all at once. They asked scientists for a plan that, on a time scale far longer than the age of ern to house the detector and other construc- to build it piecemeal (Science, 30 March, the universe, protons fall apart. tion at Homestake is priced at $449 million. p. 1553). But, as became clear at a workshop A new beamline at Fermilab to generate * last week at the lab, the affordable options Carving Up LBNE the neutrinos would run $400 million, and for the fi rst stage of the Long-Baseline Neu- WHAT’S AFFORDABLE a smaller “near” detector at Fermilab that trino Experiment (LBNE) would severely would compare the neutrinos leaving the lab • 10-kilotonne detector on surface $750 million limit its scientifi c potential and could leave it at Homestake Mine in South to those reaching Homestake is pegged at only marginally more capable than an exist- Dakota and new beamline $100 million. Those prices do not account www.sciencemag.org ing Fermilab experiment. • 17-kilotonne detector on surface $500 million– for any infl ationary growth. “We want to pick no more than a couple at Soudan mine or Ash River $600 million To make the fi rst phase affordable, phys- of options [for the experiment’s fi rst stage] in in Minnesota icists would have to give up key features of which the physics is good enough to justify LBNE. The fi rst casualty would be plans to the cost,” says Young-Kee Kim, deputy direc- ORIGINAL WHAT'S TOO EXPENSIVE build the detector underground, as excava- PLAN OR NOT WORTH DOING tor at Fermilab and chair of the LBNE recon- tion for even a 5000-tonne detector, one of figuration steering committee. But some • 34-kilotonne • 5-kilotonne underground the reduced sizes now under consideration, detector detector at Homestake Downloaded from physicists worry that the affordable options would cost $266 million. But some phys- underground and new beamline won’t be exciting enough scientifi cally to get at Homestake, $1.0 billion–$1.2 billion icists say a surface detector makes little funded. “When my colleagues go to some new beamline • 17-kilotonne detector sense because cosmic rays would swamp and small underground at Soudan mine congressional committee and say that they any signals from supernovae or proton detector $900 million–$1.1 billion want to spend $600 million to measure one at Fermilab • 17-kilotonne or 34 kilotonne decay. “Why would you cut out half your parameter, they’re going to get killed,” says $1.9 billion detector alone at Homestake program by putting your detector on the John Learned, a LBNE team member from $700 million–$1.2 billion surface?” asked Alexander Friedland, a • New beamline and small the University of Hawaii, Manoa. detector at Fermilab theorist at Los Alamos National Laboratory If built as proposed, LBNE would be a $600 million–$700 million in New Mexico. world-beater, say physicists at Fermilab, Physicists also say a much smaller detec- the sole remaining U.S. particle physics tor would be less likely to nail down the lab. LBNE would deploy a state-of-the-art complete picture of neutrino oscillations. detector fi lled with 34,000 tonnes of frigid A delicate bal- In particular, physicists know that two types ance. Fermilab’s liquid argon deep in the abandoned Home- Young-Kee Kim of neutrinos have nearly the same mass, stake Mine in Lead, South Dakota. That leads a panel but they don’t know if there are two lighter detector would study nearly massless par- that’s revising types and one heavier type, or the other way ticles called neutrinos fi red through Earth plans for the around. A 34,000-tonne LNBE detector from Fermilab, 1300 kilometers away. Such Long-Baseline would easily resolve that “mass hierarchy.” TABLE SOURCE: JAMES STRAIT/FERMILAB; PHOTO: CINDY ARNOLD particles come in three types—electron neu- Neutrino Most importantly, if neutrinos and anti- trinos, muon neutrinos, and tau neutrinos— Experiment. neutrinos oscillate differently, then LBNE that morph or “oscillate” into one another could make a defi nitive measurement of that as they zip along. LBNE would search for a effect, provided it’s not very small. phenomenon called CP violation, an asym- If scaled to 5000 tonnes, however, the detector would be able to resolve the mass * LBNE Reconfi guration Workshop, 25–26 April. hierarchy only somewhat better than Fer- 4 MAY 2012 VOL 336 SCIENCE www.sciencemag.org 528 Published by AAAS

NEWS milab’s NOυA experiment. That project, Physicists may even have to give up on physicists feeling rushed. “I spent 3 months to begin next year, will study neutrinos Homestake entirely. Some researchers want choosing my last car; we’re going to make a fi red 810 kilometers to a lower-tech surface to reuse Fermilab’s existing beamline, which decision to go to Soudan in 3 weeks?” asked detector in Ash River, Minnesota. (Fermi- is more powerful than neutrino beams in Robert Svoboda of the University of Cali- lab also runs an experiment called MINOS Europe or Japan, and build the LBNE detec- fornia, Davis, who is co-spokesperson for that uses the same beamline to fi re neutri- tor at Soudan or Ash River. But others argue the LBNE collaboration. nos 735 kilometers to a detector in the Sou- that the distance to either site in Minnesota But nothing will be gained by waiting, dan mine in Minnesota.) At 10,000 tonnes, is too short to ever fulfi ll LBNE’s complete says Fermilab Director Pier Oddone. “If you LBNE could resolve the mass hierarchy and scientifi c program. want to take a year to make a decision when detect evidence of CP violation—although The two most likely options appear to everything is known, you’re only adding a it couldn’t make a definite discovery. be a 17,000-tonne detector on the surface year to an already long process,” he says. And “I would feel that anything less than at Soudan or—if DOE is willing to spend the clock is ticking. LBNE’s recon fi guration 10,000 tonnes wouldn’t be compelling,” just a bit more—a 10,000-tonne detector steering committee has promised to deliver a says Fermilab’s Regina Rameika. But small on the surface at Homestake, said Charles report to DOE on 1 July, in time for agency doesn’t mean cheap. The 5000-tonne detec- Baltay, a steering committee member from offi cials to digest it before submitting their tor would cost $132 million; the 10,000- Yale University. But his summary of the 2014 budget request to the White House. tonne model would run roughly $170 million. day-and-a-half-long workshop left some –ADRIAN CHO INFLUENZA on May 3, 2012 One H5N1 Paper Finally Goes to Press; Second Greenlighted They have been called the most famous papers initial recommendation, the Dutch gov- that were never published. But now, one of two ernment insisted that Ron Fouchier of controversial studies that shows how to make Erasmus MC in Rotterdam apply for H5N1 avian infl uenza more transmissible in an export license before submitting his www.sciencemag.org mammals is up on Nature’s Web site for all the revised manuscript (Science, 20 April, world to scrutinize—including, some worry, p. 285). He called the decision “pure censor- would-be bioterrorists who might use the ship,” but on 24 April he fi led the applica- information to set off a pandemic. The other tion, still disputing his obligation to do so and paper received a crucial go-ahead from the stressing that he did not want to set a prece- Dutch government last week and will likely dent. Fouchier sent the paper to Science soon be published by Science soon. after the Dutch government issued the permit Downloaded from In December, the U.S. National Science on 27 April. Advisory Board for Biosecurity (NSABB) Early this week, the paper was still under recommended that the two studies—both of review and being edited. Both Fouchier and which use ferrets, a popular model for human Kawaoka had hoped the two papers, whose infl uenza—not be published in full. But after fates had been closely linked for 6 months, an expert panel convened by the World Health would appear simultaneously, which Science Organization (WHO) disagreed with the Executive Editor Monica Bradford says would decision, NSABB reviewed revised versions have been “ideal” as well. “I regret that both of the manuscripts and changed its position papers will not appear online together, but our (Science, 6 April, p. 19). That cleared the way priority must be to serve our authors and read- for Nature on 2 May to publish the fi rst of the ers,” Nature Editor-in-Chief Philip Campbell two experiments, led by Yoshihiro Kawaoka said in a statement. “You can’t blame them,” of the University of Wisconsin, Madison, and Fouchier says. the University of Tokyo. First to fi nish. Yoshihiro Kawaoka (above) had his Despite the massive debate about these Kawaoka’s unusually long, 11-page article paper published this week. two papers, the Kawaoka study adds only a describes how his group stitched a mutated piece to a puzzle that his and other groups version of the hemagglutinin protein of the lets. Although the researchers don’t know have been putting together for years. Infl uenza bird flu virus—the H5—onto the H1N1 whether these mutations would “support sus- researchers have long attempted to understand CREDIT: M. ENSERINK/SCIENCE in 2009. The team explains that introducing virologists worry mightily about this scenario. strain spread readily in humans. Kawaoka’s tained human-to-human transmission,” many the mutations and mechanisms that make a virus that caused a relatively mild pandemic into H5 a mere four mutations, which are deli- To date, H5N1 has not spread easily between study is an “important additional step along humans, but in 355 of 602 confi rmed cases, cately balanced with each other, allowed this the way,” says Malik Peiris, a fl u researcher at the University of Hong Kong, who co-wrote the patient has died. hybrid virus to bind more strongly to mam- malian cells and copy itself at high enough an article in Nature about the Kawaoka paper. The second paper has been held up in an Infl uenza infection begins when hemag- levels to readily transmit via respiratory drop- extra bureaucratic tangle. After NSABB’s www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 529 Published by AAAS

NEWS milab’s NOυA experiment. That project, Physicists may even have to give up on physicists feeling rushed. “I spent 3 months to begin next year, will study neutrinos Homestake entirely. Some researchers want choosing my last car; we’re going to make a fi red 810 kilometers to a lower-tech surface to reuse Fermilab’s existing beamline, which decision to go to Soudan in 3 weeks?” asked detector in Ash River, Minnesota. (Fermi- is more powerful than neutrino beams in Robert Svoboda of the University of Cali- lab also runs an experiment called MINOS Europe or Japan, and build the LBNE detec- fornia, Davis, who is co-spokesperson for that uses the same beamline to fi re neutri- tor at Soudan or Ash River. But others argue the LBNE collaboration. nos 735 kilometers to a detector in the Sou- that the distance to either site in Minnesota But nothing will be gained by waiting, dan mine in Minnesota.) At 10,000 tonnes, is too short to ever fulfi ll LBNE’s complete says Fermilab Director Pier Oddone. “If you LBNE could resolve the mass hierarchy and scientifi c program. want to take a year to make a decision when detect evidence of CP violation—although The two most likely options appear to everything is known, you’re only adding a it couldn’t make a definite discovery. be a 17,000-tonne detector on the surface year to an already long process,” he says. And “I would feel that anything less than at Soudan or—if DOE is willing to spend the clock is ticking. LBNE’s recon fi guration 10,000 tonnes wouldn’t be compelling,” just a bit more—a 10,000-tonne detector steering committee has promised to deliver a says Fermilab’s Regina Rameika. But small on the surface at Homestake, said Charles report to DOE on 1 July, in time for agency doesn’t mean cheap. The 5000-tonne detec- Baltay, a steering committee member from offi cials to digest it before submitting their tor would cost $132 million; the 10,000- Yale University. But his summary of the 2014 budget request to the White House. tonne model would run roughly $170 million. day-and-a-half-long workshop left some –ADRIAN CHO INFLUENZA on May 3, 2012 One H5N1 Paper Finally Goes to Press; Second Greenlighted They have been called the most famous papers initial recommendation, the Dutch gov- that were never published. But now, one of two ernment insisted that Ron Fouchier of controversial studies that shows how to make Erasmus MC in Rotterdam apply for H5N1 avian infl uenza more transmissible in an export license before submitting his www.sciencemag.org mammals is up on Nature’s Web site for all the revised manuscript (Science, 20 April, world to scrutinize—including, some worry, p. 285). He called the decision “pure censor- would-be bioterrorists who might use the ship,” but on 24 April he fi led the applica- information to set off a pandemic. The other tion, still disputing his obligation to do so and paper received a crucial go-ahead from the stressing that he did not want to set a prece- Dutch government last week and will likely dent. Fouchier sent the paper to Science soon be published by Science soon. after the Dutch government issued the permit Downloaded from In December, the U.S. National Science on 27 April. Advisory Board for Biosecurity (NSABB) Early this week, the paper was still under recommended that the two studies—both of review and being edited. Both Fouchier and which use ferrets, a popular model for human Kawaoka had hoped the two papers, whose infl uenza—not be published in full. But after fates had been closely linked for 6 months, an expert panel convened by the World Health would appear simultaneously, which Science Organization (WHO) disagreed with the Executive Editor Monica Bradford says would decision, NSABB reviewed revised versions have been “ideal” as well. “I regret that both of the manuscripts and changed its position papers will not appear online together, but our (Science, 6 April, p. 19). That cleared the way priority must be to serve our authors and read- for Nature on 2 May to publish the fi rst of the ers,” Nature Editor-in-Chief Philip Campbell two experiments, led by Yoshihiro Kawaoka said in a statement. “You can’t blame them,” of the University of Wisconsin, Madison, and Fouchier says. the University of Tokyo. First to fi nish. Yoshihiro Kawaoka (above) had his Despite the massive debate about these Kawaoka’s unusually long, 11-page article paper published this week. two papers, the Kawaoka study adds only a describes how his group stitched a mutated piece to a puzzle that his and other groups version of the hemagglutinin protein of the lets. Although the researchers don’t know have been putting together for years. Infl uenza bird flu virus—the H5—onto the H1N1 whether these mutations would “support sus- researchers have long attempted to understand CREDIT: M. ENSERINK/SCIENCE in 2009. The team explains that introducing virologists worry mightily about this scenario. strain spread readily in humans. Kawaoka’s tained human-to-human transmission,” many the mutations and mechanisms that make a virus that caused a relatively mild pandemic into H5 a mere four mutations, which are deli- To date, H5N1 has not spread easily between study is an “important additional step along humans, but in 355 of 602 confi rmed cases, cately balanced with each other, allowed this the way,” says Malik Peiris, a fl u researcher at the University of Hong Kong, who co-wrote the patient has died. hybrid virus to bind more strongly to mam- malian cells and copy itself at high enough an article in Nature about the Kawaoka paper. The second paper has been held up in an Infl uenza infection begins when hemag- levels to readily transmit via respiratory drop- extra bureaucratic tangle. After NSABB’s www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 529 Published by AAAS

NEWS&ANALYSIS glutinin binds to receptors Paulson, a co-author of the H5N1 labs in January, the moratorium was on the host cell. The pro- Virology paper with Cox who extended indefi nitely at a February meeting tein is shaped like a mush- studies infl uenza binding at organized by WHO. room, with a long stalk and the Scripps Research Insti- A related, vigorous debate continues about a globular head that con- tute in San Diego, California. whether H5N1 modifi cation studies should tains the binding site. Three Keiji Fukuda, a fl u expert be confi ned to the most secure laboratories— of the mutations Kawaoka’s at WHO, says the paper will known in the United States as biosafety level group describes are in or near help guide surveillance for 4 facilities—or “enhanced” BSL-3 laborato- the binding site. They make viruses that may cause great ries, where both Kawaoka and Fouchier per- the virus prefer receptors on harm in humans. That’s not formed their experiments. WHO will not human cells to avian ones. just because they highlight take sides, nor will it advise on the morato- Several groups revealed specifi c mutations, Cox adds. rium, Fukuda says. Others say the morato- similar binding site mutations “What we’re really look- rium should remain in force until the safety earlier. Indeed, on 5 Novem- ing for is generalizable pat- issues are resolved. “We should not rush for- ber 2011, while NSABB terns of changes that occur ward when the stakes are so high,” Thomas was debating the wisdom when viruses become more Inglesby, director of the Center for Biosecu- of publishing the Kawaoka transmissible in a mamma- rity at the University of Pittsburgh Medical and Fouchier papers in full, lian model. … You can’t be Center in Pennsylvania, told a U.S. Senate a report appeared online in focused on a set of four spe- committee at a hearing on 26 April. Virology that showed respi- cifi c mutations.” Anthony Fauci, head of the U.S. National ratory transmission in one Hot spots. Mutations near hemag- Now, infl uenza scientists Institute of Allergy and Infectious Dis- on May 3, 2012 of two ferrets with a lab- glutinin’s binding site (yellow) and are eagerly awaiting publica- eases, which funded the two studies, agrees. made H5 virus that had two stalk increased transmissibility. tion of Fouchier’s study, still Before U.S. offi cials support lifting the ban, of the binding-site mutations under wraps, which Kawa- he said at last week’s hearing, they will have also reported by Kawaoka’s group. But these oka recently said has “striking similarities” to “feel comfortable” that H5N1 labs under- researchers stressed that respiratory transmis- with his own. It’s unclear how these publica- stand how to evaluate the dual-use poten- sion required additional mutations. tions will affect a self-imposed moratorium tial of their work and take steps to mitigate Nancy Cox, a flu researcher at the U.S. on studies that involve modifying the trans- safety and security risks. Centers for Disease Control and Preven- missibility or lethality of H5N1. Announced –MARTIN ENSERINK AND JON COHEN www.sciencemag.org tion in Atlanta who co-authored that study— by researchers from the world’s most active With reporting by David Malakoff. which an internal biosecurity committee said could be published—applauds Kawaoka and his colleagues for their “absolutely fantastic ARCHAEOLOGY work” and says their mutant “defi nitely moved the transmission bar to the right towards being New Light on Revolutions That Weren’t fully transmissible.” But she notes that even Downloaded from the new mutant does not spread as readily as MEMPHIS, TENNESSEE—Back in 2000, a now- of much later sites, suggest that the dramatic common, seasonal fl u strains. famous scientifi c paper called “The Revolu- rise of farming villages in the Near East also Cox and others say the most novel fi nding tion That Wasn’t” argued that the then-con- had early and deep roots. in the Kawaoka study involves a mutation in ventional wisdom that modern human behav- The pair of talks provides still more rea- the stalk. This fourth mutation surfaced after ior had erupted in a “creative explosion” sons “why we should be skeptical of revo- a series of experiments that coaxed out muta- about 50,000 years ago in Europe was wrong. lutions in archaeology,” says archaeologist tions to make the virus spread more easily in Rather, anthropologists Sally McBrearty and Nicholas Conard of the University of Tübin- ferrets. The effort included screening 2 mil- Alison Brooks contended that modern behav- gen in Germany. Indeed, many archaeolo- lion randomly created mutants and infecting ior, including creativity, has deep and ancient gists now think that apparent “revolutions” ferrets to let strains further adapt to them. The roots, going back some 300,000 years ago in are due to gaps in the record or to behav- best transmitter spread from infected animals Africa (Science, 15 February 2002, p. 1219). ioral shifts triggered by changing conditions, * to four of six healthy ferrets in neighboring At a meeting here last month, research- rather than sudden advances in cognition. CREDIT: H.-L. YEN AND J. S. M. PEIRIS, NATURE (ADVANCED ONLINE EDITION) ©2012 MACMILLAN PUBLISHERS LIMITED cages. It did not kill any of the animals. ers heard new evidence that human evolution What appear to be precociously sophisti- The role of the stalk mutation became took a gradual, rather than revolutionary, cated behaviors are really refl ections of what clear in a set of additional experiments. Hem- course during two other key junctures in pre- prehistoric humans were capable of all along, agluttinin’s second job—after latching onto history. A study of ancient stone tools from says archaeologist John Shea of Stony Brook the host receptor—is to fuse viral and host South Africa concludes that hunters manu- University in New York state. cells’ membranes as the virus enters the cell. factured spears with stone points—a sign Humans were getting smart about how to The mutations at the binding site make it dif- of complex behavior—200,000 years ear- hunt wild animals much earlier than previ- fi cult for the protein to do that in the slightly lier than had previously been thought. And ously known, according to a talk by archae- acidic environment of human mucosa, the new excavations at a 20,000-year-old settle- ologist Jayne Wilkins of the University of researchers say, but the mutation on the stalk ment in Jordan, laden with artifacts typical Toronto in Canada. Wilkins, Benjamin Scho- compensates by enabling the protein to oper- ville of Arizona State University (ASU), ate in a more acidic environment. “It’s the * Paleoanthropology Society 2012 Annual Meeting. Tempe, and Kyle Brown of the University of major discovery in the study,” says James Memphis, Tennessee, 17–18 April. Cape Town in South Africa analyzed stone 4 MAY 2012 VOL 336 SCIENCE www.sciencemag.org 530 Published by AAAS

NEWS&ANALYSIS glutinin binds to receptors Paulson, a co-author of the H5N1 labs in January, the moratorium was on the host cell. The pro- Virology paper with Cox who extended indefi nitely at a February meeting tein is shaped like a mush- studies infl uenza binding at organized by WHO. room, with a long stalk and the Scripps Research Insti- A related, vigorous debate continues about a globular head that con- tute in San Diego, California. whether H5N1 modifi cation studies should tains the binding site. Three Keiji Fukuda, a fl u expert be confi ned to the most secure laboratories— of the mutations Kawaoka’s at WHO, says the paper will known in the United States as biosafety level group describes are in or near help guide surveillance for 4 facilities—or “enhanced” BSL-3 laborato- the binding site. They make viruses that may cause great ries, where both Kawaoka and Fouchier per- the virus prefer receptors on harm in humans. That’s not formed their experiments. WHO will not human cells to avian ones. just because they highlight take sides, nor will it advise on the morato- Several groups revealed specifi c mutations, Cox adds. rium, Fukuda says. Others say the morato- similar binding site mutations “What we’re really look- rium should remain in force until the safety earlier. Indeed, on 5 Novem- ing for is generalizable pat- issues are resolved. “We should not rush for- ber 2011, while NSABB terns of changes that occur ward when the stakes are so high,” Thomas was debating the wisdom when viruses become more Inglesby, director of the Center for Biosecu- of publishing the Kawaoka transmissible in a mamma- rity at the University of Pittsburgh Medical and Fouchier papers in full, lian model. … You can’t be Center in Pennsylvania, told a U.S. Senate a report appeared online in focused on a set of four spe- committee at a hearing on 26 April. Virology that showed respi- cifi c mutations.” Anthony Fauci, head of the U.S. National ratory transmission in one Hot spots. Mutations near hemag- Now, infl uenza scientists Institute of Allergy and Infectious Dis- on May 3, 2012 of two ferrets with a lab- glutinin’s binding site (yellow) and are eagerly awaiting publica- eases, which funded the two studies, agrees. made H5 virus that had two stalk increased transmissibility. tion of Fouchier’s study, still Before U.S. offi cials support lifting the ban, of the binding-site mutations under wraps, which Kawa- he said at last week’s hearing, they will have also reported by Kawaoka’s group. But these oka recently said has “striking similarities” to “feel comfortable” that H5N1 labs under- researchers stressed that respiratory transmis- with his own. It’s unclear how these publica- stand how to evaluate the dual-use poten- sion required additional mutations. tions will affect a self-imposed moratorium tial of their work and take steps to mitigate Nancy Cox, a flu researcher at the U.S. on studies that involve modifying the trans- safety and security risks. Centers for Disease Control and Preven- missibility or lethality of H5N1. Announced –MARTIN ENSERINK AND JON COHEN www.sciencemag.org tion in Atlanta who co-authored that study— by researchers from the world’s most active With reporting by David Malakoff. which an internal biosecurity committee said could be published—applauds Kawaoka and his colleagues for their “absolutely fantastic ARCHAEOLOGY work” and says their mutant “defi nitely moved the transmission bar to the right towards being New Light on Revolutions That Weren’t fully transmissible.” But she notes that even Downloaded from the new mutant does not spread as readily as MEMPHIS, TENNESSEE—Back in 2000, a now- of much later sites, suggest that the dramatic common, seasonal fl u strains. famous scientifi c paper called “The Revolu- rise of farming villages in the Near East also Cox and others say the most novel fi nding tion That Wasn’t” argued that the then-con- had early and deep roots. in the Kawaoka study involves a mutation in ventional wisdom that modern human behav- The pair of talks provides still more rea- the stalk. This fourth mutation surfaced after ior had erupted in a “creative explosion” sons “why we should be skeptical of revo- a series of experiments that coaxed out muta- about 50,000 years ago in Europe was wrong. lutions in archaeology,” says archaeologist tions to make the virus spread more easily in Rather, anthropologists Sally McBrearty and Nicholas Conard of the University of Tübin- ferrets. The effort included screening 2 mil- Alison Brooks contended that modern behav- gen in Germany. Indeed, many archaeolo- lion randomly created mutants and infecting ior, including creativity, has deep and ancient gists now think that apparent “revolutions” ferrets to let strains further adapt to them. The roots, going back some 300,000 years ago in are due to gaps in the record or to behav- best transmitter spread from infected animals Africa (Science, 15 February 2002, p. 1219). ioral shifts triggered by changing conditions, * to four of six healthy ferrets in neighboring At a meeting here last month, research- rather than sudden advances in cognition. CREDIT: H.-L. YEN AND J. S. M. PEIRIS, NATURE (ADVANCED ONLINE EDITION) ©2012 MACMILLAN PUBLISHERS LIMITED cages. It did not kill any of the animals. ers heard new evidence that human evolution What appear to be precociously sophisti- The role of the stalk mutation became took a gradual, rather than revolutionary, cated behaviors are really refl ections of what clear in a set of additional experiments. Hem- course during two other key junctures in pre- prehistoric humans were capable of all along, agluttinin’s second job—after latching onto history. A study of ancient stone tools from says archaeologist John Shea of Stony Brook the host receptor—is to fuse viral and host South Africa concludes that hunters manu- University in New York state. cells’ membranes as the virus enters the cell. factured spears with stone points—a sign Humans were getting smart about how to The mutations at the binding site make it dif- of complex behavior—200,000 years ear- hunt wild animals much earlier than previ- fi cult for the protein to do that in the slightly lier than had previously been thought. And ously known, according to a talk by archae- acidic environment of human mucosa, the new excavations at a 20,000-year-old settle- ologist Jayne Wilkins of the University of researchers say, but the mutation on the stalk ment in Jordan, laden with artifacts typical Toronto in Canada. Wilkins, Benjamin Scho- compensates by enabling the protein to oper- ville of Arizona State University (ASU), ate in a more acidic environment. “It’s the * Paleoanthropology Society 2012 Annual Meeting. Tempe, and Kyle Brown of the University of major discovery in the study,” says James Memphis, Tennessee, 17–18 April. Cape Town in South Africa analyzed stone 4 MAY 2012 VOL 336 SCIENCE www.sciencemag.org 530 Published by AAAS

NEWS&ANALYSIS points from the site of Kathu Pan 1 (KP1); less, Brooks, who co-organized the meeting, Berkeley, suggests that the novel behaviors of the tools came from a level dated by two calls the work “fantastic” and agrees with the Natufi an culture, and by extension those relatively new dating techniques to about Wilkins that technologies often associated of the Neolithic Age, were also the result 500,000 years ago. with modern humans, such as spear points, of a long and gradual process. Maher and Archaeologists have considered two were invented by hominins who lived long Tobias Richter of the University of Copen- primary uses for stone points: as knives to before the fi rst Homo sapiens appeared about hagen lead a dig at a site called Kharaneh IV cut animal fl esh and plants, a function that 200,000 years ago. in Jordan, where they see glimpses of Neo- dates to the earliest days of hominin evolu- If the evolution of modern behavior is lithic origins. Radiocarbon dating puts occu- tion; or as weapons to hunt animals, prob- no longer seen as sudden, a similar fate may pation of Kharaneh IV between 19,900 and ably hafted to long wooden handles and used be in store for one of archaeology’s great- 18,600 years ago, near the beginning of what as spears, a behavior thought to date to the est upheavals: the so-called Neolithic Revo- is called the Epipaleolithic Period. The site beginning of the Middle Stone Age (MSA), lution in the Near East, which began about is “incredibly dense in archaeological mate- about 300,000 years ago. During the MSA, 11,000 years ago, when hunter-gatherers rial,” including thousands of stone tools, ani- hominin stone tools shifted from large, sym- began to farm and settle down in seden- mal bones, and perforated shell beads, along metrical hand axes to smaller and more tary villages. Many researchers have seen with a few ritual human burials, Maher said sophisticated blades, which at the meeting. may refl ect the beginnings of In many ways, Kharaneh modern behavior. IV looks like a typical Natufi an Wilkins’s team studied site, complete with residential the shapes and use wear of huts and evidence of nearly 210 stone artifacts from KP1 year-round occupation, Maher on May 3, 2012 as compared to ancient tools said. It also provides evidence from other sites. The KP1 of long-range social networks points met several criteria more typical of the Neolithic for use as spears but were not itself. Many of the shells used consistent with cutting. For to make personal ornaments came from the Red Sea and CREDITS (TOP TO BOTTOM): J. WILKINS & M. CHAZAN, JOURNAL OF ARCHAEOLOGICAL SCIENCE (ADVANCED ONLINE EDITION) 4 FEBRUARY; LISA A. MAHER example, both smaller and larger points were symmetri- the Mediterranean, several cal rather than asymmetrical, hundred kilometers away, and www.sciencemag.org as would be expected if they some came from the Indian had been used as spear points Ocean, more than 2000 kilo- rather than cutting tools. meters away. The “changes The KP1 points also showed we see in the Neolithic extend a clear pattern of fractures back over 10,000 years of at their tips, typical of the prehistory. If we want to look impact damage seen when for their origins, we need to Downloaded from spears are thrown or thrust look at least to the beginning at animals. To verify this, the of the Epipaleolithic,” Maher team manufactured 32 of its said. “It’s a second revolution own experimental spears and that wasn’t.” thrust them into the carcass of Marean agrees that a springbok; the experimen- Kharaneh IV suggests a “long tal points showed fracture and run-up” to the Neolithic use wear patterns very similar accompanied by far-flung to those found at KP1. social networks. Says Shea, Wilkins concluded that Evolutionary, not revolutionary? 500,000-year-old spear points from South Africa “The ‘holy shit’ moment the spear points from KP1 are (top) and 20,000-year-old shell ornaments from Jordan suggest that sophisticated in Lisa’s talk was when she the “oldest known evidence” human behaviors developed gradually over time, rather than in sudden bursts. announced they had shells of this type of weapon. Their from the Indian Ocean. That early appearance suggests that the fi rst glim- the roots of the Neolithic Revolution in a tells us these Epipaleolithic people were net- mers of modern human behavior “could be hunter-gatherer culture that immediately working over immense spans of geography.” pushed back to 500,000 years ago,” she said. preceded it called the Natufi an, which lasted But Conard cautions that despite the grow- The KP1 study provides “convincing evi- from about 15,000 to 11,500 years ago. The ing evidence that the development of farming dence that the pointed fl akes were hafted to practices of Natufi ans apparently foreshad- and settled life was a gradual process, archae- spears,” says archaeologist Curtis Marean owed many of the features of the Neolithic: ologists should not understate the enormous of ASU Tempe. “If the ages are correct, this sedentary communities of huts, elaborate changes that the Neolithic ultimately brought would set this technology back 200,000 years ritual burials, cultivation of wild plants, about, such as the rise of cities. “Life as we earlier than previously known in Africa.” and intricate personal ornaments (Science, know it today would not be possible without He and Brooks of George Washington 22 January 2010, p. 404). these major changes,” Conard says. “Revolu- University in Washington, D.C., caution that But a presentation here by archaeologist tions are in the eye of the beholder.” the dating needs to be confi rmed. Neverthe- Lisa Maher of the University of California, –MICHAEL BALTER www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 531 Published by AAAS

NEWS&ANALYSIS Work hard, play hard. AIMS Senegal students Diogène Pongui and Odu- modu Nneka Chigozie, and lecturer Abdellah Sebbar (left to right). Turok says. “The fi rst 2 months, they are typ- ically very unhappy. T Then, a light bulb goes o on, and they realize they c can learn by playing a and discovering.” DEVELOPMENT To avoid distractions, First Spinoff of African Math Institute AIMS deliberately picked this regional city as a home; Dakar, the capital, has more intel- Takes Root in Senegal lectual life but also a famed music and night- life scene. The students have mostly stayed focused, Sangharé says, and have grand ambi- M’BOUR, SENEGAL—Golden sand, the aren’t among the U.N.’s Millennium Develop- tions. Several have lined up Ph.D. training at on May 3, 2012 Atlantic Ocean, beach volleyball—these ment Goals (wrongly, Turok says). The plan universities in Europe and North America. are just occasional distractions for the to open a second AIMS institute in Nigeria, Perhaps the main attraction here is the 31 students from all over Africa who are doing Africa’s most populous country, was stranded lecturers: internationally renowned math- 10 months of intensive training at the newest over differences with the local partner, the ematicians, who each come to spend 3 full branch of the African Institute for Mathe- African University of Science and Technol- weeks. They’re extremely accessible; dis- ur- matical Sciences (AIMS). A few steps from ogy in Abuja. Small-scale by nature, AIMS cussions often continue dur- the beach on a small nature reserve in this didn’t feel at home in the grandiose plans ing the communal meals and d town 2.5 hours south of the Senegalese capi- for the university, a World Bank project. into the night. “It’s amazing www.sciencemag.org tal, Dakar, the institute is their home, cafete- AIMS also insists on not charging tuition and and very inspiring,” says ria, and lecture hall. Top lecturers are fl own recruiting women as 30% of its student body. Nigerian student Odumodu AFRICA in from around the world to teach; in this fi rst The past 2 years have brought a “trans- Nneka Chigozie. It’s a big year, two Fields Medal winners were among formation,” Turok says. Several big donors investment for the faculty, them. Life at AIMS Senegal is mostly “very came through—most notably the Canadian says Abdellah Sebbar of the hard work,” says Diogène Pongui, a student government, which pledged $20 million in University of Ottawa, who Western Sahara from the Republic of the Congo. 2010 to expand the network. The money did his stint earlier this Downloaded from AIMS Senegal is the little sister of AIMS supports not just the Senegal franchise but year—especially because South Africa—a similar institute founded in also one in Ghana, to be opened in Septem- he has three children and a 2003 just outside Cape Town—and part of ber, and a fourth slated to launch in Ethiopia wife with a job of her own. Mauritania a story that has captivated mathematicians next year. Each will be co-administered by But Sebbar, who hails and triggered an outpouring of support in local universities. from Morocco, says money, time, and brainpower. The institutes In Senegal, the plan found a willing ear that as an African, Dakar are the brainchild of Neil Turok, a South in then-president Abdoulaye Wade, whose “I want to be in M’bour Senegal African–born mathematician who heads the government donated €1 million for a new this process for The Gambia Perimeter Institute for Theoretical Physics building that will replace the current, mod- the long run.” in Waterloo, Canada. est dwellings loaned from a French institute. Turok, too, has Guinea-Bissau Turok, whose parents were jailed as anti- Wade was defeated in elections in February, plenty of plans for Guinea apartheid activists, believes excellence in but his successor, Macky Sall, is a geological the long run. After Atlantic math is one of the keys to development in engineer and a science supporter as well, says next month’s gradua- Ocean Sierra Leone Africa. He has a dream to create a network Mamadou Sangharé, a mathematician at Uni- tions here and in South of 15 AIMS institutes around the struggling versity Cheikh Anta Diop in Dakar and the Africa, AIMS will have generated Liberia president of AIMS Senegal. continent. He ambitiously dubbed it the Next 450 alumni. With more money, there CREDITS: (PHOTOS) M. ENSERINK/SCIENCE 21st century’s most revolutionary mathemati- South Africa—both English and French on, leading to a pan-African network of thou- could be a fi fth AIMS, and a sixth, and so Despite some differences from AIMS Einstein Initiative—the idea being that the cians might well be Africans (Science, 2 May are spoken here, and the atmosphere is a bit sands of well-trained alumni—including, per- 2008, p. 604). more relaxed, Turok says—the idea behind haps, that new Einstein. “I really think that At fi rst the dream proved harder to real- will transform development,” Turok says. And AIMS Senegal is the same. Students come for months of day-and-night immersion ize than Turok hoped. Despite lots of sympa- then, as the mathematician takes over from the thy, “we were often at the brink of bankruptcy in high-level mathematics. For many stu- dreamer: “It would cost $100 million over the next 10 years—that’s about 0.003% of Afri- during the fi rst few years,” he says. Big donors dents, the focus on problem-solving rather ca’s total aid budget.” than rote learning is like “shock therapy,” tend to shun higher education projects, which www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 –MARTIN ENSERINK 533 Published by AAAS

NEWSFOCUS NEWSFOCUS Threading the pore. With nanopore sequencing, single molecules of DNA will be deciphered as they pass through a tiny channel. going through the pore could yield a more direct, faster way to sequence genomes. Yet until the Florida meeting, no one had claimed success in reading DNA as it moved through a pore, leaving many to wonder whether the technology would ever pan out. “Over the years, the number of people who truly believed in nanopore sequencing you could probably count on your two hands,” says Mark Akeson, a molecular biologist at UCSC. “Now both companies and aca- demics are seeing [evidence] that this stuff actually works. This technology is going to really take off.” Sequencing gold rush Over the 2 decades that nanopore sequenc- on May 3, 2012 ing has lingered backstage, many other advances have greatly reduced the cost and increased the speed of reading the strings of adenines, guanines, thymines, and cyto- sines that compose strands of DNA. Whereas that first human genome sequence cost an estimated $1 billion to complete, the all- inclusive price at a high-throughput sequenc- www.sciencemag.org ing center today is about $18,000, and a few Search for Pore-fection companies are promising costs approaching $1000 per genome. The pace has also quick- ened. It took 3 years at the turn of the century to produce a draft of a human genome; the At long last, nanopore sequencing seems poised to leave the lab, same can now be done in a week. Since the promising a new and better way to decode DNA human genome sequence was completed in Downloaded from 2003, researchers have decoded hundreds of In a packed Florida conference center Although they’ve gotten much cheaper genomes of plants, animals, cancer cells, and 3 months ago, Clive Brown introduced an and smaller in recent years, machines that even ancient humans, proving that sequenc- audience of scientists, engineers, and biotech read DNA and RNA still usually cost hun- ing is a valuable tool for biomedicine and analysts to a device resembling an oversized dreds of thousands of dollars, take up entire all sorts of other disciplines, from ecology thumb drive. He promised it would decipher lab benches, and require much upfront to anthropology. Researchers are calling for almost a billion DNA bases in 6 hours and sell and postsequencing processing to gener- 10,000 vertebrates to be sequenced, for exam- for $900. As backing for that claim, Brown ate a genome. Nanopore sequencing could ple, and physicians may soon routinely order described how Oxford Nanopore Technolo- change all that. This new technology “really up a patient’s genome sequence for diagnostic gies, where he is chief technology offi cer, had requires you to think about things or preventive purposes. used a prototype to decode the genome of a in a completely different way,” Online Nanopore sequencing has virus in a single pass of a complete strand of says Elaine Mardis, co-director not been part of this revolution. its DNA. “There was an audible gasp from of the Washington University sciencemag.org Instead, it was an appealing idea Podcast interview the audience,” recalls Oxford Nanopore’s Genome Institute in St. Louis. with author for which every aspect needed to CEO, Gordon Sanghera. As the tweeters and blog- Elizabeth Pennisi (http:// be developed. When they fi rst con- If Oxford Nanopore’s claims and prom- gers in Brown’s audience went scim.ag/pod_6081). sidered the concept, Deamer and ises are borne out—and some scientists wild, sending missives out onto Branton didn’t have an appropriate remain skeptical—the company is set to the Internet, David Deamer, a biophysicist pore or a way to control DNA’s fl ow through achieve the first commercialization of a at the University of California, Santa Cruz such a pore, and they didn’t know for sure that long-awaited and oft-doubted technol- (UCSC), and Harvard University cell biol- they could distinguish the different bases on ogy called nanopore sequencing. The tech- ogist Daniel Branton sat in the front row, a strand of nucleic acid. Ever so slowly, they nology, based on protein pores so tiny that beaming. In 1996, 7 years after Deamer ini- and a handful of others have made advances CREDIT: DR. IAN M. DERRINGTON 25,000 of them can fi t on the cross section of tially had the idea, they had publicly pro- on all those fronts, with several key publica- a human hair, could be the next big thing in posed that threading DNA through a tiny tions in the past 2 years signaling progress, genome sequencing and analysis. pore and monitoring changes in the current not just with protein pores but also with solid 4 MAY 2012 VOL 336 SCIENCE www.sciencemag.org 534 Published by AAAS

NEWSFOCUS state ones (see sidebar, p. 536). Showstopper. If it works, this device could enable Oxford Nanopore has promised to sell DNA sequencing to be done from a laptop. its new protein-pore sequencers by the end of the year, and if those machines pan out, join forces and eventually fi led for a patent it could set off another genomics revolution, together. The chief missing ingredient was many scientists predict. “Current sequencing still a big enough pore. Church moved on to has an awful lot of complications that just go other sequencing projects, but Deamer kept away with nanopore sequencing,” says Stuart an eye out for a way to make his idea reality. Lindsay, a physicist at Arizona State Univer- Deamer learned about α-hemolysin, a pro- sity, Tempe. tein that Staphylococcus aureus uses to bust Nanopore sequencing should require lit- open red blood cells. John Kasianowicz, a tle upfront preparation beyond isolating an researcher at the National Institute of Stan- organism’s DNA, and even that might be done triphosphate (ATP) across a lipid membrane dards and Technology (NIST) in Gaithers- away with in some applications. In contrast, to supply energy to enzymes trapped inside burg, Maryland, was testing pores formed by current approaches require that the DNA be his synthetic “cell.” He quickly realized that this protein as biosensors for toxic heavy met- copied many times over and, typically, labeled his theoretical solution—to insert a channel als in solution. Working with Hagan Bayley, with a fl uorescent tag that can be read by an of some sort into the membrane—had other now at the University of Oxford in the United optical sensor. Such preparation takes time possibilities. If ATP could squeeze through, so Kingdom, he had embedded an α-hemolysin and money and erases any of the chemical might DNA. And as DNA crossed the chan- pore in a membrane and applied a voltage to modifi cations that result in the epigenetic con- nel, he reasoned, it would alter the ion fl ow produce an electrical current of potassium and trol of gene expression—something research- through the channel. Finally, if the changes chloride ions through the pore. Sensitive elec- on May 3, 2012 ers increasingly want to know about that in this hypothetical channel’s ionic current tronics measured the ion fl ow. Kasianowicz nanopore devices may be able to read. differed with each of DNA’s bases, then that hoped the heavy metals would bind to the pore Furthermore, current sequencers work could open up a whole new way of sequenc- and alter the ionic current in distinctive ways. by decoding many short stretches of DNA— ing. At the time, the idea seemed fanciful even “It occurred to me that this pore might in typically 200 bases or so—and that informa- to Deamer. For starters, he recalls, “there was fact be large enough” to allow strands of RNA tion has to be painstakingly pieced together. no pore available.” Nevertheless, he sketched or DNA to move through, Deamer says. In Nanopore technology can read much longer out his idea in a lab notebook. 1993, he went to NIST with some RNA to test stretches of DNA: At the February meet- Deamer also shared the scheme with the concept. Because DNA and RNA are neg- www.sciencemag.org ing, Brown reported decoding a 48,000- Branton, and they approached Harvard about atively charged, they would be pulled through base genome of a bacteriophage, a virus that patenting it. They weren’t the only ones think- the pore. As Deamer suspected, as the strand infects bacteria, by fi rst linking the ends of ing along those lines: They discovered that of RNA passed the narrow point of the pore, it the two strands of its DNA, then threading the a colleague, geneticist George Church, had interfered with the ion fl ow, changing the cur- entire genome, fi rst one strand and then the independently come up with a similar plan rent. “We immediately got huge numbers of other, through a pore in one pass. “That really to sequence DNA using a pore from a bac- signals from the recorder,” indicating that the CREDITS: (TOP) NIGEL CHAPMAN PHOTOGRAPHY; (BOTTOM CLOCKWISE FROM LEFT) DAVID DEAMER (2); PAUL HOROWITZ stunned the audience,” Deamer says. teriophage. The three of them decided to RNA was blocking the pore’s ionic current as Downloaded from While no scientist outside of Oxford Nanopore has reported seeing the proto- type sequencers Brown bragged about in Florida, the company says it will eventually have an 8000-pore version—many pores will be needed to sequence genomes much larger than a phage’s DNA. With 20 of these machines, it should be possible to reveal a human genome sequence in 15 minutes. “You don’t have to wait 2 weeks to do the assembly; you are watching it on the fl y,” Akeson says. “If [nanopore sequencing] works, there’s not going to be anybody in genomics who is not using the device in some fashion.” That’s a big “if,” Mardis notes. “It’s such a beautiful possibility, but there are many tech- nical hurdles to getting it to actually produce sequence data.” Not just an idea Deamer began trying to jump those hurdles almost 25 years ago, long before Oxford Nanopore formed. In 1989, Deamer was work- Nanopore dreamers. After David Deamer (top ing on the origins of life and was struggling to right) sketched out nanopore sequencing in 1989, fi gure out how to get the molecule adenosine he teamed up with Daniel Branton (bottom right). www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 535 Published by AAAS

NEWSFOCUS it threaded its way through, Deamer says. ment through the pore. Reza Ghadiri of the Yet although the ϕ29 polymerase slowed In 1996, he, Kasianowicz, and Branton Scripps Research Institute in San Diego, the DNA down as desired, the stem of the published a paper in the Proceedings of the California, was also interested in nanopore mushroom-shaped pore was so long that more National Academy of Sciences, in which they sequencing and had taken the first steps than a dozen bases were passing through at reported that they could unravel a coiled toward controlling DNA movement using any one time, creating a fuzzy ionic current nucleic acid so that its bases move through a polymerase, an enzyme that copies DNA signal at best. The signals weren’t distinctive the pore single fi le. They could tell the length by ratcheting a DNA strand along base by enough to tell one base from another. They of a strand of DNA going through the pore by base, like a sprocket moving the links of a needed a different pore. the amount of time the ionic current signal bicycle chain, as it adds the complemen- was altered. In the article, they suggested that tary base. Independently, Akeson, working A better pore this approach could also be used to sequence with Deamer, started buying and testing Fortunately, Jens Gundlach, a gravitational DNA. “That was the pioneering paper,” says various polymerases from different species physicist at the University of Washington, Henry White, a chemist at the University of and other proteins. The fi rst ones he and his Seattle, had heard about nanopore sequenc- Utah in Salt Lake City. colleagues tested quickly fell off the DNA, ing and was intrigued enough to move into Even with a potential pore in hand, only briefl y moving the strand through the biophysics. In 2003, Gundlach started look- Deamer and his colleagues realized that pore. After many years of trying, in 2010, ing into alternatives to α-hemolysin. A lit- DNA’s bases were whipping through the they discovered that a polymerase from a erature search yielded no promising candi- channel too fast to be identifi ed. One solu- phage called ϕ29 would move long stretches dates, but then he saw in Science a pore in a tion was to harness another protein to of DNA, one base at a time, at a reasonable different bacterium with a potentially better latch onto the DNA and control its move- pace through α-hemolysin. geometry—it was shaped like a funnel—for on May 3, 2012 Going Solid-State a simulation showing the potential of this approach, and they have since been working on making a device. “We are pushing the limits” of chip The fi rst nanopore sequencers will depend on protein pores, but many in technology, says Gustavo Stolovitzky of IBM. the fi eld envision replacing these biological channels with solid-state ones. Like Kawai, Stolovitzky and his colleagues aim to detect tunneling dif- They also foresee controlling DNA’s movement through a sequencer’s chan- ferences. But his team decided that simply placing the electrode pair in nels electrically rather than depending on another protein to ratchet the the pore would work poorly, so they approached Stuart Lindsay, a physicist bases along the pore. Ditching the proteins could pave the way to even at Arizona State University, Tempe, who has developed a way to fi t each www.sciencemag.org cheaper devices that take advantage of semiconductor manufacturing tech- electrode with a small organic molecule that is prone to making hydrogen nology to mass-produce and shrink these sequencers. bonds. These molecules recognize and latch onto each DNA base, briefl y Since 2005, Tomoji Kawai, a physical chemist at Osaka University in holding on to it until a signal is registered. In 2011, Lindsay licensed the Japan, and his colleagues have experimented with a pore in a silicon wafer. technology to Roche. In Kawai’s device, a quantum-dynamics effect known as electron tunneling, Neither IBM nor Roche will say exactly where their collaboration is in which electrons jump from one place to another through what should be a in the development of this nanopore-sequencing technology. The “main barrier, has replaced the ionic current challenges” are engineering, Lindsay Downloaded from of the protein pore nanosequencers says—”These are tiny devices that (see main text, p. 534) as a means of need to be made precisely.” reading the bases. Two nanoelectrodes Another potential solid-state fl ank the pore and are close enough to pore material is graphene, which produce quantum tunneling across the consists of a layer of carbon mol- pore. As they pass between the elec- ecules arranged in adjoining hexa- trodes, DNA’s four bases alter the tun- gons. In theory, a graphene pore neling current in specifi c ways that are could be one atomic layer thick, detected by the electrodes. just deep enough for a single base Instead of controlling the move- to pass by at one time, which might ment of the RNA or DNA strands with make detection more precise. In motor proteins, Kawai uses an electri- Quantum sequencing. One way to read 2010, Daniel Branton and Jene DNA in a nanopore would be to monitor cal fi eld that starts and stops the pas- changes in the tunneling current. Golovchenko of Harvard University CREDIT: MASATERU TANIGUCHI/THE INSTITUTE OF SCIENTIFIC AND INDUSTRIAL RESEARCH, OSAKA UNIVERSITY sage of the negatively charged nucleic and colleagues, along with two other acids through the wafer. Thus far, he independent groups, reported that has used the technology to read up to 20 bases of RNA. Toshiba is looking they could detect DNA moving through graphene pores. They have since into using the technology to detect viruses, and Toray Industries Inc. plans been working on building pores more reliably. to develop a test for an RNA cancer marker. The idea would be to apply semiconductor manufacturing technology Working together, IBM and Roche are also exploring an electronics- to build large arrays of solid-state pores that allow for very fast sequenc- based approach. At the core of their nanopore-sequencing technology is ing. If these can be developed, they “offer the possibility to obtain genome a “DNA transistor,” a chip that consists of a stack of alternating metal and sequences in less time than it takes to unravel a stethoscope” and could be insulating layers, with the pore drilled through the layers. Sequential elec- a “compelling” technology for personalized genome sequencing, Hagan tric fi elds will pull the DNA through base by base. In 2010, researchers at Bayley, a pioneer in nanopore sequencing at the University of Oxford in IBM T. J. Watson Research Center in Yorktown Heights, New York, published the United Kingdom, wrote in 2010. –E.P. 4 MAY 2012 VOL 336 SCIENCE www.sciencemag.org 536 Published by AAAS

NEWSFOCUS getting a strong ionic current signal. Called started looking at α-hemolysin in the 1980s tial protein candidates. The company licensed MspA (for Mycobacterium smegmatis porin to learn how water-soluble proteins made it technology developed and patented by A), this channel has a single narrow section through membranes, but he got interested in Bayley, Deamer, Branton, Akeson, and others. long enough for just four bases. The natural engineering pore proteins for biotechnology. Because the natural lipid bilayers of the cell MspA had limitations, however: The con- Bayley envisioned pores that would help kill membrane originally used to hold the pores stricted section carries a negative charge, tumor cells or detect metals, sugars, and other are not very stable, the company developed making it hard for the similarly charged proteins, and he had been modifying this pore a polymer alternative that could withstand DNA to get through. for these different applications, making much exposure to blood or pollutants. And Oxford Gundlach and his colleagues tweaked progress. In 2005, he started a company to Nanopore has its own proprietary motor pro- MspA’s gene, changing the protein so that commercialize these biosensors. tein to control the DNA’s fl ow through the the constricted part of the pore was neutral, About the same time, the push for the pore. The company won’t disclose any details and produced the modifi ed pore by express- $1000 genome (Science, 17 March 2006, yet but says it will have data and machines for ing the altered gene in bacteria. They had p. 1544) had resulted in a new U.S. National academics to evaluate in the coming months. also added some positive charges One challenge, the company at the pore entrance to enhance the acknowledged in Florida, is getting inflow of DNA. When DNA was the error rate down from its current suspended in the modifi ed pore, the 4%. Academics concur that errors signal for each base was almost 10 are a problem. As a polymerase times stronger than the signal for ratchets along, it sometimes back- immobilized bases in α-hemolysin, tracks so that a base is read twice; Gundlach’s team reported in 2010. other times, the base gets through on May 3, 2012 A sequencer using this unnatural the pore without being read. One MspA in theory “could resolve in can compensate for these ran- much fi ner detail the DNA strands,” dom errors by sequencing each Akeson says. DNA strand multiple times. With But each base still zipped by in the pore setup developed by Ake- a microsecond, 1000 times faster son and Gundlach, they can read than could be read. And the only the DNA as it is fi rst pulled down way Gundlach could slow them through the pore and then again www.sciencemag.org down required modifying the DNA as it is pulled up and turned into itself, an impractical solution. So double-stranded DNA by the poly- last year, he and Akeson joined merase. In theory, one could repeat forces. “The ϕ29 polymerase pro- those two steps with the same vides a mechanism to move the strand as many times as needed. DNA through the pore at a reason- Perfecting pores. Cross sections of the MspA (left) and α-hemolysin (right) With its sequenced viral genome, able speed,” about one base every pores show their different geometries. Oxford Nanopore showed it could Downloaded from 30 milliseconds, Gundlach says. tackle the problem by connecting With the combination of Gundlach’s pore Human Genome Research Institute (NHGRI) the DNA’s two complementary strands so that and Akeson’s polymerase, nanopore sequenc- program for technology development. Bay- each is sequenced, the second providing an ing fi nally made its public debut, at least in ley decided to apply and see what his modi- accuracy check on the fi rst. the academic sense. Gundlach and his col- fi ed α-hemolysins could do with respect to Neither approach solves another prob- leagues reported at the Florida meeting and sensing DNA. Since he knew that he could lem, accurately reading long stretches in online 25 March in Nature Biotechnology make pores that could distinguish mirror ver- which the same base is repeated, a not- that they had could distinguish the bases in sions of the same molecule, he was confi - infrequent occurrence in genomes. But six DNA strands ranging from 42 to 53 bases dent he could distinguish DNA’s bases. With nanopore proponents point out that this long. “This is the fi rst paper where somebody Ghadiri, he got an NHGRI grant and eventu- repetitive DNA is diffi cult for all sequenc- has actually [read] DNA,” says chemist Geof- ally published that the pore could tell DNA’s ing techniques. frey Barrall, president of Electronic BioSci- building blocks apart when they were in solu- How solvable this and other problems ences in San Diego, California, which is also tion. He decided to pursue the idea of feeding are and whether they can be overcome in the developing nanopore sequencing technology. individual bases through the pore and started coming months is not yet clear. Oxford Nano- (Oxford Nanopore has yet to publish a scien- looking into using an enzyme that would pore has a good reputation, but some rival tifi c paper on the phage genome sequencing break off each base as the DNA entered the sequencing companies and genome experts Brown described in Florida.) Gundlach says pore. In 2008, his company, now renamed won’t believe the sequencers work as adver- he has since tested longer stretches of DNA. Oxford Nanopore Technologies, stepped up tised until they can test one. They caution its efforts in nanopore sequencing, fi rst pur- that nanopore technology has been “coming” CREDIT: IAN M. DERRINGTON While Deamer and the other U.S. research- later following the path others had taken, dles are fi nally overcome. However, “if they for so long that it’s hard to believe the hur- suing the idea of reading cut-up bases and A company is born decoding long, intact DNA strands. ers were struggling to make nanopore could pull it off,” Mardis says, “it would be Oxford Nanopore went after a better pore a complete game changer.” And Deamer and sequencing a reality, Bayley was modifying Branton’s smiles may get even wider. the α-hemolysin pore with a different pri- in earnest, developing a high-throughput approach toward testing and modifying poten- mary goal in mind: sensing devices. He had www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 –ELIZABETH PENNISI 537 Published by AAAS

NEWSFOCUS it threaded its way through, Deamer says. ment through the pore. Reza Ghadiri of the Yet although the ϕ29 polymerase slowed In 1996, he, Kasianowicz, and Branton Scripps Research Institute in San Diego, the DNA down as desired, the stem of the published a paper in the Proceedings of the California, was also interested in nanopore mushroom-shaped pore was so long that more National Academy of Sciences, in which they sequencing and had taken the first steps than a dozen bases were passing through at reported that they could unravel a coiled toward controlling DNA movement using any one time, creating a fuzzy ionic current nucleic acid so that its bases move through a polymerase, an enzyme that copies DNA signal at best. The signals weren’t distinctive the pore single fi le. They could tell the length by ratcheting a DNA strand along base by enough to tell one base from another. They of a strand of DNA going through the pore by base, like a sprocket moving the links of a needed a different pore. the amount of time the ionic current signal bicycle chain, as it adds the complemen- was altered. In the article, they suggested that tary base. Independently, Akeson, working A better pore this approach could also be used to sequence with Deamer, started buying and testing Fortunately, Jens Gundlach, a gravitational DNA. “That was the pioneering paper,” says various polymerases from different species physicist at the University of Washington, Henry White, a chemist at the University of and other proteins. The fi rst ones he and his Seattle, had heard about nanopore sequenc- Utah in Salt Lake City. colleagues tested quickly fell off the DNA, ing and was intrigued enough to move into Even with a potential pore in hand, only briefl y moving the strand through the biophysics. In 2003, Gundlach started look- Deamer and his colleagues realized that pore. After many years of trying, in 2010, ing into alternatives to α-hemolysin. A lit- DNA’s bases were whipping through the they discovered that a polymerase from a erature search yielded no promising candi- channel too fast to be identifi ed. One solu- phage called ϕ29 would move long stretches dates, but then he saw in Science a pore in a tion was to harness another protein to of DNA, one base at a time, at a reasonable different bacterium with a potentially better latch onto the DNA and control its move- pace through α-hemolysin. geometry—it was shaped like a funnel—for on May 3, 2012 Going Solid-State a simulation showing the potential of this approach, and they have since been working on making a device. “We are pushing the limits” of chip The fi rst nanopore sequencers will depend on protein pores, but many in technology, says Gustavo Stolovitzky of IBM. the fi eld envision replacing these biological channels with solid-state ones. Like Kawai, Stolovitzky and his colleagues aim to detect tunneling dif- They also foresee controlling DNA’s movement through a sequencer’s chan- ferences. But his team decided that simply placing the electrode pair in nels electrically rather than depending on another protein to ratchet the the pore would work poorly, so they approached Stuart Lindsay, a physicist bases along the pore. Ditching the proteins could pave the way to even at Arizona State University, Tempe, who has developed a way to fi t each www.sciencemag.org cheaper devices that take advantage of semiconductor manufacturing tech- electrode with a small organic molecule that is prone to making hydrogen nology to mass-produce and shrink these sequencers. bonds. These molecules recognize and latch onto each DNA base, briefl y Since 2005, Tomoji Kawai, a physical chemist at Osaka University in holding on to it until a signal is registered. In 2011, Lindsay licensed the Japan, and his colleagues have experimented with a pore in a silicon wafer. technology to Roche. In Kawai’s device, a quantum-dynamics effect known as electron tunneling, Neither IBM nor Roche will say exactly where their collaboration is in which electrons jump from one place to another through what should be a in the development of this nanopore-sequencing technology. The “main barrier, has replaced the ionic current challenges” are engineering, Lindsay Downloaded from of the protein pore nanosequencers says—”These are tiny devices that (see main text, p. 534) as a means of need to be made precisely.” reading the bases. Two nanoelectrodes Another potential solid-state fl ank the pore and are close enough to pore material is graphene, which produce quantum tunneling across the consists of a layer of carbon mol- pore. As they pass between the elec- ecules arranged in adjoining hexa- trodes, DNA’s four bases alter the tun- gons. In theory, a graphene pore neling current in specifi c ways that are could be one atomic layer thick, detected by the electrodes. just deep enough for a single base Instead of controlling the move- to pass by at one time, which might ment of the RNA or DNA strands with make detection more precise. In motor proteins, Kawai uses an electri- Quantum sequencing. One way to read 2010, Daniel Branton and Jene DNA in a nanopore would be to monitor cal fi eld that starts and stops the pas- changes in the tunneling current. Golovchenko of Harvard University CREDIT: MASATERU TANIGUCHI/THE INSTITUTE OF SCIENTIFIC AND INDUSTRIAL RESEARCH, OSAKA UNIVERSITY sage of the negatively charged nucleic and colleagues, along with two other acids through the wafer. Thus far, he independent groups, reported that has used the technology to read up to 20 bases of RNA. Toshiba is looking they could detect DNA moving through graphene pores. They have since into using the technology to detect viruses, and Toray Industries Inc. plans been working on building pores more reliably. to develop a test for an RNA cancer marker. The idea would be to apply semiconductor manufacturing technology Working together, IBM and Roche are also exploring an electronics- to build large arrays of solid-state pores that allow for very fast sequenc- based approach. At the core of their nanopore-sequencing technology is ing. If these can be developed, they “offer the possibility to obtain genome a “DNA transistor,” a chip that consists of a stack of alternating metal and sequences in less time than it takes to unravel a stethoscope” and could be insulating layers, with the pore drilled through the layers. Sequential elec- a “compelling” technology for personalized genome sequencing, Hagan tric fi elds will pull the DNA through base by base. In 2010, researchers at Bayley, a pioneer in nanopore sequencing at the University of Oxford in IBM T. J. Watson Research Center in Yorktown Heights, New York, published the United Kingdom, wrote in 2010. –E.P. 4 MAY 2012 VOL 336 SCIENCE www.sciencemag.org 536 Published by AAAS

MEETINGBRIEFS>> AMERICAN ASSOCIATION OF PHYSICAL ANTHROPOLOGISTS | 11–14 APRIL 2012 | PORTLAND, OREGON For Early Hominins in Africa, Many two newly discovered partial skeletons of Au. sediba, considered a relative of Au. afri- Ways To Take a Walk canus, shows that this species walked with “excessive” pronation. It landed on its prim- itive, narrow heel and shifted its weight to If the bureaucrats of Monty Python’s Ministry old Orrorin tugenensis, have pushed back the the inside of its sole. “The big question now of Silly Walks were to establish a hall of fame, origins of bipedalism to 6 million years ago is why did it walk this way?” DeSilva says. they might consider inducting Australopithe- (Science, 2 October 2009, p. 36). All this variation in bipedalism shows that cus sediba, who walked with its weight bal- This spring, researchers unveiled the “through much of human evolution, there anced oddly on the inside edge of its soles more primitive foot of a still-unnamed were several experiments in bipedalism about 2 million years ago in South Africa. Or species of Australopithecus from Burtele, going on,” he adds. they might ponder the contrasting way two near Hadar, Lucy’s home in Ethiopia. That One long-standing hypothesis holds that types of australopithecines strolled across showed that at least two kinds of hominins bipedalism arose because it’s energetically the same region of Ethiopia’s Rift Valley walked upright in different ways at the same more effi cient to walk upright on two legs about 3.4 million years rather than on four. But paleoanthropologist ago. While one strode Herman Pontzer of Hunter College in New much like humans do York City and David Raichlen of the Univer- today, the other tucked sity of Arizona in Tucson reported in a poster on May 3, 2012 in its opposable big that that idea doesn’t hold up. They modeled toe and swayed from the energy cost of walking and found that side to side. “The long-legged hominins are energetically effi - take-home message cient because they walk with straight legs, here this morning is with their knees directly over their lower … there were differ- legs. In contrast, the crouched, bent-knee ent ways of being a posture of the earliest hominins, such as good biped through- Ardipithecus, required more muscle activa- www.sciencemag.org out early human evolu- tion and energy. Simply walking on two legs tion,” paleoanthropol- instead of four doesn’t save energy, so the ogist Jeremy DeSilva earliest hominins must have begun walking of Boston University upright for other reasons. Taken together, the re ported. fl urry of new reports suggest to Pontzer that Of course, the Different steps. The Burtele foot from “our models of the origins of bipedalism are walks weren’t silly to Ethiopia (left) and the Au. sediba foot overly simple.” Downloaded from these early hominins, from South Africa show different ways the group that includes of walking upright. humans and our ances- How the Modern Body tors but not other apes. At the time, these time 4 million to 3 million years ago (see gaits were adaptive, and so they shed light http://scim.ag/EarlyAncestor). Shaped Up on how upright walking evolved in differ- In a talk, paleoanthropologist Yohannes ent habitats. Several new studies of incred- Haile-Selassie of the Cleveland Museum Modern humans have gone through a lot of ibly rare fossils of feet and partial skeletons of Natural History in Ohio showed how the changes in the past 30,000 years. We switched reported at the meeting reveal the complex- new foot shared features such as an oppos- from hunting and gathering to farming and ity of early bipedalism. “By seeing subtle able big toe with older Ar. ramidus, which herding; from life as nomads to settling in differences in different species, we’re mov- suggests that both hominins still spent con- urban centers; from eating meat, nuts, and CREDITS (LEFT TO RIGHT): COURTESY OF YOHANNES HAILE-SELASSIE/CLEVELAND MUSEUM OF NATURAL HISTORY; JEREMY DESILVA ing beyond the (simple) debate of whether siderable time in trees. The foot also shared tubers to consuming grains, sugars, and dairy a hominin had a humanlike bipedalism or a key trait (the shape of a toe bone) with products. Now, a remarkably comprehensive not,” says paleoanthropologist Brian Rich- Au. africanus, which lived about 2 million analysis of more than 2000 European skel- mond of George Washington University in years ago in South Africa. Neither of those etons presented at the meeting reveals how Washington, D.C. features is found in Au. afarensis, suggest- these cultural changes have altered our phy- Until recently, many thought that ing that Lucy’s species cannot be the direct siques. “When you become a modern human, upright walking—a defi ning trait of being a ancestor of Au. africanus. That means that what happens to your body?” asked paleo- hominin—evolved step by step in one lin- a second hominin lineage, with a different anthropologist Christopher Ruff of Johns eage relatively quickly, perhaps just before way of walking, must have led to Au. afri- Hopkins University in Baltimore, Maryland, the emergence of Au. afarensis—the species canus, Haile-Selassie notes. (Lucy’s species co-chair of the session on skeletal adaptation of the famous fossil Lucy—about 3.6 million is still the leading candidate for ancestor to in recent Europeans. years ago. But the discovery of older upright early Homo.) While other studies have documented walkers, including the 4.4-million-year-old Meanwhile, DeSilva reported at the a decrease in height after the transition to Ardipithecus ramidus and the 6-million-year- meeting that his analysis of the feet of agriculture, this is the fi rst systematic study 4 MAY 2012 VOL 336 SCIENCE www.sciencemag.org 538 Published by AAAS

NEWSFOCUS Older Dads Have Healthier Kids Than You Think Older fathers often get blamed for passing on genetic mutations to their of younger dads: For each children, causing some types of autism, schizophrenia, and other disorders. additional decade of age in But new data presented at the meeting suggest that children of older fathers fathers at conception, sons and grandfathers may inherit at least one advantage from aging patriarchs: and daughters had 4% longer telomeres, structures at the tips of chromosomes that may protect longer telomeres, a fi nd- against aging and disease. And the effect is amplifi ed over the generations: ing that corroborates ear- “We’ve shown that the paternal grandfather’s age is associated with longer lier work. The Northwest- telomeres in his grandchildren,” graduate student Dan Eisenberg of North- ern group also found that western University in Evanston, Illinois, reported in a talk. for every additional decade Telomeres are repetitive sequences of DNA that prevent the ends of of age in grand fathers, the chromosomes from unraveling, much like the plastic tips on the ends of grandchildren’s telomeres shoelaces. As cells divide and replicate, telomeres get shorter and even- added another 4%. But tually can no longer prevent the fraying of DNA and the decay of aging. grand fathers did not pass Recent studies have found a link between living to 100 and having a on their longer telomeres hyperactive version of telomerase, an enzyme that keeps telomeres long. to their daughters’ chil- Grandfather effect. Older fathers in the Telomeres in sperm cells, however, are exceptional: Several studies dren, only their sons’, sug- Philippines passed on long telomeres to their have shown that they grow longer, not shorter, over the years, probably gesting that this is a pater- sons and grandsons. because telomerase activity is high in testes. As a result, sperm cells from nal effect. on May 3, 2012 older men have longer telomeres than those of younger men. That would The increase in telomere length per year of fathers’ age is just about the suggest that the older a father is at conception, the longer the telomeres same amount as telomere length lost per year in normal aging, Eisenberg his sons and daughters inherit. says. So the longer telomeres in sperm roughly offset normal aging, giving Working with Northwestern biological anthropologist Christopher children of older dads an advantage. “It’s as if you delay reproduction, you Kuzawa and anthropological geneticist Geoff Hayes, Eisenberg examined earn this kind of higher fi tness for your offspring,” says biological anthro- data from a long-term study of 3327 women who were pregnant in 1983 pologist Koji Lum of Binghamton University in New York. in the Cebu Longitudinal Health and Nutrition Survey in the Philippines. Any benefi t in telomere length may still be swamped out by the risk They had gathered the ages of fathers and in 2005 measured telomere of passing on more mutations, Eisenberg warns: “We don’t know yet the www.sciencemag.org length in the blood of 1845 moms and 1681 children. net health effect.” So at the moment, he’s not advising anyone to delay Children of older fathers did indeed have longer telomeres than those fatherhood. –A.G. of how the skeleton changed from the time Bronze Age, 3000 years ago. The modern humans spread through Europe researchers suspect that this stems 30,000 years ago until they were circling from using both arms to make fl our Downloaded from the globe in jets by the 1960s. In 10 post- with grinding stones. ers, Ruff and his colleagues focused on how As for overall height, about each part of the body, from the spine to leg 30,000 years ago, European men and arm bones, evolved over time through stood 1.72 meters tall, almost as tall CREDITS (TOP TO BOTTOM): E. A. QUINN; PETER V. BIANCHI/NATIONAL GEOGRAPHIC COLLECTION both genetic and cultural change. as Europeans today. Their height One of the most signifi cant fi ndings is a and weight dropped steadily until dramatic drop in strength in leg bones. Leg 4000 years ago, probably because bending strength, or resistance to fracture, of poorer nutrition and health, par- declined by 25% to 33% from 27,000 years ticularly with the advent of agri- ago to 1900 C.E., as shown by the cross- culture 10,000 years ago. With a few sectional dimensions of the upper and lower exceptions—for example, milk- leg bones of 1834 men and 786 women, drinking Scandinavians—Europeans according to a poster by Brigitte Holt of the got even shorter during the Medieval University of Massachusetts, Amherst, and period and stayed short until 1900. her colleagues. This is “huge,” Ruff says. Strong-arm tactics. Men had stronger right arms, perhaps The study has produced “an “We interpret this to refl ect the move from a from throwing spears and other activities, before the invention awesomely comprehensive picture hunting-gathering lifestyle to a more seden- of agriculture. of skeletal adaptation,” says bio- tary agricultural lifestyle across Europe.” Our archaeologist Clark Spencer Larsen ancestors needed stronger legs to walk farther, ing. One trend through time is that the right of Ohio State University in Columbus, especially if carrying goods. arm lost much of its asymmetric larger size who was not part of the team. Jay Stock of Over the same 30,000-year period, upper compared to the left arm, perhaps due to the University of Cambridge in the United body strength declined after the introduction fewer strongly lateralized activities such Kingdom agrees that the study is a “major of agriculture. In males, it then increased in as spear throwing. Women show particu- milestone. … It is a major achievement to the Medieval period, possibly due to inten- larly symmetrical arms from the beginning quantify human variation through time and sive upper-body labor such as blacksmith- of agriculture 7000 years ago to Europe’s space with this resolution.” –ANN GIBBONS www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 539 Published by AAAS

COMMENTARY Environmental Blood fl ow effects control 543 546 LETTERS I BOOKS I POLICY FORUM I EDUCATION FORUM I PERSPECTIVES LETTERS edited by Jennifer Sills Food Price Complexities Require Nuance Response I WAS DISAPPOINTED BY J. SWINNEN AND P. SQUICCIARINI’S POLICY FORUM, “MIXED MESSAGES ON KRIPKE TAKES ISSUE WITH THE REFERENCES prices and food security” (27 January, p. 405). Ironically, in making their case that the nuanced we cited in our Policy Forum. We based our challenges of food prices are “too often absent in public debate,” the authors paint a misleading arguments on a thorough analysis of many on May 3, 2012 picture of Oxfam’s positions, lacking exactly the type of nuance they claim to promote. reports and communications of all the insti- To represent Oxfam’s views, the authors cite an obscure press release, the primary pur- tutions we discussed, including Oxfam’s pose of which was to announce celebrity photos. In choosing this source, they excluded (1). For example, a substantive 2008 Oxfam dozens of communications and policy papers on trade and agriculture policy that provide report (2) (written after prices increased) more extensive analysis, some of which directly undermine the authors’ core case. For concludes that “only in a few countries are example, an Oxfam report on the 2008 food price crisis goes to great lengths to describe a small producers benefiting from higher “false dilemma,” arguing that food prices, prices,” and emphasizes that farmers are whether high or low, are like a double- often net consumers who face many con- www.sciencemag.org edged sword bound to hurt either consum- straints, implying that they would ben- ers or producers (1). efi t from lower prices. Yet a 2005 Oxfam Swinnen and Squicciarini also imply report (3) (written before prices started to that maintaining consistent policy positions rise) does not mention that small farmers is bullheaded. They fail to consider that and rural households are net consumers of Oxfam has a coherent understanding of the food. These inconsistencies demonstrate our impact of food prices on poor people. We points. Kripke argues that the issue of food Downloaded from have highlighted both the dangers of dras- security is too complex to fi t into a head- tic price spikes (2) and the hazards of unfair line, but we found simplistic explanations in trade policies for poor farmers (3). If the lengthy reports as well. messages seem “mixed” at fi rst glance, it is We agree with Kripke that massive sub- because the problems are complex and not sidies for agriculture in rich countries are an well suited to headline-length explanation. ineffi cient way to reduce food prices for poor Providing massive subsidies for agriculture in rich countries is unfair and an extremely people. However, tariffs on food imports are ineffi cient way to reduce food prices for poor people (1); likewise, spiraling food prices ineffi cient as well (4, 5), as a policy instru- can harm vulnerable people, so measures to moderate the price volatility and mediate the ment to address farmers’ weaknesses and impacts on poor families are needed. If one’s concern is for the well-being and livelihoods of certainly as a mechanism to reduce food poor people, as ours is, then these are consistent positions. prices for poor people. Yet Oxfam has Ultimately, the authors’ argument rests on the idea that press releases are not nuanced defended these policies, both before (6) and enough and advocacy messages oversimplify problems. This may be a compelling revelation after (2) the food price crisis. for some academics. But in the real world, where Oxfam works to respond to emergencies, Finally, our concerns did not emerge fi ght special interests, and empower the most vulnerable, we recognize that some measure of from “academic” considerations. We are simplicity and accessibility in our messaging is required to achieve change. intensely involved in policy discussions on GAWAIN KRIPKE food policy and poverty (7–9), and we have Oxfam America, Washington, DC 20005, USA. E-mail: [email protected] seen fi rsthand that the absence of nuance in communications and reports has real-world implications on public debate and decision- References 1. Oxfam International, “Double-edged prices” (Oxfam Briefi ng Paper 121, 2008); www.oxfamamerica.org/fi les/ making. For instance, there is currently CREDIT: DON BAYLEY/ISTOCKPHOTO.COM double-edged-prices.pdf. extensive lobbying about the future of Euro- 2. Oxfam International, “Global food prices in 2011: Questions & answers” (www.oxfam.org/en/campaigns/agriculture/ pean agricultural policy—at stake are about food-price-crisis-questions-answers). 3. J. M. Alston, D. A. Sumner, H. Brunke “Impacts of reductions in US cotton subsidies on West African cotton producers” US$500 billion of farm subsidies over the (Oxfam America, Boston, MA, 2007); www.oxfamamerica.org/fi les/paying-the-price.pdf. next 7 years. Pressure groups are referring 4 MAY 2012 VOL 336 SCIENCE www.sciencemag.org 540 Published by AAAS

Ice sheets and Biodiversity and country. The only way out is to adopt strict sea-level change ecosystem function peer-review rules for the allocation of all research funds, at all times. 550 552 IGNAZIO ROBERTO MARINO Department of Surgery, Jefferson Medical College, Philadel- phia, PA 19107, USA, and Senate of the Republic of Italy, Piazza Madama snc, 00186 Rome, Italy. E-mail: ignazio. [email protected] to simplistic statements about the effects of policy post-2013” (Copa-Cogeca, Brussels, 2010); CORRECTIONS AND CLARIFICATIONS high food prices on poverty and food secu- www.copa-cogeca.be/img/user/fi le/7142_PAC_E.pdf. 11. European Landowners’ Organization (ELO), BirdLife Letters: “Finding a good research question, in theory” by rity to argue that these subsidies are help- International, “Proposals for the future CAP: A joint posi- N. Bodemer and A. Ruggeri (23 March, p. 1439). The vol- ing to address global food security (10, 11). tion from the European Landowners’ Organization and ume in Reference 1 should be 52, not 57. The correct refer- Those who do not realize that simplistic BirdLife International” (ELO and BirdLife International, ence is: A. W. Kimball, J. Am. Stat. Assoc. 52, 133 (1957). Brussels, 2010); www.birdlife.org/eu/pdfs/Proposal_for_ messages may lead to undesirable policy the_future_cap_FINAL_21_01_2010.pdf. News & Analysis: “New institute aims to help academ- outcomes are the ones who seem to live in ics make medicines” by R. F. Service (16 March, p. 1288). an ivory tower. A Step Backward Merck should have been referred to as Merck & Co. based in 1,2 JOHAN SWINNEN AND Whitehouse Station, New Jersey. 1,3 PASQUAMARIA SQUICCIARINI * for Italy’s Meritocracy Reports: “Sexual deprivation increases ethanol intake in 1 LICOS Centre for Institutions and Economic Performance Drosophila” by G. Shohat-Ophir et al. (16 March, p. 1351). and Department of Economics, University of Leuven, Leu- ITALIAN SCIENTISTS HAVE LONG LAMENTED THE In the abstract of the print version, the sentence “Activation on May 3, 2012 2 ven, 3000, Belgium. Center for Food Security and the Envi- or inhibition of the NPF system in turn enhanced or reduced ronment, Stanford University, Palo Alto, CA 94305, USA. lack of resources, political attention, and ethanol preference” should read: “Activation or inhibition 3 Anderson School of Management, University of California meritocracy in assigning taxpayers’ money. of the NPF system in turn reduced or enhanced ethanol Los Angeles, Los Angeles, CA 90095, USA. In 2007, things began to change. The 2007 preference.” The error has been corrected in the HTML and and 2008 national budget laws allocated PDF versions online. *To whom correspondence should be addressed. E-mail: [email protected] €81 million (US$107 million) to projects Editorial: “Worldwide lessons from 11 March” by K. Omi (9 submitted by researchers under 40 years old. March, p. 1147). The Editorial referred to “statement issued References They were judged by an international com- in October 2010 by the Science and Technology in Society 1. J. F. M. Swinnen, Dev. Pol. Rev. 29, 667 (2011). mittee of scientists under age 40 that was forum.” The statement was issued in 2011. The date has www.sciencemag.org 2. Oxfam International, “Double-edged prices” (Oxfam been corrected in the HTML and PDF versions online. Briefi ng Paper 121, 2008); www.oxfamamerica.org/fi les/ appointed according to impact factor and double-edged-prices.pdf. citation index scores. Even though this fund 3. Oxfam International, “A round for free” (Oxfam Briefi ng accounted for only 10% of the entire pub- TECHNICAL COMMENT ABSTRACTS Paper 76, 2005); www.maketradefair.com/en/assets/ english/aroundforfree.pdf. lic research money, it was a crucial turning 4. J. Brooks, Ed., Agricultural Policies for Poverty Reduction point toward meritocracy. Finally, the inter- Comment on “Global Resilience (OECD Publications, Paris, 2012). national rules of peer review were entering of Tropical Forest and Savanna to 5. World Bank, Agriculture for Development; World the Italian system, acknowledging meritoc- Development Report 2008 (World Bank Publications, Critical Transitions” Downloaded from Washington, DC, 2008). racy and setting researchers free from the Zak Ratajczak and Jesse B. Nippert 6. Oxfam International, “The rural poverty trap” (Oxfam virtual servitude under which they had been Briefi ng Paper 59, 2004); www.tanzaniagateway.org/ kept by old academicians. Hirota et al. (Reports, 14 October 2011, p. 232) used docs/Why_agricultural_trade_rules_need_to_change_ Recently, inexplicably, Italy has fallen spatial data to show that grasslands, savannas, and for- and_what_UNCTAD.pdf. ests represent opposing stable states. Reanalyzing their 7. Bureau of European Policy Advisers, EU Budget Review— back to the old way of allocating taxpayers’ data and drawing from temporal studies, we argue that Workshops (http://ec.europa.eu/dgs/policy_advisers/ research money and has done so in spite of spatial analyses underestimate the bistability of grass- activities/conferences_workshops/budget3_en.htm). government promises of open competition lands and savannas due to limitations of substituting 8. CEPS, 1st Brussels High Level Lecture on Food Security and meritocracy. The so-called “Simplifi ca- space for time. We propose that temporal and spatial and Development (www.ceps.eu/content/1st-brussels- data are needed to predict critical transitions between high-level-lecture-food-security-and-development). tion Decree” includes anti-crisis measures grasslands and savannas. 9. FAO Investment Centre, Investment Days—Staff Invest suggested by several departments, includ- Full text at www.sciencemag.org/cgi/content/full/336/ Time in Sharing Their Work (www.fao.org/investment/ ing the one led by the Minister of Educa- 6081/541-c newsandmeetings/meetings-archive/detail/en/?dyna_ tion, University, and Research: Francesco fef%5Buid%5D=48875). Response to Comment on “Global 10. Copa-Cogeca, “The future of the common agricultural Profumo. He has canceled the articles of the laws that brought peer review to Italy, Resilience of Tropical Forest and explaining that the method introduced in Savanna to Critical Transitions” Letters to the Editor 2007 was too cumbersome to apply. Min- Egbert H. Van Nes, Milena Holmgren, Marina Letters (~300 words) discuss material published in ister Profumo now promises a new, simpler Hirota, Marten Scheffer Science in the past 3 months or matters of gen- law, but for the time being, young research- Ratajczak and Nippert note that transient states between eral interest. Letters are not acknowledged upon ers applying for grants in Italy will have to treeless and savanna states are more common than receipt. Whether published in full or in part, Let- rely on the old questionable, nontransparent between savanna and forest, and suggest that this can be ters are subject to editing for clarity and space. evaluation method that rewards clients of explained by a slower rate of change in the intermediate Letters submitted, published, or posted elsewhere, godfathers, rather than merit. conditions at drier sites. We show that probability distri- in print or online, will be disqualifi ed. To submit a butions of tree cover rather refl ect the interplay between Letter, go to www.submit2science.org. It is not only money for valuable research- intrinsic rates of change and perturbation regimes. ers that will be lacking from now on, but Full text at www.sciencemag.org/cgi/content/full/336/ hope for their future and for that of the 6081/541-d www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 541 Published by AAAS

Comment on ''Global Resilience of Tropical Forest and Savanna to Critical Transitions'' Zak Ratajczak and Jesse B. Nippert Science 336 , 541 (2012); DOI: 10.1126/science.1219346 This copy is for your personal, non-commercial use only. If you wish to distribute this article to others , you can order high-quality copies for your colleagues, clients, or customers by clicking here. Permission to republish or repurpose articles or portions of articles can be obtained by following the guidelines here. The following resources related to this article are available online at on May 3, 2012 www.sciencemag.org (this information is current as of May 3, 2012 ): Updated information and services, including high-resolution figures, can be found in the online version of this article at: http://www.sciencemag.org/content/336/6081/541.3.full.html A list of selected additional articles on the Science Web sites related to this article can be found at: www.sciencemag.org http://www.sciencemag.org/content/336/6081/541.3.full.html#related This article cites 15 articles , 2 of which can be accessed free: http://www.sciencemag.org/content/336/6081/541.3.full.html#ref-list-1 Downloaded from This article has been cited by 1 articles hosted by HighWire Press; see: http://www.sciencemag.org/content/336/6081/541.3.full.html#related-urls Science (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. Copyright 2012 by the American Association for the Advancement of Science; all rights reserved. The title Science is a registered trademark of AAAS.

TECHNICAL COMMENT peak magnitude when the proportion of two op- posing stable states is equal (Fig. 1). Peaks probably occur at these junctures because the attraction Comment on “Global Resilience of to any one stable state is not particularly strong, making the system more response to internal and Tropical Forest and Savanna external variation, and the unstable intermediates slightly more stable than usual. to Critical Transitions” savanna intermediate is actually common at some More surprisingly, we found that the grassland- levels of precipitation (Fig. 1). The grassland- Zak Ratajczak* and Jesse B. Nippert savanna intermediate reaches a ~13.5% frequency for both 600 and 900 mm precipitation per year, Hirota et al. (Reports, 14 October 2011, p. 232) used spatial data to show that grasslands, which is 30% of either stable state and equivalent 2 savannas, and forests represent opposing stable states. Reanalyzing their data and drawing to 2000 km (1). This frequency is impressive con- from temporal studies, we argue that spatial analyses underestimate the bistability of grasslands sidering that the grassland/savanna intermediate and savannas due to limitations of substituting space for time. We propose that temporal and only encompasses a 5% tree cover range, compared spatial data are needed to predict critical transitions between grasslands and savannas. with an average range of 25% for stable states and a 10% range for the savanna/forest interme- etermining the bistability of tree cover To test the potential influence of confounding diate. In contrast, the savanna/forest intermediate is critical to forecasting how terrestrial factors, we reanalyzed frequency diagrams of peaks for just one value of mean annual precip- Decosystems will respond to global change. tree cover from Hirota et al.(1), reporting the itation (MAP) and reaches a 7% frequency (i.e., Using spatial satellite data, Hirota et al.(1) found frequency of unstable intermediates as discrete 15% as common as the opposing savanna/forest on May 3, 2012 that tree cover in the tropics and subtropics is states, instead of including them as part of the states). distinctly trimodal: Areas with a tree cover of 0 savanna state. We used the same tree-cover classes The low frequency of the savanna-forest in- to 5% (grassland), 10 to 50% (savanna), or 60 to as (1) because a limited number of sites were termediate suggests that savannas and forests 80% (forest) predominate, whereas ecosystems used to calibrate low tree cover of satellite data are highly bistable and that state shifts could with a tree cover of ~5 to 10% (grassland/savanna (2), making narrower tree-cover classes inap- occur rapidly in low-resilience areas identi- intermediate) and ~50 to 60% (savanna/forest in- propriate. However, we note that using narrower fied by Hirota et al.(1). The high frequency termediate) are comparatively rare. The authors tree-cover classes results in similar, if not more of the grassland/savanna intermediate could propose that the frequency of these tree-cover dramatic, results than those reported below [figure indicate that grasslands and savannas are less www.sciencemag.org ranges is proportional to stability and, thus, low- S1 in (1)]. bistable but several lines of evidence suggest frequency ranges of tree cover constitute unstable Along a precipitation gradient, the frequency that this over-representation is due to slow tran- intermediates situated between high-frequency of both unstable intermediate types reaches their sition rates in semiarid ecosystems (600 mm stable states. These spatial analyses can reach un- paralleled levels of replication but are limited by Grassland Grass-Sav Intermediate Savanna Sav-For Intermediate Forest an inability to distinguish between environmental 1.0 variability and error due to substituting space for time. In this comment, we test assumptions of spa- Downloaded from tial analyses by reanalyzing data from Hirota et al. 0.8 (1) to determine the frequency of unstable states. Our results suggest that spatial techniques accu- rately capture savanna-forest bistability but under- 0.6 estimate the bistability of grasslands and savannas. Spatial analyses of bistability ultimately seek Frequency to quantify temporal processes. Even if all patches of vegetation are strictly bistable, patches with 0.4 an “unstable” level of tree cover occur as patches transition from one stable state to another. In a given area, the frequency of “unstable intermedi- 0.2 ates” will be greater when (i) state changes occur slowly; (ii) state changes occur frequently; and (iii) patches do not conform to stable-state dy- 0.0 namics and exist as otherwise unstable levels of 0 600 1200 1800 2400 tree cover. The first two factors are confounding Mean Annual Precipitation (mm/yr) and will make unstable intermediates appear stable Fig. 1. The frequency of unstable states: grassland/savanna intermediate (black) and savanna/forest across space, even if they are unstable across time. intermediate (green), compared with the frequency of stable states: treeless (yellow), savanna (orange), Differentiating these transitional patches from non- and forest (red). Following Hirota et al.(1), the grassland/savanna intermediate is all areas with a tree bistable patches is impossible with temporally cover of 5 to 10%, the savanna/forest intermediate is 50 to 60%, the grassland state is 0 to 5%, the limited satellite data. savanna state is 10 to 50%, and the forest state is 60 to 80%. Even though the unstable range for savanna/forest is smaller for some continents (e.g., 55 to 60%), we used this wider range of 50 to 60% Division of Biology, Kansas State University, 116 Ackert Hall, because the results presented by (1) consider all continents together. Thus, the frequency of the savanna/ Manhattan,KS66506,USA. forest intermediate should be considered to be an overestimate. Curves are fit to frequency diagrams *To whom correspondence should be addressed. E-mail: using the same logistic regression model as Hirota and colleagues (1). Data encompass the tropics and [email protected] subtropics of Africa, Australia, and South America, excluding mountainous and developed areas. SCIENCE 541-c www.sciencemag.org VOL 336 4 MAY 2012

TECHNICAL COMMENT Table 1. A summary of existing fine-scale studies on grassland/savanna transitions over time. highly susceptible to critical transitions. We argue that these techniques are appropriate for savanna- Min. Max. Min. forest transitions but that temporal studies are MAP Transition transition transition time- Transition Woody needed to properly quantify grassland-savanna Country plant Ref.† (mm) type time time step mechanism bistability and predict how these ecosystems will type (years) (years) (years)* respond to global change (Fig. 1, Table 1). It will North America 300 Grassland→ 5 37 5 Soil Shrubs (12) be 10 to 20 years before Moderate-Resolution Savanna feedbacks Imaging Spectroradiometer (MODIS) data can North America 600 Savanna→ 2 >2 2 Acute Trees (14) provide such temporal records; therefore, identi- Grassland drought fying existing records is crucial to understanding North America 635 Savanna→ 5 >5 5 Fire/soil Trees (11) and predicting often-catastrophic tree-cover state Grassland feedbacks shifts in grasslands and savannas. Swaziland 675 Grassland→ 8 50 8 Grazing/fire Shrubs (10) Savanna manipulation References and Notes Botswana 680 Grassland→ 3 – 3 – Trees (15) 1. M. Hirota, M. Holmgren, E. H. Van Nes, M. Scheffer, Savanna Science 334, 232 (2011). North America 850 Grassland→ 2 – 1 Fire feedbacks Tall (9) 2. M. C. Hansen et al., Earth Interact. 7, 1 (2003). Savanna shrubs 3. W. J. Bond, G. F. Midgley, F. I. Woodward, S. Afr. J. Bot. 69, 79 (2003). *Minimum time-step refers to the minimum number of years between temporal samplings. This variable is included so that 4. N. N. Barger et al., J. Geophys. Res. Biogeosci. 116, minimum transition rates can be compared to the minimum transition rates detectable by each study. †We identified G00K07 (2011). studies using the Thomson Reuters Web of Knowledge (wokinfo.com) and searching for “‘tree cover’ time.” We included 5. Z. Ratajczak, J. B. Nippert, S. L. Collins, Ecology 93, 697 only studies with reasonably small time-steps between sampling and excluded areas where the grassland state was (2012). dominated by C 4 grasses (the dominant type of grasses in most tropical and subtropical grasslands). 6. P. D’Odorico, G. S. Okin, B. T. Bestelmeyer, on May 3, 2012 Ecohydrology, published online 20 October 2011; 10.1002/eco259 precipitation per year) and frequent state tran- silience is qualitatively lower than that of semi- 7. A. C. Staver, S. Archibald, S. A. Levin, Science 334, sitions in mesic ecosystems (900 mm precip- arid ecosystems, which can withstand several 230 (2011). 8. S. Archibald, D. P. Roy, B. W. Van Wilgen, R. J. Scholes, itation per year). decades of exogenous forcing before under- Glob. Change Biol. 15, 613 (2009). In semiarid regions, population growth rates, going a state change [e.g., (11, 12)]. 9. Z. Ratajczak, J. B. Nippert, J. C. Hartman, T. W. Ocheltree, especially for trees and shrubs, should be limited The limited number of temporal tree-cover Ecosphere 2, art121 (2011). by water availability (1, 3–5). Likewise, the pri- records supports our hypothesis that grassland/ 10. K. G. Roques, T. G. O’Connor, A. R. Watkinson, J. Appl. mary feedback mechanism responsible for semi- savanna transitions occur slowly in drier ecosys- Ecol. 38, 268 (2001). www.sciencemag.org 11. R. J. Ansley et al., Rangeland Ecol. Manag. 63, 286 arid state shifts (changes in soil properties) can tems (Table 1). For example, it takes ~35 years (2010). take decades to act but creates highly stable states for desert grassland to increase from 5 to 10% 12. D. M. Browning,A.S. Laliberte, A.Rango, Int. J. Geogr. Inf. in the process (6). Together, these factors should shrub cover (12), whereas the fire-driven tran- 25, 913 (2011). make semiarid state shifts less frequent, but slow sition of wetter tallgrass prairie to savanna can 13. M. Hirota, C. Nobre, M. D. Oyama, M. M. C. Bustamante, New Phytol. 187, 707 (2010). when they occur. occur in 2 years (9). Temporal studies also sup- 14. M. J. Clifford,N.S.Cobb, M. Buenemann, Ecosystems (N.Y.) In mesic areas, grassland/savanna transi- port the ideas that grasslands and savannas are 14, 949 (2011). tions should occur quickly because population opposing stable states and that 5 to 10% tree cover 15. J. M. Kalwij et al., Ecol. Appl. 20, 222 (2010). growth is less water-limited (1, 3–5) and, along is also an unstable ecosystem state across space Downloaded from with savanna/forest transitions, these transi- (1) and time (Table 1). In both tallgrass prairie of Acknowledgments: We thank S. M. Matherly, J. M. Blair, T. W. Ocheltree, A. C. Staver, and S. Archibald for valuable tions are almost exclusively facilitated by fire North America and savanna of southern Africa, input on an earlier version of this comment. This work was (3, 5, 7). Fire feedbacks have an almost im- the cover of tall shrubs increases slowly when the supported by the Konza Prairie LTER Program (DEB-0823341). mediate effect and are more easily reversed system is within 0 to 5% cover, but increases rap- Z.R. was supported by a Graduate Assistance in Areas of (3, 8, 9), which should theoretically lead to idly and consistently when the system is between National Need fellowship from the U.S. Department of Education. quicker, but more frequent, state shifts. Indeed, 5 and 10% cover (9, 10). dramatic tree-cover changes have occurred in Spatialdataandnoveltechniques[e.g.,(1,7,13)] Africa and North America after just 10 to 20 can greatly expand the understanding of tree- 19 January 2012; accepted 22 March 2012 years of fire manipulation (3, 9, 10). This re- cover stable states and identify areas that are 10.1126/science.1219346 541-c 4 MAY 2012 VOL 336 SCIENCE www.sciencemag.org

Response to Comment on ''Global Resilience of Tropical Forest and Savanna to Critical Transitions'' Egbert H. Van Nes et al. Science 336 , 541 (2012); DOI: 10.1126/science.1219711 This copy is for your personal, non-commercial use only. If you wish to distribute this article to others , you can order high-quality copies for your colleagues, clients, or customers by clicking here. Permission to republish or repurpose articles or portions of articles can be obtained by following the guidelines here. The following resources related to this article are available online at on May 3, 2012 www.sciencemag.org (this information is current as of May 3, 2012 ): Updated information and services, including high-resolution figures, can be found in the online version of this article at: http://www.sciencemag.org/content/336/6081/541.4.full.html A list of selected additional articles on the Science Web sites related to this article can be found at: www.sciencemag.org http://www.sciencemag.org/content/336/6081/541.4.full.html#related This article cites 5 articles , 2 of which can be accessed free: http://www.sciencemag.org/content/336/6081/541.4.full.html#ref-list-1 Downloaded from Science (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. Copyright 2012 by the American Association for the Advancement of Science; all rights reserved. The title Science is a registered trademark of AAAS.

TECHNICAL COMMENT erning mechanisms in such large complex systems will inevitably require a multifaceted approach (5), and the potential analysis is a modest but useful Response to Comment on “Global addition to the toolbox we have. Importantly, the frequency of intermediate Resilience of Tropical Forest and states does not imply that bistability would be underestimated, as suggested by Ratajczak and Nippert. As the results in Fig. 1 illustrate, rather Savanna to Critical Transitions” than a problem, slowness of transients and sto- chasticity are actually a prerequisite for detect- ing basins of attraction. Obviously, there is a 1 2 1 Egbert H. Van Nes, * Milena Holmgren, Marina Hirota, Marten Scheffer 1 limit to that, in the sense that attraction basins are no longer found if stochasticity overwhelms Ratajczak and Nippert note that transient states between treeless and savanna states are the rates of return to underlying attractors. How- more common than between savanna and forest, and suggest that this can be explained by a ever, in such situations, the relevance of alter- slower rate of change in the intermediate conditions at drier sites. We show that probability native attractors is questionable. The elegance of distributions of tree cover rather reflect the interplay between intrinsic rates of change and the potential analysis is that the results directly perturbation regimes. reflect the interplay between stochasticity and determinism that shapes the dynamics of ecosys- lthough the concept of a stable state is a experiments are better in this sense but are not tems in nature. The fact that we find three distinct useful abstraction, fluctuations in the en- easy to realize at relevant scales of time and space. modes in the frequency distributions of tropical A vironment and perturbations prevent Unraveling the stability properties and their gov- tree cover indicates that alternative attractors are on May 3, 2012 ecosystems from being in a stationary stable state. Our approach to reconstruct the alterna- tive states and their basins of attraction (1)is based on the idea that the probability distribu- tion of states reflects the balance of such stochas- ticity with the tendency to return to underlying attractors. To illustrate this, we simulate dynamics of a www.sciencemag.org simple model with alternative stable states, sub- ject to stochastic forcing (Fig. 1). The system tends to be farther away from the equilibrium if its dynamics are slower (Fig. 1B) but also if the level of stochastic forcing is higher (Fig. 1D). Al- though it seems plausible that the transition from a treeless state to savanna is slow, one cannot directly deduce that from the stability landscapes. Downloaded from Also, the results from six (mostly nontropical) studies on treeless-savanna transitions summa- rized in table 1 of Ratajczak and Nippert (2)are too variable to infer the suggested relationship between rainfall and rates of change. This is not surprising in view of the likely role of factors such as initial tree cover, grazing, soils, and other factors that will differ between the cases. We do not agree that our substitution of space for time would be problematic for reconstructing stability landscapes. As sampled points from sat- ellite images can be considered snapshots from different time series, the theory, albeit original- Fig. 1. The effect of the speed of change and the noise level to the occurrence of transient states in a ly developed for time series (3), still holds. Al- simple bistable model. We use a stochastic version of a classical model of an exploited population (6) though we fully agree that there is an urgent need 2 N for long-term research, time series are certainly (N): dN = g rN 1 – N – c H 2 +N 2 dt + NdW,where r is the growth rate, K the carrying capacity, K no panacea when it comes to inferring the exis- c the maximum grazing rate, H the half-saturation of the Holling type II functional response, W anormally tence of multiple attractors (4). Controlled field distributed Wiener process, and the scaling factor g is used to tune the slowness of the system. To obtain snapshots of this model in time, we drew 1000 random initial conditions (between 0 and 10) and ran the model for 1100 steps. The first 100 steps were discarded, and after that, for each 100 steps one value was 1 Department of Aquatic Ecology and Water Quality Man- saved. We analyzed these values using potential analysis (1, 3). The nonstochastic version of the model agement, Wageningen University, Post Office Box 47, NL-6700 2 AA, Wageningen, Netherlands. Resource Ecology Group, canhavetwo alternativestablestatesoverarange of conditions (A). The red dashed line indicates the Wageningen University, Post Office Box 47, NL-6700 AA, used grazing rate. The probability density function (pdf) and the estimated potentials (3)are calculated Wageningen, Netherlands. for (B) a slow system (g =0.03);(C) the default conditions (g =1; c =2.1; H =1; K =10; r =1;and  = *To whom correspondence should be addressed. E-mail: 0.05) [the bandwidth of the kernel distribution was twice the default value (3)to get acontinuous [email protected] potential]; and (D) a highly stochastic system  =0.2. SCIENCE 541-d www.sciencemag.org VOL 336 4 MAY 2012

TECHNICAL COMMENT sufficiently pronounced to dominate dynamics de- 2. Z. Ratajczak, J. B. Nippert, Science 336,541 5. M. Scheffer, Critical Transitions in Nature and spite stochasticity and slow transients. (2012); www.sciencemag.org/cgi/content/full/336/ Society (Princeton Univ. Press, Princeton and Oxford, 6081/541-c. 2009). 3. V. N. Livina, F. Kwasniok, T. M. Lenton, Climate of the 6. R. M. May, Nature 269, 471 (1977). References Past 6, 77 (2010). 1. M. Hirota, M. Holmgren, E. H. Van Nes, M. Scheffer, 4. M. Scheffer, S. R. Carpenter, Trends Ecol. Evol. 18, 648 13 February 2012; accepted 22 March 2012 Science 334, 232 (2011). (2003). 10.1126/science.1219711 on May 3, 2012 www.sciencemag.org Downloaded from 541-d 4 MAY 2012 VOL 336 SCIENCE www.sciencemag.org

BOOKS ET AL. LITERARY CRITICISM sell Banks’s depiction of economic and eco- logical connections in the northeast United The Place of Words States, many of these close textual readings will not be of particular interest. It’s worth noting, though, that many contributors do an Christopher Cokinos excellent job of showing their natural history chops in contextualizing the poems, essays, A editors explain in a useful introduction, bio- and fiction under consideration. As well, conference room in a Reno casino regionalism sought “to address matters of readers can fi nd moments of example praxis was the unlikely birthplace in 1992 of the Association for the Study of Literature and Environment (ASLE). It pressing environmental concern through a in articles even about material that may not be personally or environmentally compelling. politics derived from a local sense of place, formed because many literary critics and an approach ... [that] would effectively com- For example, one essay reveals the fascinat- nature writers felt that English departments plement efforts focused at the national and ing ways strollers encounter an installation of needed to add place and international levels.” A kind Sherman Alexie’s poem “That Place Where environment to the lenses of rooted counterculture the Ghosts of Salmon Jump” in Spokane. of race, class, gender, and The Bioregional Imagination of art and activism, biore- Two chapters that likely will interest a arcane philosophical forms Literature, Ecology, and Place gionalism contrasted with broader range of scientists, especially ecolo- of literary criticism such as by Tom Lynch, Cheryll Glotfelty, the corporate-style envi- gists and anthropologists, consider science- deconstruction when eval- and Karla Armbruster, Eds. ronmentalism that began to fiction authors Ursula Le Guin and Frank uating texts of all kinds— University of Georgia Press, take hold with such groups Herbert, and both papers are mostly free of from traditional nature Athens, GA, 2012. 454 pp. $69.95. as the National Audubon the often-dense jargon that (still and alas) on May 3, 2012 writing to, say, car com- ISBN 9780820341712. Paper, Society during the era of big obfuscates much prose in literary studies mercials fi lmed in apparent $24.95. ISBN 9780820335926. federal legislation. Biore- these days. (The same cannot be said of all wilderness settings. Impor- gionalists typically point to the contributions; e.g., Anne Milne’s discus- tantly, ASLE was an offshoot of a place- similar geographic features and watersheds sion of ferality and bioregionalism will be based literary studies organization, the when they try to defi ne the local; they also hard going unless you are used to critical the- Western Literature Association. From the insist on place-based expressions of citizen- ory and the deployment of a great deal to say start of this organized “ecocritical” move- ship, which include poems, essays, stories, something simple.) This inclusion of science- ment, then, linking textual study to environ- and art of all kinds. fi ction studies in a text essentially focused on www.sciencemag.org mental awareness was fi ltered through an This hefty critical collection contains a place-based realist work is a breath of fresh emphasis on the local, on place itself. diverse mix of close readings of place-based air and a continuing acknowledgment that While some critics, such as Ursula Heise, texts, philosophical discussions of bioregion- there are important intellectual connections have pushed back—arguing for a more glob- alism, and practical advice on engaging the between these two genres—each, after all, ally infl ected approach to studying the rela- public and students in bioregional studies that being concerned with change. tions among environments, texts, animals, combine science and creative expression. It is It’s really the last two sections that may plants, and people—the bulk of ecocriticism this latter category of work that will be most shine brightest for conservation-minded Downloaded from partakes of an investment in the local because useful to readers of Science. The anthology scientists. “Reimagining” includes two the bulk of nature writing does so. And has an international fl avor, with contributions pieces that give bioregionalist perspectives to speak of the local is to ask just what we on places in the United States, Canada, South of large territories—Australia (with a focus mean by that. The question is not academic. Africa, Nigeria, Australia, and Italy. Nature on nomadic connections to the local) and As The Bioregional Imagination makes very writing and ecocriticism have been criticized the circumpolar north—as well as an anal- clear, it is ecological and historical. To under- as being elitist, white, and First World. Those ysis of the work of South African marine stand literary expressions of the environment seeking a range of work that defi es this ste- biologist–poet Douglas Livingstone and his is almost always to grapple with place, with reotype will fi nd the volume welcome. surprisingly lyrical explorations triggered scales of place, and, therefore, to encounter Following the editors’ overview, a relaxed by water-quality monitoring. Most useful (or be immersed in) “bioregionalism.” narrative conversation with two bioregion- of all are the descriptions (in “Renewal”) The anthology’s editors—well-known alist pioneers, David Robertson and Robert of three classes: Canadian Laurie Ricou’s writers and ecocritics Tom Lynch, Cheryll L. Thayer Jr., serves to introduce some of habitat studies course (his contribution Glotfelty, and Karla Armbruster—note: “As the philosophy and history associated with is a compelling hybrid of an essay and a part of the development of the environmen- bioregionalism. The fi rst section (“Reinhabit- syllabus, a really engaging read, and a tal movement during the 1970s, a school of ing”) continues with essays about public bio- course I plan on using), Kentuckian Wes thought emerged calling itself bioregion- regional projects in Spartanburg, South Car- Berry’s energy-focused eco-literacy general- alism. Located primarily in western North olina, and Chicago, Illinois, which inspired education class, and New Englander Laird America, especially California and British everything from local atlases to anthologies of Christensen’s discussion of an online master Columbia, this movement included think- place-based writing. Much of the material in of science in environmental studies at Green ers such as Peter Berg, Raymond Dasmann, here and in the second section (“Rereading”) Mountain College. These are well suited for Gary Snyder, and Stephanie Mills.” As the may be best suited for casual page-fl ipping. adaptation in either humanities or science Bioregionalist works, by defi nition, have a courses—or, better yet, for team teaching. local fl avor. So unless you know (or want to Rounding out the anthology are an engag- The reviewer is at the Department of English, University of Arizona, Post Ofi ice Box 210067, Tucson, AZ 85721, USA. know) about Italy’s Po Valley, Australian Bev- ing and perceptive discussion of student atti- E-mail: [email protected] erley Farmer’s novel The Seal Woman, or Rus- tudes by Unity College’s Kathryn Miles and 4 MAY 2012 VOL 336 SCIENCE www.sciencemag.org 542 Published by AAAS

BOOKS ET AL. Mitchell Thomashow and Kyle Bladow’s Topeka, 1953. Linda and Terry Lynn Brown helpful bioregionalist book list. walking to their school bus stop. Overall, The Bioregional Imagination makes a valuable contribution to the Venn environmental histories of the pivotal diagram fi eld of ecocriticism, where liter- election of 1800, the legendary sit- ature, science, and, yes, activism, can and down strikes in the auto industry in the should coexist. If the contents are of vary- late 1930s, and the conservative move- ing interest to specifi c readers, that’s to be ment since the 1980s might look like. expected. Your locale may not speak to me. Practicing scientists will fi nd lit- But it’s reassuring to know that from places tle grist for their professional mills I may not be especially interested in there in Fiege’s pages. They may need little comes creativity rooted in the ground and convincing that nature is always pres- crafted with a natural historian’s approach ent in history in one way or another. to understanding the world almost literally Fiege wrote the book for his fellow at hand. historians, steeped in their standard 10.1126/science.1221362 accounts of American history, and for their students, struggling to under- stand these accounts. Both audiences HISTORY are unaccustomed to seeing a role for the environment in the important The Environment parts of American history. Nature on May 3, 2012 typically makes only cameo appear- Makes History ances in connection with Theodore Roosevelt and the fi rst conservation J. R. McNeill movement of a century ago, the 1930s Indeed, Fiege (a historian at Colorado Dust Bowl, or the rise of popular environ- hile seated at a diplomatic din- State University) thinks that everything in mentalism in the 1960s and 1970s. But for ner in Paris in the 1780s, Benja- American history has environmental com- readers swayed by Fiege’s persuasive pages, Wmin Franklin sought to refute the ponents to it. In The Republic of Nature, he American history will never look quite the www.sciencemag.org Comte de Buffon’s famous contentions that in argues the case by selecting nine familiar same again. America a decadent nature produced degen- episodes in U.S. history; recounting them Environmental historians will fi nd Fiege erate human beings. at chapter length; and stands their fi eld on its head. He intention- Franklin asked the com- The Republic of Nature emphasizing how the ally skips over Henry David Thoreau and pany, half Americans An Environmental History environment constrained Aldo Leopold, the national parks movement, and half Frenchmen, to of the United States freedom of action, how the Dust Bowl, and the agro-ecosystems of rise and judge for them- by Mark Fiege the events changed the California. He has only a little to say about Downloaded from selves. They did. As one University of Washington Press, Seattle, environment, or how the West, the arena where U.S. environmental of the Americans saw 2012. 600 pp. $34.95. ISBN 9780295991672. participants’ thoughts history was born, and the standard fare of that it, “there was not one Weyerhaeuser Environmental Books. about nature affected history is conspicuous by its absence. This is American present who their actions. So, for unconventional environmental history just as could not have tost out example, he presents the it is unorthodox American history. of the Windows one or perhaps two of the 1954 Supreme Court case Brown v. Board of Practicing scientists might enjoy the book rest of the Company, if this effort depended Education in an unorthodox way, in which even if it provides them no grist. They may merely on muscular force.” Franklin’s strap- social change and ideologies take a back seat need no convincing that nature matters, but ping Americans did not have to defenestrate to the racial geography of Topeka, Kansas, they too will fi nd American history in a new their French friends to convince themselves as it evolved from the 1860s onward and to light. Lee’s gamble in the 1863 Gettysburg there was something special about America. the physical layout of the city. If young Linda campaign was a response to the desperate Mark Fiege thinks that Americans’ dif- Brown had not had to walk through an envi- food situation in Virginia that summer. Sev- CREDIT: CARL IWASAKI//TIME LIFE PICTURES/GETTY IMAGES American and to think that it was right and mark case might well never have been heard. none of the jargon that mars much academic eral scientists at Los Alamos had a keen love ronment unfi t for children, a switching yard ferent experience of nature (which included of the Rock Island railroad, to get to her of the outdoors and did their best thinking in better childhood nutrition, leading to greater New Mexico’s pine groves. school bus stop in the early 1950s, that land- stature) helped them to see themselves as The Republic of Nature reads well, having proper that they should have a government In addition to the American Revolution history. Wherever possible, Fiege tells his sto- of their own. Part of the explanation for the and the school desegregation case, Fiege ries through the lives of individuals, whether offers environmental histories of the Massa- American Revolution, he claims, lies in the schoolgirl Linda Brown or theoretical physi- chusetts witch craze of the 1690s, the slave- American environment. plantation South, the life of Abraham Lincoln, cist Robert Oppenheimer. It is not a book to whip through in search of useful data—there Gettysburg and the Civil War, the building of The reviewer is in the Walsh School of Foreign Service are no charts or tables—but one to savor on the transcontinental railroad, the race to make and the Department of History, Georgetown University, the fi rst atomic bomb, and the 1973–74 oil cri- Sunday afternoons. Washington, DC 20057–1035, USA. E-mail: mcneillj@ sis. At the end of the book, he wonders what georgetown.edu www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 10.1126/science.1221363 543 Published by AAAS

BOOKS ET AL. Mitchell Thomashow and Kyle Bladow’s Topeka, 1953. Linda and Terry Lynn Brown helpful bioregionalist book list. walking to their school bus stop. Overall, The Bioregional Imagination makes a valuable contribution to the Venn environmental histories of the pivotal diagram fi eld of ecocriticism, where liter- election of 1800, the legendary sit- ature, science, and, yes, activism, can and down strikes in the auto industry in the should coexist. If the contents are of vary- late 1930s, and the conservative move- ing interest to specifi c readers, that’s to be ment since the 1980s might look like. expected. Your locale may not speak to me. Practicing scientists will fi nd lit- But it’s reassuring to know that from places tle grist for their professional mills I may not be especially interested in there in Fiege’s pages. They may need little comes creativity rooted in the ground and convincing that nature is always pres- crafted with a natural historian’s approach ent in history in one way or another. to understanding the world almost literally Fiege wrote the book for his fellow at hand. historians, steeped in their standard 10.1126/science.1221362 accounts of American history, and for their students, struggling to under- stand these accounts. Both audiences HISTORY are unaccustomed to seeing a role for the environment in the important The Environment parts of American history. Nature on May 3, 2012 typically makes only cameo appear- Makes History ances in connection with Theodore Roosevelt and the fi rst conservation J. R. McNeill movement of a century ago, the 1930s Indeed, Fiege (a historian at Colorado Dust Bowl, or the rise of popular environ- hile seated at a diplomatic din- State University) thinks that everything in mentalism in the 1960s and 1970s. But for ner in Paris in the 1780s, Benja- American history has environmental com- readers swayed by Fiege’s persuasive pages, Wmin Franklin sought to refute the ponents to it. In The Republic of Nature, he American history will never look quite the www.sciencemag.org Comte de Buffon’s famous contentions that in argues the case by selecting nine familiar same again. America a decadent nature produced degen- episodes in U.S. history; recounting them Environmental historians will fi nd Fiege erate human beings. at chapter length; and stands their fi eld on its head. He intention- Franklin asked the com- The Republic of Nature emphasizing how the ally skips over Henry David Thoreau and pany, half Americans An Environmental History environment constrained Aldo Leopold, the national parks movement, and half Frenchmen, to of the United States freedom of action, how the Dust Bowl, and the agro-ecosystems of rise and judge for them- by Mark Fiege the events changed the California. He has only a little to say about Downloaded from selves. They did. As one University of Washington Press, Seattle, environment, or how the West, the arena where U.S. environmental of the Americans saw 2012. 600 pp. $34.95. ISBN 9780295991672. participants’ thoughts history was born, and the standard fare of that it, “there was not one Weyerhaeuser Environmental Books. about nature affected history is conspicuous by its absence. This is American present who their actions. So, for unconventional environmental history just as could not have tost out example, he presents the it is unorthodox American history. of the Windows one or perhaps two of the 1954 Supreme Court case Brown v. Board of Practicing scientists might enjoy the book rest of the Company, if this effort depended Education in an unorthodox way, in which even if it provides them no grist. They may merely on muscular force.” Franklin’s strap- social change and ideologies take a back seat need no convincing that nature matters, but ping Americans did not have to defenestrate to the racial geography of Topeka, Kansas, they too will fi nd American history in a new their French friends to convince themselves as it evolved from the 1860s onward and to light. Lee’s gamble in the 1863 Gettysburg there was something special about America. the physical layout of the city. If young Linda campaign was a response to the desperate Mark Fiege thinks that Americans’ dif- Brown had not had to walk through an envi- food situation in Virginia that summer. Sev- CREDIT: CARL IWASAKI//TIME LIFE PICTURES/GETTY IMAGES American and to think that it was right and mark case might well never have been heard. none of the jargon that mars much academic eral scientists at Los Alamos had a keen love ronment unfi t for children, a switching yard ferent experience of nature (which included of the Rock Island railroad, to get to her of the outdoors and did their best thinking in better childhood nutrition, leading to greater New Mexico’s pine groves. school bus stop in the early 1950s, that land- stature) helped them to see themselves as The Republic of Nature reads well, having proper that they should have a government In addition to the American Revolution history. Wherever possible, Fiege tells his sto- of their own. Part of the explanation for the and the school desegregation case, Fiege ries through the lives of individuals, whether offers environmental histories of the Massa- American Revolution, he claims, lies in the schoolgirl Linda Brown or theoretical physi- chusetts witch craze of the 1690s, the slave- American environment. plantation South, the life of Abraham Lincoln, cist Robert Oppenheimer. It is not a book to whip through in search of useful data—there Gettysburg and the Civil War, the building of The reviewer is in the Walsh School of Foreign Service are no charts or tables—but one to savor on the transcontinental railroad, the race to make and the Department of History, Georgetown University, the fi rst atomic bomb, and the 1973–74 oil cri- Sunday afternoons. Washington, DC 20057–1035, USA. E-mail: mcneillj@ sis. At the end of the book, he wonders what georgetown.edu www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 10.1126/science.1221363 543 Published by AAAS

POLICYFORUM RESEARCH ETHICS Human subjects research ethics needs to Rethinking Research Ethics: directly address threats to the evidence base of the medical information economy. The Case of Postmarketing Trials 2 1 Alex John London, Jonathan Kimmelman, * Benjamin Carlisle 2 rom the Nuremberg Code onward, companies use the simulacrum of scientifi c mises informed consent ( 13). If volunteers the core mission of human subjects investigation to hawk their products. Stud- are unaware that a trial is a branding exercise, Fresearch ethics has been to protect ies sometimes enlist hundreds of physicians they may not be adequately informed about study participants from infringements moti- to recruit only a few patients each, thereby the ends to which they are contributing. vated by a zeal for medical progress. How- exposing more prescribers to the product; These criticisms accord well with the ever, with individuals, clinicians, and policy- other studies are alleged to pay investigators reigning model of research ethics, which makers increasingly dependent on scientifi c extravagant fees ( 6). Sponsors sometimes locates the moral tension in clinical research information for decision-making and with obscure the nature of their interest in phase at the interface between subjects—who may vast social resources invested in develop- IV studies from volunteers and investigators. be unable to adequately safeguard their own ing and utilizing the fruits of research, actors Using research in this way allows drug and welfare—and investigators. However, by have powerful incentives to coopt research device companies to circumvent rules against shoehorning the problems of phase IV stud- for narrow ends. Contemplated revisions to on May 3, 2012 human subjects research ethics policies in the United States ( 1) and existing policy in Current ethical guidelines …[are] inadequate … for challenging Canada ( 2) and the United Kingdom ( 3) fail studies that pose little risk but that generate biased evidence. to capture harms that, although they may not threaten participants, nonetheless undermine the social value of research. This is illus- directly remunerating physicians for prescrip- ies into the familiar categories of risk and trated by postmarketing (phase IV) research. tions ( 7). Recruiting physician-investigators informed consent, they miss much of what As a corrective, research ethics should focus with the promise of peer-reviewed publica- makes these practices objectionable. www.sciencemag.org on safeguarding the integrity of research as tion confers an aura of scientifi c authenticity Concerning the first objection, many a critical component of an evidence-driven, to the enterprise. postmarketing studies have little impact on health information economy. In 1996, several postmarketing stud- participant welfare and involve no more ies of the antiseizure medication gabapentin than a chart review or inclusion in a regis- Postmarketing Research as a Case Study were exposed as “seeding” use of the drug try. Studies that go beyond this often enroll Phase IV studies investigate drugs, devices, for unapproved indications ( 8). The promi- patients only after they have opted for an or biologics that have already received reg- nently published ADVANTAGE trial of the intervention in a clinical setting or entail lit- Downloaded from ulatory licensure. Generally, they are funded anti-infl ammatory drug rofecoxib also was tle departure from standard of care. Current by drug companies and provide a means of revealed to be a seeding study ( 6). Postmar- ethical guidelines evaluate social value only testing fi ndings from fastidiously designed keting studies instigated over safety concerns insofar as it justifi es risk to volunteers: the trials in less stylized settings. They also surrounding two recently withdrawn drugs less the risk, the less the need to substantiate provide greater statistical power for safety were found unsuited to the goal of pharma- social value. Thus, they provide inadequate assessment. Initiatives like the U.S. Patient- covigilance ( 9, 10). More systematic analysis bases for challenging studies that pose little Centered Outcomes Research Institute shows that many other phase IV studies suf- risk but that generate biased evidence. These (PCORI) in the 2010 Affordable Care Act fer various defi ciencies, including statistical diffi culties would be exacerbated by propor- signal a renewed commitment to harnessing underpowering, absence of comparator arms, tionate review, a central plank in many poli- phase IV studies to address evidentiary gaps and publication bias ( 11). cies governing human subjects research, in comparative effectiveness, drug safety, including proposals to amend those in the and real-world utility ( 4). Yet studies often The Current Research Ethics Framework United States ( 1– 3). This approach, which fall short of these ambitions. In contrast with Because few, if any, of these branding prac- calibrates depth of protocol scrutiny to the premarketing trials, drug regulators have tices violate laws and because institutional level of volunteer risk, is motivated by the very limited infl uence over the production of review boards (IRBs) may be the only venue sensible observation that low-risk studies phase IV evidence ( 5). This removes a critical where phase IV protocols receive formal- can divert review resources from riskier check on design and reporting quality. ized prospective review, critics have turned ones. Yet many problematic phase IV prac- To their harshest critics, postmarketing tri- to research ethics to mount objections. These tices pose little threat to volunteers and thus als are a backwater in which pharmaceutical take two forms. First, policies stipulate that escape review. risks to volunteers must be reasonable in light As for the second objection, disclosure of of benefi ts to volunteers, if any, and society. marketing aims would defuse concerns about 1 Department of Philosophy, Carnegie Mellon University, 2 Pittsburgh, PA 15213, USA. Biomedical Ethics Unit, McGill Some critics charge that marketing objec- deception, but do little to improve the value University, Montreal, Quebec H3A 1X1, Canada. tives cannot justify risks to study participants of such studies or diminish the social harms ( 6, 12). Second, some argue that phase IV caused by production of biased evidence and *Author for correspondence. E-mail: jonathan.kimmelman@ mcgill.ca studies’ hidden marketing agenda compro- the cooptation of research systems. 4 MAY 2012 VOL 336 SCIENCE www.sciencemag.org 544 Published by AAAS

POLICYFORUM The Integrity of the Research System motives on evidence production. have to be expanded to permit greater scrutiny A more robust ethical framework should Those who fund, conduct, take part in, of study quality, reporting plans, and clinical focus on preserving the integrity of research and ultimately benefit from the results of relevance. This might also require strengthen- as the foundation of an evidence-driven, scientifi c inquiry participate in research to ing their membership to ensure the relevant health information economy. By a health advance a diverse mix of personal or social scientifi c and statistical expertise. Neverthe- information economy, we mean a system in goals. Whether this is antithetical to the effi - less, such changes would have limited impact which various parties collaborate in produc- cient production of reliable medical evi- on defi cient trial reporting. ing health-related information that is then dence depends on whether ethical and policy Second, medical journals could adopt consumed by others. Sometimes information frameworks bring individual interests into phase IV–specific review and reporting is used to produce interventions, improve alignment with the social goals of research. criteria. These might include expanded health services, or set policy. Other times it is When demand is driven by high-quality evi- requirements for review; submission (e.g., an input into further inquiry. The ability of the dence of superiority on clinically relevant provision of an approved protocol); and parties who use this information to advance comparisons, expanding an intervention’s disclosure of data. Even if studies are not care, improve knowledge, and increase effi - market share advances both parochial and published, the clear articulation of quality ciency depends critically on its validity, rel- social ends. Influencing clinician practice benchmarks and registration obligations can evance, credibility, and accessibility to stake- and increasing stakeholder familiarity with impact the upstream conduct of sponsors holders. Although studies are often fi nanced such treatments advances social ends when it and investigators. and performed by private actors, they have reduces unwarranted variation and expense, Finally, there should be a broad-based public repercussions. How research is con- and improves patient outcomes. Profi t seek- discussion of the responsibilities of medical ducted not only affects the quality of the ing advances social interests when incentives societies for articulating and implementing information that others consume, but also channel human ingenuity toward bridging standards for member participation in post- on May 3, 2012 patient expectations, provider practices, the knowledge gaps about best practices. marketing studies ( 18). expenditure of scarce resources, and the effi - Preserving the integrity of the research Unlike private transactions in many other ciency of health-care systems. system also requires protecting the rights and spheres, research transactions serve cru- Deficiencies in phase IV studies like welfare of participants, because knowledge cial social ends. Because those ends can be those above are not always detectable for edi- cannot be produced within a liberal democ- frustrated without putting study participants tors, policy-makers, or other evidence users. racy without the participation of volunteers at risk, research ethics and policies need to Adverse events might be withheld, primary who are confi dent that their basic interests adopt a broader focus—one that directly end points altered, and provider practices or will be safeguarded. But subject protections addresses threats to the evidence base of the www.sciencemag.org patient expectations influenced by engag- should be seen as one important facet of a medical information economy. ing with a trial rather than its results. These broader effort to ensure that, as contributors threaten the integrity of research as the foun- to the health information economy advance References and Notes dation of an evidence-driven health informa- their individual agendas, they are also help- 1. U.S. Department of Health and Human Services, Fed. Regist. 76, 44512 (2011). tion economy in three ways. ing to produce important social benefi ts. 2. Canadian Institutes of Health Research, Natural Sciences First, policy-makers, clinicians, and third- and Engineering Research Council of Canada, Social party payers who base treatment decisions, Ethics Should Inform Oversight Sciences and Humanities Research Council of Canada, Tri-Council Policy Statement: Ethical Conduct for Research Downloaded from guidelines, or reimbursement on biased stud- A framework that highlights the ethical sig- Involving Humans (CIHR, NSERC, SSHRC, Ottawa, 2010). ies harm patients and misallocate resources. nifi cance of threats to the health information 3. U.K. Department of Health, Research Governance Frame- As the social resources dedicated to the economy should facilitate a search for mech- work for Health and Social Care (HMSO, London, ed. 2, 2005). health sector balloon, so, too, do the stakes anisms that empower actors and institutions 4. Patient Protection and Affordable Care Act. Public Law of ensuring that resources are used effi ciently. to promote more informative and valuable 111-148 (2010). Second, the “bench-to-bedside” pro- forms of inquiry. 5. D. Carpenter, Reputation and Power (Princeton Univ. cess of translating basic research into clini- One strategy would be to rectify disconti- Press, Princeton, NJ, 2010). 6. H. C. Sox, D. Rennie, Ann. Intern. Med. 149, 279 (2008). cal treatments is a series of investigations in nuities between pre- and postmarketing over- 7. B. M. Psaty, D. Rennie, JAMA 295, 2787 (2006). which many different actors both produce and sight by granting regulators greater authority 8. M. A. Steinman, L. A. Bero, M. M. Chren, C. S. Landefeld, consume scientifi c information. Just as unre- over postmarketing research ( 15). Creating a Ann. Intern. Med. 145, 284 (2006). 9. B. M. Psaty, C. D. Furberg, W. A. Ray, N. S. Weiss, JAMA liable preclinical research can derail promis- centralized entity for certifying phase IV trial 292, 2622 (2004). ing therapeutic avenues ( 14), the cumulative protocols or expanding the purview of exist- 10. S. E. Nissen, Eur. Heart J. 31, 773 (2010). human and capital investment in inquiry and ing institutions, such as the U.S. Food and 11. J. Hasford, T. Lamprecht, Eur. J. Clin. Pharmacol. 53, 369 development can be squandered where biased Drug Administration or the PCORI, could (1998). 12. C. Elliott, Mother Jones 2010 (September–October), 55 phase IV evidence promotes inappropriate provide incentives for conducting higher- (2010). application of interventions. quality studies ( 16). At least, registration and 13. J. N. Rao, L. J. Cassia, BMJ 325, 36 (2002). Third, confi dence in scientifi c medicine reporting requirements should be expanded to 14. A. J. London, J. Kimmelman, M. E. Emborg, Science 328, 829 (2010). and the social infl uence associated with it is include phase IV observational studies ( 17). 15. D. Carpenter, Health Aff. W5, 469 (2005). eroded when the outward signs of scientifi c Absent these ambitious institution-making 16. B. P. Falit, Seton Hall Law Rev. 37, 969 (2007). merit are used solely as a vehicle for mar- proposals, the burdens of promoting high stan- 17. D. A. Zarin, T. Tse, Science 319, 1340 (2008). 18. M. Teehan, Can. J. Psychiatry 39, 629 (1994). keting. To ensure that confi dence in medical dards of design and clinical relevance would information is warranted for those who rely fall to three actors that presently have some— Acknowledgments: Funded by the Canadian Institutes of on it, the system of knowledge production albeit limited—role in shaping incentives in Health Research (EOG 102824). and utilization must be designed to either this arena. First, if IRBs are to play a role in leverage or limit the infl uence of parochial strengthening such studies, their mandate will 10.1126/science.1216086 www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 545 Published by AAAS

Superresolution Subspace Signaling W. Jonathan Lederer et al. Science 336 , 546 (2012); DOI: 10.1126/science.1222540 This copy is for your personal, non-commercial use only. If you wish to distribute this article to others , you can order high-quality copies for your colleagues, clients, or customers by clicking here. Permission to republish or repurpose articles or portions of articles can be obtained by following the guidelines here. The following resources related to this article are available online at on May 3, 2012 www.sciencemag.org (this information is current as of May 3, 2012 ): Updated information and services, including high-resolution figures, can be found in the online version of this article at: http://www.sciencemag.org/content/336/6081/546.full.html A list of selected additional articles on the Science Web sites related to this article can be found at: www.sciencemag.org http://www.sciencemag.org/content/336/6081/546.full.html#related This article cites 15 articles , 9 of which can be accessed free: http://www.sciencemag.org/content/336/6081/546.full.html#ref-list-1 Downloaded from Science (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. Copyright 2012 by the American Association for the Advancement of Science; all rights reserved. The title Science is a registered trademark of AAAS.

PERSPECTIVES CELL BIOLOGY Superresolution Subspace Highly localized activity of ion channels in vascular endothelial cells controls the Signaling contraction of surrounding muscle cells and blood fl ow. W. Jonathan Lederer, Brian M. Hagen, Guiling Zhao xquisitely local signal- centrations of intracellular ing provides robust, free calcium ([Ca ] i ) called 2+ Eprecise, and rapid com- “pulsars” ( 4). In the other munication in single cells. pathway, clustered transient Nanometer-wide regions receptor potential vanilloid constitute the signaling con- 4 (TRPV4) channels in the duit that separates interacting plasmalemma can produce ion channels, organelles, and regions with locally very 2+ sensor and effector proteins. high [Ca ] i called “spark- Such signaling domains are lets” ( 10– 12). In both cases, primary features of many sys- local increase of [Ca ] i 2+ 2+ tems, including those respon- activates nearby Ca -acti- on May 3, 2012 sible for excitation-contrac- vated K channels [intermedi- + tion coupling in the heart ( 1, ate-conductance (IK; K Ca 3.1) 2), smooth muscle tone in the and small-conductance (SK; vasculature ( 3, 4), and Ca K Ca 2.3)] to hyperpolarize 2+ signaling in neurons ( 5). These endothelial cells. These two intimate pathways, also known signaling pathways converge as “fuzzy spaces” ( 1), “sub- on the same functional tar- + spaces” ( 6), or “nanoscopic get—the K channels. The www.sciencemag.org spaces,” permit effi cient sig- efficacy of this activation naling with rapid and reliable depends in part on the prox- information transfer, yet are imity of the K channels to the + too small to be seen with a Ca source, hence the impor- 2+ standard optical microscope. tance of subspaces or fuzzy Such superresolution domains spaces ( 1, 3). As endothelial may become experimentally cells hyperpolarize relative to Downloaded from visible with the implementa- smooth muscle cells, current tion of optical superresolution flows from smooth muscle microscopy ( 7– 9). On page cells to hyperpolarize and thus 597 in this issue, Sonkusare relax the smooth muscle cells et al. ( 10) identify a spe- ( 3).The effect is to increase cific and broadly important blood flow. Sonkusare et al. local signaling organization point out that there may also in small mesenteric arteries Arterial relaxation. The superresolution signaling system in vascular endothelial be a role for the increase in (~100 μm in diameter) that cells may be organized with respect to smooth muscle cells. Sonkusare et al. examined nearby extracellular [K ] in + uses nano meter-wide com- 100-μm-diameter arterioles in mice. Cooperative gating of clustered TRPV4 channels the restricted extracellular of a vascular endothelial cell (EC) allows Ca infl ux. This localized increase in [Ca ] I 2+ 2+ munication regions to regulate activates local K channels, hyperpolarizes endothelial cells, and increases nearby [K ] spaces between the cells. If so, + + local vascular blood fl ow. in the internal elastic lamina (IEL). Activated IP 3 Rs in the endothelial cell ER produce they can increase inward-rec- + Endothelial cells form locally high [Ca ] i signals. Locally elevated [K ] increases inward-rectifi er K channel tifi er K channel (K ir ) effl ux of + + 2+ + intimate spot-welded con- (K ir ) current in the smooth muscle cell (SMC) to hyperpolarize the cells, which underlies K to augment smooth mus- tacts with vascular smooth vascular relaxation and increased blood fl ow. ACh, acetylcholine; PIP 2 , phosphatidylino- cle cell hyperpolarization and muscle cells at “holes” in the sitol 4,5-bisphosphate. relaxation ( 4, 13). Perhaps this internal elastic lamina that is also how the restricted but are micrometers in diameter (see the fi gure). duit from the endothelial cells to the effector larger internal elastic lamina (up to several These regions of close contact can include smooth muscle cells. Sonkusare et al. sug- micrometers) between endothelial cells and gap junctions that create an electrical con- gest that this specifi c organization is used by smooth muscle cells, of presumed varying endothelial cells in two signaling pathways. thickness ( 14), contributes to this process. In one pathway, inositol tris phosphate recep- Important to the study by Sonkusare et CREDIT: C. BICKEL/SCIENCE Center of BioMedical Engineering and Technology and tor (IP 3 R)–dependent Ca release from endo- al. and other investigations was the develop- 2+ Department of Physiology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, plasmic reticulum (ER) in endothelial cells ment of a critical tool: the expression of the 2+ USA. E-mail: [email protected] can produce regions with very high local con- genetically encoded Ca indicator protein 4 MAY 2012 VOL 336 SCIENCE www.sciencemag.org 546 Published by AAAS

PERSPECTIVES GCaMP2 specifi cally in endothelial cells in fl ow regulation in heart. Here, the electrical 7. T. A. Klar, S. Jakobs, M. Dyba, A. Egner, S. W. Hell, Proc. 2+ mice ( 4, 10), which provides a Ca sensor consequences of cardiac myocyte metabolism Natl. Acad. Sci. U.S.A. 97, 8206 (2000). 8. E. Betzig et al., Science 313, 1642 (2006). tool with high signal to noise specifi c only are linked to smooth muscle cell tone in pre- 9. S. A. Jones, S. H. Shim, J. He, X. Zhuang, Nat. Methods 8, to endothelial cells. This tool allows the sys- capillary sphincters via endothelial cells ( 15). 499 (2011). tematic identifi cation of signals that depend The energetic demand of gut smooth muscle 10. S. K. Sonkusare et al., Science 336, 597 (2012). 11. S. Q. Wang, L. S. Song, E. G. Lakatta, H. Cheng, Nature on fuzzy-space Ca that would otherwise be would appear to be equally important for mes- 410, 592 (2001). 2+ masked by neighboring cell signals if stan- enteric vascular fl ow and the regulation of fl ow 12. M. F. Navedo, G. C. Amberg, M. Nieves, J. D. Molkentin, 2+ dard Ca probes were used. in other important vascular beds. Understand- L. F. Santana, J. Gen. Physiol. 127, 611 (2006). 13. J. A. Filosa et al., Nat. Neurosci. 9, 1397 (2006). The principle demonstrated by Sonku- ing the intricate signaling of various vascular 14. V. D. Aiello et al., Mod. Pathol. 16, 411 (2003). sare et al. is critically important for the rapid beds will allow for identifi cation of potential 15. W. J. Lederer et al., in Molecular Understanding of Exci- regulation of tone in small mesenteric arter- therapeutic targets—especially important in tation-Contraction Coupling and Vascular Flow Control ies. This fi nding is likely to be broadly rele- diseases that result in vascular remodeling in Heart Muscle, G. G. Haddad, G. Lister, Eds. (Dekker, New York, 1996), vol. 95, pp. 497–513. vant to all tissues where local factors control such as diabetes and hypertension. blood fl ow. For example, smooth muscle cells References and Notes Acknowledgments: This work was supported by National encircle the endothelial cells in an end arteri- 1. W. J. Lederer, E. Niggli, R. W. Hadley, Science 248, 283 Heart, Lung, and Blood Institute grants R01 HL106059, P01 ole from rat heart. This 15- to 20-μm-diameter (1990). HL67849, and R01 HL36974 (W.J.L.); the Leducq North Ameri- can–European Atrial Fibrillation Research Alliance (W.J.L.); arteriole has little or no apparent internal elas- 2. B. L. Prosser, C. W. Ward, W. J. Lederer, Science 333, European Union Seventh Framework Program (FP7), Georg 1440 (2011). tic lamina, consistent with its smaller size 3. M. T. Nelson et al., Science 270, 633 (1995). August University, “Identifi cation and therapeutic targeting ( 14). The functional consequences of the fi nd- 4. J. Ledoux et al., Proc. Natl. Acad. Sci. U.S.A. 105, 9627 of common arrhythmia trigger mechanisms” (W.J.L.); and the American Heart Association National Scientist Development ing of Sonkusare et al. in regulating cardiac (2008). grant 10SDG4030042 (G.Z.). 5. K. Ouyang et al., Proc. Natl. Acad. Sci. U.S.A. 102, blood fl ow are clear and consistent with the 12259 (2005). on May 3, 2012 speculative hypothesis of electrotonic blood 6. G. S. Williams et al., Biophys. J. 101, 1287 (2011). 10.1126/science.1222540 PHYSICS The Impact of Ionic Frustration The frustrated ordering of dipoles created by copper and antimony ions in an oxide www.sciencemag.org on Electronic Order material may help to create an exotic quantum electronic state. Leon Balents or some metal oxides, the simplest on nanometer dimensions, and it strongly lattice planes normal to the c direction (see applications of band theory predict that affects the spin and orbital character of the the fi gure). Each dumbbell has a large elec- Fthey should be good electrical conduc- electronic state. tric dipole moment, caused by the difference Downloaded from 2+ 5+ tors, but in fact they are Mott insulators— The authors’ study of Ba 3 CuSb 2 O 9 of charge of the Cu and Sb ions, and this that is, the electrons that should be mobile revealed that its key structural elements are moment can point up or down (i.e., parallel or are localized to metal atoms. These elec- Cu-Sb “dumbbells” aligned along the crystal- antiparallel to the c axis). Neighboring dipoles trons retain internal degrees of freedom; they lographic c axis and distributed on triangular would prefer to align antiparallel to lower may occupy more than one type of orbital of the metal (they have an orbital degree of freedom) and also may adopt different spin states. These degrees of freedom, along with accompanying structural changes, can create materials with exotic electronic ordering that have potential applications such as magne- toelectric devices and quantum computing. If the spins and orbital degrees of freedom can both adopt more than one quantum state, they may entangle—that is, a measurement of spin determines the orbital state, and vice versa ( 1). On page 559 of this issue, Nakat- suji et al. ( 2) introduce a new ingredient, an ionic degree of freedom that creates a lattice Frustrated ordering. Artist’s conception of a nanoscale region of honeycomb lattice of ionic and spin struc- of dipoles that is “frustrated”—incapable of ture in Ba 3 CuSb 2 O 9 studied by Nakatsuji et al. Copper-antimony (Cu-Sb) dumbbells are oriented vertically, completely ordering locally. Ordering is seen with Cu atoms in red and Sb in blue. The Cu sites that are out of the honeycomb plane are separated from other Cu sites, and so may host quasi-free spins (green arrows). The Cu sites in the plane form a quantum spin liquid state composed of spin singlets, drawn as translucent ellipsoids enclosing two Cu sites. Oxygen sites are Kavli Institute of Theoretical Physics, University of Califor- nia, Santa Barbara, CA 93106, USA. E-mail: balents@kitp. not shown, so neither Jahn-Teller distortions of the oxygen octahedral (which may be structurally inhomoge- ucsb.edu neous or time-dependent or both) nor the consequent orbital ordering are depicted. www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 547 Published by AAAS

The Impact of Ionic Frustration on Electronic Order Leon Balents Science 336 , 547 (2012); DOI: 10.1126/science.1221364 This copy is for your personal, non-commercial use only. If you wish to distribute this article to others , you can order high-quality copies for your colleagues, clients, or customers by clicking here. Permission to republish or repurpose articles or portions of articles can be obtained by following the guidelines here. The following resources related to this article are available online at on May 3, 2012 www.sciencemag.org (this information is current as of May 3, 2012 ): Updated information and services, including high-resolution figures, can be found in the online version of this article at: http://www.sciencemag.org/content/336/6081/547.full.html A list of selected additional articles on the Science Web sites related to this article can be found at: www.sciencemag.org http://www.sciencemag.org/content/336/6081/547.full.html#related This article cites 8 articles , 1 of which can be accessed free: http://www.sciencemag.org/content/336/6081/547.full.html#ref-list-1 Downloaded from Science (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. Copyright 2012 by the American Association for the Advancement of Science; all rights reserved. The title Science is a registered trademark of AAAS.

PERSPECTIVES GCaMP2 specifi cally in endothelial cells in fl ow regulation in heart. Here, the electrical 7. T. A. Klar, S. Jakobs, M. Dyba, A. Egner, S. W. Hell, Proc. 2+ mice ( 4, 10), which provides a Ca sensor consequences of cardiac myocyte metabolism Natl. Acad. Sci. U.S.A. 97, 8206 (2000). 8. E. Betzig et al., Science 313, 1642 (2006). tool with high signal to noise specifi c only are linked to smooth muscle cell tone in pre- 9. S. A. Jones, S. H. Shim, J. He, X. Zhuang, Nat. Methods 8, to endothelial cells. This tool allows the sys- capillary sphincters via endothelial cells ( 15). 499 (2011). tematic identifi cation of signals that depend The energetic demand of gut smooth muscle 10. S. K. Sonkusare et al., Science 336, 597 (2012). 11. S. Q. Wang, L. S. Song, E. G. Lakatta, H. Cheng, Nature on fuzzy-space Ca that would otherwise be would appear to be equally important for mes- 410, 592 (2001). 2+ masked by neighboring cell signals if stan- enteric vascular fl ow and the regulation of fl ow 12. M. F. Navedo, G. C. Amberg, M. Nieves, J. D. Molkentin, 2+ dard Ca probes were used. in other important vascular beds. Understand- L. F. Santana, J. Gen. Physiol. 127, 611 (2006). 13. J. A. Filosa et al., Nat. Neurosci. 9, 1397 (2006). The principle demonstrated by Sonku- ing the intricate signaling of various vascular 14. V. D. Aiello et al., Mod. Pathol. 16, 411 (2003). sare et al. is critically important for the rapid beds will allow for identifi cation of potential 15. W. J. Lederer et al., in Molecular Understanding of Exci- regulation of tone in small mesenteric arter- therapeutic targets—especially important in tation-Contraction Coupling and Vascular Flow Control ies. This fi nding is likely to be broadly rele- diseases that result in vascular remodeling in Heart Muscle, G. G. Haddad, G. Lister, Eds. (Dekker, New York, 1996), vol. 95, pp. 497–513. vant to all tissues where local factors control such as diabetes and hypertension. blood fl ow. For example, smooth muscle cells References and Notes Acknowledgments: This work was supported by National encircle the endothelial cells in an end arteri- 1. W. J. Lederer, E. Niggli, R. W. Hadley, Science 248, 283 Heart, Lung, and Blood Institute grants R01 HL106059, P01 ole from rat heart. This 15- to 20-μm-diameter (1990). HL67849, and R01 HL36974 (W.J.L.); the Leducq North Ameri- can–European Atrial Fibrillation Research Alliance (W.J.L.); arteriole has little or no apparent internal elas- 2. B. L. Prosser, C. W. Ward, W. J. Lederer, Science 333, European Union Seventh Framework Program (FP7), Georg 1440 (2011). tic lamina, consistent with its smaller size 3. M. T. Nelson et al., Science 270, 633 (1995). August University, “Identifi cation and therapeutic targeting ( 14). The functional consequences of the fi nd- 4. J. Ledoux et al., Proc. Natl. Acad. Sci. U.S.A. 105, 9627 of common arrhythmia trigger mechanisms” (W.J.L.); and the American Heart Association National Scientist Development ing of Sonkusare et al. in regulating cardiac (2008). grant 10SDG4030042 (G.Z.). 5. K. Ouyang et al., Proc. Natl. Acad. Sci. U.S.A. 102, blood fl ow are clear and consistent with the 12259 (2005). on May 3, 2012 speculative hypothesis of electrotonic blood 6. G. S. Williams et al., Biophys. J. 101, 1287 (2011). 10.1126/science.1222540 PHYSICS The Impact of Ionic Frustration The frustrated ordering of dipoles created by copper and antimony ions in an oxide www.sciencemag.org on Electronic Order material may help to create an exotic quantum electronic state. Leon Balents or some metal oxides, the simplest on nanometer dimensions, and it strongly lattice planes normal to the c direction (see applications of band theory predict that affects the spin and orbital character of the the fi gure). Each dumbbell has a large elec- Fthey should be good electrical conduc- electronic state. tric dipole moment, caused by the difference Downloaded from 2+ 5+ tors, but in fact they are Mott insulators— The authors’ study of Ba 3 CuSb 2 O 9 of charge of the Cu and Sb ions, and this that is, the electrons that should be mobile revealed that its key structural elements are moment can point up or down (i.e., parallel or are localized to metal atoms. These elec- Cu-Sb “dumbbells” aligned along the crystal- antiparallel to the c axis). Neighboring dipoles trons retain internal degrees of freedom; they lographic c axis and distributed on triangular would prefer to align antiparallel to lower may occupy more than one type of orbital of the metal (they have an orbital degree of freedom) and also may adopt different spin states. These degrees of freedom, along with accompanying structural changes, can create materials with exotic electronic ordering that have potential applications such as magne- toelectric devices and quantum computing. If the spins and orbital degrees of freedom can both adopt more than one quantum state, they may entangle—that is, a measurement of spin determines the orbital state, and vice versa ( 1). On page 559 of this issue, Nakat- suji et al. ( 2) introduce a new ingredient, an ionic degree of freedom that creates a lattice Frustrated ordering. Artist’s conception of a nanoscale region of honeycomb lattice of ionic and spin struc- of dipoles that is “frustrated”—incapable of ture in Ba 3 CuSb 2 O 9 studied by Nakatsuji et al. Copper-antimony (Cu-Sb) dumbbells are oriented vertically, completely ordering locally. Ordering is seen with Cu atoms in red and Sb in blue. The Cu sites that are out of the honeycomb plane are separated from other Cu sites, and so may host quasi-free spins (green arrows). The Cu sites in the plane form a quantum spin liquid state composed of spin singlets, drawn as translucent ellipsoids enclosing two Cu sites. Oxygen sites are Kavli Institute of Theoretical Physics, University of Califor- nia, Santa Barbara, CA 93106, USA. E-mail: balents@kitp. not shown, so neither Jahn-Teller distortions of the oxygen octahedral (which may be structurally inhomoge- ucsb.edu neous or time-dependent or both) nor the consequent orbital ordering are depicted. www.sciencemag.org SCIENCE VOL 336 4 MAY 2012 547 Published by AAAS

PERSPECTIVES their electrostatic energy, but the triangular ways, in the more ideal material. The differ- the underlying triangular structure. A sim- arrangement makes this impossible for all ence between local and averaged measure- ple nearest-neighbor antiferromagnet on neighbors, hence the alignment is frustrated. ments might be caused by fl uctuations: The a honeycomb lattice would be expected to The frustrated ordering of these ionic distortions might vary with time, so measure- undergo a robust magnetic transition. Evi- dipoles, which was only revealed by neutron ments that average over longer times would dently, the impact of the nanoscale dumbbell scattering for single-crystal samples, creates reveal octahedra that appear largely undis- pattern and local J-T distortion on the spin a nanoscale pattern of short-range order con- torted. A more likely explanation is that the physics is nontrivial and unexpected. Could sistent with a honeycomb structure. Such a J-T distortions are static but spatially inhomo- it be that ionic disorder actually facilitates honeycomb structure is indeed expected from geneous, tracking in some way the nanoscale quantum spin liquid formation? An alterna- theoretical models of frustrated dumbbells, dumbbell pattern, so that the spatially aver- tive picture might be that the local ionic and dating back to the classic work of Wannier on aged structure remains hexagonal. lattice structures favor a frozen but random the so-called antiferromagnetic Ising model While these local J-T distortions are pattern of pairs of anti-aligned spins, known on the honeycomb lattice ( 3). Because of the occurring (and orbitals are ordering, at as a random singlet phase ( 7). Either way, short-range nature of the dumbbell order, the least on short time scales), the spins in this work points to new directions for theo- corresponding Bragg peaks are diffuse and Ba 3 CuSb 2 O 9 appear to remain strongly fl uc- retical and experimental searches for exotic would probably be entirely unobservable in tuating. The spins remain paramagnetic, magnetism. Certainly, the interplay of ionic powder measurements. Indeed, the structure with no static moments down to at least 100 and electronic degrees of freedom seen here reported by Nakatsuji et al. disagrees with the mK, which is much less than the structural suggests reexamination of the physics of results of previous diffraction studies on pow- transition temperature in the nonstoichio- quantum spin liquid states in other materials der samples ( 4). metric samples (~200 K) and the estimated for which only powder samples have been This structure affects the types of spin and exchange coupling between spins (~50 K). studied, such as related Ba 3 NiSb 2 O 9 com- on May 3, 2012 orbital states that can be manifested. Each At these low temperatures, quantum fl uctua- pounds ( 8). 2+ Cu ion has a single unpaired hole (posi- tions of spins must be involved. This result tive charge carrier) that can adopt two spin raises the possibility of a quantum spin liq- References 1. L. F. Feiner et al., Phys. Rev. Lett. 78, 2799 (1997). states and two orbital states, as well as super- uid ground state ( 6), a massive coherent 2. S. Nakatsuji et al., Science 336, 559 (2012). positions of these states. Situations of this quantum superposition of spin states capa- 3. G. H. Wannier, Phys. Rev. 79, 357 (1950). type are not uncommon [and were seen in ble of supporting strange excitations that 4. H. D. Zhou et al., Phys. Rev. Lett. 106, 147204 (2011). 5. J. B. Goodenough, Annu. Rev. Mater. Sci. 28, 1 (1998). ( 2)] and have the potential to lead to intrigu- behave like particles with fractional quan- 6. L. Balents, Nature 464, 199 (2010). www.sciencemag.org ing exotic states. However, this ordering is tum numbers and statistics. 7. R. N. Bhatt, P. A. Lee, Phys. Rev. Lett. 48, 344 (1982). almost always thwarted in real materials by The lack of spin ordering or freezing is 8. J. G. Cheng et al., Phys. Rev. Lett. 107, 197204 (2011). Jahn-Teller (J-T) effects ( 5), in which degen- surprising because the short-range ionic erate states with unpaired electrons or holes ordering naïvely reduces the frustration of 10.1126/science.1221364 undergo a structural distortion. This dis- tortion lifts the degeneracy and lowers the electronic energy by placing the carriers in PLANETARY SCIENCE a lower energy level. The atoms around the Downloaded from move so that their electronic potential selects A Dynamic Twist in the Tail unpaired electron or hole (usually oxygens) a preferred orbital (and often spin) state. This distortion creates a rather classical ordered James A. Slavin magnet below the J-T transition. Observations by Venus Express suggest that the magnetic tails of Venus and, by implication, Usually a J-T effect manifests itself as a comets may be more dynamic than originally thought. structural phase transition, visible in aver- aged probes such as x-ray or neutron scat- ll planetary bodies with intrinsic the northern lobe from the antisunward fl ux tering. Indeed, the experiments in ( 4) see just magnetic fi elds or atmospheres pos- in the southern lobe lies at the center of the such a transition in samples for which the A sess very long magnetic tails ( 1, 2). plasma sheet. The intrinsic magnetotails of concentration of Cu to Sb is different from If they possess the same intrinsic magnetic Mercury and Earth store magnetic energy the ideal 1:2 ratio. For temperatures below field dipole orientation as Earth, then the in their tail lobes and then rapidly convert it about 200 K, these samples became ortho- northern half of the tail is composed of open into plasma heating and high-speed jetting rhombic rather than hexagonal. However, magnetic fields oriented back toward the ( 3, 4) through the process of magnetic recon- for the samples with the ideal stoichiometry, planet, and the southern half has the opposite nection ( 5). Venus and comets lack intrinsic the structural transition was apparently sup- orientation (see the fi gure, panel A). Sand- magnetic fi elds, but magnetotails still form pressed or absent, and macroscopic hexago- wiched between these two lobes of the tail is as a result of the heliospheric magnetic fi eld nal symmetry was retained. a sheet of hot plasma derived from the solar lines carried by the solar wind draping about Remarkably, the CuO 6 octahedra were wind and the atmospheres of the planet and these bodies (see the fi gure, panel B). The distorted even in the hexagonal samples, its moons. The cross-tail electric current sheet Venera 9 and 10 and Pioneer Venus Orbiter −16 as shown by very fast (10 s) local x-ray that separates the sunward magnetic fi eld in missions to Venus found that the structure of absorption measurements, and this distortion its draped fi eld magnetotail has many simi- was indistinguishable from that of their coun- larities to those of magnetized planets, but Department of Atmospheric, Oceanic and Space Sciences, terparts in the orthorhombic samples. The J-T University of Michigan, Ann Arbor, MI 48176, USA. E-mail: found no evidence for magnetic reconnection effect still operated, although in more subtle [email protected] ( 6, 7). Now, on page 567 of this issue, Zhang 4 MAY 2012 VOL 336 SCIENCE www.sciencemag.org 548 Published by AAAS

A Dynamic Twist in the Tail James A. Slavin Science 336 , 548 (2012); DOI: 10.1126/science.1221805 This copy is for your personal, non-commercial use only. If you wish to distribute this article to others , you can order high-quality copies for your colleagues, clients, or customers by clicking here. Permission to republish or repurpose articles or portions of articles can be obtained by following the guidelines here. The following resources related to this article are available online at on May 3, 2012 www.sciencemag.org (this information is current as of May 3, 2012 ): Updated information and services, including high-resolution figures, can be found in the online version of this article at: http://www.sciencemag.org/content/336/6081/548.full.html A list of selected additional articles on the Science Web sites related to this article can be found at: www.sciencemag.org http://www.sciencemag.org/content/336/6081/548.full.html#related This article cites 15 articles , 4 of which can be accessed free: http://www.sciencemag.org/content/336/6081/548.full.html#ref-list-1 Downloaded from Science (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. Copyright 2012 by the American Association for the Advancement of Science; all rights reserved. The title Science is a registered trademark of AAAS.