Volume 328, Issue 5858 COVER DEPARTMENTS Ahir bearingan annotated gene sequence 1827 trap of huan Gvomsone Asymbaizes the 1829 THe Week Instence Breathroug ofthe Year for 2007—the 1835 Editon” Chae realization hat DNA cfs fom psn o Comact Science person much more than eseorchers had 1839 Random Sam ‘suspected. This conceptual advance, driven 1841 Newsmakers by reals em sve els, may vanetorm 1856 ANAS hens & Notes medicine bt coud as theten personal 1901 NewPreduas privacy. See the special section beginning on. 1942 Science Careers ae EDITORIAL Phot iusration: Joe Zl O2sgn ine i 1833 Breaktvough ofthe Year by Donel Keanedy SPECIAL SECTI Breakthrough of the Year WINNER ] suman Genetic Variation | 1842 inios te RUNNERS-UP feprgiamming Cells esa Tracing Cosmic Ballets 1845 fcepor Visors 1846 Beyond Sion? 1846 Electors lak New Spin 1046 Dive to Conquer 1818 Daing Nore With Less 1048 News Ge Tie Week Back tn the Stare ges Grassroots Effort Pays Dividends on Presidential 1850 cae Over 1849 Canpsign ra UK catback Rate Poss, Atonomy 1051 OTHER FEATURES Trials of NIH's AIDS Vaccine Get a Yellow Light 1852 Scorecard: How'd We Do? ae Bruce Alberts Named Scfence Editor-in-Chief 1852 Gabel Wioriping, Metter Thea Ever 1% Detoxifying Enzyme Helps Animals Stomach Bacteria 1853 Aesth 048 saeesceee ae >> Edy 8% nn cnn chin tet Ws sen Did an Atri Shons Kid Sarthe 1054 trata ete, p's menace cere Great Dvestaten? Questions Swirl Around Kessler's Abrupt Dismissal 1855 UCSE NEWS FOCUS Animal Exversts Got Personal 1856 {Global Warming Coming Home to Roost in the 1059 ‘American West CChieungunya: No Longer a Third World Disease 1860 U.K. Science Adviser Offers Some Parting Shots 1862 CONTENTS continued >> SCIENCE VOL318 21 DECEMBER 2007 1821CONTENTS i Science SCIENCE EXPRESS asics Timesteslved Observation andCortroLo Supernchange nteadions _APPLEDPHYSICS th Ulracld Atoms in Optical ates GaN Photoniccrstal Suac-Emitng Laser at lu Vet Wavelenoths Sraatyet H Matabar, 5. tshimot,H Sito Jngin, Tonka 5 Hoda Uta tars vn et otal tke tesa ed ett the Sudace ering ner oat with pti cys srucrescn ro ert siperehege eaten srs technol van baie wong .uizesiene 1150041 rOALRsscine 3150603 LETTERS PERSPECTIVES Cancer Fer Oa Vu RL. Hlecer LG. Koss end 1864 Hope's Equation 1876 1 Nelaeé bd. Caton One Woman’ Balancing Act Alec whe tun foce ti ; Stas el estnale bask fe Eh? lero Beneroatemm cm 0, Eisions Geting Bang forthe Buck. Fisher Revising One Depletion 1978 RB. Homarth and R. B. Norgaaid ‘M. von Hobe Response i D. Nordheus Js Therapeutic Cloning Dead? 1879 CORRECTIONS AND CLARIFICATIONS 1066 1 Gbelt >> tgorsen 117 261920 The Fw of Gas 1980 BOOKS E7 AL MUL lt > pet p30 TheEchoNatera Newel 1270 B. Powers evened byC. W.Bermen REVIEW LeLaboatare 1671 EvOLUTION 4 raed Boao, Paris reviewed by Whiley Seual Selection in Males and Females 1882 Tdlaton Brock EDUCATION FORUM BREVIA Linking Student interests Science Curcla 1872 LA Deno 8. Russel 0, Lobat,¥ta arocuemisray Combinatorial Synthesis of Petde hvesonto 1060 POLICY FORUM rico The thc af tematonl Resse wth 1374 Arete elcraly deci amin as one ta beta ‘Abandoned Children precise spots on 2 microchip can be used for combinatorial 4. Milnor). Emanue {stu syne of 4,00 petices pr square center, REPORTS: avis Obsanation of Bers Phase in aSoUdState Qutst 1869 Ay tecketal ‘A canelaie grerre pase or Ber’ phase, praducety smoringa supercnducting quit along a path and may provide ‘oust quasum information rage MATERIALS SCIENCE High-Performance Carbon Nanotube Fiber 1892 K- Koziol eal ‘eroge ofatbonranovdbes can betwisied and conpactes to produce bers of exceptional sregth and stifcs CONTENTS continued >> vwwscioncemag.org SCIENCE VOL318 21 DECEMBER 2007 1823Science REPORTS CONTINUED. MATERIALS SCIENCE Structural Rearrangements That Govern Fl Colloidal Glasses PrSchall D.A. Weite Spoepen Confocal miracony shone thatthe large cxplacement of fw particles stabilizes shear bands in delomedclleida eles, 2 proces thar may als occur in molecular lasses. 1895 cHeMsTRY Role of Intermolecular Forces in Defining Material 1900 Properties of Protein Nanofibrls Gonfoel mirexcopy sho that the large ilacement fo few panicles sais shear ands in defoemed clita oases, 2 proces that may alo ccur in molecular loses CHEMISTRY Role of Intermolecular Forces in Defining Material 1900 Properties of Protein Nanofibrils TP Knowles etal Ane iss semble Hema varity of polypentde ‘molecules, an ther rigidity can be tune over awe ange by controling hydragen bonding between sores. PLANETARY SCIENCE A sutur Dioxide Climate Feedback on Early Mars 1903 1 Holey, M. Zuber, 0. Schrag ‘buna sulle di, 2 grennouse gas, in Mars’ aacont atmosphere cou have alloned cui water to exis, exoaiing ‘holadk a carbonate mines GEOCHEMISTRY Coupled #2Nd-#% 1d lotopic Evidence for Hadean 1907 Mantle Dynamics VEC Bennett, A.0. Bralon, AP Nutman els ofan isotope wth a short hall ie ny some of Earth's oldest ‘oct an dat the eration and incomplete ea of tie: silicate resevoitsin the cay Earth GeorHYsics High-Pressure Creep of Serpentine, Interseismic 1910 Deformation, an initiation of Subduction Ne Hileiret et aL ‘ngerimerts on serpentine a commen produc of hydration ofthe ‘ocean cst show that it ceerms esa nsuaduton zones ad may be imovedin generation of eathauaks EVOLUTION Comprehensive Phylogeny of Beetles Revealsthe 1913 Evolutionary Origins ofa Superradiation Hunt etal Apavlgeny ofthe bees, which orstute 20 percent animal secs, redefines maj family groups end estimates eerie oriins 2 aesication Inthe js DEVELOPMENTAL BIOLOGY Induced Plutipotent Stem Cell Lines Derived fom 1917 Human Somatic Celis J uetal ‘uma fibro ats tonsfected wth eu gees eahibit the properties a embryonic stem es. > Pesce 1579 MEDICINE Treatment of Sickle Cell Anemia Mouse Modelwith 1920 |S Cells Generated from Autologous Skin J Hanno etal. Shin cals ama mouse wt ste ct anemia ca be geneally ‘egregranmed tbe pluripotent stem cls, tented and iad to at the aseasd mouse. => Pereciveg 1879 MEDICINE ‘eatment of Sickle Cell Anemia Mouse Model with 1920 ‘PS Cells Generated from Autologous Skin J. Hanna eta ‘Skin cls earn mouse wit se cll enema can be genetically ‘eoregranmed tbe plrpoten ten cells, tencitferentited ane sed toteat the diseased mouse. => Perectve 9 1079 BIOCHENSTRY Structure of Gy pé3RhoGEF-RhoA Complex Reveals 1923 4 Pathvay for the Activation of RhoA by GPCRS 5. lute etal 6 prowio-coupled receptors activate the sal GTPase Ro trouch Iteration of tre Gq ubunitol the receptor wth te exchange fac 10: GEFtorelevelahioiton of Fo. MOLECULAR BIOLOGY Regulation of Replication Fork Progression Trough 1928 stone Supply and Demand A.Grath eta. During cromesome cupication the chaperone At corcnats renova of histone proteins fort DNA, ONA yess and replacement ot hisones onthe new sands. MOLECULAR BIOLOGY Switching from Repression to Activation: McroRNAS. 1931 Can Up-Regulate Tanslaion 5. Vesudevan, ¥.Tong.].A.Stete ‘Atheuch thy inhib talon in ding cel, eukaryotic ‘mroRAs can bind to the 3-unvandaed region of messenger iis and actoteramation upon cl clearest. NEUROSCIENCE Rapid Changes in Throughput from Single Motor 1934 Cortex Neurons to Muscle Activity AG. Davidson, Char, R. O'Dell M. H. Schieber ‘sa result subcortal processes, nual nauronsin the motor ceteccan quick i from contaling motoneurons inthe spinal rd to maving nol 9a then. NEUROSCIENCE Cognitive Recovery in Socially Deprived Young 1937 Children: The Bucharest Ealy Intervention Project, CA. Melson i etal ‘na tadorized consoled al chee in Romania who were sed fn fstr car snowed Deter cogntvecevlanmer than scien raised iinsittions AovaNene SOENEE sthvNg JoClErY nasitanremnirGhoatamey Rta sa mart nm rnin ous Printed on 30% post-consumer recycled paper. ‘anarncn atObe non Re elas Lone MT somone caearitastaatne xt ww scioncemag.org SCIENCE VOL318 21 DECEMBER 2007 CONTENTS iDeep diver } SCIENCENOW ‘uousclencenod.org DALY ENS Coven i Wry Bo wales Get the Beds? Recognition fer young geneticists. Shallow divesin response to naal sonar testing may arm ore SCIENCE CAREERS ‘A 40-Hour Laptop Battery? er slencecateers.org CAREER RESOURCES FOR SCIENTISTS ‘con whiskers could improve echargeale hater apadty byatacerof 10, GLOBAL Young Genetiiss Making e Ditference Why Seniors Say "When" Too Soon E Poa . Brain otch may enian yt ery dink ess water Te stare foraenetcrariations between ndiuas fered yuna Suivi Scintitth vai backgrounds a chance te make a erence GLOBAL: Mastering Your Ph.0.—Writng Your Thesis Wit sive P Gosling ond 8. Norden Carettlanning and outing can meke wating your tess lessdauning US:Teoting Up—Three Categories of Rules DJensen Therules fr sucess industy ae cifferent rom the ones you lemmodin grad school. US: From the Archives —Dr. Bridget’ New Year's Rescl kamey For Or. Bridal aN Yearenaendesa strc of pointless enthusiasm, Highiighs fom AScé in Oc SCIENCE'S STKE nikon) SIGNAL IRAUSDUCTION KNOMLEDGE EUIRONNLN 2 FORUM: Highlights from ASCB Symposia I 5 NR. Gough SCIENCE PODCAST. The Ache dt Spring Sens" ssn inde 2 fcstonel hapa appl: of nee bi : Lletietataiaiee eee: Listen to the 21 December. § FORUM: Highiights from ASCE Symposium V ‘Science Podcast for a review LF Foley ‘of some of the biggest and see SB Eelam Plan toatend acl signaling conference. ; events y g 5 8 ‘Separeteindviduol or nstttional subscriptions to these products mey be required for fil-text access. vwwscioncemag.org SCIENCE VOL318 21 DECEMBER 2007 1827Aging in Glasses Glasses age over tne, but an understanding of the structural errangements that underlie ese processes in small molecule sytem ificalt because itis not posible to track the mation of inevual molecules, ane the areal changes in ordering ay be sal Schall et al (p. 1895, see the Perspective by Fal) tracked the motions of clloka lasses under smal stain mations using confocal microscopy oclized zones form are the colloidal pats underge ievrsible shear transformations. Further analysis revealed how the sheared colloidal glasses are activated and ow they interconnect nt networks, Mechanics of Amyloid Fibrils Amyloig structures assecited wth a number of diseases fxm trom a wide range of unrelated polypeptides and show intriguing but poorly Understood physical properties. Using atomic force micoscopytoimace ase of protein fbi Knoles eta. (p. 1900) measue the local mechanical propeties and correlated these results with coarse-grained atomistic molecular simulation. By cotraling the hydrogen bond ing, iri stability can be altered o enforced and used to offset speci side-chain teractions. Heating Mars with SO, Evidence that Mats ha gud water ont sur face when the planet nas youn impli tet at temperatures were above the freezing paint of ater, unl toy. these conditions exe mainly the result of greenhouse gas heating by (CO, then th partial pressure of CO, should have been high enough that carbonate minerals vould have formed—yet these minerals have not baen observed on Mars’ surtace. Halewy et al. (p. 1903) propose thet volcancally degassed 50, emitted under more reducing conditions along with H,S, woul in combination with CO, have pushed temperatures over the threshold requited by Uguid water. Dissolved $0, also vould have ecdifes the oceens enough topre vent carbonate minerals rom forming. A similar mechanism operating on Earth may explain the absence of carbonate rocks from the Archean. An Exercise in Quantum Geometry {Quantum computation relies onthe abitty to ohecenly manipulate the quantum state of qubts. However, unavoidable coupling tothe environment gives the qubit finite lifetime Ithas been proposed thatthe use of a geo metic phase (or Bry’ phase, atpologiat phase that accumlates asanobjecttrav- ere path shouldbe more robust the elflets of decoher fence. Leek et a. (p.1889, published online 22 November) describe the observation ofthis geemetrc phase na superconducting qui, whi they clo ight bring foul tolerant quantum com puation a step cosa. << Battle of the Sexes ‘Much research on sexual selection has focused either (on intrasexual competition between males or on female ‘mating preferences. Clutton-Brock (p. 1882) reviews recent studies which show that intrasexual competition between females and male preferences for particular categories of partners are also common and can generate secondary sexual characters that are more highly devel ‘ped in females. Sexval selection may now need a new conceptual framenork that incorporates the effects of intrasexual competition and mating preferences in both sexes. Carbon Nanotube Fiber Fabrication By twisting together even short segments of string oF sta, strong fiber oF rope can be formed 3s long 2s the starting materials tong ‘enough to properly twist together and is com pressed sufficiently to ensure ses transfer between the segments. In theory, carbon nano tubes (CTs) should be abe to form very stiong fibers because of thee impressive intrinsic properties. Keriol etal (p. 1892, published online 15 Noverbes) show that they ‘an generate CNT aerogels and directly spin them ito strong and sbi fibers. Further don sification by treatment with actor maximal ses tansfr between ad fiers. The authors compare the strength and stiffness of these fibers to other CNTs and cm mercial materials suchas Kevlar. Slippery Serpentine Sheets Serpentine layers that coat te topo sinking lithospheric slabs have been thought to play 2 tol in subuction zone earthquakes because these layers become heavily deformed. Hilaiet etal (p. 1910) deormed the serpentine entigorite at high pres sures ad temperatures and found that * account for pesseismic deformations after large earthcuakes within subduction zones. This property may also enable subduc tion initiation and may govern convection within subduction cones wwwscioncemeg.org SCIENCE VOL318 21 DECEMBER 2007 1829‘This Week in Science Conte pongo 188 Planet of the Beetles From Beetles represent more than 20% of all described species, although relationships within the order are life on Mars st spective Hone (1913) rons te pyiery o> 30% ef cognce eee ea tamiles an denied previnlyuntrawn relationship for many grup. By pefordng ana: of to life sciences diversity pattems acoss the entre order, the authors estimated that civersfcation of major beetle ‘groups may have ocurred inthe Jurassic earlier than previously thought For careers in science, turn to Science Induced Human Pluripotent Stem Cell Lines Embryonic stem cel can grow for an unlimited time and can tur into essentially every ype of el, which makes thom an ideal candidate for regeneratie medicine (see the Petspctve by Cibelli. Honever ther applications ae hindered by potential problems such es immune rejection and ethical > REPROGRAMMING CELLS. tie rite oF Doity ihe Sheep bas purzled biologists for more than a decade: Wha sit about the ooeyte that rejuvenates the nucleus of ifferertztedcel,prompringthe genome tyretum to theembeyonie st and form a new individual? This yea, scientists came closer to solv ing that riddle. Ina seriesof papers, hat by adding justa handful of gones wo skin cells, they could reprogram those cells t0 look and act like embryonic stem (ES) cells. ES cells are famous for their potential to become any kind ‘of cell in the body. Bur because researchers derive them from eatly cembryes; they are also infamous foe the political and ethical debates that they have sparked The new work is both a scien: tifie and a political breakthrough, shedding light on the molecular besis of reprogramming and, perhaps, promising a way out ofthe political storm that has surrounded the ster cell field The work grows out of a breakthrough a decade ago. In 1997 Dolly the First mammal cloned from an adult cell, demonstrated that unknown factors in the oocyte can turn back the developmental clock in @ differentiated cell, allowit nome to go back 10 its embryonic state, Various exper researchers show shave shown how readily this talent is evoked. A few years ago, researchers discovered that fusing ES cells with differentiated cells could zlso reprogram the nucleus, produc= ing ES-like cells but with twice the normal number of chromosomes. World-weary? Hardly. Four spacecrat returned torents of data from around the sola 5s tem. The Venus Express orbiter probed the vious atmosphere of Earth's near-twin, On itsway to Pluto, New Horizons snapped pictures of Jupiter the Mars Recon- naissance Orbiter revealed unforesgen hazards for future lan ders. And Europe’ Earth-obiting COROT discovered its fist planet orbiting another sta, showing that COROT can detect exoplanets small as Earth, inet PROVED wos HOW'D WE DO? Rating the predictions we made last year in “Rreas to Watch” CEMBER 2007 VOL3I8 SCIENCE Recently, they also showed that a fertilized mouse e ‘with its nucleus removed cauld also reprogram a somatic cell, ‘Meanwhile, the identity ofthe reprogramming feetors continued to purse and tantalize biologists In 2006, Ispanese researchers announced that they were close to at least part of the answer, By adding just four es to meAse tal cells hey pro= duced what they call induced pluripotent stem (iPS) cells: cells that looked and acted like This yea, intwo announcements ed the ster cell field, scientists close the deal Ina series ‘of papers in June, the sme Tapanese oup. along with two American ‘groups, showed that the iPS cells made from mouse skin could, like ES colls, contribute to chimeri mbryos and proxkice all the body's cell, meluding eges and sperm. The iPS cells were indeed equivalent to calls thar elec eres rt ror fe proitedto Poa ae work convinced most observer [ES ells at least in mice Then in November carea triumphno one ud expectedthis soon: Not fone, bt 1 teams repeated the feat in human cells. The Japanese team showed that their mouse recipe could werk ia human cell and an Amer- ‘can team found that aslighty diferent recipe would do the ob as wel: both the science and the pol ties of stem coll research, Seientistssay the work demnstratesthat the riddle of Dolly may be simpler than they had dared © hope: Jus. oar sn make all the difference. Now they can ness of understanding how to guide the development of these high- potential cells in the laboratory. In December, scientists reported that a2 ‘Skulls and beads ofnew bones. In 2007, primate genes. paleoanthce Thepubishes A pologists ‘genome sequence unveiled the long-awaited post. ‘cranial bones ofa 1.7-milion year-old Homo erectus trom Danis) Georgia, bits of a puta tive gorilla ancestor, and new early Homo specimens from Africa, Bu the world stil waits for publication of te skeletan ofthe enigmatic Ardipthecus romidus, a 4.4-million-year-old Ethiopian hominid that may she¢ light on the murky roots ofthe human family tee. ofthe thesus macaque dié help larly genetic changes that led to humans, but the anayses ofthe ‘genomes ofthe gorilla orangutan, ‘marmoset, gibbon, gala, tree ‘Stew, and mouse emur have yet toeppear. Eventually though, these sequence maps wil bring a host of evolutionary insights ‘A climate of change? High profile reports, an agenda setting meeting in Ball, Indonesia, ndaCO en ae) they had already used mouse iPS cells to successfully treat a mouse TRACING COSMIC BULLETS. whars sma model of sickle cell anemia, The next big challenge will be finding a than an atom but crashes into Earth with as much energy way 0 Fe sing as a golf ball hitting a fairway’ Since the 1960s, that ri viruses to inser the genes, dle has tamtalized physicists studying the highest en Politicians and ethicists on both sides of the debate about research ate jubilant. Supporters hope the new technique will ene sm human cells without using possible eancer-< smbryo | rays, particles from space that strike t le | 100 million times higher than particle acceleracors h atory in A stmosphere with eneraies reached, supplied key erlopers come fron, them to conduc research without politcal restrictions, and opponents | This year, the hopeit will eventually ender embxyo research unnecessary, Indeed, sev- | clues to determine where in space the ‘eral scientists said the new work prompted then to abandon their plans | Ma for further research on human cloning. protons from distant galaxies. That notion took a hit in the COfficialsat the National Insiutes of Health said there was no reason | 1990s, when researchers with the Akeno Giant Air Shower work with iPS cells would not be eligible for federal funding, enabling | Array (AGASA) near Tokyo reported I rays with ener; scientists inthe Linited States to sidestep restrictions imposed by the | above 100 exa-electron volts (EeV)—about 10 times more th Bush Administration. And President George W. Bush himself grectedthe | expected. The abundance was tantalizing. On their lo an ght to interact with radiation lingering from the big, physicists had assumed the extremely rare protons ou 3 ethical problem, bang in a way that saps their energy and leaves few with more 3 Burir's much to carly to predictan end to the political contmersies | than 60 EeV. So the excess suggested that the rays might be born about stem cell research, Some researchers Sty they sil need to beable | in our galactic neighborhood, perhaps in the decays of supe © tw dosescarch cloning to find out just what proteins the exe uses for its | massive particles forged in the big bang. But researchers with reprogramming magic. And now that seience has come a step closer to | the Hi-Res detector in Dugway, Uta, sew only two 100-EeV (erm goalofsiem celltherapy.mnoxsemodels won'tbeadeguate | rays, about as The Auger team set out to beat AGASA and Hi-Res at their tion appreaches with primates, meve dat will inevitably stir up resise | awn games. When a casmic ray strikes th any as expected from far-off sources. for animal studies. Rather, researchers will ood to test cell transpla mosphere, it ets off ance from animal-rightsactviss, aan avalanche of particles. AGASA used I detectors spread over 100 square kilometers to sample the particles and infer the ray’s € energy and direction; Auger comprises nearly 1500 detectors ©) Nobel Peace Prize tracking down spread over 3000 square kilometers, The avalanche also causes the Placed global cis genes linked air to fluoresce, Hi-Res used two buiteries of telescopes tosee the mmatesquareyinthe to disease. Tight; Auger boasts four, In July, the Auger team reported its first WD bic eye, but potcy eS big result: no excess of rays above 60 Ee. makers inthe United ht crystal. Auger stil sees a couple of dozen rays above that level, how: States, China, and India have Physicists hope to explore high: | ever. Last month, the team reported that they seem to emanate passed mandatory Uinitson green- temperature supercenductty and | from active galactic nuclei (AGNs): enormous black holes in the house gas emission that scientists other bizarre properties of solids | middles of some galaxies. The AGNs lie within 250 million say are needed. See “Global Warm- by emulating them inopticallat- | light-years of Earth, close enough that cosmic radiation would, ing, Hoter Than Eves,” p 1846.) tices, artiidal “crystals” based on | not have drained the particles’ energy en route. Auger ‘corrugated patterns of laser light. | researchers haven't yet proved that AGNs ate the sources of the whole-genome association The year'shundreds of | rays, and no one knows how an AGN might accelerate a proton studies. In work that made up papers on optical | to such stupendous energies. part of this years Breakthrough of lattices aid not Expect the controversy to continue. Hi-Res researchers say the Year (seep. 1842), more than include a supe that they sce no correlation with AGNs, With Japanese colleagues, a dozen large scale comparative ‘conductor stand-in, | they are completing the 740-square-kilometer Telescope Array in ‘ules of human DNA showed the butagrand entrance | Millard County, Utah, which has 312 detectors and three tele technique's enormous promise for can't be far of. scope batteries. But with a much bi surely be fist to tt its own claims soe 1845 ciencemag.org SCIENCE VOL3I8 21 DECEMBER 200:1846 Breakthrough of the Year RECEPTOR VISIONS. sus: sien some cystlogs hers were etting that the ash wes impossible, researchers habbed 3 elose-yp of sdtenaline’ target, the By-adrenergie receptor. Its structure has long been on the to-do ist, bat the fea also got pulses racing because ofthe molecles faily connec tions The receptor is one of roughly 1000 membrane-spanning moke- calesalled G protein-coupled receptors (GPCRs) By detecting igh, ovr and tastes, the recepons cue us nto ou surroundings. GPCRS ao help manage our iniemal conditions by relaying messages from hormones, the aeurviransiterserton ‘and myriad other molecules. From anihisterines to beta blockers, the pharmacopoeia brims with med ines cmd ot GPCRS-al of which researchers discovered without the benefit of higherescltion sates {A clea piture of, say. a receptor binding site might spar development of more potent, safer drugs. But Scientists had cracked only one PCR structure, for the GGoteha! Researchers have worked ‘out the architecture ofthe aden line recente hetdrenergic receptor took the leaders of two overlapping erystallographic teams almost 2 decades. The effort pail of this fall with four papers published in the journals Science, Nature. and Nature Methods. The lb ingenuity «hatother expertscalla technical tour de force showsinthe way the ams restrained the molecule’ flexible third loop, They ether replaced it with «he stolid enzyme lysozyme or tacked it dowa with an antibody. But this snapshor of the receptor is just the beginning. Before researchers can design compounds fo jam the molecule. they needto pic ‘ure it in its different “on” states. And the other GPCRS avaiting analysis mean that forerystallographers, i's avo dexyn and 10000 go. BEYOND SILICON? sixty years ago, semisoniue- tors were a scientific curiosity. Then researchers tried puting ‘one type oF semiconductor up against another, and sudden! ‘ve had diodes, transisiors, microprocessors and the whole electronic age. Strling results this year may herald similar burst of discoveriesat ‘be interfaces of different class of materials: transition mex oxides. ‘Transition metal oxides frst mode headlines in 1986 withthe Nobel Prize-winning discovery of high-temperature superconductors. Since «hen, solidsate physicists keep finding unexpected propertics in these ‘materials including colossal magnetoresistance, in which small changes in applied! magnetic fields cause huge changes in electrical ‘sistance, Butthe fn should really start when one oxide rubs shoulders ‘with anosher, Iifferent oxide erystalyare grown in ayers with sharp interfices, the effect of one crystal strue ‘ure on another can shift the positions of atoms atthe inter- Face, alter the population of clectrons, and even change how Tunable sandwieh. In lanthanun alninatesandniched bebveen layers of strontium ttanate, a thick middle ayer (gh) produces conduction a the lower inertace: thin one dos nt 21 DECEMBER 2007 VOL318 SCIENCE fying the effects of global warm- ing. A steady stream of media reports thisyear noted record melt ing of Greentand ice, recorc-high temperatures in the United States, and surging Aarti glaciers. And the enetgy crisis deepened as oil prices increased to $100 a barrel, bbocsting asieties about the future of fossil fuels Politicians weren't idle, although US. climate policymak cers sil have litle to show for their ‘concern. Since gaining contol of Congress in January, Democrats have transformed the debate from “ifte when for mandatory limitson US. emissions,” says Paul Bledsoe of the National Commission on Energy Policy in Washington, D.C But hundreds of hearings and ‘reams of leaislative proposals have not wanslated into legislation. The status ofthe most promi: nent Senate proposal, offered by senators Joseph Lieberman (I-CD) ang John Warner (R-VA), iustrates the pitfalls that lie ahead for Democrats, Introduced in October after months of negotiations with corporate lobbyists and environ- menial arcups, the bill would cut USS. emissions by coughly 15% of 2005 levels by 2020 with innova tive proposals for emissions credits to spur new technologies. But the éebate at a § December markup ‘exposed seme ofthe hurdles that the lecislation wil face in what experts expect willbe 3 multiyear GLOBAL WARMING, HOTTER THAN EVER Climate change, a perennial runner-up for Breakthrough ofthe Year, broke from the pack this, year—both in the pages of this section and inthe public arena. In 2007, the debate about the realty of elobal narming ended, a {east in the political and public ‘realms inthe Urited States. After 6 years of silence, the United Nations’ Intergovernmental Pane fon Climate Change (IPCC) drew heavy and wholly positive media comage fora seties of wide-rang ing ports. The werld is warming, IPCC declared; human activity Is behind mostof it, and fitkeeps up ‘ell pay price. But the panel also said that much ofthe climate pain ‘might be avoided if the world agrees to begin sharing the eco ‘nomi¢ pain. impressed with that performance, the Nobel committee ‘anointed IPCC, as well as climate ‘campaigner Al Gre, wth ts Peace Prize, ‘Other reminders also drove hore the gravity of the climate change situation, Scientists now worry that the record malt-back of sea ice during the summer might Indicate that feedbacks ae ampli ‘electrons’ charyes ave distribued around an atom, Teams have grown together two insulating oxides to produce an interfece that conducts |iketa metal or, in another example, superconductor. Other combina tions have shown magnetic properties more familiar in metals, as well asthe quanturn Hall effect, in which conductance becomes quantized ntodiscrete values ina magnetic field, Researchersare optimissic that they may be able to make combinations of oxides that outperform semiconducor svctues, With almost limitless variation in these complex exides, propertios not yer dreamed of may be found where they meet ELECTRONS TAKE A NEW SPIN. chstione up forthe theorists. Theoretical physicisis in California recently preditod tha semiconductor sandwiches with thin layers of mercury telluride (HgTe) in the middle should exhibit an behavior oftheir electrons called the quantutn spin Hall effect (QSHE), This year, they teamed up with experimental physicists in Germany and found just what they were looking for emuuecioncemag.crge i £ slog. Democrats from Midwestern and coal states, for example, helped killa proposed measur that wo have civen the Eriermen {a Protection Agency the aly e tighten the caps scents deer mined that warming was going to be moe than 2°C above the pein dustialaveage. Meanatile the House is even further behind on emissions its. 8s Science went ae pies, Congress was posed to ps a mobile fuel tan i thet, if it survives threatened a White Hou miles pot gallon (149 kilometer per 00 Kio meter ficiency by 2020. | Elsewhere, Ihere have been mized signs of progres. At press tie in Ball, ndoneia,negatia tot ftom Europe and the develop ing worts landmark au veto, will require 35 4 per ler, 0° 6.7 2 striving to per suade the United States to con ~ sider binging cuts for the 2012 i follow-on to the Kyoto treaty. China has warmed slightly to car bom timits—if the ceadline is far ‘enough anay. Meanwhile, growing numbers of prominent climate [iam experts are calling for research ( into geoensineering, the with Earth's climate to reverse narming, Given the slow political progress, says atmos biter scientist David Batisti of the Univers Co re oma ern ec y of Washington, Poiana Seattlo, “ae might eda olan 8. Peace SECM cosvallies of mold ricuaroa.xere [toa beatae The effect is the | ies of oddball behave when placed researchersin Germany and the UK. dsemveredone ofthese anomalies, called the quartum [ll effect, When they changed the strength of magnetic field applied perpendicular to charges moving through thin layers of metals or semiconductors, they found thatthe conckctance cha 2 stepwise, of quantized. 1 (One upshot was that char Awed in tiny channels along thy mat tially no ene’ Channeled. Elecrons vith spin oiete in epposite direction flow SCIENCE es CAIN Be The find seal hopes of new families of computer chip devices. But because the elect requinal high magnetic fields and low tempera tures such devices remained pipe dreams Luckily for physicists electrons harbor not only ‘electri charge but also another property known as spin. Inrecent years theoristshave predicted that ‘materials with the right electronic structure should imeract with elect fieklsw resil the QSHE—anda spin-riven version of near lossless conduction, Such materials wi do away with the need for his and perinaps even for kv temps ‘one of them—the HgTe sandwich—showed tell tale (although not ironcl 3 of the effect at temperatures below 10 kelvin, If researchers ean do the same trick at room temperature, the discovery could ‘open the door to new lenv-power*spintroni devices that menipulaie lections by boxh charge an spin, DECEMBE!1848 Breakthrough of the Year 7 DIVIDE TO CONQUER. tics cidsnc itanina ing how immune cells specialize fer immedi of long-term path protection had researchers litle feverish this year When a ‘others morph into memory cell that loiter fr decades in case the same atacks, some CDS T eels become short-lived soldiers, while imterloper ties again. The new work demonstrates how one cell ean spain both cell types. AT cell wemins passive until i meets a denditic cll carrying spe- cific pathogen molecules. The liaison between the two lasts For hours. As the cellsdaly.recepeorsan rher molecules congrezate ateach endothe Teel, A US, based team tested the proposal that ifthe T cell then divided, its progeny would inherit different molecules that might steer them onto distinct paths. Such asymmetric divisions are a common methed for f 1g development In March, the team reported experiments showing that cifferen specalization-contoling proteins amassed at cach pole of aT cell during its dance with a dendritic cell, When the researchers nabbed newly divided T cell, they Found that progeny that had been adjacent to the dendritic cell carried receptors typical of sol- showed the call diversification durin Separate and unequal s3 Tet éivides, the upper and omer cell port inctmolecle diets, whereas their counterpart molecular signagure of memory cells Unequal divisions could also help diversity among CD§ T eels, immune regulators that df tneetyjes. Practical applications the discovery will have to walt ail researchers know more aboutmemory-cell specialization, buteventually ‘hey mightbe able wo weak the process DOING MORE WITH LESS. socicry may finally be embracing energy efficiency and waste reduction, but these attributes have always been prized among synthetic 1 plaudits and stature go to chemisis who & Conan’ tree ane Pree! CEMBER 2007 VOL 318 desired reactions inthe simplest and most ele- ‘on: Fewer synth s saves cash. And 2 isa perennial goal, this year an of synthetic successes shoxted gant ways, One nlmos: al impressive that chemists are gaining new level of contol over the molecules they make and how they make them, Achicving this control has not been ea Many desired molecules, such as pharmace tival and electronic compounds, consist of a backbone of carbon atoms with hydrogen atoms or other mote complex Fianetional groups dangling oif the sides. When chemists convert a starting compound into one they really want, they typically aim to modify just one of those appendages but not the ethers, They normally do so cither by adorning the starting material with chen that prompt the molecule to react only atthe tag “activators” cor by slap sroupson the sites they want left umouched This year, researchers around the globe made major strides in doing away with these accessories. One group in Israel used! a ruthe- niu-based catalyst to convert starting compounds ealled amines scientists have seen the kinship as both literal and pra Remembering the past, they propose, helps us picture cil into another class of widely useful compounds BACK TO THE FUTURE. ts creck mythology, osyne, gave birth to the succes ifthe LMC produces even a litte ata next year AREAS TO WATCH A smashing start? Next sum mer, physicists wil start up the Large Hadron Collider (LHO) atthe European particle physics lab, CERN, outside Genova, Switz land. Researchers hope this high esteenergy collider will reveal plenty of new paiticles and puz ales, but the immediate question is hon fast will it come on? The ultracomplex machine runs at 2 frigid L.9 kelvin, ane if for some reason researchers have to warm part of up it wll take months to ool it again. Still, CERN has @ record of bringing new machines ‘on tine smoothly. Call it a major Micromanagers. Research on ‘mall RNA molecules that control gene expression continues at 2 rapid cp, and microRNAs are surg Ingo the front ofthe pack. Roughly {800 papers on the tiny molecules vere published in 2007, ying them toaslew of concer, heart alent, healthy immune system, stem cel, differentiation, and move. Bu it's stllealy days. In 2008, researchers wil start using microRNAS to umvel disease mechanisms and wil make Jncoads into solving fundamental ppuzles about how they function, Cell to order. t's hard to separate the hype from the har scence, but SCIENCE wmuscioncem:| | | i : § cnet td ne ate ce | pare for the future, The notion got a boost this year from sev eral studies hinting at common neural mechanisms for memory and imagination, In January researchers in the United Kingdom reported that five people with amnesin caused by damage tothe hippocampus, a er ‘cial memory center in the brain, were less adept than healthy volun- teers at envisioning hypothetical situations such as a day at the beach or a shopping trip. Whereas healthy subjects described such imagined events vividly, the amnesic patients could muster only a few loosely connected details, suggesting that their hippocampal uze had impaired imagination as well as memior In April, a brain-imaging study with healthy young volunteers, found that recalling past life experiences and imagining future ‘experiences activated a similar network of drain regions, includ: 1g the hippocampus. Even studies with rats suggested that the hippocampus may have a role in envisioning the future: One team reported in November that when a rat faces a fork in 2 fall ‘maze, neurons in the hippocampus that encode specific locations fire in sequence as ithe rat were weighing its options by mentally running down one path and then the other. (On the basis of such findings, some researchers propose that the brain's memory systems may splice together remembered fragments of past events to construct possible futures. The idea is far from proven, but if future experiments bear it out, memory may indeed turn out wo be the mother of imagination, ntti biologists say humanmade rierobes are in reach. By this time niet yea, one group hopes to put a synthesized genome into DNA tess bacteria; anether i incrementally Species rolling out ofthe seauenc Ing pipeines. Multiferroics. Relatives of Ceramic oxide superconductors. replacing natural DNAwith synthetic the compounds called multferois DDNA.The points tomakebefuole— forma group in which single mate pethapseven miciobe-derived gaso- rials cisplay multiple electronic, line—or pharmacoutical. magnetic, and structural behav. iors. Physicists recently used elec- tric fields to manipulate magnetic domains in a multiterroic. Now, they are racing to better control this svitching anc shape the mate Flals into novel computer chip devices. Success could pave the nay for chips that combine the logic functions normally handled by semiconductors wit the mem- ory functions now carried out by magnetic materials. Leogenomics. Expect a very rough draft of the Neandertal ‘genome by the end of 2008 and ‘more comparisons between the ‘genes of Neandertals andé Homa sapiens that will continue to flesh ‘out those fossil boas, filing out many features of this extinct ‘human, Thanks to cheaper, faster technologies, there will be more genomes, from more extinct vowusciencomag.org SCIENCE VOL318 21 DECEMBER 2007 SPECIALSECTION GAME OVER. Compuicr sciemists finally 1 took some of the fun out of the game of checkers. After 18 years of uying,2 Canaan team proved that iff neither player makes a misiake, a game of checkers will inevitably end ina draw: The proof makes checkers also known as draughts— the most complicated game ever “solved.” It marks another victory for ‘machines over humans: A mistake-prone person will surely lose 10 the team’s computer program, Proving that Flawless checkers will end in a stalemate was hardly childs play. Inthe United States, the game is played on an eight-y- eight gn of red and black squares. The 12 red and 12 black checkers slide diagonally from black square to black square, and ane player ean ‘capture the other's checker by hopping over it imo an empty space just beyond. All old, there are about SOO billion billion sxrangementsor ‘enough fo overwhelm 's best computers. So the researchers compiled a database ofthe mere 39,000 billion arrangemenis oF 10 0 fewer pieces and determined which onesled toa twin for red, a win for black, ora draw They then considered a spe cific opening move and used a search algorithm toshow that play cers with perfect foresight would imvanably euide the game 10 acon= figuration that yields a dan. Reported in July, the advance exemplifiesan emerging trend inari- ficial intelligence. Human thinking reliesona modest ameunt of mem- ory anda laraer capacity to prosess information. In contrast, the check- cers program emplays elatvely less processing and a whole lato mem- ‘ory the 39,000-billion-configuration database, The algorithms the team developad could find broad applietions others say, such as deci- phering the information encoded in DNA. THE NEWS STAFF ‘Megamicrobes. Featured in both the U.S. National Institutes ‘of Health and the European Union plans for 2008, the human micro biome will go under the micro- scope this year in many labs around the world. Expect the ‘genomes of 200 of the bacteria that call humans home to be sequenced, a5 well as the first steps tonard extensive surveys of {ut skin, mouth, and reproduc: ive-tract micobial communities. Meanahile researchers are map- ping the distribution of microbes in other environments, including Icebergs and hot ash, ‘neurons process information and ‘mediate behavior. Recently, neu- ‘oscientists mapped neural con nections in mice by genetically tagging neurons with nearly 100 fluorescent hues. Others have been using lasers to control the of individual ‘neurons inthe brains of rodents, thanks to light-sensitive ion channels introduced by genetic ‘engineering. Meanwhile, a mag: netic resonance methed called diffusion tensor imaging is pro- viding nen deta about connec: tions between regions of the ‘human brain, These techniques should yield important insights into how neural circuits work— and how they break down in brain disorders. New light on neural circuits. Exciting nen methods ate poised to start revealing hon circuits ofia Rovner) renin Vena rere 1850 CLIMATE CHANGE Grassroots Effort Pays Dividends On Presidential Campaign Trail PLAISTOW, NEW HAMPSHIRE—Activists in 4 pol ¢ fro at candidate town meetings. Editorials newspapers in New Hampsh Most major presidential candidates: liberal Democratic senator Barack Obat former Arkansas governor Mike Huckabe conservative Republican «apson the emissions o “The run-up to th lection camp: from 2008 U.S. presidential which kicks off with the anwary and the New Hampsire primary 5 days later has been a “Cli ‘coming-out party for climate chai mate change is bigger politically than is been.” says Navin Nayak of the League of Conservation Voters in Washington, D.C which tacks the issue, There are plenty of reasons ‘xhy. A drumbeat of media stories ‘on imateis an obvious one, and the recent Nobel Peace Prize to Al Gore and the 1 Panel on Climate Change for the tainly hada big impact. Known, but possibly just as pis xl inthis New En 2-year campaign by a group of sciemtigscive leaders ander ronmental activists called the Carbon Coalition, Their rallyin 204-word resolution on mate change that they ha mered out in late 2006 and managed to put before New Hampshire's round of public m March across the state. A Tat majority 164_-of those towns adopted the resolution, which eal fora “national program requiring [emissions] reductions” new enctsy ;ch, and “local steps to save energy 221 towns at a ngs held in Members of the coalition have used the doc ment to pressure candidates at hundrods ofthe preprimary events, small and large, i 21 DECEMI of More than hot. process that affords citizens repeated Fae-to “T've boen thrilled to b climate scientist Cameron Wake of th versity of New Hampshire, Duthar, a ening beard. a pat of i” says jered roughly 30 speeches around the state on the topic and writen a report on the impacts of global warm §400-million- uty. “But the volunce tion deserve the m adds, And the coalition ishappy to aeeepe the time [a skeptical candi slate] turns around, there's someone with & Stop Global Wartning sticker. Ir makes them think” says the group's co-chair, Ted L 2 former Republican state legislator, on the tate’. +-year Winter tourism indus: atthe Carbon Coali jority of the ered.” he CORI) Voted for Bush 2008 In Towa, there’s been a smaller effort to publicize the issue by a coalition of green groups called the Lowa Global Warming sampaign. Its small staff works with volun. teers to attend the dozens of candidate ‘events that oscurcach week." The goal is to x Towwans to talk 10 candidates about eli- 2007 VOL318 SCIENCE he University of New Hampshire's Berrien Moore speaks a an Octcber conference sponsored by groups that pushed sucessuly for @ Climate change resoiution passed by many towns across the tte ‘mate change when they get here" says Joe Wilkinson of the Lowa Wildlife Federa in Des Moines, Both the lowa and the New Hampshire efforts lay heavy emphasis on how climate ‘might impact local ecosystems and businesses. “I used to g legitimacy of the] science, ks he’ ¢ effet me? So Wake and a hand of climate sciea- ists have worked hard to document both near-term and long-range effects. In lowa, he National Wildlife Federation has distri reed a report ealled The Werorfowter & Gude to Gl of how warmer temperatures could alt questions on the says Wake of wind the state dari Jw i's, “How will arming that cites federal stud ‘migration routes and disr tems, “Global warming already has ducks fying in lterand leaving earlier” proclaims ‘radio ad in Towa paid for by the founda. fon’s political arm, National Wildlife Action. “When the presidential candidates ‘come to town, make sure they spell out the plan te combat global wari In New Hampshire, Wake and other scientists have focused on ppossibie effects to the ski and tn ber industries. In recent years, areas have had fo make more and nore oftheir snow, nd warming tHweatens the winter ands tha attracts tourists, says Janice Crawford, director of the Mount Washington Valley Chamber of Commeree, The bipartisan success ‘ofthe March coalition siatement Jed Senator John McCain (R-AZ), bon apshire a longtime advocate of e ‘caps, to remind New Ha ‘eters in a adosad that he has “lis: snd 1o their concerns. And. October candidates’ debate spon sored by the Carbon Coalition, Huckabeeannouneed support for a andetory cap-and-trade system, callin “our responsibility Even candidates who have taken relative! aggressive approaches to slow climate change have fave pressure on the stump. In October Friends of the Earth (FOE) Action ran adver tisements in lowa asking Senator Hillary Clin ton (D-NY) remove “giveanaaysto gh greenhouse gas buildup enwwnsciencemag.orgwarming polluters” rom a climate bill before a committee on which she sits (Science 14 Decernber, p. 1708), Cli offered an amendment thar would exe wxgh ened the bill, by au sion centficasinses on subsequently ining more of the emis of making them freeto industry. Although the amendments filed. *we were pleased.” says.a spokesperson for FOE RESEARCH FUNDING Ts Action, which has stopped running Activists are also applying pressure 10 those whose positions are considered fluid, ‘Once Huckabee emerged render, note activists, he topped mentioni mandatory caps whet ‘nergy. That possible the Reverend Richard Cizik of the influential sketl abou climate or backtracking” worries Caen Ras National Association of Eva ton, D.C researchers to combat warming (Scrence 24 February 2006, p, 1082), “I call and say to his campaign stafl; “Look, don’t listen to his i who has teamed with climate ‘conservatives who are critical of your position: they'll come around, have to be educated says Cizik, “They just “EU KINTISCHL U.K. Cutbacks Rattle Physics, Astronomy Theres litle seasonal cheer for British physi cists and astronomers this month. A change 1 the funding arrangements for their disci plinas has led 0 th projects and a Likely cut of ‘grants pot for the pecied casualty Collider (ILC), now in its design phase The sad tii n the 2008-2011 budget “delivery plan” released by the U.S Seience and Technol ‘ogy Facilities Council (STFC). The council \was especially blunt about the ILC, conclud ing: “We do not see a pra h towards the realization ofthis facility as cur~ 5% in theie 3 years. One unex. 1 were revealed last week ieticab rently conceived on reasonable timescale That sent shock waves through the physics “Irs terrible because a domino It develop.” with other countries oat, says Albrecht Wagner, director ‘of Germany’s DESY particle physies lab znd chair of the International Committee for Future Accelerators The United Kingdom currently con- ributes only 5% of the ILC’s development Diigo but plays leading role. “The problems is {losing} the intellectual made by the UK." says Barry Ba the ILCs Global Design Effort The roots of STEC'S woes lie in its ori gins. twas formed earlier this year byn ing two of the ULK.S seven research-funding were folded into the council responsible for lab infrastructure, Physicists were reassured thatthe new STFC would not be sade with the liabilities ofthe old facilities council and things looked good inthe fll when the gow ments Comprehensive Spending Review showed a healthy overall increase for research (Science, 19 October p. 379). cioncemagorg SCIENCE VOL3I8 Poor autlonk. U.K astronomers could lowe acces to G But last month, STFC announced that it was withdrawing support for the Observatory. aniniemational facility with win S-metertelewopes in Hawaii and Chile. The reascn is now clear STFC received one ofthe smallest funding increeses among the researeh ‘councils, rising from £573 million (S12 bil lion) in 2007-08 to £652 million in 2010-11 Aanincrease of 13.6% aver 3 yeas, An STFC spokesperson sa that increase ill pay in part for closing the Synchrotron Raaliation Source atthe Daresbury Laboratory twill also Fund an increase inthe size grants re university scientists to cover the full eco nomic costof thet esearch, STFC was denied funding for, among other items, expected increases in the running costs of the newly ‘opened Diamond synchrotron and the second target station of the [SIS spallation neutron, souree, due to open in 2008, ‘This leaves STFC with an £80 million hole in its bu ‘cuts to shrink that hole, including the ILC Gemini, high-energy gammasay astionony. al physics fors and ground-based solar-errest The council will:Isoreview fund 4. STFChas listed astring of 21 DECEMBER 200; i plu) and oer fc eral other astronomy facilites and projects nd ISIS. British astronomers were as angry as The ‘astrophysics, space anc! will ikely limit use of Diamond seience, and solar system science make & direct contribution to the U.K. economy.” says Michae! Rowan-Robinson, president of he Royal Astronomical Society Physicists are particularly concerned about 3 cuts because funding in recent years thas been increasingly directed to big, success- fulphysics departments, causing many smaller university departments to close (Science 4 Febeuary 2005, p. 658). “The STFC seers landed ina ination where it could inflict seri ously damaging cuts on university physics departments” says Martin Rees, Astronom Royal an president of the Re Society Researchers have been thrown somethit of a lite nt last week ofa review into the health of key scientific disciplines, starting with physics. Mearns, STFC iseontinuing with itsplanned ews. “DANIEL CLERY ‘at epeting by enn Yas antes cho. pe by the government's announcea NEWS OF THE WEEK 1852 AIDS RESEARCH Trials of NIH's AIDS Vaccine Get a Yellow Light POTOMAC, MARYLAND—In late September, the US, National Insticutes of Health (NTH) in Bethesda, Maryland. at thelast minute scotched a massive $130 million uial ofan AIDS. ‘accinemadeby itsresearchers, The reason: Much ro the diss may ofthe field atestofasim- ilar vaccine made by Merek & Co. fond that it ma; Rec study tes, ~ a actually increased son ple risk of becom \with HIV, Last wes AIDS Vaccine Re committee met here w discuss the future of | the NIH vaccine, Although no final decision has been made, the consensus was t0 con: that design Feasible to carry out?" The Merck vaccine and that made by Ga Nabel’ the NIH Vaccine Research tinue testing the vaccine to see whether it Center (VRC) both deliver HIV genes into the \works butina redesigned study that reduces body using a cold views as.a veetoe, The pres the chance of doing harm. lence of thisadenovinus 5 (Ad5)—there are to think the produets are different enough more than SO subtypes-varies greatly, infect to warrant further testing.” said Peggy ingane-hird of the population in some locales Johnston, who heads AIDS vaccine and nearly everyone in others. In the Merck research at NIH. “The issue becomes, study, vaccinated pecple who had high levels What's the trial design going to be, and is of antibody to AdS atthe wia’s start mere rea SCIENTIFIC PUBLISHING Bruce Alberts Named Science Editor-in-Chiet Bruce Albers professor of biochemist an biophysics atthe University of Califia, SanFran- «sco (UCSF, ne president emeritus ofthe U.S National Academy of Sciences, has been named the neste‘ in chef ofSenceAprominertcal bioagst best kncwn forhis work on he pro tein complexes that allow chromesomes te be replated, Alberts has focused in recent years on Public isues, especially the improvement of scence ecucation. ‘Albertss appointment was announced on 17 Oacember by the toad of diets of AAAS, pulse of Science. AAAS President David Baltimore, ho chaired the search commit that nominate Abts ysis “experince stil andinerestin llefscience mee | rime cet person to contave the taiten of super ciersho | have nace Science the pres juin forthe scenic commu ay.” Alberts il ake over he editorship on 1 March 2008 fom Donal Kenney. no announce eas this yer that he wuld be ‘eng. Kennedy has served as etn het since 2000. Alberts, 69, eared edoxtorate from Harvard Universityin 1965, spert 20 yeas n the act of Princeton Unive, and moved to SEB, Sin 1976. Hehespbtshed mace than 150reearhpapes end ‘sone ofthe orginal authors cf a leading tntbook, lector Bit 97 ofthe Cl. He sewed tensas president ofthe National adem of Sciences, fem 1993 0 27005. Then ne etme to UCSF to continue otk onisses he emphasied durin Mis tenure at the ceemies:interntenalzing cience—esoecaly bina inks to cet the develoing wold and strengthening scenic inkasvuctures—ane improving Science education. ‘Albers wl retain his UCSF faculty position and expects to devote half of his ime o Sconce “view cence magaine crt verve for maintaining the standards of science aswel s for spreading an understanding and appreciation for ence around tre wr,” says Albers. “With the ‘emendous cuilenges aed, bh ol thse pata as ned onstane ation” 21 DECEMBER 2007 World of difterence. The proportion of peoplewithotantboiesto AS ates dramatically acess proposed cal soo nici ily became infected by HIV. Ques tions remain about the mechanism and whether the finding is even statistically significant (Seéence, lo November, p. 1048). But out of caution, the group last week argued to exclude people with AdS ant huis fom the VRC t Originally. Scott Hammer of Columbia University planned to lead a test of the VRC vaccin in $500 people in the Americas and Africa, Now, as Magdalena Sobieszezyk from his group explained, they think it'spradent to ceneoll only 2000 9 3300 people in the Ame teas and Arica who are negative for AdS ant bodies. Sobieszezyk described study designs that would include both heterose: who have sex with men, Yet staging atrial of a vaccine that, event it works, could not be used by people with AdS immunity raises ethical kK ‘may net be avceptable in thirds of people ate seropositive [for AdS) Hammer conceded. Another option is to change the veetor altogether, but that would delay the trial inderinively ‘Some participants argued that the trial should be focused more narrowly—for instance, on mea inthe United States who have sex with men, Subcommittee member Je Lifon of SAIC in Frederick, Maryland, ca ticned thatthe Merck results have been bef ling in pct because the vaccine was tesed ‘many different populations and locations.“ ‘am really concerna.. 1 show that we can do clear studies” Lifton said David Watkins, 2 primate researcher atthe University of Wisconsin, Madison, argued ‘against doing the trial ata as monkey sts hhave suggested the VRC vaccine will fal reganlless ofthe safety sues “I just don’t i? Watkins tld Science. “The: tobe really ignored Anthony F isandiien sued, head oF the Natonal Institute of Alley and nections Diseases said he doesnt think the feld has the luxury of waiting for omvincing efficacy data studies, which could take more than a decaae, But Fauci did nox offer hisopin {on during the mesting explaining, "I'm going tohave w make the final decision, and I don't ‘want to preempt anybody.” The Columbia team will present a redesigned study to the ‘sume subcommittee in January. then Favei will amounce the fate ofthe VRC vaccine “JON COMEN AND BEN) AMUN LESTER VOL318 SCIENCE wwwnsciencomag.orgMICROBIOLOGY Detoxifying Enzyme Helps Animals Stomach Bacteria Sciemtisis since Louis Pasteur have purrrled ‘vera visceral issue: How ean we live in peaceful coexistence with the scads of poten tially noxious bacteria in our guts? Last we a University of Oregon team reported a key insight: When bacteria colonize vertebrate intestines, the tissue produces anenzyme that appears to defuse a dangerous toxin the microbes wield. The work “offers a novel ‘explanation forthe abi ist with our microflora” says Lora Hooper. an ‘ofhumans to coes- inmunologist at the University of Texas Southuvestern Medical Center in Dallas. It provides “satisfying explanation for how we ‘can maintain a friendly relationship with the hundred tilion bacteria in our guts Inmany partsofthe bouy, usta few bacte ia may spark a massive inflammaory reac- tion, One bacterial compound. lipapolysac= ‘haride LPS), for example, can trigger septic shock, organ failure, and death, But in our dense populations of bacteria hout eliciting more than 2 blink from the immune system, These microbes benefits in multiple ways. They makeessen- tial vitamins, keep menacing germs at bay help digest food for us, and influence our and paysiology. To probe how animal intestines tolerate their microbial colonizers, microbiologist Karen Guillemin ofthe University of Oregon, developm Eagee, sce asa how Thee fh ices mide Mer thea ine Into thowo ra Last year, Gullemin and colleagues tore tht cel nesta iho icaish ised under gree condivons i ot produce meta aaline pos J phnancUAP). an eneyme tht lips phon nceomag.org, phates from a wide range of molecules bat ‘whose function in living organisms is uneleat Adding back typical gut bacteria or LPS restored IAP production, Guillemin found, ‘Other groups have shown that IAP ean ove phosphate groups from LPS, which reduces its toxicity, "So we thought, ‘Aha, maybe the normal substrate for LAP is LPS associated with the normal flora,’ says Guillemin. If the enzyme neutralizes LPS, fish with compromised IAP activity should be especially susceptible to LPS, Guillemin ywarting LAP in zebrafish by chemical or genetic means Increased their sensitivity to LPS-indue death, she and her colleagues report in the 13 December issue of Cell Host & Microbe ‘Next, the researchers found thatthe ines: tines of germlree fish lacked neutrophils, bacteria-killing cells that migrate to infection sites. When bacteria were allewed tocolonize the animals” guis, these inflammatory cells shorted wpas well And blocking LAP prodc- tion or activity boosted their numbers, “The hyperinflammation we see in the absence of IAPs in esponse to something associated with the normal bacteria, most likely LPS.” says Guillemin, These findings suggest thar TAP dampens the inflammatory response to the normal gut microflora, thus promoting hhostcolerance to the hacer, “Its such a straightforward way to deal fg" says micrabiol: 1 Victor DiRita of the University of School in Ann Arbor. "We teach medical students that LPS froma nosinal fora are nontoxic. [Guillemins] work sug ges that itS more complicated LPS {from some bacteria] are toxic, but the host has a \way to deal with that ‘Other researchers have established that ® reasoned. As predicted, 2 oxin: Just detox Se cone ee) SIC. Cc Op New Animal-Rights Attacks Lastwee, rts police arrested wellknown animal-right activist Mel Broughton in connec tion with arson attacks las year and in the spring against the Universi of Orlord The police have nt, honeve, chaiged him with et ting fire to two Oxford profess” cars in eatly ‘Novernbe, actions that als appeat related 19 animal rights protest, Someone posting onthe ‘rimal Liberation Fron’ Web ite has claimed ‘aed on bel ofthe group fe those pre cushy unreported fresatthe homes “esaaches coneected tothe [unversty’] notorious Department of Experimental Psychology.” A Lniversty spokesperson confined the car fires but cectined to revealthe professors’ names The cr asons rellect a trend of more personal attacks by animal rights extemiss Gee p. 1856. In contrast, Broughton wes arrested in relation to attempted arsons on univetsiy facilities He's charged with wo counts of possession ofan explosive sub stance, tho counts of having an attile with nent to damage, and one count of consi ‘cyto blackmail. Broughten’s lawyer did not respond toa recuest for comment ~JONN TRAVIS ‘Save the Fish For the ist time, siemistsat the U.S. National, Marine Fisheries Service in Seattle, Washington, have recommended a cut in Alaska's commer: Cal harvest of pallck (ferara chalcograra). Although the move wil os this bilion-dollar Industry ter of mitons of dollars, ishing inter sts have acepted the scientists’ eduction. ‘next years harvest il be Gecreased from realy 1.4 milion metic torsto 1 milion met Fic tons—an almost 28% drop and its lowest. level since 1999. further cut may be recuited in 2009. Te reduction stems from annual sur vey that track these and heath of eterent age classes of this grounds For S yeas ina row now, the numberof jeniles successfully taining adulthood has been belon average, possibly because of unus: aly warm bottom waters. Some sence advisers tothe Nott Pacific Fishery Management Coun clan 1-member panel charged with regula ing commercial ising of the coast of Aleska think hat the harvest should be reduced even fut, 0 55,000 metic tos, citing concerns frorn many fishers tha the lara aggregations cof plloc nthe Bering Sea that have fules the fer for30 yeas are ffi to find. “W's time to alter course an further reduce the hae vet fo seve tis incretlylucatve fishery, says uneau, Alaska, ecologist Michele Ridgnay, coun adviser “VIRGINIA MORELL SCIENCE VOL318 21 DECEMBER 2007 1853a NEWS OF THE WEEK 1854 administering LAP to animals protects them fiom LPS, and inhibiting the enzyme’. ity with chemicals renders rats susceptible © death from injected bacteria, But Guillemin’s paper i the frst published study’ to show tht animals use IAP to rein in LPS from regular {gut bacteria under natural conditions, says Aevelopmental biologist José Luis Millin of EVOLUTION the Burnham Institute for Medical Research in San Diego, California. His unpublished ‘work on mice that lack IAP bolsters thenotion thatthe enzyme helps hosts maintain healthy relationship with their guthacterin If these results extend to humans an indi vidual’s degree of TAP activity could shape predisposition to serious ailments, six sepsis and Crohn’ disease, “Perhaps people with lessactive LAP would be more resistant ions but more prone to on,” Guillemin speculates. If so, turning LAP activity up or down either with drugs or by odministering the enzyme itself might reset the bi ~EVELIN STRAUSS. Did an Asteroid Shower Kick-Start the Great Diversification? You've heard ofthe Cambrian Explosion, the ‘ofall the basie ani And ‘of course, the igonic dinosaurs went out ith the bang ofa huge impact 6S mil lion years ago. But what about the zat Ordovician Biodliversitica on Event? That was when Som ancharismatie critters living gui- cily on the sea floor exploded in and taxonomic variety in anal forms, about 540 million years 3 lite's biggest burst of evolutionary variety, about 465 million yea Why some but not all e should have taken matine i off like that has puzzled scien isis as thoroughly asthe death ‘of the dinosaurs ever did This week, a team of geole and pa reports that a collision in the asteroid belt showered Earth with debris just when theOrdovie cian diversification was close coincidence of impacts snl diversifi tion suggests although it does not prove—a cause-and-effect connection, researchers say. “It intriguing.” siyspaleon- ‘ologist Jan Smit of the Free University of Amstendaa, “The coincidence is very good, The question is, how do you induce an increase in diversity with impacts There hasn’t been any doubt about the shower of meteorites in the middle of the Orkrician period. Geologist Birger Schmitz of Lund Uniersityin Sweden and colleagues retrieved weathered but recognizable. sizes meteorites ftom mid-Onkevieian rock in uch abundance that they could in meteorite Falls over a few October 2001 p. 39). At about the same tine as the shower ‘on Earth, aceording to meteorite analyses. 2 collision had shattered a. larg asteroid bek, presumably pelting the sort of debris Schmitz eoo%e In work reported on asteroid in the Earth with a ne this week in 21 DECEM! Nature Geoscience, Schunitz and colleagues sharpened their view of the asteroid shower by ‘ffascroidal material at wo sites in southem, snsively sampling for smaller markers Bringer of diversity? impacts of aster {carrying chromite, above) may have the cversitcation of brachiopods Ut ‘Sweden and one in China. They analyzed the ssumples for iscopes ofthe element osniut because extraterrestrial rock is richer in ‘osmium-I87 relative to osmium-188, And they dissolved several score 10-f0 30-Kilogra. mples of limestone in acid in search of microscopic grains of the mineral chromite. That is the one extraterrestrial mineral that can survive hundreds of millions of years unaltered, They bw sification into clearer focus by compiling data from more than 30,000 fossil bra- chiopods stalked, elamlike bottom ross strata ofthe same ag the Ordovician diver- dwellers southem Sweden ‘Thetwo detailedrecords ffom rocks ofthe showed thatthe onset of the rain of (hand the main burst of debris on E fication “coincide precisely.” writ roup. A sharp spike in new brachiopod species, families, and genera and the begin hing of the resulting steep tise in diversity coincide within few decimeters of rock (a few tens of thousands of years) witha rise in 2007 VOL318 SCIENCE he osmium isotopic ratio. Such an osmium marks the arrival of dust from the dust isthe first debris to arive from the asteroid bel, Within less than a meter (oughly half a million years), abundan: chromite asteroid disruption, beca ‘grains appear at all three site borne by large. later-arviving bits er stil, the rate of impacts increased five to I0-fold, by Schmitz’ ex mate, still during the ongoin diversification, ‘We have shown the coinei: dence.” says Sehmitz, “and th data are reproducible [at thr widely separated sites}. There «could be same connection b the biggest [asteroid] breakup nd evolution going on in oid debris promoted this interval lates that che puma few million years mig favored brachiopods and other immobile, Piter-feeding pimals such as trilobi Perhaps impacts ereated a more varied eri ronment with new ecological niches on the sea floor that brachiopods were more alee filing ‘Veterans ofthe debates about the impact gered death of the dinosaui The group specw ‘carried over fan the Cambrian, impressed by the Ordovician evidence Claims of other impact-evolution connes ne. but in the Ordeni- the timing is really perfec.” says geo! ‘ist Philippe Claeys of the Free University gium. “That is very convine ive a temporal coincidence: 1 Kabel of th University of Vienna, Austria, “but they a very vague about linking imypects anddiversification. Morekindsof fos sils from more plaes are in order, says Cla and, adds K@berl, a search for really Ia impact raters the right age would hop. RICHARD. KERR ist Christ enwwnsciencemag.orgUNIVERSITIES Questions Swirl Around Kessler's Abrupt Dismissal From UCSF Davi Kesler, the high profile dean ofthe University of California, San Francisco (UCSF), School of Meine, was i ast ‘ech, fr reasons that have so far nt been Adsclosed by the university. Kessler andthe tuners Fad en els ver final itreglarites” Kessler says he discovered Shortly ter king the post 2003, tha 7 Decerber stems, the aniveriy ssi ht Chalo Michael Bishoy asked Kessler firmer desn of le Schoo! of Me inc and former commissioner of te Food Amnon Je oan in nd othe yer Wath no Bishop formally dlamssed hon 13 Decenber.“Thereasons fon Dt Kesler dismiss. cannot be ds- cussed, a they represent pencnnel mate tht are bed confidential in compliance with University policy anda the saerent read. As Science went 0 press, Bishop vas nerves UCSF hada lngrinning ds agreement involving the amount of ds onary fund avaiable tothe dan offic for sess as research and educational tives, faulty recruitment, and renovations Kessler sphere wt fires ney than he sas ka belive whan UCSF rcruied him vay fom bisa post At tht te, Kesler says UCSF gave him documents, which he forwarded to Scénce showing gross income 46 lion rahe nx ‘2001-2002, resin ina $9. nilion sur phisafer expats Kesler sys his ve ffindingwhich the univers projected ‘ould sonnets kein is deison mae UCSF Bt when Kesslerashed Jed Shiver shen vice dean for adminisiation, Finance, and linia programs, to conducta review inlate 2004, the numbers dt mateh--even for fiscal yearstha at akeady come ce For 2001 2002, for example, Shivers’ anaiysis showed income of us $283 ie Ton and deficit of 97.8 million, which would deplete the dean’ account within few year. Kessler sys he wis bald: "For the came closed year, haw ca you have to diferent revenue numbers Shivers nwa Albert EinscinCollge of £ Medians m Neve York City sap hs eam a $F cam never abet are the miners ik ally given, “To this day, we wt how the data he received pumusciencemag.org could be reconciled tothe books ofthe une versity.” he told Seience. Yet according to UCSF 17 December starement, the univer: sity auditor found no financial irmegularities, neither did two additional reviews, one by & group of senior financial officers and anther ‘an outside accountant. In that statement, UCSF “categori Lenies” that Kessler “was dismissed in ret ation for his allegations larities in the UCSF School of Medicine.” cveral senior faculty members say they are confident that Bishop had just cause, “From my experience, Chanceller Bishop would not have made such a decision without consider able reflection and reason,” says Peter Carroll, chair of the urology department. “My sense isthae this ismmuch more than sin ply the finances in the dean’ offic.” UCSF biochemist Bruce Alberts (who was named this week as the next editor in chief of Science) offers a different hypothesis: ‘Ousted. David Kessler was fred fran his post as ‘dean of UF's School of Meine. “David is a very capable person, but he got fixated on this [ea] that he was misled and hhe was being sabotaged by not having the resources he needed to bean effective dean, and it got in the way ofthe medlcal school’s ionship with the rest ofthe university Kessler plans to rein his post as profes- sor of pediatricsepidemiology and biostatis- ties at UCSE Samuel Hawgcod, chair ofthe pediatties depariment and physician in chie? of UCSF Children’s Hospital, has been appointed imerim dean, ~GREG MILLER SCIENCE VOL318 21 DECEMBER 2007 Researchers: Folly in Bali Last week's United Nations meeting in Bali, Indonesia, broke litle naw ground on manda tory emission targets, sy disappointed scien: tists who attended the conference. The meet ing was held o discuss how to follow up the 11997 Kyoto agreement on climate change, wich expires in 2012. it was extended for 1 day so that delegetes could isue joint call for negotiations to achieve 3 “long tem ‘global goa fr emission reductions.” The conferees also agreed to allow developing countris to protect rainforests now and get ceditlate, Kevin Trenberth of the National Center for ‘Atmospheric Research in Boulder, Colorado, called the US. role at the meeting “ebstruc Lions” Trenberth joined mare than 200 sc ents in supportine mancatory caps of at least 0% below 1990 loves by 2050, a pos: tion thatthe Bush Administtion opposes. ELL KINTISCH Moon Shot Gets Nod Astronauts may sereday again walk onthe ‘moon, but before then, a new mission nl look Ceply into the lunar interior. NASA last week. backed a $375 milion effort to measure the ‘moon's crv field using two orbiting space cea. The Gravy Recovery and interior Labora- tory mission, led by geophysics Maria Zuber cof te massachusetts Institute of Technology in Camisidge, beat out 24 ther proposal in INASKs Discovery competition. The spacectalt is slated fora 2011 launch, and NASAScience hel S- Alan ter says te approach could be ‘sed on future misions to Mars and other salar system bodies ANDREW LAWLER New Euros Flow Tho fledeting European Research Counc has selected 300 applica to receive its fist se of rans, aimedat thos in their ist decade of independent research, Chosen irom more than $000 appications, the inners represent 32 nationalities working in 21 counties and wilreceve toa funding of approximately £€290 millon. The United Kingdom will host the ‘most awardees th more than 5O planning to vk there. Martin Berg of Gteborg Univesity in Sweden, who was awarded €17 millon to study the pater involved in cancer and pre ‘mature aging, ays the application process nas “absolutely flawless” and devoid of Weta ‘mous European Union bureaucracy. The appt Cation proces forthe second round of grants ow under wy, ~GRETCHEN VOGEL 18551856 As animal-rights extremism wanes in the United Kingdom, US. researchers have faced increasing threats and harassment EARLY ONE SUNDAY MORNING LASTJUNE, Arthur Rosenbaum wa 10 yoga class when his doorbell rang. A. acighbor had noticed a suspicious bundle ander Rosenaumns white BMW sda. The ‘wo walked ou ting ready t0 go car, which was parked aly neighborhood the campus of the University of Califor bo UCLA), where Rosenbaum is chiefof pediatric ophthalmology and strabis- mus atthe Jules Stein Eye Institute. Under the right fiont wheel was a plastic container full ofan orangish liquid wit out of anal matchbook with a half wsoven throu thought it was a prank Tt urned out to be a crude incendiary device. At his neighbor u called the police, who quickly ealled in the bomb squad. By midmorning, Rosenbaum's block had heen evacuated, and investigators jold Rosenbaum that the devige could have destroyed his carifithad gone offs intended They suspected it was the work of animal rights © UCLA rese cod several andl half. ersin the past ye 21 DECEMBER 2007 sorteet the cle disorders. H Atte! sa project, apilot study to & twical stimulator that could be eye muscles hack t life, That one project tured out to be enough to pur Rosentauumen the hit list of itself he Animal Liberation Br Vandalized This summer, AF sproyed researcher at Oregon Health and Scie ‘eceived similar eatment earths month VOL318 SCIENCE of children with e Rosenbaum says that atthe time he did't believe i geo, opera Ihe is primarily 2 sar hundreds of times a year co ffi onthe home of one Univesity 2 colleague claimed responsibility forthe inc ne communiqué on the subsequent months, Sune, ln Rosenbaum says, antt-animal rescatch activiss vd sev night, anes and Ski cera prote ‘concealing their faces with ba masks and using bullhors to sho hemos obnoxious vile kan wsithin p90 blocks of Rosenbaum’s house have re phic pamphlets cond imprisonment, cortre, and murder of inno= cent prim: i bis wife received a Lt stuffed with razor blades and threatening phys ical harm unless she convinced Rosenbaum to Animal researchers ia the United endured such personal teats and harassment. Inthe United States, however, research facilities, not individuals frequent dom have long ete the CURE and SURE surveys. tor bars eps vowusciencomag.org visiting academic and industrial laboratories, such 2s Abbott Laboratories and the Indiana Siate Police Laboraiory. as well as scientific ‘meetings, such as annual meetings of the American Chemical Society and the Ameri- scan Association for the Advancement of Science. These trips serve as an eye-opening, and motivating experience for the students, Because these field tips build communi among the studenss, we now do the scientific ‘meeting fie wip toward the beginning of the semester, Course activities after the wip become livelier asthe students interact with ‘each other more free Assessment The effectiveness of assessed through online CURE surveys con= ducted before and after the spring semester of 20079, 4). The presurveys found no pattern ‘oF differences between our students and the Denchmark group on background variables such as science attitude and learning style However, cpinionsof their own learning gains atthe end of the semester are higher among students who took CBEL than among the ret= erence cohortof students who completed the CURE survey in the spring of 2007 at other colleges and universities (see below). The mean learning gains of students in our course are also compared with a national cohort of students who took the ‘Summer Undergraduate Research Experience (SURE) survey in summer 2006, The general trends of the self-reported gains by our star dents resemble the national trends, even though the gains are higher for CBEL stu- dents, For example, the self-reported gain in ‘knowing the “research process” is higher than thatof “knowledge con- ssruetion” for both our students and the nat- ional average. There areexceptions however e course has been the highest. our students did not rate themselves as this area, because most ‘ofourstudentsarefesh- menorsophomoresvsho have not had time in the laboratory. Our st dents did eport stoner gains in “oral presen- ion bucking thenate ees Wy L rom the CURE surveyin © ional trend, which may reflect our focus on rt 2 SEM, EDUCATIONFORUM I oral presentations by feshmen. The next challenge is to make our program adoptable and sustainable (19), ‘The primary challenge is the resources it requires, especially time. Analyzing exch student’s interests and giving individual attention require considerable time from teaching assistants and instructors. Further= more, many students have diificulty fitting the course, which is not yet requited, inco their schedule, To address these issues, we idopting small modules from this course into other existing courses aiming to integrate our most successful ideas into the mainstream curriculum. If peer mentors ean provide some of the ind vidualized anention, the course model can be applied to other courses, in ether dise plines or in other institutions. References and Wotes 1 Natal Seer Faurdatn SP, Shas the Fre, vol 2 Pests en Urdeeredi Econ in iene, Mathenoti. rien, od tor (5t Aingtn, vA, 190, 2, Nona Reese Cour e201. Fosaig UneadtEdvcato jor fou Reseach lets (iar Aaeries fe eso 2003) 3 WB. ove, ene, cone 302, 1510 200. 4 J.tandeb ta Scece 304,52 200 5. Babes cet 123,739 G00. 6 ALE Sumas A Mba e006. 1. Nant Rese Cour, Han Pegler: Bln, ‘nd prence, ord Soa, pared Ei tars A Brown et cokrg Ee ata ‘ate es Meshing OC, 2000 2 ESeynou 8. re SL Lube, Deana $i edo 88, 493 200, 9, Os Lap, eo Ee 3, 2702008. 10. LL Hae et, Sere 314, 1880208. 1 ALG UT FKL Ch See 5313, 1099 2000, Fay, CD Ec Res ru 40,95 ry 13,5, de Che ng, Mews 008 912002 14 Swooning mates we able Scere Onin. 15. C Phan. Pie.) rach, 5. ae 1 arise, Scere 342473 290. 16 MAC Be EA Mga, 5 5. Stan, A. Money Sic 318, 1266 290. 17. € Goer, Desging Geupwod Sosa te etwapeees Casa Teac Cotege Pes New verk 180 1, | arden CP, tes A Ber, {rer etang Rest of Win Ps, eso, 2005. ata, How Soa Taped Races: Cherge to heen a aves Cra, cig ed ‘cor, 1650-1950 aces Caley rs, Men a9", ew wthark tbe Hon Meghes Medals Presa Aaron he Unive a tina Prove Inkster Tada adraceme har noes ‘udtexhing moans, ve psn andl lattice toe nats a ated in fe ei. eth ofr ste ye eases ftcator ad eed ‘ice 33,3870 2 Supporting Orie mateat secertnag eaters 38548720 SCIENCE VOL318 21 DECEMBER 2007 18731874 ETHICS The Ethics of International Research with Abandoned Children Joseph Millum and Ezekiel J. Emanuel esi oftuman abject ecachisto "Tt sceiiah ii at penis re kets, Cansei parspans for te grater ood of (verti st esas nate biomed = sates cate Inequalies bs octsed decision on forth! sce () nt fe (0) infrme cms i allay ca oblige ond (vo) postal benefits (os bl, tla tothe Bectrest Early Intervention Pra starred at thea of moving insiacaled young Chrno kr FourInternational Bioethical Isues The siandard-ofcare debate erupted in the 1990s around placebo-controlled trials in developing countries of for prevention of materral-fetal HIV transmis sion. Shor-course AZT was expeetedto be less effective than the standard AZT treatment available in developed countries, Critics argued that using placebo controls, rather than st dad teament as am active control, constituted a double standard research forbidden on the vweally would be eartied xt on the poor (2,3. Supporters countered that it is permissible to fle research participants in developing coun vies lesseffective interventions than those used in developed countries if doing 50 (i) is sciemifically necessary w angweran important question; (if) does not deny anyone treatment they would otherwise receive: and (ili) is, imended to develop interventions that will benefit the developing country (4), Informed consen is fundamental to ethical research, But somte commentators argue that vali informed consent cannet be obtained in developing countries, whose inhabitants are impoverished, poorly educated, deprived of medical services, and. unt with research (5.6), Others reply that this is patron: izing and inaccurae. Poverty may consi Department of Biotic, The Cnial Cente, Mail ‘Author tor corespercence. Emat: eemanuel@ce akgor 21 DECEMBER 2007 choices, but it does not make people coer ‘or incompetent, and participants in develop. ing eouraties seem to understand the elements of research as well, or badly. as their wealthior Ancillary prowl by and beyond whatis require forsety or sien tific validity. Athough researchers in develop ng countries often fel obliged 0 provide other treater that ther subjects desperately need. the nature and extent ofthese obligations e refers to medical treatments archers during the tial above Research with abandoned children dees not necessarily involve exploitation, personnel, employment, and economic stim lation, as well as the study intervention. The total mustbe consierad fir by the community Participating in he research (/0), ‘The Ethics ofthe BEIP Study The BEIP was a randomized ti institutional and foster cx children currently in institutions It wok pl in Romania, where there are thoussind of inst tutionalized children, Because, atthe tial’ Sundsdotcare ——_-Mastntrentos aay be tated Exceptions wher sentially recesay, again the weatment avail ro barm apd fstarch ans to beet evlped courte? ‘Gnmenty lufomed cersent Gn poor pooper developing centri: Avalable dat drat shew informed shevald nlomod conn to ree? cere inl tay are What etment shoud be provided ty Depends onthe aspects ofthe th ‘eserhes dung thei beyond hose that partys ents fo searches teed for safety or scenic rab Fostalbenefts What should te provide io wscach, _Twomainapptonhes:reaserable paras ane ost conmuntis ater ferent? Four main ethical issues in international research, no well defined. The most complete account justifies ancillary care obligations because research participants entrust aspects of their Fheath w investigatoxs through the procedures. they undergo (8). ‘Many believe that researchers have obliga tions to provide participants postal benefits. These benefitsate intended wo prevent exploita- tion, which occurs when one pry takes alae advantage of another (H, 10). In international research, the fear is tha the developed weld wsill got too much of the benefits of medical research and the develeping world t00 much of its burdens. According to the Council for International Organizations of Medic Sciences (CIOMS). research ina communi permissible only if researchers or their spon sorsensurethar interventions resulting from the researchare made “reasenably available” tothe community (J), Analtemative, the “fair ben efits” famencrk, proposes that postal bene fits may comprise a myriad of benefits includ ancillary care, taining of health care avaattiy of ty mtervertion nt {poate appoted byte commiety the researchers developed their enn, foster parentsand preniding social sport. The study found significantly improved cognitive development a 42 and 54 months for children transferred to foster care befowe 2 yearsof aze ‘compared with insiturionalized children, ‘The inital reaction to the BEIP may be that theextreme vulnerability of ubandoned insite tionalized children renders any research @ ‘hemunethica. Notonlyarethey unableto give informed consent, there is no clear guaria ‘acting in theie best interests This puts them at _greater risk of being selected for reasons of convenience rather than scientific necessity While these are valid concerns, familzr sa ‘guards can protect such children, People who sted by enrolling them aly risks donotencced these of everyday life. None of the study's assessments of function likely harm she chiklren. Restricting t tiepation of vulnerable groups, suk! cers and the instvutionalize. 0 re al rison- ch that VOL318 SCIENCE wwwnsciencomag.orgaddresses important questions relevant to their situation protects against unfair subject selec tion (/2). The BEIP study aimed w produce results that would primarily benefit abandoned, insitutionalized children, ‘Tho BEIP has many of the features that seraed special concer about medical ch in developing countries. Romania, the host country, is transition economy with relatively poor health-care infrastructure and 4 large number of underserved institutional- ized chikdren. The funding and research leal- cerhip for the trial came from the United States, Although the results may be relevant to the United States and ether developed coun tries, there have been no American random- ized ieials comparing foster and instiational ‘care, and no American children would be ‘encolled in the BEIP, Of greatest concern are the standards of care affected in the wial arms and the distribution of postrial benefits, “The appropriate standard of care for acne an impaet on these children’s lives: tae policy was ikely w adop the BEIP conclusions. This impact is not guarantest social and economic circumstances or gevern- ‘ment policies might change, resources may not ‘bemade avaible for foster care, oF the concht- sionsof the research may be dispute. Cerainty bout mplemenaaioncannot be required tot ily proceed with a study: Instead, researchers ‘must julge the likelihood that their work will ‘generate health benefits, and proceed on the basis ofits expected benefit. The expected benefits 10 Romania's abandoned children appeartoprevide ample justification forthe BEIR, Finally judging whether exploitation has ‘been avoided by using the responsiveness to needs and reasonable availability criteria can bbe problematic. These enteria consider bene- Fits othe participants’ commanity. Bu isthe participants not the community who bear the risks of research and are therefore most vulnerable to exploitation. Even when 2 sic ‘cessful intervention will be available to 8 pop- ation afer the tral'scompletion, supplying it tthe rescareh participants themselves may ‘ot be possible iy. many cases harm to par inherent in generating valid scien tifie results. In some trials, data on the effec= tiveness of an intervention cannot be obtained ‘without some risk tothe subjects, perhaps of serious or fatal outcomes. For insiance, for a ‘vaceine trial tobe successful, some paripants must acquire the disease the vaccine is intended to prevent, Otherwise, no intervention can be shown to be stperior. But the preventive bene- fits ofthe yagcine do no good for participants ‘who became infected during the study. Similar issuesarise in many cancer al cardiovascular trials The BEIP raises the same concern; the children who remained in institutional care POLICYFORUM I ‘cannot now receive the benefit of early foster care, which the trial showed 10 be superior for some developmental outcomes. “This consideration does not make the BEIP sty unethical, justas it doesnot make vaccine trials unethical. However, it docs indicate that researchers need to pay special stention to how resus get implemented shen the benefits can ‘not accrue to participants, For instance, tial designs thar mene partcjpants into the ata that ‘sdoing bette during the course ofthe til can be employed. According to the researchers, limited funds foreclosed this option. Alter- natively, as done in the BEIP researchers ean present valid scientific results as soon poss ble to those partis who ean act on them, The: parties have responsibilitiestothe paricipans, too: because the children were involved in research for the benefit of Romanian society, the representativesof sicity should ensure that the children get the care they deserve. ‘The BEIP researchers didnot createandare not responsible for Romania's insitutionaliza- tion of abandoned children. They conducted research to determine what interventions ‘would benefit these children, Ths is not ex ploization, but shows how research can help benefit participants, as wellasthe wider popu jon oF abarwdoned insttsionalize children, References and Notes 1, CANA etal, scence 318.1937 200 2, Moga M9 Me 387. B47 987. 4m le, Wg J et 337, B53. 4 Ce Etna C Gey, 9 Werder ne Ee 30180 2000, 5. Gama, n.d A). BL Heth 560-555 Goa. 6. LA Critti Moss Cet Rep 1,35 nea 1980) 7. CCG Gad | Eman Sade, Aun 8S Rear, Lay Mog: Cor Rep 38,25 (amex eran 2008 9. terme Eaten rien Un es, Prneen 1999.10. 10, Theyermagntsin he 2001 Conference on ic Aectot Resa Dering Cees, str: Cntr ey 2,1 Way e708, 11, trematana tne Guten fr Benes Resarth rats aonb Cure eines (tga Mesa Svcs Geer, 202) Gade 12, US nies Commis ft Petco othe Sabet Boned and Behavral ea, Te hoon! apo el Gidea fre Potton of amon utes of aes. Covet ig (tes, wash, 0, 1979) 13, ier, rey sings Cnt Rp. 33,18 ay uee 14. Era, Wendl Gey, Je 283, 2701 com 1S, Wear C dy ile, esa. Schales, Dees hertvie Ie pr cp ethan oan ty de et act ary poten Pl ote tata aes thea, US Poe Heath sevice oDeparmerto Hatha Hanan Sic ra n20eeee 89827 SCIENCE VOL318 21 DECEMBER 2007 1875