Tạp chí khoa học số 2006-08-18

INTERNATIONAL CONFERENCE 2020 Vision: Variation and Function in the Genome For more information and to register visit www.genomecanada.ca/conference WYLIE BURKE, Professor and Chair of t

18 August 2006 | $10

www.sciencemag.org SCIENCE VOL 313 18 AUGUST 2006 881

CONTENTS

CONTENTS continued >>

NEWS OF THE WEEK

Congress Quietly Tries to Craft Bill to Maintain 898

U.S Lead in Science

Panel Confirms Report of Early H5N1 Human Case 899

in China

Judge Slaps Hawaii Over Mauna Kea Telescopes 900

New ‘Supercapacitor’ Promises to Pack More 902

Electrical Punch

>> Science Express Report by J Chmiola et al.

Nearby Cluster Shows Extremes of Stardom 903

>> Research Article p 936

NEWS FOCUS

Widening the Attack on Combat-Related 908

Mental Health Problems

>> Report p 979

Candidate Sites for World’s Biggest Telescope Face 910

First Big Hurdle

From KAT to FAST, Telescope Project Sprouts Test Beds

A wildfire consumes ponderosa pine trees

in the Santa Catalina Mountains nearTucson, Arizona, in May 2002 This blazecovered 18,300 hectares and was one ofdozens of large wildfires during an extremedrought in the western United States

L Kratochvíl Response B L Stuart and

L L Grismer

Roles of CITES in Protecting New Species

F J Vonk and W Wüster

A Problem in Archaeology Too B W Powell

Photosynthesis in Balance with Respiration?

M E Clark Response A W King et al.

In Search of Memory The Emergence of a 919New Science of Mind

E R Kandel, reviewed by N C Andreasen

The First Human The Race to Discover Our 920Earliest Ancestors

A Gibbons, reviewed by D R Begun

POLICY FORUMIntegrity in International Stem Cell Research 921Collaborations

Traversing the Adaptive Landscape in Snapdragons 924

E M Kramer and K Donohue >> Report p 963

J Silk

Is Global Warming Causing More, Larger Wildfires? 927

S W Running >> Research Article p 940

CONTENTS continued >>

SCIENCE EXPRESS

www.sciencexpress.org

NEUROSCIENCE

PirB Restricts Ocular-Dominance Plasticity in Visual Cortex

J Syken, T GrandPre, P O Kanold, C J Shatz

A molecule that is usually thought of as a hallmark of the immune system

interacts with a receptor in the brain to limit the plasticity of the visual system

during development

10.1126/science.1128232GENETICS

Dok-7 Mutations Underlie a Neuromuscular Junction Synaptopathy

D Beeson et al.

An inherited muscle disease in which certain muscles are weak is caused by

mutations in a protein needed for proper formation of the neuromuscular junction

10.1126/science.1130837

CONTENTS

REVIEWASTRONOMY

Cosmic Reionization

R Barkana

BREVIAASTRONOMY

P Tuthill et al.

The five enigmatic stars in the Quintuplet Cluster in the center

of the Milky Way are old, massive binaries with outflowing winds that appear as rotating pinwheels

RESEARCH ARTICLESASTROPHYSICS

Probing the Faintest Stars in a Globular Star Cluster 936

H B Richer et al.

Hubble telescope images of a globular star cluster show that thesmallest star capable of burning hydrogen is about 0.08 solar masses,consistent with theoretical predictions >> News story p 903

CLIMATE CHANGEWarming and Earlier Spring Increase Western U.S 940Forest Wildfire Activity

A L Westerling, H G Hidalgo, D R Cayan, T W Swetnam

Climate change in the western United States has dramaticallyincreased the number of large forest wildfires during the past

35 years >> Perspective p 927

CELL BIOLOGYThe Molecular Architecture of Axonemes Revealed by 944Cryoelectron Tomography

J Chmiola, G Yushin, Y Gogotsi, C Portet, P Simon, P L Taberna

Pores comparable in size to solvated anions and cations unexpectedly improve thecapacitance in a carbon-based supercapacitor

>> News story p 902

10.1126/science.1132195

TECHNICAL COMMENT ABSTRACTS

MICROBIOLOGY

Comment on “Computational Improvements Reveal 918

Great Bacterial Diversity and High Metal Toxicity

in Soil”

I Volkov, J R Banavar, A Maritan

full text at www.sciencemag.org/cgi/content/full/313/5789/918a

Response to Comment by Volkov et al on

“Computational Improvements Reveal Great Bacterial

Diversity and High Metal Toxicity in Soil”

J Gans, M Wolinksy, J Dunbar

full text at www.sciencemag.org/cgi/content/full/313/5789/918b

Comment on “Computational Improvements Reveal

Great Bacterial Diversity and High Metal Toxicity

in Soil”

J Bunge, S S Epstein, D G Peterson

full text at www.sciencemag.org/cgi/content/full/313/5789/918c

Response to Comment by Bunge et al on

“Computational Improvements Reveal Great Bacterial

Diversity and High Metal Toxicity in Soil”

J Gans, M Wolinksy, J Dunbar

full text at www.sciencemag.org/cgi/content/full/313/5789/918d

www.sciencemag.org SCIENCE VOL 313 18 AUGUST 2006 885

Electrons from a scanning tunneling microscope can excite the Cu-Co

bond at the end of a chain of copper atoms and cause the cobalt atom

to flop rapidly between lattice sites

APPLIED PHYSICS

Controlling the Electronic Structure of 951

Bilayer Graphene

T Ohta, A Bostwick, T Seyller, K Horn, E Rotenberg

Doping one layer of a pair of graphene sheets with excess electrons

allows the energy gap between the valence and conduction bands to

be controlled, creating tiny switches

MATERIALS SCIENCE

Two-Dimensional Nematic Colloidal Crystals 954

Self-Assembled by Topological Defects

I Mul˘sevi˘c, M ˘Skarabot, U Tkalec, M Ravnik, S ˘Zumer

Colloid particles positioned within ordered liquid crystals using laser

tweezers will grow and self-assemble into specific two-dimensional

structures

CHEMISTRY

Y Liu et al.

Emulsions in water can be formed on demand by treatment of

amidine compounds with CO2to form surfactants and reversed by

exposure to nonpolar gases such as air or argon

CHEMISTRY

Cu(111) Surface

G Pawin, K L Wong, K.-Y Kwon, L Bartels

Competition between attractive hydrogen bonding and repulsive

interactions causes anthraquinone to form a network with 50

angstrom pores on a copper (111) surface

EVOLUTION

Evolutionary Paths Underlying Flower Color 963

Variation in Antirrhinum

A C Whibley et al.

The genetic differences underlying various color morphs of two

snapdragon species can be identified and used to construct their

likely evolutionary path

>> Perspective p 924

ECOLOGY

Plant Genotypic Diversity Predicts Community 966

Structure and Governs an Ecosystem Process

G M Crutsinger et al.

An increase in the genetic diversity of a dominant plant species

in an ecosystem also increased arthropod diversity and net primary

productivity

SCIENCE (ISSN 0036-8075) is published weekly on Friday, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue, NW, Washington, DC 20005 Periodicals Mail postage (publication No.

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MEDICINEp53-Mediated Inhibition of Angiogenesis Through 968Up-Regulation of a Collagen Prolyl Hydroxylase

J G Teodoro, A E Parker, X Zhu, M R Green

A tumor suppressor protein inhibits tumor formation in part by stimulating the production of the body’s own inhibitors of the tumor’s blood supply

MEDICINE

Mutations That Increase the Life Span of C elegans 971Inhibit Tumor Growth

J M Pinkston, D Garigan, M Hansen, C Kenyon

A strain of worm that develops cancer as it ages is protected fromtumor growth by mutations that extend its life span

NEUROSCIENCEGraded Regulation of the Kv2.1 Potassium Channel 976

by Variable Phosphorylation

K.-S Park, D P Mohapatra, H Misonou, J S Trimmer

A proteomic method identifies which seven of the potential phosphorylaton sites are regulated in vivo by a phosphatase

in a delayed rectifier potassium channel

PSYCHOLOGYThe Psychological Risks of Vietnam for U.S 979Veterans: A Revisit with New Data and Methods

B P Dohrenwend et al.

An extensive reanalysis of a previous study of the effects of the Vietnam War on its veterans provides a more reliable estimate

of the rate of posttraumatic stress disorder

>> News story p 908; Perspective p 923

908, 923, & 979

SCIENCE’S STKE

www.stke.org SIGNAL TRANSDUCTION KNOWLEDGE ENVIRONMENT

PERSPECTIVE: A RSK(y) Relationship with Promiscuous PKA

M D Houslay

The often-studied cyclic AMP–dependent protein kinase still has a

few tricks up its sleeve

REVIEW: Localizing NADPH Oxidase-Derived ROS

M Ushio-Fukai

Subcellular targeting of NADPH oxidase allows reactive oxygen

species to stimulate specific signaling processes

SCIENCENOWwww.sciencenow.org DAILY NEWS COVERAGE

Who You Calling Fruity?

Belligerent fruit flies reveal clues about the genetics of aggression

Why Mussels Can Stick to Anything

Amino acid in mussels’ glue ensures that they’re not slippery whenwet

Wine’s Benefit Knows No Color

Some white wine is as good as red for lowering heart attack risk,and here’s why

SCIENCE CAREERSwww.sciencecareers.org CAREER RESOURCES FOR SCIENTISTS

US: Tooling Up—Are You “Management Material”?

Are you fit for management?

Separate individual or institutional subscriptions to these products may be required for full-text access

www.sciencemag.org

Listen to the 18 August Science

Podcast for stories about thepsychological toll of war, thefaintest hydrogen-burning stars,challenges in fetal surgery, andmore

www.sciencemag.org/about/podcast.dtl

SCIENCEPODCAST

ROS at the leading edge

fested itself as low-frequency “telegraph” noise.

Density functional calculations help explain whythe tip location that maximizes this hopping isnot directly over the Co atom and how the bar-rier for motion increases with Cu chain length

com-to form ordered tures such as rows thatleave areas uncovered

struc-Pawin et al (p 961)

report an examplewhere competing inter-actions create a honey-comb network that hasopen pores with a diam-eter of 50 angstroms

The network formed byvery low coverage ofanthraquinoneadsorbed on theCu(111) surface hasopenings that are aboutfive molecular diame-ters The structureappears to balance hydro-gen-bonding contacts, which facilitate the forma-tion of molecular rows, but which compete withintermolecular repulsive forces

Assessing Wildfire Activity

Understanding the underlying causes of the

increases in wildfire activity in the western United

States during the last several decades will impact

how to manage the risk that wildfires pose

Westerling et al (p 940, published online 6

July with the Perspective by Running; see the

cover) compiled a comprehensive time series of

large forest wildfires in the western United States

for the period from 1970 to 2003, and compared

those data with corresponding observations

of climate, hydrology, and land surface

con-ditions Wildfire activity increased suddenly

in the mid-1980s Hydroclimate and fires are

closely related, and climate variation has

been the primary cause of the increase in

fires during the period of their study,

although land use changes can also be

important Longer springs and summers that

could result as the world warms will continue

to lengthen the fire season and continue to

cause more large wildfires

Stimulated Atomic

Hopping

The tip of the scanning tunneling

micro-scope can be used to pick up atoms and

move them on surfaces, as well as induce

motion through electronic excitations

pro-duced by the tunneling electrons Stroscio

et al (p 948) assembled short chains of Cu

atoms terminated by a Co atom on a Cu(111)

surface and analyzed the hopping induced by

tunneling electrons of the Co atom between

dif-ferent sites at the end of the chain, which

mani-Graphene Sheets on the Double

Single sheets of graphene can display unusualand potentially useful electronic properties, andtheoretical work on coupled bilayer systems hasindicated that a controllable gap may beinduced if there is an asymmetry between thelayers, which could be induced either by dopingwith atoms or application of an external electric

field Ohta et al (p 951) have used

angle-resolved photoemission spectroscopy to mine the band structure of graphene bilayers inwhich asymmetry was induced by doping onesheet with adsorbed potassium atoms Theauthors confirm that such control over theenergy gap between the valence and conductionbands is possible

deter-Emulsions on Demand

Surfactants are widely used to stabilize emulsions

in products, such as cosmetics, whose constituentswould otherwise fail to mix Many industrialprocesses, however, have multiple steps thatrequire separating emulsion components after

reaction or transport Liu et al (p 958) show that

amidine molecules bearing long hydrophobic tailscan be cycled reversibly between surfactant andnonsurfactant forms Room-temperature treat-ment of the amidines with an atmosphere of CO2produces bicarbonate salts that stabilize aqueous-hydrocarbon emulsions Bubbling of air throughthe system at 65°C reverses the reaction andbreaks the emulsion In the absence of CO2, theamidines act as effective de-emulsifiers of aque-ous−crude oil suspensions

EDITED BY STELLA HURTLEY AND PHIL SZUROMI

18 AUGUST 2006 VOL 313 SCIENCE www.sciencemag.org888

Light and Hydrogen

Soon after the universe formed, it was filled with hydrogen atoms, yet today

almost all the diffuse hydrogen between galaxies is ionized Barkana (p 931)

reviews how and when the first stars and black holes lit up and ionized primordial

hydrogen gas throughout the universe Some understanding has come from

com-puter simulations of the change that show the ionization is patchy and happens

first in the densest regions of space However, a full picture must await a new

gen-eration of radio telescopes that will map out this key epoch Stars must exceed a

certain size if they are to burn hydrogen through fusion, and Richer et al.

(p 936; see the news story by Bhattacharjee) have identified this fundamental

mass limit in a deep census of globular cluster stars in our Milky Way taken with

the Hubble Space Telescope They also see a characteristic change in the color of

white dwarfs in the cluster caused by the onset of molecular hydrogen formation

in their atmospheres Both effects had been predicted by theorists, and this

experimental confirmation helps improve our understanding of the physics of

low-mass stars and white dwarfs

This Week in Science

Revisiting Vietnam’s Psychological Toll

The magnitude of the Vietnam War’s psychological toll on U.S soldiers has been a subject of heated

debate since 1988, when two major government-funded studies reported widely divergent rates of

posttraumatic stress disorder (PTSD) in Vietnam veterans Interest in this question has intensified as

comparisons are now being made between the Vietnam War and the ongoing conflict in Iraq

Dohrenwend et al (p 978; see Perspective by McNally) have reexamined PTSD rates in Vietnam

War veterans using improved diagnostic methods and military records (rather than self-reports) to

document exposure to war zone stress Their analysis revealed a lifetime PTSD rate of 18.7%, in

between the two previous estimates (of 30.9% and 14.7%) An even stronger dose-response relation

seen between war-related stress exposure and PTSD confirms that the war’s psychological toll was real

and substantial

Nailing the Axoneme

Cilia and flagella are motile appendages that project from eukaryotic cells that play roles in motility

and sensing in a variety of organisms and tissues Nicastro et al (p 944) present cryoelectron

tomography of frozen-hydrated, eukaryotic flagella to reveal structural features of life-like axonemes

at ~4 nanometer resolution that are important for axoneme function

Mixed Bouquets

Flower color in plants is often

selected through pollinator

prefer-ence Intermediate colors, when

they arise in hybrids between two

closely related species, are often

selected against Whibley et al.

(p 963; see the Perspective by

Kramer and Donohue)

investi-gated the genetic basis of flower

color differences between closely

related species of snapdragon By

analyzing a hybrid zone involving

two color morphs, they identified

three loci underlying color

varia-tion Modeling of the genotypic

space of color variation was used to map species into this space The colors of flowers found in the

hybrid zone occupied a distinct position in this space, one that is presumably less fit These

find-ings increase our understanding of adaptation in natural populations and suggest a new way of

thinking about transitions between adaptive peaks

p53 and Tumor Angiogenesis

The tumor suppressor protein, p53, transcriptionally activates genes that control cell cycle arrest,

apoptosis, and other cellular processes that help to prevent tumor development Teodoro et al.

(p 968) now show that p53 appears to keep tumors in check by activating the gene encoding α(II)

collagen prolyl-4-hydroxylase This enzyme is required for the extracellular release of

collagen-derived peptides, such as endostatin and tumstatin, that are potent inhibitors of tumor angiogenesis

The p53 gene is inactivated in many human cancers, presumably leading to reduced production of

endogenous antiangiogenic peptides that defend against tumor growth

Aging and Cancer

Is there a link between organismal aging and cancer? Pinkston et al (p 971) address this

ques-tion in a worm model of aging and tumor development and find that different signaling pathways

implicated in the aging process also control tumorigenesis Mutant worms with long life spans

appear immune to the life-shortening effects of tumors because of enhanced defense

mecha-nisms, including increased apoptosis and decreased cell proliferation within the tumors Signaling

pathways that control longevity may have coevolved with tumor suppressive mechanisms

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INTERNATIONAL CONFERENCE

2020 Vision: Variation and Function in the Genome

For more information and to register visit www.genomecanada.ca/conference

WYLIE BURKE, Professor and Chair of

the Department of Medical History and

Ethics, University of Washington and

Director of the University of Washington

Center for Genomics and Healthcare

Equality (Seattle, WA)

JOE ECKER, Director, Salk Institute

Professor of Biology, Salk Institute for

Biological Studies (La Jolla, CA)

TOM HUDSON, Acting Scientific

Director, McGill University and

President and Scientific Director, Ontario Institute for Cancer Research

FOTIS KAFATOS, Chair in

Immunogenomics, Division of Cell and

London (London, UK)

STEPHEN LEWIS, Director, Stephen

Lewis Foundation, Scholar-in-Residence,

2006, McMaster University (Hamilton, ON)

ALLEN D ROSES, Senior Vice

President, Pharmacogenetics,

Genome Canada’s first international conference is designed to anticipate the future of genomics and

pro-teomics science and its impact on society over the next decade and beyond Keynote speakers include:

Brain Injury Research

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EDITORIAL

The Road to Balanced Oversight

EARLIER THIS YEAR, AN INTERNATIONAL GROUP OF SCIENTISTS AND OTHERS CONVENED ATHinxton, England (see the related Policy Forum in this issue, p 921), to address the moral chal-lenges facing collaboration in human embryonic stem cell research that emerge from differences

in national laws Although a focus on embryo research is understandable, it is not the only area ofscience in which societies differ in values and laws Scientists throughout the world work underdifferent regulatory regimes governing human subjects, nonhuman animals, pathogens and bio-hazards, genetic modification of organisms and plants, and access to medical and public healthrecords In some cases, these differences reflect disagreements about ethically permissible con-duct that approach the intensity of debates about the moral status of the embryo

Whether the issue is research on chimpanzees, the creation of novel organisms, or the tion of human embryos, scientists need to consider whether it is ethical to travel to other countries

destruc-to engage in research practices that would not be legally missible in their home countries Many scientists may see this

per-as a personal decision that should turn largely on whetherthey accept or reject the moral premises that underlie theirnation’s laws Scientists also need to consider, however, thepotential impact of “research tourism” on the public’s trust inthe scientific community and on the ethics of science itself

An English stem cell scientist who failed to follow dards set by the United Kingdom’s Human Fertilization andEmbryology Authority (HFEA) when working outside theUnited Kingdom would probably be viewed by colleagues

stan-as acting unethically Moreover, such conduct might mise public trust in the effectiveness of the HFEA to keep embryo research within sociallyacceptable ethical bounds, and thus might have negative effects on public support for the sci-ence itself Similarly, a U.S clinical scientist who elected to conduct research in a countrywhose regulations were more lax than those set by the U.S Common Rule governing research

compro-on human subjects would probably also be viewed by colleagues as acting unethically In manycontexts, this scientist would also be subject to government and institutional penalties

By contrast, the Hinxton group concluded that scientists living in countries that restrict ments of human embryonic stem cell research should be free to engage in those practices in morepermissive countries without legal repercussions At the same time, however, many in the grouprecognized the tension that taking this position raises for the ethics of science overall Scientistsshould welcome societal oversight of their research, much as all citizens should welcome the ben-efits of a well-ordered, lawful society more generally The question is not whether science should

ele-be given a special pass when it comes to the reach of national laws Rather, it is how ele-best to strike

a balance between ensuring that science conforms to a society’s values and respecting the globalcontext in which science increasingly operates

Of course, striking this balance is made more complicated when there is substantive moral agreement not only between societies but also within societies about whether a particular researchpractice or line of investigation is ethical The case is complicated still further when, as seems to betrue with regard to human embryonic stem cell research, much if not most of the scientific commu-nity lines up on one side of the moral issue These specific conditions of moral disagreement maywarrant particular circumspection on the part of lawmakers with regard to extraterritorial jurisdic-tion That said, even if there is complete consensus within the global scientific community about theethics of a particular scientific practice, scientists should not expect societies to defer to their viewswhen it comes to matters of morality Rather, scientists must continuously make their case to soci-ety by appealing to public moral reasons that are accessible to all This is hard work that requiresscientists to leave their laboratories and make themselves available to lawmakers, the public, andthe media At the same time, however, most scientists operate in institutional and professional cul-tures that rarely reward, and certainly do not prepare, scientists for engaging with the public Untilthese structural disincentives to effective interaction between scientists and societies are remedied,

dis-we can expect the road to balanced oversight of science to be more complicated than it need be

Ruth Faden

10.1126/science.1129124

Ruth Faden is the Philip

Franklin Wagley Professor

of Biomedical Ethics and

executive director of the

Phoebe R Berman

Bioethics Institute at

Johns Hopkins University,

Baltimore, MD

reducing kinetic barriers More recently, analternative approach has relied on thereversible assembly of comparatively simplebuilding blocks that relax eventually into thedesired topological conformation because it isthe most favorable thermodynamic arrange-

ment Northrop et al apply this second

strat-egy to the preparation of [4]pseudorotaxanes,

in which a Y-shaped core bears a ring on each

of its three axes, and the rings in turn arelinked to one another through either one or two central capping groups parallel to the planar core

The rings in this case are crown ether tives attracted to the core axes through hydrogen

deriva-bonding to cationic ammoniumgroups Capping is achieved

by reversible imine bond mation between formyl groups

for-appended to theends of therings andamine groups

on the phenylcap The singlycapped complexassembled within 2hours of mixing thecomponents in solution, whereas the doublycapped analog (in which the caps straddled thecore) required 8 days to wend through assortedkinetic intermediates Both complexes werecharacterized by nuclear magnetic resonanceand mass spectrometry — JSY

Org Lett 8, 10.1021/ol061262u (2006).

18 AUGUST 2006 VOL 313 SCIENCE www.sciencemag.org892

One In, One Out

The successful development of optical-based

quantum information processing and quantum

cryptography will require the ability to store

and retrieve known numbers of photons in a

medium of choice Despite significant progress

in techniques to store single photons within a

cloud of rubidium or cesium atoms, the overall

efficiency of the storage and retrieval process in

such systems has been limited by low retrieval

efficiencies and relatively high noise levels

Laurat et al show that the retrieval efficiency of

single excitations stored in an

ensem-ble of cold cesium atoms can be

increased by careful optimization

of the experimental parameters The

authors found that by increasing the

number of photons in each read pulse

to approximately 107and increasing the

optical depth of the atomic ensemble, they

could raise retrieval efficiency to ~50%,

with a concurrent order-of-magnitude

reduc-tion in two-photon emission events They argue

that such an improvement bodes well for

long-distance quantum communication — ISO

Opt Express 14, 6912 (2006).

C H E M I S T R Y

Relaxing Toward Rotaxanes

Traditional approaches to the chemical

synthe-sis of complex molecular topologies, such as

knots and interlocked rings, have focused on

C E L L B I O L O G Y

RNAin

The uptake of double-stranded RNA (dsRNA) from the medium is the stay of many an RNA silencing strategy, but what is the mechanism by whichanimal cells take up these macromolecules? It has been difficult to addressthis directly because in some cases, cells seem to take up dsRNA directlyfrom the medium, yet in others there can be cell-to-cell transfer

main-Because Drosophila cells can take up dsRNA but do not transport it between cells, Saleh et al used Drosophila tissue culture cells to character-

ize the uptake pathway In a genome-wide screen for participants, nents of the receptor-mediated endocytosis pathway were found to predom-inate The receptors involved were members of the pattern-recognitionreceptor family, which is important in innate immunity and antimicrobialdefense Furthermore, similar mechanisms are likely to be widespread in evolution: Knockdown of orthologous endocytic players in nematodes also prevented RNA interference How incoming dsRNA is diverted from the endocytic pathway so as toavoid degradation in lysosomes remains a mystery — SMH

compo-Nat Cell Biol 8, 793 (2006).

InDrosophila cells, added

dsRNA (red) accumulates in internal vesicles.

I M M U N O L O G Y

Pattern Formation in Mosquitos

Like the innate immune systems of vertebrates,those of the insect world possess pattern recog-nition receptors that detect the broad signa-tures displayed by different classes ofpathogens In contrast, the narrow immunereceptor specificity afforded by mechanisms ofgenetic recombination has been considered afeature unique to adaptive immunity in highervertebrates This view has recently undergonesome revision, however, with the observationthat lower vertebrates and invertebrates arealso adept at manufacturing diverse immune

receptors For example, Drosophila use

alternative splicing of transcripts from animmunoglobulin domain–containing locus—the Down syndrome cell adhesion molecule

gene Dscam—to generate recognition

recep-tors that assist in the phagocytosis of bacteria

Dong et al observe that in the mosquito Anopheles gambiae (the vector for malaria), the large number of exons in AgDscam could

yield as many as 31,000 alternatively splicedproducts, a range similar to that calculated for

Drosophila Challenging mosquito cell lines

with different pathogens resulted in a variedrepresentation of these exons via alternativesplicing and AgDscam molecules with distinctspecificities Evidence for alternative splicing

of AgDscam was also demonstrated in adult

mosquitos, and RNA interference–mediatedsilencing decreased the resistance of mosquitos

to bacterial infection and to oocytes of the

EDITED BY GILBERT CHIN AND JAKE YESTON

Interlocked cular bundles

mole-malaria parasite carried in the insect midgut.

As in Drosophila, the AgDscam forms appeared

to enhance phagocytosis of bacteria by

hemo-cytes, although it is likely that the mechanism

of Dscam action extends to other modes of

immune defense A further series of

experi-ments revealed that the repertoires of AgDscam

molecules could be tailored, in terms of

bind-ing affinity, to the infectbind-ing pathogens,

under-scoring the degree to which specificity provided

by the Dscam system might help refine

pathogen pattern recognition in insects — SJS

PLoS Biol 4, e229 (2006).

M I C R O B I O L O G Y

One of Everything

Recent molecular analyses of marine microbes

(see, for example, DeLong et al Reports,

27 January 2006, p 496) have documented how

the environmental pressures of living in the

ocean at depths down to several kilometers are

reflected in the corresponding genomic

comple-ments Derelle et al provide the genome

sequence of Ostreococcus tauri, a green alga of

extraordinarily small size (about 1 μm in

diame-ter) and remarkably high gene density This

picoeukaryote achieves the feat of packing over

8000 genes into less than 13 Mb by making the

average gene just slightly longer than 1.2 kb

and reducing the intergene distance to 0.2 kb

Nevertheless, it still contains entire plantlike

metabolic pathways, such as the enzymes for C4

photosynthesis (an evolutionary adaptation to

low CO2levels) and for storing glucose as one

large starch granule within the single

chloro-plast Also appearing in only one copy each are

the mitochondrion, a Golgi body, and the

EDITORS’CHOICE

I read my Science

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home Thank you, Science, for

being so informative, able, and abreast of times, andfor giving me the intell-ectual stimulation I crave

knowledge-AAAS is committed to advancingscience and giving a voice to scien-tists around the world Helping ourmembers stay abreast of their field

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AAAS member Professor Fioretta Benedetto Mattia

nuclear pore, which presumably reflect the ical advantages of small intracellular distancesand a high surface-to-volume ratio — GJC

phys-Proc Natl Acad Sci U.S.A 103, 11647 (2006).

M A T E R I A L S S C I E N C E

Advantages of Neutrality

Electron beam lithography, often used to tern the smallest features on semiconductingsilicon substrates, can also modify insulatingsubstrates However, at typical beam energies,the insulating surface builds up negativecharge that deflects the beam and so distortsthe desired pattern Several approaches havebeen developed to overcome this problem, butthey require additional sample processing steps

pat-or complex gas-handling and vacuum

equip-ment Joo et al note that at lower energies,

electron beams caninstead induce pos-itive charging ofinsulating surfaces;

therefore, a criticalenergy exists forwhich the surfacewill remain neutral

For 65-nm-thickpoly(methylmethacrylate) films

on glass, theydetermine a critical energy value of 1.3 keV Bytuning the incident beam to this energy, theysuccessfully create features finer than 100 nm

on this substrate A 5-keV beam, in contrast,produces distortions that are clearly evident inscanning electron micrographs — PDS

Nano Lett 6, 10.1021/nl061211q (2006).

<< Moving PIP3About

Phosphatidylinositol-(3,4,5)-phosphate (PIP3), the product of phatidylinositol 3-kinase (PI3K), is important in the establishment of

phos-cell polarity Horiguchi et al provide evidence that PIP3is produced notonly at the plasma membrane by local activation of PI3K, but also atinternal membranes that are then transported as PIP3-containing vesi-cles on microtubules to the growing tips of neuronal projections First, they determined that

GAKIN (guanylate kinase–associated kinesin) interacted with PIP3binding protein (PIP3BP); in

vitro, GAKIN and PIP3BP mediated the movement of PIP3liposomes on microtubules In PC12 cells

and in cultured hippocampal neurons, tagged GAKIN, tagged PIP3BP, and a marker for PIP3 were

colocalized at the tips of neurites, and in hippocampal cells, these three molecules were most

abundant in the longest neurite, the axon Overexpression of a dominant-negative form of GAKIN

(with the kinesin motor domain deleted) in PC12 cells decreased the abundance of PIP3at neurite

tips In hippocampal neurons, overexpression of wild-type GAKIN or dominant-negative GAKIN

disrupted the formation of the morphologically distinct axon-dendrite structure and produced

cells with multiple, highly branched neurites The authors suggest that PIP3produced at internal

membranes or PIP3produced at the cell body may contribute to cell polarity – NRG

J Cell Biol 174, 425 (2006).

www.stke.org

Precisely patternedinsulator

18 AUGUST 2006 VOL 313 SCIENCE www.sciencemag.org894

John I Brauman, Chair, Stanford Univ.

Richard Losick, Harvard Univ.

Robert May, Univ of Oxford

Marcia McNutt, Monterey Bay Aquarium Research Inst.

Linda Partridge, Univ College London

Vera C Rubin, Carnegie Institution of Washington

Christopher R Somerville, Carnegie Institution

George M Whitesides, Harvard University

Joanna Aizenberg, Bell Labs/Lucent

R McNeill Alexander, Leeds Univ

David Altshuler, Broad Institute

Arturo Alvarez-Buylla, Univ of California, San Francisco

Richard Amasino, Univ of Wisconsin, Madison

Meinrat O Andreae, Max Planck Inst., Mainz

Kristi S Anseth, Univ of Colorado

Cornelia I Bargmann, Rockefeller Univ.

Brenda Bass, Univ of Utah

Ray H Baughman, Univ of Texas, Dallas

Stephen J Benkovic, Pennsylvania St Univ

Michael J Bevan, Univ of Washington

Ton Bisseling, Wageningen Univ

Mina Bissell, Lawrence Berkeley National Lab

Peer Bork, EMBL

Robert W Boyd, Univ of Rochester

Dennis Bray, Univ of Cambridge

Stephen Buratowski, Harvard Medical School

Jillian M Buriak, Univ of Alberta

Joseph A Burns, Cornell Univ

William P Butz, Population Reference Bureau

Doreen Cantrell, Univ of Dundee

Peter Carmeliet, Univ of Leuven, VIB

Gerbrand Ceder, MIT

Mildred Cho, Stanford Univ

David Clapham, Children’s Hospital, Boston

David Clary, Oxford University

J M Claverie, CNRS, Marseille

Jonathan D Cohen, Princeton Univ

F Fleming Crim, Univ of Wisconsin William Cumberland, UCLA George Q Daley, Children’s Hospital, Boston Caroline Dean, John Innes Centre Judy DeLoache, Univ of Virginia Edward DeLong, MIT Robert Desimone, MIT Dennis Discher, Univ of Pennsylvania

W Ford Doolittle, Dalhousie Univ.

Julian Downward, Cancer Research UK Denis Duboule, Univ of Geneva Christopher Dye, WHO Gerhard Ertl, Fritz-Haber-Institut, Berlin Douglas H Erwin, Smithsonian Institution Barry Everitt, Univ of Cambridge Paul G Falkowski, Rutgers Univ

Ernst Fehr, Univ of Zurich Tom Fenchel, Univ of Copenhagen Alain Fischer, INSERM Jeffrey S Flier, Harvard Medical School Chris D Frith, Univ College London

R Gadagkar, Indian Inst of Science John Gearhart, Johns Hopkins Univ.

Jennifer M Graves, Australian National Univ.

Christian Haass, Ludwig Maximilians Univ.

Chris Hawkesworth, Univ of Bristol Martin Heimann, Max Planck Inst., Jena James A Hendler, Univ of Maryland Ove Hoegh-Guldberg, Univ of Queensland Ary A Hoffmann, La Trobe Univ.

Evelyn L Hu, Univ of California, SB Olli Ikkala, Helsinki Univ of Technology Meyer B Jackson, Univ of Wisconsin Med School Stephen Jackson, Univ of Cambridge Daniel Kahne, Harvard Univ.

Bernhard Keimer, Max Planck Inst., Stuttgart Elizabeth A Kellog, Univ of Missouri, St Louis Alan B Krueger, Princeton Univ

Lee Kump, Penn State

Mitchell A Lazar, Univ of Pennsylvania Virginia Lee, Univ of Pennsylvania Anthony J Leggett, Univ of Illinois, Urbana-Champaign Michael J Lenardo, NIAID, NIH

Norman L Letvin, Beth Israel Deaconess Medical Center Olle Lindvall, Univ Hospital, Lund

Richard Losick, Harvard Univ.

Ke Lu, Chinese Acad of Sciences Andrew P MacKenzie, Univ of St Andrews Raul Madariaga, École Normale Supérieure, Paris Rick Maizels, Univ of Edinburgh

Michael Malim, King’s College, London Eve Marder, Brandeis Univ.

William McGinnis, Univ of California, San Diego Virginia Miller, Washington Univ.

Edvard Moser, Norwegian Univ of Science and Technology Andrew Murray, Harvard Univ.

Naoto Nagaosa, Univ of Tokyo James Nelson, Stanford Univ School of Med

Roeland Nolte, Univ of Nijmegen Helga Nowotny, European Research Advisory Board Eric N Olson, Univ of Texas, SW

Erin O’Shea, Univ of California, SF Elinor Ostrom, Indiana Univ.

Jonathan T Overpeck, Univ of Arizona John Pendry, Imperial College Philippe Poulin, CNRS Mary Power, Univ of California, Berkeley David J Read, Univ of Sheffield Les Real, Emory Univ.

Colin Renfrew, Univ of Cambridge Trevor Robbins, Univ of Cambridge Nancy Ross, Virginia Tech Edward M Rubin, Lawrence Berkeley National Labs Gary Ruvkun, Mass General Hospital

J Roy Sambles, Univ of Exeter David S Schimel, National Center for Atmospheric Research Georg Schulz, Albert-Ludwigs-Universität Paul Schulze-Lefert, Max Planck Inst., Cologne Terrence J Sejnowski, The Salk Institute David Sibley, Washington Univ

George Somero, Stanford Univ

Christopher R Somerville, Carnegie Institution Joan Steitz, Yale Univ.

Edward I Stiefel, Princeton Univ

Thomas Stocker, Univ of Bern Jerome Strauss, Univ of Pennsylvania Med Center Tomoyuki Takahashi, Univ of Tokyo Marc Tatar, Brown Univ.

Glenn Telling, Univ of Kentucky Marc Tessier-Lavigne, Genentech Craig B Thompson, Univ of Pennsylvania Michiel van der Klis, Astronomical Inst of Amsterdam Derek van der Kooy, Univ of Toronto

Bert Vogelstein, Johns Hopkins Christopher A Walsh, Harvard Medical School Christopher T Walsh, Harvard Medical School Graham Warren, Yale Univ School of Med

Colin Watts, Univ of Dundee Julia R Weertman, Northwestern Univ

Daniel M Wegner, Harvard University Ellen D Williams, Univ of Maryland

R Sanders Williams, Duke University Ian A Wilson, The Scripps Res Inst

Jerry Workman, Stowers Inst for Medical Research John R Yates III, The Scripps Res Inst

Martin Zatz, NIMH, NIH Walter Zieglgänsberger, Max Planck Inst., Munich Huda Zoghbi, Baylor College of Medicine Maria Zuber, MIT

John Aldrich, Duke Univ.

David Bloom, Harvard Univ.

Londa Schiebinger, Stanford Univ.

Ed Wasserman, DuPont Lewis Wolpert, Univ College, London

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netwatch@aaas.orgArchive: www.sciencemag.org/netwatch

E D I T E D B Y M I T C H L E S L I E

E D U C A T I O NLighting Up Life

To learn why biologists are all aglow about a luminous jellyfish molecule called green fluorescent protein (GFP),check out this brief primer from Marc Zimmer of ConnecticutCollege in New London

By allowing scientists totrack proteins and cells,GFP has become a labworkhorse The site, whichsupplements Zimmer’sbook on the topic,describes the molecule’sstructure, introduces theresearchers who isolatedGFP and pioneered its use,and surveys its applications

This GFP-making mouse (above) allows researchers to observeinteractions between tumors and the surrounding tissue >>

www.conncoll.edu/ccacad/zimmer/GFP-ww/GFP-1.htm

W E B L O G S

More Than Skin Deep

For the real scoop on cosmetics and hair care, forget stylists—ask the scientists at

The Beauty Brains On this new blog, a pair of cosmetic chemists weigh product claims,

answer reader questions, and highlight research that’s germane to the beauty business

Although most of the answers aren’t very technical, they usually touch on scientific

issues, from the dangers of mixing hair-care products to the harmless mites that inhabit

your hair follicles For example, the question, “Can you fix split ends?” prompts a short

discussion of hair structure No matter what the shampoo ads assert, the site concludes,

split ends are unfixable because hair isn’t alive and can’t heal >>

thebeautybrains.blogspot.com

E D U C A T I O N

<< When Molds Attack

The fungus Penicillium marneffei (left) is a sinister

cousin of the molds that make penicillin On the loose

in Southeast Asia, P marneffei invades the skin, eyes,

lungs, and other organs, often picking on HIV-infectedpatients Doctors and researchers can brush up on

pathologic fungi such as P marneffei at Mycology Online,

hosted by David Ellis of the University of Adelaide in Australia

After you pore over the descriptions of medically significant fungi, try your hand at the

identification quiz Browse the laboratory methods section to learn how to culture molds

from skin swabs or mix a stain that delineates fungal filaments inside tissue The site

also features a gallery and lets you download 500 slides of fungi and their symptoms

gathered by the eminent Australian mycologist Geraldine Kaminski >>

www.mycology.adelaide.edu.au

D A T A B A S EPowered by CiliaFluttering cilia speed a paramecium across a microscope slide,but the hairlike filaments are more than cellular equivalents

of outboard motors New research suggests that cilia detectfluid movement in the kidney, tune in molecular signals that help orchestrate embryonic development, and perform

other stationary tasks (Science, 14 October 2005, p 216)

The new Cilia Proteome site from Johns Hopkins University

in Baltimore, Maryland, is sweeping up data on all proteinsfound in cilia and basal bodies, the sockets that hold the filaments You can browse the known human proteins or call

up comparable molecules from model organisms such as themouse and fruit fly >>www.ciliaproteome.org

Botanists, ecologists, students,and even gardeners will find abumper crop of information atPLANTS The U.S Department ofAgriculture’s online encyclopediaprofiles some 43,000 species andvarieties of native and introducedplants, emphasizing their role insoil conservation Entries featureimages and taxonomic information,and some include an exhaustive list

of the plant’s characteristics, frommaximum height to flowering time tosoil pH preference Range maps usuallybreak down distribution to the countylevel Separate sections let you quicklyfind noxious invaders, endangered species,and wetland residents The gallery is aneyeful, displaying more than 30,000 photosand drawings of species such as the wild sweet

William (Phlox maculata; left), a native of the

eastern and Midwestern states >>

plants.usda.gov

R E S O U R C E S

Botanical Bounty

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the leading source for news, research, and leading edge presentation of contentcontinues to grow Looking for news and research that will impact the world

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For news and

CREDITS (TOP TO BOTTOM): A OSBORNE

Clay samples (above) drawn from a set of interconnected

caves west of Sydney, Australia, suggest that the caverns may be

340 million years old, making them the most ancient accessible

ones anywhere in the world If the result holds up, the Jenolan

Caves would be more than 200 million years older than the

current record holder

Although dating caves can offer insights into geological

history, it’s also exceedingly difficult to accomplish In part

that’s because the materials inside caves, and the stone from

which they’re made up, often predate the cave itself by millions

of years To date the Jenolan caves, which are a popular tourist

destination, geologist Armstrong Osborne of the University of

Sydney and his colleagues turned to clay considered a remnant

of volcanic ash that helped the caves take shape, they write in

the Australian Journal of Earth Sciences.

The researchers estimated the age of the clay samples by

com-paring levels of radioactive potassium, which decays over time, to

those of argon gas, which appears as the potassium decays “The

implication … that the caves formed by alteration of volcanic

ash” is “entirely possible,” says Paul Renne, director of the

Berkeley Geochronology Center at the University of California,

Berkeley Still, he’s not convinced the clay didn’t erode from

preexisting rocks, although Osborne insists that’s not the case

A veterinary anesthetic also favored as a rave drug is offering a glimmer

of hope for treating depression

Ketamine, or “Special K” to clubgoers, improved the mood of 12 of the

17 depressed volunteers who received a single injection of it, Carlos Zarate,

a psychopharmacologist at the U.S National Institute of Mental Health

in Bethesda, Maryland, and his colleagues

report in this month’s Archives of General

Psychiatry A placebo offered to the same

group helped much less The antidepressant

effect lasted up to a week, but most exciting

to pharmacologists was that ketamine

started working in just 2 hours; typical

anti-depressants can take up to 2 months to kick

in Because suicidal behaviors are

associ-ated with the first days of standard therapy,

that difference could prove critical

The study adds to mounting evidence

that the brain’s glutamate signaling

system, controlled in part by the receptor

hit by ketamine, is a specific target for

depression therapies, says John Krystal, a

psychopharmacologist at Yale University:

“The glutamate story as it has emerged

is very promising.”

Police in the German city of Dresden are hunting for a rapist,and they’re ready to collect DNA from up to 100,000 men tocatch him German police netted a killer in Cloppenburg in

1998 after 18,000 men were tested, but the Dresden effortcould become the largest DNA dragnet ever performed in acriminal investigation

Dresden police devised the plan after finding identicalgenetic blueprints from sperm in two rape cases since lastSeptember More than 3000 men so far have submitted tosaliva swabs Participation is voluntary, but the policeacknowledge that those who refuse will be scrutinized,according to German media reports

“I think the strategy is worth it,” says Michael Brand,director of the Biotechnology Center at the TechnicalUniversity in Dresden, even at its maximum cost of $3.5 mil-lion The Dresden police have said publicly that after testingfor a match, they will discard DNA from all men who do nothave a serious criminal record, as the law requires

But “even if privacy is protected, to ask for DNA underthreat of special scrutiny for those who do not cooperate may

be coercive,” says Peter Lipton, a philosopher at theUniversity of Cambridge, U.K “Is this justified?”

Gene Hunt

There’s not much good news aboutinvasive species these days, so biologists were thrilled last month todeclare victory in a 6-year, $7 millionbattle to rid the coastal waters ofsouthern California of an exotic alga

“It’s quite an achievement,” saysecologist Daniel Simberloff of theUniversity of Tennessee,Knoxville, who was notinvolved in the effort

The enemy was Caulerpa taxifolia, a tropical species

that has run rampant in theMediterranean Sea, causing problemsfor commercial fishing, recreationaldiving, and pleasure boating After itwas discovered in two lagoons nearSan Diego in 2000, divers repeatedly searched every square meter of the

murky waters (Science, 22 March 2002, p 2201) They covered patches of Caulerpa with tarps weighted by sandbags and pumped in chlorine

Quarterly surveys have come up empty-handed since 2002 “We can say

with 99.9% confidence that the Caulerpa is gone, so we declared success,”

says Robert Hoffman of the National Marine Fisheries Service in Long Beach

“It feels great,” adds team member Lars Anderson of the U.S Department ofAgriculture in Davis, California “We just hope we never see it again.”

Eradicated >>

MOOD BOOST

SPELUNKING THROUGH TIME

All out In a major effort, diverskilled this invasive alga before

it spread out of control

NEWS >>

In the dog days of August, while

most members of Congress are

back home campaigning for

reelection or on holiday, a small

group of staffers is at work in

Washington, D.C., on legislation

that could influence science

spending for years to come Their

goal is to craft a broad bill aimed

at bolstering U.S

competitive-ness that Congress could pass

before the November elections

They face long odds The

W h i t e H o u s e h a s a l r e a d y

ex pressed reservations about

some aspects of the legislation,

and the congressional calendar is

short and already very crowded

Although Senate leaders say they

are committed to the goal, House

leaders appear less enthusiastic

But a powerful coalition of

forces, including business leaders

who can bend a member’s ear, is

keen for Congress to act

“Legis-lation would show the public that

our nation’s leaders have a

long-range plan of action on U.S

com-petitiveness,” says Susan Traiman

of the Business Roundtable, a

consortium of 160 CEOs from

across U.S industry

The legislation draws upon

several efforts over the past year

examining the status of U.S

science and technology,

includ-ing the National Academies’

Rising Above the Gathering

Storm report and the National

Summit on Competitiveness

(Science, 21 October 2005,

p 423; 16 December 2005,

p 1752) In February, the Bush

Administration proposed starting a 10-year

doubling of basic research at the National

Science Foundation (NSF), the Department

of Energy’s (DOE) Office of Science, and

the National Institute of Standards and

Technology’s (NIST) core labs (Science,

17 February, p 929) as part of its 2007 budgetrequest And the initial funding for what theAdministration has dubbed the AmericanCompetitiveness Initiative (ACI) is working its

way through the legislative process

Science advocates can’t say enough aboutthe importance of ACI But they believe evenmore is needed to improve math and scienceeducation and enhance U.S innovation Tak-

ing their cue from Gathering Storm and other

reports, legislators from both parties duced a fistful of bills earlier this year thatwould expand existing research and educa-tion activities at several agencies and set upnew programs (see table)

intro-Unlike annual appropriations bills, whichdetermine how much each federal agency canspend in a given year, these authorization billsset desired funding levels over several years.Although they don’t provide the cash, theycan build political support for ongoing spend-ing increases Notes one university lobbyist:

“You want Congress on record and the keycommittees behind an authorization bill, sothat they can bail out appropriators when theyhit rough seas.”

The goal of the quiet negotiations takingplace this summer is a single bill But the callsfor increased spending are a sticking point for

a Republican Party whose president, George

W Bush, has repeatedly pledged to reduce thefederal deficit and whose congressional lead-ers hope to campaign this fall on their success

in shrinking government Several of the billsalso expand NSF’s role in science and matheducation, a position that clashes with theAdministration’s plans for the Department ofEducation to lead efforts to improve math andscience education and manage all the ACI’seducation components

P r e s i d e n t i a l s c i e n c e a d v i s e r J a c kMarburger emphasized those points in hard-line letters this spring to the chairs of the com-mittees as they prepared to vote out one of theSenate bills (S 2802) and two House bills(HR 5356/5358) The Senate measure,Marburger warned Senator Ted Stevens(R–AK) on 17 May, “would undermine anddelay” ongoing research at the three agencies,

“duplicate or complicate existing educationand technology programs,” and “competewith private investment” in both areas TheHouse bills, he told Representative SherryBoehlert (R–NY) on 5 June, “would diminishthe impact” of the requested increases for thethree ACI agencies

Boehlert says he was “quite disappointed”

by Marburger’s letter, noting the president’sdeclaration in his January State of the Union

Congress Quietly Tries to Craft Bill

To Maintain U.S Lead in Science

U.S SCIENCE POLICY

18 AUGUST 2006 VOL 313 SCIENCE www.sciencemag.org

FOCUS Surgery’s tiny

910

address that the country “must continue to

lead the world in human talent and creativity.”

Boehlert added, “I thought that we had been

working with OSTP on these issues,”

refer-ring to the White House Office of Science and

Technology Policy that Marburger heads

Three weeks after the House committee

passed both bills, überstaffer Karl Rove, new

domestic policy chief Karl Zinsmeister, and a

score of high-tech industry and academic

lob-byists met at the White House to discuss the

pending legislation Although nothing was

resolved—some participants say Rove and

Marburger scolded them for supporting the

bills, whereas others say there was confusion

over the various components—the White

House told the lobbyists that its Office of

Leg-islative Affairs, led by Candida Wolff, would

be taking the lead in trying to craft an

accept-able bill, pushing OSTP to the sidelines In the

Senate, lobbyists are heartened by the ness of Senate Majority Leader Bill Frist(R–TN) to negotiate with the three chairswhose panels must sign off on the legisla-tion—Stevens, Senator Pete Domenici(R–NM), who leads the Energy and NationalResources Committee, and Senator MikeEnzi (R–WY), who heads the Health, Educa-tion, Labor, and Pensions Committee

willing-Another important player, Senator LamarAlexander (R–TN), acknowledged when heintroduced a trio of bills in January that some

of his colleagues “may wince at the price tag”

of the legislation But he cautioned that

“maintaining America’s brainpower tage will not come on the cheap.”

advan-Although none of the staffers involvedwould speak on the record, several confirmedthat talks are taking place “on a regular basis.”

They say Frist is determined to cobble

together a single bill—with lower tion levels and fewer new programs than inany of the pending versions—that the Senatecould adopt during a 4-week window in Sep-tember Prospects in the House are less cer-tain, although Boehlert says, “Hope springseternal that we’ll get an opportunity to go tothe floor in September.”

authoriza-Optimists, who hope that all sides willview a competitiveness bill as an asset head-ing into the November elections, dream of anAdministration that accepts a competitive-ness bill in return for getting its ACI educa-tion programs authorized Pessimists worrythat the House leadership will scuttle theeffort by portraying the bills as a vehicle for

“wasteful spending” and “a bloated cracy.” And although nobody’s betting thatCongress will act this year, nobody has

Panel Confirms Report of Early H5N1 Human Case in China

An international panel of experts has

con-firmed that China’s first human death from

H5N1 avian influenza occurred in

Novem-ber 2003, and not 2 years later as Chinese

authorities had previously reported The

finding raises as many questions as it settles

The case was f irst repor ted in the

22 June issue of the New England Journal

of Medicine (NEJM) by Wu-Chun Cao of

the State Key Laboratory of Pathogens and

Biosecurity, Beijing, and colleagues at

insti-tutions mainly affiliated with China’s

mili-tary In a strange twist, someone claiming to

be Cao tried to withdraw the letter, but the

magazine had gone to press; Cao later told

the editors the request did not come from

him (Science, 30 June, p 1855).

To verify the results, China’s Ministry of

Health retested tissue samples and

assem-bled an international panel of flu experts to

review the results with the cooperation of

the World Health Organization (WHO) On

8 August, the ministr y announced the

panel’s conclusion: The death of a

24-year-old male in November 2003, from what

were then called unknown causes, was

actu-ally due to H5N1 The death occurred

3 months before China reported its f irst

H5N1 outbreaks in poultry and 2 years

before it reported any human cases Chinese

media reported that Vice Minister of HealthJiang Zuojun said at a 10 August press con-ference in Beijing that the case indicatesthe need for researchers “to improve com-munication and contact with disease pre-vention organizations.”

Flu experts widely believe H5N1 hasbeen circulating in southern China at leastsince the virus was first identified in HongKong in 1997 It has never been clear if itwas undetected or if local or nationalauthorities were withholding informationfrom the international community—orwhether they were even aware of how seri-ous a threat the virus posed

Reached by phone, Cao said his teamconcluded the man died of H5N1 onlyshortly before submitting their letter to the

NEJM He said he is willing to discuss the

results with scientists but not reporters “It’s

a very sensitive issue,” he said, declining totake further questions

Roy Wadia, a WHO spokesperson inBeijing, says that when two members of aHong Kong family tested positive forH5N1 after a trip to the mainland’s FujianProvince in February 2003, WHO askedChinese authorities to investigate Wadiasays the agency was told that the H5N1virus was not present in Fujian Confirma-tion that the virus was in circulation earlierthan reported “begs the question of whethermore aggressive action might have made adifference in the (near worldwide) spread

of this virus,” he says

18 AUGUST 2006 VOL 313 SCIENCE www.sciencemag.org900

NEWS OF THE WEEK

A Hawaii state judge has found

fault with the process of

approv-ing new telescopes at the world’s

largest astronomical observatory

A 3 August ruling by Third

Cir-cuit Court Judge Glenn Hara

could affect the pace of

develop-ment atop the 4200-meter Mauna

Kea, a mountain with special

sig-nificance to native Hawaiians

The case involves a 2004

permit issued to the University

of Hawaii’s Institute for

Astron-omy (IFA) to house a quartet of

1.8-meter telescopes that would

have worked in conjunction with

the twin 10-meter Keck

tele-scopes on the summit to hunt for

planets outside the solar system

The $70 million Outrigger

inter-ferometry project, which NASA

canceled in February because of

a tight budget after spending

$20 million on the telescopes and domes,

would have operated in a protected area that

requires a special permit from the state’s

Board of Land and Natural Resources

(BLNR) But Hara said the board should not

have approved Outrigger in the absence of a

“comprehensive management plan” for the

summit, which already hosts 13 telescopes

“The resource that needs to be conserved,

protected, and preserved is the summit, not

just the area of the project,” Hara wrote in

an eight-page decision (Civ No 04-1-397,

Mauna Kea v BLNR) Although only

Outrigger has been canceled, the ruling willaffect all future development on Mauna Kea

“Astronomers always want the next bestthing, and they don’t want any restrictionsplaced on them,” says Lea Hong, a Honoluluattorney who represented the plaintiffs,which included local groups and the Sierra

Club “My clients aren’t antiastronomy Butthey do want meaningful community repre-sentation in a process that respects the envi-ronmental, cultural, and aesthetic aspects ofthe mountain.”

The judge’s ruling “highlights an guity” in the current procedures, admitsFrederic Chaffee, director emeritus of theKeck Observatory The university, whichmanages activities at the summit, adopted aMauna Kea master development plan in

ambi-2000, Chaffee notes, but the state neverapproved it or any similarly comprehensiveplan That loophole allowed critics of theOutrigger telescope project to argue suc-cessfully that the state was ignoring its ownrules for managing the summit

“The board needs to adopt a master plan,”agrees BLNR chair Peter Young, adding that

t h e r e ’s n o t i m e t o w a s t e b e c a u s e aU.S government-funded panoramic surveytelescope (Pan-STARRS 4) project is moving

ahead quickly (Science, 12 May, p 840) and

the enormous Thirty-Meter Telescope, beingplanned by a public-private consortium, iswaiting in the wings (www.tmt.org) “Weplan to work with the university to come upwith something that would incorporate boththose projects and others down the road.”IFA Director Rolf Kudritzki says that, inretrospect, the process used for the Outriggerproject “wasn’t the best way to proceed.”But he says, “I don’t see a problem forastronomy” in the wake of the judge’s

r u l ing Chaffee estimates that “we’vealready done 80% of the work” on a com-prehensive plan for the summit in preparingthe Outrigger permit

–JEFFREY MERVIS

Judge Slaps Hawaii Over

Mauna Kea Telescopes

ASTRONOMY

U.S Loosens Policy on Ties to UNESCO

The United States government has

with-drawn restrictions it placed a year ago on

contact between U.S citizens and the

United Nations Educational, Scientific, and

Cultural Organization (UNESCO) U.S

sci-entific societies are relieved by the move,

which they say should help restore free

exchange between U.S researchers and the

international body

In May 2005, Louise Oliver, the U.S

ambassador to UNESCO, sent a memo to

UNESCO Director General Koichiro Matsuura

asking the organization to consult U.S

offi-cials before partnering with anybody in the

United States or planning any U.S events

Last month, in a memo to Matsuura, Oliver

effectively retracted that directive by

explaining that the U.S government merelywants to stay informed about contactsbetween UNESCO and U.S entities

Last year’s memo seems to have been

“misinterpreted by some individuals withinthe UNESCO Secretariat,” Oliver says inher 25 July letter “We understand that therehave been instances where UNESCO staffinformed U.S individuals and nongovern-mental organizations that they wererequired to obtain U.S gover nmentapproval before making contact withUNESCO or before entering into any con-tracts with UNESCO.”

Wendy White of the U.S National emies, which last year wrote to Oliverexpressing its concern, says she hopes the

Acad-new memo will repair any breaches betweenthe U.S scientif ic community andUNESCO caused by last year’s memo ButIrving Lerch, of the American PhysicalSociety and Americans for UNESCO, won-ders if the status quo can be restored “Somelinks between U.S organizations andUNESCO have already snapped as a result

of last year’s directive,” he says, noting that

a UNESCO staffer recently declined ameeting invitation that had not been routedthrough the U.S government Moreover,Lerch says, the U.S government still wantsUNESCO to give it advance notification ofany contacts with U.S organizations—astep that he says hinders free exchange

–YUDHIJIT BHATTACHARJEE

SCIENTIFIC EXCHANGES

Dawn of creation The twin 10-meter Kecktelescopes explore the early universe atopHawaii’s sacred Mauna Kea

Biopharming Rules Broken

The first U.S biopharming field trials toundergo legal scrutiny weren’t kosher, says aU.S Hawaiian district judge who ruled lastweek in a case involving research done severalyears ago in Hawaii

The Department of Agriculture (USDA)broke national environmental laws when itallowed four companies to grow HIV vaccinesand other pharmaceuticals in geneticallymodified (GM) crops on four Hawaiian islands,explained Judge J Michael Seabright in a

10 August ruling Environmental groupsargued successfully that USDA should haveconsidered the potential impact on endan-gered species and other questions The agency,Seabright said, showed an “utter disregard forthis simple investigation requirement.”

Next week, Seabright will hear argumentsfor a moratorium on field trials while theUSDA reviews its biopharming permit pro-gram In the meantime, Paul Achitoff, a plain-tiff representing the advocacy group Earth-justice in Oakland, California, says the rulingputs USDA on notice that ignoring the envi-ronmental impacts of biopharm GM cropsmakes it “a sitting duck for future lawsuits.”

–ERIK STOKSTAD

A Mighty Wind Blowin’

The U.S government should consider a10-fold increase in research to help under-stand and protect against hurricanes,according to an upcoming report from a task force of the National Science Board convened in response to Katrina’s devasta-tion of the Gulf Coast last August

Panel chair Kelvin Droegemeier, a ologist at the University of Oklahoma, says thecountry needs a $300-million-a-year NationalHurricane Research Initiative along the lines ofthe multiagency National Earthquake HazardResearch Program

meteor-created in thewake of the great

1964 earthquakethat struck Alaska

Droegemeier saysthe panel hopes tocapitalize on thecurrent hurricaneseason to grab theattention of U.S

policymakers “We’re trying to build supportfor an integrative approach to this phenome-non,” he reported last week to the scienceboard, which sets policy for the National Science Foundation –JEFFREY MERVIS

SCIENCESCOPE

Doctors who treated the six young men who

became desperately ill in a botched U.K

clini-cal trial last spring have released an in-depth

record of the catastrophe They confirm, for

example, that the volunteers were given

intra-venous doses of a test drug in quick succession

(10 minutes apart), even though the drug had

never been given to humans before The

sub-jects began to show signs of illness within

50 to 90 minutes, according to the report And

within 12 to 16 hours, all six were transferred

from a company research site, which couldn’t

handle the emergency, to the Northwick Park

and St Mark’s Hospital in London, which

res-cued them The men appear to have recovered

But even 30 days after the test, according to a

paper released this week from the 7 September

New England Journal of Medicine (NEJM),

some had “short-term difficulties in finding

words (particularly names).”

This detailed account—

by Ganesh Suntharalingam

and colleagues in

North-wick Park’s intensive care

unit—fills gaps in an

ear-lier report on the incident

by an expert panel advising

NEJM paper confirms that

t h e d r u g i n t h i s t r i a l ,

a monoclonal antibody

called TGN1412, caused a

massive immune response

that flooded the

volun-teers’ blood with

inflam-matory agents, triggering

systemic organ damage

( S c i e n c e , 2 4 M a r c h ,

p 1688) The doctors do

not attempt to explain why

this happened But they

conclude that TGN1412 itself, not an

impu-rity, caused the injuries They also speculate

that TGN1412, which was designed to

acti-vate T cells and regulatory T cells at the

same time, also may have directly injured

the immune system and focused

inflamma-tion in the lungs Four patients had to receive

oxygen by mask, and two had to be put on

mechanical ventilators All six experienced

severe and “unexpected” depletion of

lym-phocytes, cells that are essential to the

immune system The likely long-term

conse-quences are not known

Others say that data in hand before the trialmake it clear that TGN1412 should have beentested with more caution Nirmala Bhogal, amolecular pharmacologist who has analyzedthe trial for FRAME, a nonprofit in Notting-ham, U.K., that advocates substitutes for ani-mal testing, says that one preclinical study ofTGN1412 in monkeys revealed a proinflam-matory response that peaked at 2 hours Thedrug company that owns TGN1412—TeGenero

of Wurzburg, Germany—discounted thisbefore the clinical trial as a minor effect How-ever, Bhogal says, in light of the monkey data,

“it defies all logic” to dose human volunteers

at intervals shorter than 2 hours TeGenerofiled for insolvency in July, and companyofficials could not be reached for comment

In its draft report issued last month, theexpert panel advising the government, chaired

by Gordon Duff, a University of Sheffield cialist in genetics and the human inflammatoryresponse, suggested that when drugs are given

spe-to human subjects for the first time, thereshould be a pause for “an appropriate period ofobservation” before the next person is dosed

The Duff panel also offered specific ideasfor improving dose-risk calculations Its broad-est proposal is that drug companies and regula-tors around the world should collect and shareunpublished data on human drug reactions

The panel suggested creating a new, openaccess database for everyone’s use The panel

is gathering comments on these and other ideasbefore issuing a final report to the U.K govern-

Lessons From a Failed Drug Trial

(2)day4 day5 day6

Time (days)

A Flood of Inflammatory Responses

Mean TNFalpha Mean IFNg Mean IL-10 Mean IL-β Mean IL4 Mean IL2

* Expert Scientific Group on Phase One Clinical Trials,

Interim Report (www.dh.gov.uk/assetRoot/04/13/75/69/

04137569.pdf)

18 AUGUST 2006 VOL 313 SCIENCE www.sciencemag.org902

NEWS OF THE WEEK

When it comes to powering laptops and

hybrid cars, batteries get most of the attention

But these gadgets and myriad others also

con-tain devices known as capacitors that provide

quick bursts of energy Capacitors can’t store

as much power as batteries, but the latest

“supercapacitors” have started to close the

gap Now, their storage capabilities may be

about to take another big jump

In a report published online this week by

Science (www.sciencemag.org/cgi/content/

abstract/1132195), researchers from the

United States and France report that by

care-fully controlling the nanoscale structure of a

carbon-based supercapacitor, they’ve

man-aged to increase the amount of electrical

charges it can hold by about 50% “It looks like

they’ve got something significant there,” says

John Miller, a physicist who runs JME Inc., a

supercapacitor materials evaluation company

in Shaker Heights, Ohio If this performancetranslates to commercial devices, it could helpmanufacturers create smaller and cheaperpower packs for everything from cameras tocars, Miller says First, however, researchersneed to learn more about how it works

Typically, a capacitor contains a pair ofelectrodes surrounded by an electrolyte

When a voltage is applied between the trodes, oppositely charged ions in the elec-trolyte snuggle up to each electrode andremain there even when the applied voltage

elec-is turned off When the two electrodes areconnected by a wire, electrons flow from thenegative electrode to balance the charges inthe positive electrode and do work en route

For many years, carbon has been the trode material of choice for supercapacitorsbecause it conducts electricity, is light, andcan be formed into a meshlike structure that

elec-sops up ions like a sponge The smaller thepores in the material, the larger its surfacearea and the more charge the capacitor canhold—at least up to a point When ions movethrough an electrolyte, other moleculesattracted to their charge normally encirclethem like groupies mobbing a rock star.Researchers have long thought that if thepores in a carbon supercapacitor got toosmall—below about 1 billionth of a meter, ornanometer—the ion would not be able tosqueeze through with its entourage, and thusthe material’s overall ability to store chargewould drop But because they had no way tocarefully control the pore size throughout alarge capacitor, they couldn’t test this notion.Yury Gogotsi and his colleagues at DrexelUniversity in Philadelphia, Pennsylvania,however, came up with a new way to do justthat They started with one of several com-mercially available compounds called a metalcarbide, a mixture of a metal such as titaniumand carbon They then heated their material in

a furnace while exposing it to chlorine gas.The gas reacted with the metal, formingvolatile compounds that could easily be sepa-rated from the mixture, leaving behind carbonshot through with a continuous mesh of voids

By controlling the temperature and other ditions in their reactor, the researchers foundthey could tailor the holes in their carbonmesh to be a uniform size, between 0.6 and2.25 nanometers across

con-When Gogotsi and his students ured the charge-storing capabilities of thematerial, they got a shock “We thought itwould be useless” to study the smallestpores, Gogotsi says But in powdered samples,their carbon with the 0.6-nanometer poresheld 50% more charge than powders of stan-dard supercapacitors Gogotsi’s group laterteamed up with Patrice Simon, a leadingsupercapacitor expert at the University ofPaul Sabatier in Toulouse, France, whoselab confirmed the results

meas-On a molecular level, it appeared thations must be wiggling into the tiny pores, byeither squeezing their entourage ions or per-haps abandoning them altogether But howthat could happen remains a puzzle, Millersays In normal carbon supercapacitors,ions nestling up to an electrode form a layerabout 1 nanometer thick So if there is lessspace than that in the pores of the new mate-rial, it’s not clear how they can get in “Thatwill be a bit controversial,” Miller says Butboth he and Gogotsi point out that thanks tothe newfound control over pore size,researchers should quickly be able to figureout just what is going on

–ROBERT F SERVICE

New ‘Supercapacitor’ Promises to

Pack More Electrical Punch

NiCd

Li-ionPb-acid

On demand New

super-capacitors store less chargethan batteries but can supply

it more quickly, makingthem ideal for hybrid cars

More Questions for NIH

Despite strict new rules on how researchers atthe National Institutes of Health (NIH) shouldinteract with industry, the issue hasn’t goneaway The latest case, reported last month by

the Los Angeles Times, involves Thomas J.

Walsh of the National Cancer Institute and hisrole in helping companies developing anti-fungal drugs

In a 28 July letter to NIH Director EliasZerhouni, the House Energy and CommerceCommittee asked if there is “a sufficient factualbasis to formally investigate [larger] questionsabout [NIH] policy” raised by Walsh’s conduct.The members requested Walsh’s financialreports and reviews of his paid and unpaid con-sulting and other activities, which include dis-cussing some companies’ products before theFood and Drug Administration NIH officials,

who tell Science that Walsh was already an

“open case,” are preparing a response

–JOCELYN KAISER

Agbio Lab List Pared

Eighteen of 29 applicant sites are still in therunning for a new $450 million high-securityagro-biodefense lab to replace Plum IslandAnimal Disease Center, the aging facility off

Long Island, New York (Science,2 September

2005, p 1475) The Department of HomelandSecurity is funding the National Bio-and Agro-Defense Facility to study animal diseases andpossibly human illnesses It plans to name asecond round of finalists by the end of thisyear and choose a winner in early 2008

–JOCELYN KAISER

Wanted: More Science Students

U.K companies say a failing education systemcould make the country a scientific also-ran

On Monday, the Confederation of BritishIndustry (CBI), the U.K.’s biggest businessgroup, outlined its concerns about the sharpdecline in students studying physics, chem-istry, and maths at A-level, the exams neededfor university entry It faults “a stripped downscience curriculum, a lack of specialist teach-ers, and uninspiring careers advice.” In arelated development, Alan Smithers andPamela Robinson of the University of Buck-ingham last week reported a 50% decline inA-level physics entries since 1982

Calling the scientific workforce “a ity,” Schools Minister Jim Knight points to a

prior-$57 million government scheme that includespay incentives to attract and retain teachersand efforts to build interest among students

–LAURA BLACKBURN

SCIENCESCOPE

In the life of every small star, there comes a

moment of reckoning when it stands on the

edge between burnout and enduring

bril-liance If the star’s mass lies below a certain

value, it runs out of nuclear fuel and begins

to fade into a husk known as a brown dwarf

If its mass exceeds that value, the center of

the star becomes hot enough to achieve a

state of self-sustaining fusion, allowing it to

burn merrily for trillions of years

The critical mass, known as the brown

dwarf limit, has been a fundamental

pre-diction of stellar evolutionary theory Now,

for the first time, researchers have

identi-fied and measured this threshold in reality

On page 936, Harvey Richer of the

Univer-sity of British Columbia in Vancouver,

Canada, and colleagues report the brown

dwarf limit for stars in the nearby NGC 6397

globular cluster (above) and show that it

matches the predicted value of 0.083 times

the sun’s mass The researchers also report

that the cluster’s faintest white dwarfs—

burnt-out remains of massive stars that

grow dim as they cool over time—confirm

another theoretical prediction, that white

dwarfs turn bluer as they age

The team’s observation of the brown

dwarf limit is “of prime importance” in

helping theorists confirm their account of

how stars evolve, says Gilles Chabrier, an

astrophysicist at the École Nor male

Supérieure in Lyons, France And by

identi-fying the coolest white dwarfs in the

popula-tion, Chabrier says, the researchers have

taken “a key step toward determining the

age of the cluster.”

For their study, Richer and his colleagues

trained the Hubble Space Telescope on a

section of NGC 6397 for 5 days at a stretch

“This was a very long exposure, so we couldsee fainter objects than had been seenbefore, even with this instrument,” saysBrad Hansen, an astronomer at the Univer-sity of California, Los Angeles, and aco-author of the paper From a computeranalysis of the images, the researchers wereable to spot stars that were barely alight

Hubble could have detected stars that werefainter still, but the researchers didn’t seeany That convinced them that they hadidentified the smallest stars capable of stablyburning hydrogen in their cores

Using a similar analysis, the researchersidentified the faintest—and hence the cold-est—white dwarfs The observation bearsout a prediction Hansen made in 1998: Asspent stars get cooler, they emit radiation oflonger and longer wavelengths, appearingredder in the process But once a star cools

to below 4000 kelvin, its atmosphere formshydrogen molecules that absorb the redderwavelengths of radiation emanating fromits core As a result, the star’s spectrumshifts from red to blue and gets bluer as thetemperature falls The white dwarfs in thestudy showed exactly that trend “It’s awonderful illustration of quantum physicstaking place in the atmosphere of stars,”

says Chabrier

The white-dwarf results open the door toestablishing the age of the cluster, Hansensays: “It’s like identifying the time of death

of a corpse from the body temperature.” Andbecause the NGC 6397 cluster is one of theoldest in the galaxy—as determined fromthe rarity of metals in its composition—

learning its history would provide valuableinsights into the early formation of the Milky

Nearby Cluster Shows Extremes of Stardom

ASTRONOMY

18 AUGUST 2006 VOL 313 SCIENCE www.sciencemag.org904

Twenty-five years after the first fetal surgery was

performed, doctors and ethicists are trying to learn

whether and when the drastic procedures work—

and whether they’re worth the frightening risks

ON 23 JANUARY 2002, SURGEONS CUT A

30-centimeter incision in Lorie Barber’s

abdomen, peeling away layers of tissue to

reach her 23-week-old fetus Delicately

removing the uterus and slitting it open, the

doctors at Vanderbilt University Medical

Center in Nashville, Tennessee, stitched

closed a gaping hole at the base of the fetus’s

spine That opening was the signature left by

spina bif ida, which can cause paralysis,

hydrocephalus, and other lifelong disabilities

Thirteen days after the surgery, Nicole Eva

Barber was born, more than 3 months early

and weighing in at 1 pound and 10 ounces

(740 grams) Nearly all fetal surgeries, the

Barbers had been warned, carry a risk of

premature birth That hadn’t deterred them

Lorie Barber and her husband had come

to Vanderbilt from their home in Ohio,

desperate and devastated Weeks earlier,

a genetic counselor had discussed the

diag-nosis and presented two options: terminate

the pregnancy or have the baby The Barbers

reached for a third choice they’d learned of

over the Internet: fetal surgery that might

offer their child a better life

But for the Barbers, as for hundreds of other

couples who have endured fetal surgery for a

variety of conditions, there were no guarantees

that the benefits of this treatment would

out-weigh its risks to both mother and fetus

Although roughly a dozen medical centers

worldwide now offer fetal surgery, it remainshighly experimental Few fetal surgeries havebeen tested systematically in clinical trials, andfor those that have, the results are decidedlymixed—suggesting anything from noadvantage to robust benefit

Part of the problem isthat fetal surgeries aremaddeningly difficult toevaluate in clinical tri-als That’s true of surgi-cal interventions gen-erally, and many entermainstream practicewithout rigorous test-ing But as diagnosticimaging advances,making it possible tovisualize still morefetal anomalies poten-tially amenable to sur-gery, a growing number

of physicians and ethicists arecalling for trials to measure fetalsurgery’s worth against standard

p o s t n a t a l c a r e Perhaps more thananything, they fearthat fetal surgeries,once conf ined tothe most dismalcases, are becom-

ing routine before their safety and ness can be rigorously tested

effective-“Oftentimes, these therapies kind of take

on a life of their own,” says TimothyCrombleholme, a pediatric surgeon anddirector of the Fetal Care Center atCincinnati Children’s HospitalMedical Center in Ohio, “and thewindow to evaluate them …goes away.” To keep thatwindow open, fetal surgerycenters banded togetherlast spring to form a clin-ical trials network thatthey hope will speedtesting of various fetaltreatments, before theybecome entrenched

First breaths

Fetal surgery began in

1981 at the University ofCalifornia, San Francisco(UCSF), as a last-ditcheffort to save otherwisedoomed fetuses The hope wasthat by correcting a life-threateningdefect early, surgeons could prevent furtherdamage and save the fetus’s life

The first successful surgery, to repair aurinary obstruction that triggers kidney andlung failure after birth, resulted in a boy born

Hazardous motion In afetus with congenitaldiaphragmatic hernia, thestomach (S) and part ofthe liver (L) have migratedtoward the chest, inhibitinglung development

Desperate

Measures

Twenty-five years after the first fetal surgery was

performed, doctors and ethicists are trying to learn

whether and when the drastic procedures work—

and whether they’re worth the frightening risks

alive who recently celebrated his 25th birthday.

In the hands of UCSF pediatric surgeon

Michael Harrison and his colleagues, rare

conditions considered fatal sometimes

proved no longer so By following the

natu-ral history of certain diseases—in other

words, how babies fared with standard,

postnatal care—the physicians felt they

could gauge fetal surgery’s effectiveness

As word spread about what the UCSF

team was doing, “people would present [us]

with a problem, often in the form

of a patient, and say, ‘Do

some-thing,’ ” says Mitchell Golbus, an

obstetrician and geneticist, now

retired, who helped develop the

UCSF program In this way, the

surgeries gradually spread to

other life-threatening conditions

Among them was twin-twin

transfusion syndrome, an often

fatal circulatory disorder that

strikes twins

Another, congenital

diaphrag-matic hernia (CDH), occurs

when abdominal organs migrate

through a hole in the diaphragm

to the chest in utero, compressing

lung development and leaving

newborns with inadequate lung

capacity The disease afflicts

about 1 in 2500 babies

world-wide, and all require surgery early

in life Intervening during fetal

development, it was thought,

might leave babies with larger,

healthier lungs at birth and thus a

much better chance of survival

When pediatric surgeons f irst

began exploring fetal surgeries

for CDH, about 30% of infants

born with the condition survived

In 1989, after 5 years of failed

attempts in fetuses who died

from the disease, UCSF

per-formed the first successful CDH

fetal surger y, closing the hole in the

diaphragm Although buoyed by their

victo-ries, even the most enthusiastic recognized

that although they might be saving some

very sick fetuses, the early surgeries had

unsettling downsides Some fetuses died

from surgery itself, and others were born

extremely prematurely Moreover, some of

the healthy women who underwent fetal

sur-gery ended up in intensive care, hit

danger-ously hard by side effects from drugs given

to prevent early labor

“You have to make sure you have very goodjustification” for these surgeries, says Golbus,

“because you’re taking a healthy mother andrunning the risk of making her unhealthy.”

With that in mind, Harrison pushed forand led the first-ever clinical trial of fetalsurgery Begun in the early 1990s, the trialwas designed to test so-called open surgeryfor CDH, the surgical approach that LorieBarber endured for spina bif ida In CDHcases, the mother’s womb is opened and thefetus partially removed for the operation

Behind the scenes, the trial was a mare Uneasy about the treatment’s novelty,

night-officials at the National Institutes of Health(NIH), which funded the trial, and UCSF’shuman subjects oversight committee took

2 years to approve it Soon after the trialbegan, it was abruptly halted amid reportsthat women inside and outside the studywho had undergone fetal surgery sufferedpulmonary edema The cause was traced tonitroglycerin, given experimentally to pre-vent early labor The study restarted, finally

ending 8 years after Harrison first proposed

it The randomized trial eventually pared the survival of four fetuses who hadopen surgery with seven who did not

com-Logistics aside, Harrison and colleagueswere convinced going in that CDH surgerywould prove benef icial “We thought forsure the randomized trial couldn’t fail,” saysRussell Jennings, then a fellow with Harrisonand now head of the Advanced Fetal CareCenter at Children’s Hospital Boston Thetruth was less kind In a paper published in

1997 in The Journal of Pediatric Surgery,

Harrison and colleagues reported that survivalrates were 75% in the treated group and 86% inthe control group, a difference that was not

statistically significant, given thesmall numbers involved One baby

in each group died

But around that time, two teamsworking with fetal lambs—one led

by Harrison and the other by JayWilson of Children’s HospitalBoston—found that they couldcorrect the defect by blocking thetrachea This less invasive mechan-ical fix had a dramatic effect, keep-ing fluid pressure in the lungs highand forcing them to grow more rap-idly (The herniated diaphragm,surgeons found, could be repairedafter birth.) “Right after our firstsheep, we said, ‘This is it; we havecured diaphragmatic hernia,’ ”recalls Jennings

A second trial testing this scopic technique, however, metwith disappointment Published in

endo-2003 in The New England Journal

of Medicine, that study found that

8 of 11 treated fetuses survived.But so did 10 of 13 in the controlgroup The treated babies wholived did have larger, healthierlungs, as the sheep studies had pre-dicted, but those benef its wereoften muted by prematurity

Although they didn’t showsurvival advantages from fetalsurgery, the trials did underscorerisks to the fetus and the mother.Both open and endoscopic surgery greatlyboosted the chance of premature birth.Babies in the open-surgery trial were born at

32 weeks, on average, and at 31 weeks in theendoscopic trial, roughly 6 weeks earlier thanbabies in both control groups Since then,other risks have surfaced Roughly 5% to15% of women undergoing endoscopic fetalsurgery experience a rupture in their uterinemembrane, which puts the mother at risk of

NEWSFOCUS

Diagnosis A woman undergoes a high-resolution

ultrasound at the Children’s Hospital of Philadelphia

to help determine whether her fetus could benefit

18 AUGUST 2006 VOL 313 SCIENCE www.sciencemag.org906

infection and may force early delivery of the

baby—a complication that can also strike

subsequent pregnancies The risk is lower,

about 4%, in open surgeries, says Scott Adzick,

who runs the Center for Fetal Diagnosis

and Treatment at the Children’s Hospital

of Philadelphia (CHOP)

Another reason for the confounding

CDH results is that while the trials chugged

along, survival odds were trending upward

for CDH babies given postnatal respiratory

support and surgery At major pediatric centers

such as Children’s Hospital Boston, 95% of

babies with CDH now survive, says Wilson,

although many suffer long-term gastrointestinal

and respiratory complications

At least some surgeons still believe

CDH fetal surgery offers the best hope for a

healthy life A variant on the endoscopic surgery

tested in the second trial is now practiced

regu-larly in Europe More than 90 fetuses have been

operated on so far, says Jan Deprest, a

gynecol-ogist at University Hospital Gasthuisberg

Leuven in Belgium Deprest says that his

tech-nique improves survival by 50%—but in

Europe, say U.S surgeons, CDH survival rates

are lower than in North America (an assertion

Deprest disputes) The surgeries, which focus

on fetuses with the worst prognoses, have

gener-ated controversy, in part given the failure of

other CDH fetal surgeries to show benefit Both

Deprest and Harrison are eager for yet another

trial, to, as Deprest puts it, “have this

discussion finished.”

Regardless, as postnatal medical

care advances, many babies with

CDH and other conditions who

once perished now pull through

But often, they’re left with lingering

disabilities That has physicians

considering fetal surgery’s power to

enhance life’s quality

A better life?

As the CDH trials continued,

fetal surgery was stretching to

accommodate its f irst non–

life-threatening defect, spina

bifida “It really shifted … fetal

treatment into another realm,”

recasting the benefit-risk balance

irrevocably, says Nancy Chescheir,

an obstetrician at Vanderbilt

Spina bifida arises very early in

pregnancy, when the fetus’s spinal

cord fails to close Children with

the disability rarely die from it, but

they often need shunts to drain

fluid from their brains and suffer

mobility, learning, and bladder and

bowel problems

Experiments on fetal lambs in the 1980sand early 1990s suggested that closing thewound in utero could reduce these complica-tions Fetal surgeons believe that sealing theopening may protect the spinal cord fromcontinuing damage, perhaps by preventingexposure to amniotic fluid and normalizingfluid dynamics in the fetus’s brain Physicians

at Vanderbilt proclaimed the first open fetalsurgery for spina bifida in 1997, and hundreds

of families streamed into Nashville

The University of North Carolina, ChapelHill, also offered the surgery Sue Estroff, ananthropologist who chairs the university’smaternal-fetal intervention advisory group,says that families typically came determined

to proceed and weren’t swayed by discussions

of risks and benef its “Our concepts of[informed] consent didn’t fit what we saw,” shesays “People brought ideas about what itmeans to be a good parent.”

One was Lorie Barber She imaginedeschewing the surgery, only to have her childlater grow up to say, “Mom, you knew aboutthis, and it was available back then Why didn’tyou try, why didn’t you go for it?”

Barber was also encouraged by preliminarydata from Vanderbilt suggesting that surgerymight lessen the need for a shunt In a paperpublished 2 years ago (although details wereshared with families earlier as they accrued),Joseph Bruner, who oversaw spina bifida fetal

surgeries at Vanderbilt and now works inTennessee, and his colleagues reported that of

116 fetuses who had the surgery, 54% required

a shunt before 1 year of age The shunt rate forchildren who don’t have fetal surgery has beenestimated at as high as 85%, although it’sthought to be drifting downward as neuro-surgeons shunt more conservatively

Even so, substantial questions about thesurgery’s benefit remained For one, “spinabifida in humans happens at 8 weeks’ gesta-tion,” says Harrison “We cannot work [on afetus] at 8 weeks.” It’s possible that by the timetechnology permits surgeons to operate—atabout 20 weeks—the bulk of the damage hasalready occurred, making the drastic surgerylargely futile At the same time, because babieswith spina bifida have an excellent chance ofsurvival, life-threatening fetal surgery was cre-ating ethically tenuous scenarios At CHOP,says Crombleholme, who trained there beforemoving to Cincinnati, three babies with spinabifida who underwent fetal surgery were born

so prematurely that they died “These are threepatients who would have survived,” he says Many physicians and ethicists became con-vinced that the only way to assess this surgerywas in a clinical trial with a control group Withthat in mind, NIH launched a trial in 2003,based at Vanderbilt, CHOP, and UCSF Origi-nally slated to end next year, the trial randomlyassigns 100 mothers to surgery and 100 more tostandard care Success is measured by survival,the need for a shunt in the baby’s first year, andneurologic function at 30 months

By the time the trial began, physicians hadperformed more than 200 spina bifida fetalsurgeries, and demand showed no signs ofabating To ensure that women would sign upfor the trial, all hospitals halted spina bifidafetal surgeries outside the study

Despite these efforts, recruitment has beensluggish The trial was supposed to have begun

a full year ago, but so far just 99 women havesigned on Explanations include a reluctance

to be randomly assigned to either fetal surgery

or a control group and a mother’s ness to remain at the surgical center until birth,

unwilling-as the trial mandates But one thing is apparent:Continuing to recruit at this pace, “we’re up to

a 10-year trial,” double the time anticipated,says Chescheir So far, NIH has alloted morethan $14 million to it

Some surgeons quietly question whetherspina bifida fetal surgery will survive “Thesurgery itself is dying a slow death because ofthe length of the trial,” says Bruner Unlike adrug, “surgery is a living, evolving entity,” hesays Doing a trial means “you have to freeze it

in time,” halting the subtle enhancementssurgeons routinely make Safer, endoscopic

Riding high Born 3 months early after spina bifida fetal surgery,4-year-old Nicole Barber has few spina bifida symptoms—

but it’s difficult to know whether the experimental proceduremade a difference

approaches have not yet been effective at

repairing spina bifida lesions, for example As

a result, in Europe, where open fetal surgeries

are considered too aggressive to the mother,

the procedure is not offered

The heart of the matter

Some physicians are converging instead on

another new frontier: fetal heart surgery In the

operating suites at Children’s Hospital Boston,

doctors now regularly perform procedures on

fetuses with heart defects, 77 and counting

since 2000 Although Boston is the only center

in the world to have done more than a handful

of these surgeries, says Wayne Tworetzky, a

cardiologist there, other centers are

consider-ing whether to follow suit Heart defects are

ideal candidates for fetal surgery, Tworetzky

and others say High-tech fetal imaging has

made diagnosis easier, and heart defects are a

common and serious scourge in babies The

surgery to address them involves inserting a

needle into the mother’s abdomen and guiding

it via ultrasound into the fetus’s heart

But as with other fetal surgeries, the cardiac

procedures are raising difficult questions of

their own—in particular, whether cardiologists

understand enough about the defects they’re

trying to fix in utero Nor is it clear that they

can identify the fetuses most likely to benefit

Take hypoplastic left heart syndrome

(HLHS), the defect that the Boston team most

commonly targets Babies with HLHS are

born lacking a functioning left ventricle,

which leaves them with “only one pumping

chamber,” says Tworetzky Soon after birth, the

infants turn ashen and struggle to breathe and

feed normally HLHS is not curable, and

although most children can be treated with a

series of operations or a heart transplant, their

long-term prognosis is still shaky

Strategies to fix HLHS in utero, however,

are complicated by questions about what’s

driving the disease In some babies, HLHS

seems to begin with a problem that is forward enough to fix: a blocked heart valve

straight-Sophisticated tests on a pregnant woman candetermine whether her fetus has this blockedvalve The surgery targets this obstruction inthe hope that clearing it gives the left ventricletime to develop

However, although a blocked valve is tainly associated with the heart defect, it’snot yet clear that it’s the key culprit Fixing it,then, might be less likely to help than itwould be if the blocked valve were causative

cer-“It’s possible that these lesions which weconsider primary … could be secondary,[and] relieving those would not necessarilyimprove muscle growth,” says Abraham

Rudolph, a former chief of pediatric ogy at UCSF who spent decades studyingfetal circulation

cardiol-And there’s a second catch Only a subset

of fetuses with the blocked valve developHLHS Others are born with just the blockage,which can be corrected postnatally Physi-cians at Children’s Hospital Boston such asTworetzky and cardiologist James Lock havedone a number of studies to try to identifywhich fetuses with blocked heart valves go on

to develop HLHS, because the risks of fetalsurgery cannot currently be justified for theothers “We have strict criteria; you have tohave this and this and not that,” says Tworetzky

In March, he and his colleagues published a

paper in Circulation suggesting that certain

types of blood flow in fetal hearts can predictHLHS—and thus which mothers and theirfetuses are best suited for surgery

But other hospitals are hanging back

“There’s logic to it, it makes sense, but it hasn’tbeen rigorously tested,” says Jack Rychik, thehead of CHOP’s Fetal Heart Center, of thework in Boston Last month, CHOP per-formed its first fetal heart procedure—but thatfetus had multiple heart defects and an espe-cially poor prognosis Rychik wants firmerguarantees that he can pick the right mothersand fetuses for surgery and for now is not com-fortable operating on all the same classes ofwomen and fetuses treated in Boston

Instead, Rychik is working to bringtogether eight centers, including Boston, tocreate a registry of fetuses with various heartdefects who would be followed until birth

“The Boston experience has given us a kick inthe pants” to examine the natural history ofHLHS and other defects before fetal heart sur-gery becomes routine, says Rychik, who addsthat the therapy may soon merit a clinical trial

In April, 17 centers in North America launchedthe North American Fetal Therapy Network tocreate a single voice to advocate for and helpdevelop fetal treatment trials It hopes itsendorsement of certain trial proposals willencourage NIH and other funders to supply themillions of dollars these studies can cost

Rychik and others are treading cautiously

in part because families seek fetal surgerywherever possible Even the Barbers, whosedaughter spent 6 weeks on a ventilator and

103 days in a neonatal intensive care unit, saythe price of surgery was worth it Now 4 yearsold, Nicole’s moderate hydrocephalus hasnot required a shunt She’s a strong-willed,talkative little girl who walks unassisted,attends a typical preschool, and enjoys bring-ing in the mail Her mother has no regrets

–JENNIFER COUZIN

NEWSFOCUS

Fetal Surgery Trials

(women)

Congenital UCSF Open surgery 11 Published in 1997,Diaphragmatic Hernia no survival benefitCongenital UCSF Endoscopic 24 Published in 2003,Diaphragmatic Hernia no survival benefitTwin-Twin Hospitals in France, Endoscopic 142 Published in 2004,Transfusion Syndrome Belgium, and the U.S fetal surgery helped survivalTwin-Twin *Children‘s Hospital Endoscopic 42 Halted early afterTransfusion Syndrome Medical Center, European trial

CincinnatiSpina Bifida UCSF, Vanderbilt, Open surgery 200 Still recruiting

CHOP

* Trial began at CHOP.

“Oftentimes, these therapies kind of take on a life of their own , and the window to evaluate them … goes away.”

—Timothy Crombleholme, Cincinnati Children’s Hospital Medical Center

18 AUGUST 2006 VOL 313 SCIENCE www.sciencemag.org908

Airman C couldn’t shake the image of the

young Iraqi boy Days earlier, a car bomb

went off as his convoy drove down a busy city

street, injuring three fellow soldiers and

killing perhaps 10 Iraqi civilians The boy sat

at the edge of a street near a light pole The

explosion had torn off the right side of his jaw

and opened his neck, exposing his esophagus

He reached up to Airman C, as if to ask for

help, and called out “American, American,

American.” But the word had just come in

that the convoy was in danger of a second

attack, and Airman C had to move on

After the attack, the image of the boy kept

replaying in Airman C’s mind throughout the

day and at night, in frequent nightmares,

says Alan Peterson, a clinical psychologist

who treated the 22-year-old airman in the

field for symptoms of posttraumatic stress

disorder (PTSD)

Peterson, who served with the U.S Air

Force as the chief psychologist at Balad

Air-base near Baghdad until January 2005, knows

f irsthand how the tremendous stress and

horrific situations faced by the troops can

affect their mental health And increasingly,

he and others say, U.S military leaders are

showing a much greater willingness to

acknowledge—and address—these problems

than in the past More psychologists and other

mental health professionals have, like Peterson,

been deployed to the frontlines of Iraq and

Afghanistan The Department of Defense(DOD) has instituted a universal screeningprogram to monitor the health, including themental health, of troops returning from com-bat And several innovative programs aim toease their transition to civilian life

Although it’s too early to gauge the tiveness of these interventions—and thescreening program, in particular, has its detrac-tors—many observers see them as a welcomesign of progress “The leadership has taken avery proactive stance toward mental healthissues,” says Charles Hoge, a psychiatrist at

effec-Walter Reed Army Medical Center in ington, D.C “We’re well aware this time thatthere’s an expected psychological cost of war.”

Wash-Lingering effects

War has always taken a toll on soldiers’ ches After the Vietnam War, the chronic diffi-culties suffered by many returning troops—

psy-including flashbacks, nightmares, and ings of detachment—inspired a new psychi-atric diagnosis, PTSD, which off iciallyentered the psychiatric lexicon in 1980 as an

feel-entry in the Diagnostic and Statistical Manual

of Mental Disorders, third edition From the

start, however, gauging the prevalence ofPTSD in combat veterans has been difficultand controversial

A study of Vietnam vets by the Centers forDisease Control and Prevention in Atlanta,

Georgia, in 1988 put the prevalence of PTSD at15% But a short time later, the National Viet-nam Veterans Readjustment Study (NVVRS),commissioned by Congress, doubled that esti-mate—concluding that 31% of Vietnam vetshad suffered from PTSD at some point in theirlives Many researchers suspected that theNVVRS number was too high: Critics pointedout that the proportion of vets who’d sufferedPTSD was twice the proportion who’d served

in combat roles A reanalysis of the NVVRS,which attempts to exclude vets whose symp-toms weren’t severe enough to interfere withdaily living, now puts the figure at about19% (see Report on p 979 and Perspective on

p 923) But even that figure translates to morethan 500,000 cases among Vietnam vets Experts say it’s impossible to know howmany of the troops serving in Iraq orAfghanistan will develop PTSD or other com-bat-related mental problems, but preliminarydata hint at a prevalence similar to the new fig-ure for Vietnam Soldiers in all three conflictshave faced similar stressors: a constant threat ofambush, a high casualty rate among both sol-diers and civilians, and a difficulty distinguish-ing friend from foe More frequent and moreintense combat experiences raise the risk ofPTSD, and there is no shortage of these, espe-

cially in Iraq In the 1 July 2004 issue of The

New England Journal of Medicine (NEJM),

Hoge and colleagues reported that among

894 members of an Army combat unit that hadrecently returned from Iraq, 89% reportedbeing attacked or ambushed, and 95% reportedseeing dead bodies or human remains

This NEJM paper also provided one of the

first looks at how soldiers are holding upunder such conditions In an anonymous sur-vey, 17% of members of the same Army unitreported symptoms of PTSD, generalizedanxiety, or depression The researchers found

a somewhat lower prevalence of such toms, about 11%, in 1962 soldiers deployed toAfghanistan, presumably reflecting theirlower levels of reported combat experience

symp-A second study by Hoge and colleagues,based on an abbreviated sur vey but amuch larger sample of 238,938 Army andMarine personnel returning from Iraq andAfghanistan, produced similar findings In

the 1 March 2006 issue of The Journal of the

American Medical Association (JAMA), they

reported that 19% of those serving in Iraqand 11% of those serving in Afghanistanreported symptoms of PTSD or other mentalhealth problems (see table, p 909)

Although the figure for Iraq troops seemssimilar on the surface to the new figure forVietnam, there’s no way to make a definitivecomparison, says Bruce Dohrenwend, a psy-

Widening the Attack on

Combat-Related Mental Health Problems

The lessons of Vietnam have prompted U.S military leaders to do more to protect the

mental health of troops in Iraq and Afghanistan But will these efforts be effective?

MENTAL HEALTH

Stressful job The constant threat of car bombs and other attacks can take a toll on troops’ mental health

chiatric epidemiologist at

Colum-bia University who led the new

reevaluation of the NVVRS

Whereas the raw data for

NVVRS was collected in

one-on-one clinical interviews lasting an

hour or more, the data in Hoge’s

studies come from soldiers

tick-ing off symptoms on a

question-naire “I don’t know how

symp-tom scales compare to a rigorous

diagnosis by a trained clinician,”

Dohrenwend says

Concerns about the reliability

of using surveys to detect mental

problems have led some experts to

question the effectiveness of

DOD’s new postdeployment health

assessment program, instituted at

the onset of the Iraq War Every

service member must now

com-plete a three-page questionnaire

that includes about a half-page of

questions on mental health, either

immediately before or within

2 weeks of returning home Those

who screen positive for a mental

health problem get a follow-up

interview with a clinician The goal

is to catch soldiers who need help

early on, says Hoge, and get them

treatment before their symptoms develop into a

full-blown disorder or become compounded by

family, alcohol, or drug problems, as happened

to many soldiers after Vietnam The 2006

JAMA paper was the first report based on data

collected by the health assessment program

DOD recently announced plans to repeat the

assessment at 3 and 6 months postdeployment

That’s a good idea, Hoge and others say,

because little is known about the time course of

PTSD and because some problems might be

masked by soldiers’ initial euphoria over

returning home

But Simon Wessely, a psychiatrist at Kings

College London and civilian adviser to the

British Army, dismisses the DOD screening

effort as scientifically unfounded and a likely

waste of resources The main problem, he and

others say, is that such surveys haven’t proven

effective at predicting which individuals will

need mental health help On one hand, the

screen may tend to exaggerate problems by

only tallying symptoms, says Richard

McNally, a psychologist at Harvard

Univer-sity It’s possible to have a couple of symptoms

of PTSD but not a full-blown disorder that

requires intervention, he says: “Almost

every-body is changed by the experience of fighting

in a war You have to draw a distinction

between normal human emotions that are

evoked by a horrible experience and things thatimpair daily life.” The follow-up interviewsshould help cut down on false positives, how-ever, McNally says

A greater concern, in his view, is that thesurvey may fail to identify some veterans whoneed assistance Peterson agrees “The word onthe street is, ‘Don’t tell them you have symp-toms, or you’ll have to see a shrink,’ ” he says

Soldiers who take the survey before returningstateside are often tempted to hide symptoms toavoid delaying their return, and worries aboutthe confidentiality are also widespread, Peter-son says Many soldiers may not check the boxbecause they fear negative ramifications on

their careers The recent JAMA paper seems to

bolster concerns that the screening isn’t veryaccurate at identifying individuals who needhelp Hoge’s team found, for example, thatfewer than 8% of servicemen seeking mentalhealth care in the first year after their return hadbeen referred by the screening program, sug-gesting that the vast majority of those whosought help weren’t flagged by the program Atthe same time, fewer than 20% of those who didreport mental health concerns on the surveywere referred to a mental health professionalfor further evaluation In a May 2006 report, theU.S Government Accountability Office chas-tised DOD for failing to get veterans mental

health care when they need it “Thedrive to do widespread screening is

a laudable ambition, but it’s drivenlargely by politics and the desire to

be seen to be doing something andnot by any evidence I’ve seen thatit’s doing any good,” says Wessely

In their own terms

Wessely says he’s advised the U.K.government that money and effortwould be better spent on expand-ing mental health services andmaking them more amenable toveterans than on screening Hecites a U.S DOD program calledBattlemind, started by Hoge, as “apromising way forward.” In pre-sentations to returning combatunits and in videos and other mate-rials available online for soldiersand their families, Battlemindexplains how the combat-zonemindset can lead to problems athome For example, in a combatzone, constant awareness of thesurroundings is crucial for sur-vival But once soldiers returnhome, such heightened attentioncan leave them anxious and easilystartled—a PTSD symptom calledhypervigilance The program appeals to sol-diers because it uses language they understandand steers clear of mental health jargon, saysHoge: “We don’t talk about hypervigilance; wetalk about tactical awareness.”

Meanwhile, Peterson, who has retired fromthe military and is now at the University ofTexas Health Science Center in San Antonio,

is developing a training program for Air Forcemental health providers to teach them how totreat PTSD symptoms in the field Airman C’ssymptoms were severe, and in previous con-flicts, he would likely have been evacuated.But Peterson used a type of exposure therapywith him that has also proven useful with civil-ian rape and accident victims In four sessionsover the course of several weeks, Airman Ctalked through his ordeal in excruciating detailwith Peterson, who made an audiotape of thesession and asked him to listen to it at leastonce in the coming week It’s a painful process,but it helps desensitize people to the traumaticevent, Peterson says With time, Airman C’ssymptoms dissipated, and he began to feelmore like himself, Peterson reported in a casestudy published last year He now has fundingfrom DOD to evaluate the therapy in a largertrial “We think part of the key is early inter-vention,” he says

–GREG MILLER

NEWSFOCUS

Screened positive for PTSD 9.8% 4.7%

Screened positive for any 19.1% 11.3%

mental health concern Visited mental health clinic 34.6% 21.5%

within first year home Diagnosed with mental disorder 11.9% 9.7%

within first year home

18 AUGUST 2006 VOL 313 SCIENCE www.sciencemag.org910

CAPE TOWN, SOUTH AFRICA—One site is a

barren tract of South Africa’s Karoo

semi-desert, so quiet that the only sound is a hawk’s

cry Another, 12,000 kilometers away, is an

arid plain that stretches to western Australia’s

horizon Yet another site is across the Pacific

Ocean, in Argentina’s high, dry plateaus; the

fourth is nestled in natural bowls between the

angular karst hills of southeastern China

The challenge for a select group of radio

astronomers this summer is to recommend

which site would potentially make a suitable

home for the largest astronomical instrument

ever built: the International Square Kilometer

Array (SKA) Planned as a network of some

4000 radio dishes spread over an area several

thousand kilometers across, SKA—whose

name refers to the total collecting area of the

planned instruments—will be 100 times as

sensitive as today’s best radio telescopes In

choosing which locations will work, SKA’s

international steering committee is lookingfor a stable ionosphere, predictable weather,and good infrastructure But radio silence,perhaps above all else, is golden, as is the hostgovernment’s ability to maintain it

At a meeting in Germany at the end ofthis month, the committee is to whittledown, on scientific and technical grounds,the current four to a short list of acceptableSKA sites Then begins the delicate politicaldance of persuading funders to bankroll itand agreeing on the final site

With a price tag likely to be at least $1 lion, the SKA collaboration is treading care-fully The project has already been workingfor more than a decade; a reference design forthe telescope was completed only this year,and the array itself is unlikely to be finishedbefore 2020 But the team doesn’t want toforce the pace and fall into the traps that havebeset other recent international collaborations

bil-such as the International Thermonuclear

Experimental Reactor (Science, 1 July 2005,

p 28) and the Atacama Large MillimeterArray (ALMA), a telescope under construc-

tion in Chile (Science, 19 May, p 990).

From the start, SKA has been a grassrootsproject, and with scientists at more than

50 institutes in 17 countries involved, there is

a strong emphasis on collaboration Bo Peng

of China’s National Astronomical ries in Beijing says that SKA “has been a verysuccessful international project for a decade,

Observato-on the basis of cooperatiObservato-on, not so much petition for SKA science, technology, andeven site ranking.”

com-In the competing regions, the site tion has energized radio astronomy andengineering with new instruments, moregovernment backing, and scientif ic net-working “It is having a tremendous focus-ing impact on scientists,” says Netherlands-based astronomer Richard Schilizzi, director

selec-of the SKA project

“The collaboration is fantastic,” agreesAustralia’s SKA planning office chief, astro-physicist Michelle Storey, “not only withinAustralia’s radio community but also amongastronomers from all the countries involved inthe SKA.” Astronomer Justin Jonas, SouthAfrica’s SKA project scientist, foresees “atremendous boost to astronomy and to science

in general in southern Africa.” Jin Chengjin ofthe National Astronomical Observatories sayshis nation’s radio-astronomy community isbeing opened up by the SKA effort because

“the competition helps us in communicatingwith international astronomical and techno-logical communities.” Ricardo Morras of theArgentine Radio Astronomy Institute sayswinning the SKA site would be “a majorbreakthrough in the history of radio astron-omy in Latin America.”

Probing dark matter and energy

SKA’s main aim is to search for faint radiosignals from the most distant reaches of theuniverse, helping scientists examine clues towhat existed before the first stars were bornand to probe the nature of dark matter anddark energy

Candidate Sites for World’s Largest

Telescope Face First Big Hurdle

For more than a decade, the Square Kilometer Array has been a paper project, an

instrument for astronomers to dream about Now it’s time to start getting real

RADIO ASTRONOMY

Karoo contender The four sites

competing for the SKA’s core include

this stretch of the Karoo semidesert in

South Africa

What a dish China’s proposed SKA site lies in a lush valley surrounded by karst hills Proponents say natural

depressions there are ideal for building fixed dish antennas

George Miley of Leiden University in the

Netherlands says the instrument has the

potential to be “a giant step forward for radio

astronomy.” By exploiting new technologies

such as steering the observing direction

elec-tronically instead of by moving the dish,

unprecedented supercomputing power, and

multibeaming—observing several regions of

the sky simultaneously—SKA will attain

orders-of-magnitude improvement in

fre-quency resolution and the area of sky that can

be observed at any given time

Astronomer James Cordes of Cornell

Uni-versity, head of the U.S SKA team, agrees

that the telescope “will be a fantastic

discov-ery instrument.” Schilizzi points out that

“radio astronomy over the years has resulted

in many unexpected discoveries, from the

cos-mic cos-microwave background to pulsars to

quasars to dark matter in galaxies.” By

peer-ing into the early universe, SKA “will give us

a handle on the effects of dark energy and its

evolution as the universe expands,” he adds

Miley says data from SKA would help

sci-entists study astrophysical phenomena that

are impossible to probe using optical

tele-scopes or millimeter arrays such as ALMA

Examples include neutral hydrogen, a

diag-nostic of the early universe in an era before the

first galaxies formed, and synchrotron

emis-sion, radiation given off when electrons are

accelerated—a unique probe of magnetic

fields throughout the universe

Site competition, science cooperation

But there is much still to do before

observa-tions can begin Off icials of the four

national site planning off ices have been

competing hotly behind the scenes On

4 July, a parade of these officials presented

their proposals separately at a meeting in

Cambridge, U.K

The Australians argue that their core site

in Mileura and their proposed remote sites

have the lowest radio frequency interference

(RFI) and that all are located in Australia,

with the option of extra stations in New

Zealand Australia has a “very strong

tradi-tion in radio astronomy,” Storey says, and

several of its leading universities already

are intensely involved in SKA research

and development

The South Africans contend that their site,

northwest of the town of Carnarvon in the arid

Karoo region, offers “very good radio-quiet

status, excellent ionospheric and tropospheric

conditions, strong government support and

infrastructure,” says former astronomer

Bernie Fanaroff, South Africa’s SKA chief

Remote array stations would be located in

seven other African countries, bolstering

astronomy and engineering across the ern part of the continent

south-The Chinese say their bid is strongbecause of the site’s relatively quiet electro-magnetic environment and because the karstdepressions offer the possibility of building asmaller number of huge static dishes, which

would “ease the correlation process and help

in calibrating the network effectively,” Jinsays He adds that the valleys offer “goodlocal shielding against radio interferencefrom outside.”

The Argentineans maintain that their site, in

a high, arid plain about 1100 kilometers west of

NEWSFOCUS

From KAT to FAST, Telescope Project Sprouts Test Beds

High-tech radio-astronomy dishes are popping up in several remote areas of the world as strators for the International Square Kilometer Array (SKA) Although each will be only a tiny fraction

demon-of the size demon-of the planned SKA, the instruments will be capable demon-of conducting cutting-edge science.Scientists in three of the candidate countries—Australia, China, and South Africa—have persuadedtheir governments to back the design and initial construction of prototype projects that are roughly1% of SKA’s dish area or smaller but that would demonstrate key technologies near the same coresites that are proposed for SKA itself

Australia’s Extended New Technology Demonstrator (xNTD) is planned as a full-system type, making use of an innovative phased focal-plane array, a detector made of a patchwork ofantenna elements that can steer its field of view electronically The demonstrator, operating overthe frequency range of 0.8 to 1.8 gigahertz, will be built at the Mileura site, with completiontargeted for 2009 Others are in the works too: the SKA Molonglo Prototype from the University of

proto-Sydney for low-frequency radio astronomy,and the Mileura Widefield Array–Low Fre-quency Demonstrator, built in partnershipwith the Massachusetts Institute of Technol-ogy’s Haystack Observatory

Meanwhile, South Africa’s planned KarooArray Telescope (KAT) is expected to have

20 dishes, each 15 meters in diameter, withinnovative "smart" feeds in the focal plane.The South African government has committedthe equivalent of about $50 million so far,and the prototype dish will be ready next year,with first light in 2009

China's planned demonstrator ment, the 500-meter-diameter ApertureSpherical Radio Telescope (FAST), would have

instru-a cinstru-able-supported reflector minstru-ade up of

1800 hexagons—the world’s largest singledish Built in one of the karst depressions inGuizhou Province that are envisioned to bepart of SKA, FAST “may be seen as a fore-runner or prototype of the Chinese SKAconcept,” says Jin Chengjin of the NationalAstronomical Observatories in Beijing

Although FAST is a somewhat differentdesign, astrophysicist Michelle Storey, head ofAustralia’s SKA planning office, says KAT and xNTD “are similar in many ways.” That’s a reason to becautious, says Renee C Kraan-Korteweg, who heads the University of Cape Town’s astronomy depart-ment It is important for the SKA competitors to make sure their demonstrator instruments and sci-entific goals complement one another "Both the KAT and xNTD are interesting scientific instruments.But we need to communicate and avoid doing the same things," Kraan-Korteweg says

No matter where SKA itself is eventually located, director Richard Schilizzi says, “all of these ects will generate great science, and technically they are taking innovative approaches, for example

proj-in terms of utilizproj-ing focal-plane arrays.” They are also fosterproj-ing a sense of community, says Korteweg: "There is competition at one level, but there also is a great deal of collaboration, especiallywith the Australians and the groups at ASTRON [in the Netherlands] and in England The Australianand South African groups have been sharing information in a cooperative way." –R.K.

Kraan-Aussie array Artist’s drawing shows part of thearray of dishes planned for Australia’s ExtendedNew Technology Demonstrator (xNTD)

18 AUGUST 2006 VOL 313 SCIENCE www.sciencemag.org912

NEWSFOCUS

Buenos Aires, offers the best combination of

key factors Morras says the proximity of

exist-ing or planned “frontline 21st century

astro-nomical facilities,” such as ALMA, the

Euro-pean Southern Observatory’s Very Large

Tele-scope, and the Magellan 6-meter telescopes, all

sited in Chile, “will allow simultaneous

obser-vations with a great number of telescopes

oper-ating on a wide range of different frequencies.”

Each site also has its drawbacks Some

astronomers wor ry that the ionosphere

above the proposed Argentine location is

less stable than that over the others Morras

concedes that “there are signal

fluctua-tions, known as ionospheric scintillation, in

that region.” But he says the Argentinean

site’s core “is near the southern limit” of the

scintillation phenomenon

The China site, meanwhile, is in the

North-ern Hemisphere, which would limit SKA’s

ability to observe our Milky Way galaxy,

whose center is visible in the Southern

Hemi-sphere Another possible disadvantage, Jin

concedes, is that the site’s humid climate “is

not suitable for observations at frequencies

higher than 10 gigahertz.”

Regional politics may also become an

issue South Africa’s roping in of Namibia,

Botswana, Mozambique, Kenya,

Mada-gascar, Ghana, and Mauritius has the

advantage of boosting the bid’s political

clout but could also increase the risk that

politics or economic problems might affect

the remote stations The Australian site,

meanwhile, does not share any part of the

sky with Europe and may involve higherconstruction costs

In an effort to keep down levels of RFI fromhumanmade sources such as cell phones, TVtransmitters, car ignitions, and power lines, Aus-tralia, South Africa, and Argentina are establish-ing “radio-astronomy reserves” around theircandidate sites Proximity to major cities could

be another big RFI headache; one analysis gests that the SKA core site would need to be atleast 500 kilometers away from major urban cen-ters This could be another problem for theArgentinean site, which has two cities locatedabout 100 kilometers away

sug-Power and money

Although the details of the final design cannot

be fixed until the site is known, SKA will

likely include a network of 4000 or more smalldishes (each about 10 meters in diameter)operating at frequencies from 1 to 25 GHz andaperture arrays (flat collections of detectors,looking a bit like solar panels, that can seemany parts of the sky at once) operating from

100 MHz to 1 GHz, all connected together in agiant interferometer Half of the total collectingarea will be concentrated in the 5-kilometer-wide core, with the rest spread over severalthousand kilometers

SKA’s current timeline calls for systemdesign to begin in 2008—by which time thefinal site should have been chosen—and forconstruction to start on the first 10% of thecollecting area in 2011 SKA would start col-

lecting data in 2014 and would be fully tional by 2020 That scope and scheduledepends on funding So far, the largest contri-butions in the current Pathfinder phase have

national funding agencies) and from in-kindR&D contributions from South Africa andAustralia related to their demonstrator proj-ects (see sidebar, p 911)

The biggest funding question mark is theU.S National Science Foundation (NSF),which so far has avoided making a firm com-mitment “We foresee that this will be anissue for the next Decade Survey, which islikely to start in about a year from now,” saysthe director of NSF’s astronomical sciencesdivision, Wayne Van Citters He adds that,given NSF’s commitment to completeALMA and other major projects “that aremore advanced in planning” than is SKA,

“we are realistically quite a few years awayfrom any consideration of a constructionproject of this magnitude.”

Over the past 4 years, NSF has providedabout $1.8 million for SKA “technologydevelopment” in grants to Cordes’s team atCornell The U.S SKA team has also beenkept busy with university funding and moneyfrom the likes of Microsoft Corp co-founderPaul Allen Allen has part-funded the AllenTelescope Array (ATA), formerly called theOne Hectare Telescope, a joint effort by theSETI Institute and the University of Califor-nia, Berkeley The ATA project has involveddeveloping many components relevant toSKA, such as relatively inexpensive anten-nas and mounts, broadband feeds, andsome signal-processing hardware.Schilizzi says the American work on theAllen instrument “will be of crucialimportance to the technology of the SKA.”NSF’s initial reluctance to commit largesums to SKA was a major reason why theU.S SKA consortium opted last year not tosubmit a site proposal, Cordes says ButSchilizzi says he is “still hopeful” that NSFeventually will allocate substantial money tothe project “It may be that funding will come

in a phased way, with one region dominatingthe early funding and another region con-tributing more later,” he says

Such staggered funding would not be atodds with the slow but steady approach thatSKA researchers have adopted Despite theuncertainties, team members remain confi-dent Miley says that funding for large tele-scopes always seems to be up in the air: “In myview, the question is not whether SKA will be

funded but rather when this will occur.”

–ROBERT KOENIG

Big sky country Artist’s drawing (above) shows possible dish

array at SKA core site on a high, arid plain (right) near the

Andes Mountains in Argentina

CREDITS (TOP TO BOTTOM): JULIAN VOSS-ANDREAE; NA

NEWSMAKERS

EDITED BY YUDHIJIT BHATTACHARJEE

DUAL NATURE A wave-particle duality runs through Julian Voss-Andreae’slife He was a budding painter before opting for a graduate program inphysics at the University of Vienna in Austria But before long, Voss-Andreae’s artistic nature reasserted itself Since graduating 2 years ago fromthe Pacific Northwest College of Art in Portland,

Oregon, Voss-Andreae has focused on abstract sculptures of bin and other proteins “My interest is really nature,” he says “One way

hemoglo-to explore it is through science Another is through intuitive sense and asearch for metaphors.”

His latest sculpture, titled Quantum Man, will be unveiled next

month in Moses Lake, Washington The 2.5-meter sculpture is made of

115 thin steel slabs connected and spaced apart by 1000 short steel rods

Seen from the front, the figure looks dark and solid But from the sidethe quantum walker nearly disappears, as light shines through the spacesbetween the slabs “It shows that when you look at things from a different perspective, theycan look extremely different,” says Anton Zeilinger, a physicist at the University of Viennaand Voss-Andreae’s former group leader “That’s part of the quantum message.”

Two Cultures

O N C A M P U S

TERRORIZED A failed attempt to bomb the

home of a colleague was apparently the last

straw for Dario Ringach, a primate

neurobiolo-gist at the University of California, Los Angeles

(UCLA) “You win,” he wrote earlier this month

in an e-mail to several animal-rights groups

that says he plans to stop doing animal

research immediately “Please don’t bother my

family any more.”

Marie-Francois Chesselet, chair of the

school’s neurobiology department, says

Ringach was shaken by a recent attempted

bomb attack on the home of another UCLA

researcher (Science, 28 July, p 437) Ringach

continued his work on visual object

recogni-tion in monkeys even after animal-rights

activists had previously vandalized and

staged demonstrations at Ringach’s home,

frightening his children, Chesselet says But

when the FBI told him the explosive could

have blown up a house, Ringach decided to

remove his family from the line of fire “It

was his responsibility to do whatever it took

to protect them,” Chesselet says

Got a tip for this page? E-mail people@aaas.org

Some of Ringach’s colleagues haveexpressed surprise at his decision to abandonhis monkey research “Everyone is concernedthat his gesture will empower the activists,”

says Chesselet “Of course it will But heshouldn’t be blamed for that.”

I N T H E C O U R T S

JUSTICE, IN SECRET A Russian scientist hasreceived a 6-year suspended prison sentencefor selling dual-use technology to a SouthKorean company Oskar Kaibyshev, 66, whodirected the Institute for Metals

Superplasticity Problems in Ufa until he wasfired by the institution last year, has also beenbanned from holding positions of authorityfor 3 years and fined $131,000

During a closed-door trial last week in aBashkortostan court, prosecutors argued thatthe technology that Kaibyshev sold to a sub-sidiary of the Hankook Tire Manufacturing Co

in South Korea could also be used to produceweapons Kaibyshev plans to appeal the sen-tence Prosecutors, who argued for a 10-yearprison term, are also considering an appeal

Pioneers >>

“How could it be that the Romans built aqueducts 2000 years ago

that are still standing today while the ceiling on the Big Dig tunnel

came down in 2 years?”*

—Bernard Gordon, an electrical engineer and founder of Analogic Corp., citing last

month’s collapse of concrete panels in the recently completed $15 billion Boston

tun-nel project as a sign that the United States was losing its engineering prowess To stem

the decline, Gordon last week gifted $40 million to support engineering education

and research at Boston’s Museum of Science and Northeastern University

* Source: The Boston Globe

They Said It

ANCIENT MARINER Few people know muchabout Zheng He, an accomplished Chinese sea-farer who led major voyages in the early 15th cen-tury Jin Wu, an ocean scientist and former educa-tion minister in Taiwan, hopes to change that—and drum up interest in science in the process

Wu, who studied antisubmarine warfare for aU.S defense contractor before spending 20 years

at the University of Delaware, was inspired to learnmore about He from a Taiwanese documentary thatreferred to his seven expeditions, with 200 shipsand 28,000 men

The historical record is sparse because theMing Dynasty decided to destroy the ships andcancel ocean exploration But last month, Wubegan a 4-month fellowship at the Library ofCongress in Washington, D.C., to study questionssuch as whether the wooden boats were really

144 meters long and how the fleet supported acrew of 28,000 Wu also hopes China will rebuildone of He’s vessels Wu has already organizedZheng He societies in six U.S cities, and he says arecent bout with cancer won’t prevent him fromsailing full steam ahead on the project

Response

OUR LETTER USED THREE ASIAN

HERPETO-logical examples to illustrate the point that

publishing scientific descriptions of new

species may inadvertently facilitate their

over-exploitation by advertising “novelties” to

hob-byists and providing detailed locality

informa-tion to commercial collectors Kratochvíl

cor-rectly notes that one of our examples, the

gecko Goniurosaurus luii, was already being

heavily harvested in China for sale in the

inter-national pet trade (1, 2) prior to its description

as a new species (1) However, immediately

after being described, its value in the U.S pet

trade jumped from approximately $500 under

an older name to approximately $1500 under

its new name as a result of increased demand

from hobbyists seeking a unique addition to

their collections (the $2000 quote in our

Letter referred to a second reptile example,

Chelodina mccordi, provided in the same

sen-tence) Thus, we feel that G luii remains an

appropriate example of how scientificallydescribing a new species can unintentionally

fuel its commercial exploitation (3) It is nate for G luii that demand for wild-caught

fortu-individuals has now diminished, owing to theavailability of inexpensive, captive-born indi-viduals produced by hobbyists The conserva-tion merits of unregulated, private, captivebreeding programs are beyond the scope of

our Letter, but it does seem that G luii paid a

high cost for the end result of inexpensive,captive-born substitutes in the pet trade

BRYAN L STUART1,2AND

L LEE GRISMER3

1 Department of Zoology, The Field Museum, 1400 South Lake Shore Drive, Chicago, IL 60605–2496, USA 2 Department of Biological Sciences, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607–7060, USA.

3 Department of Biology, La Sierra University, 4500 Riverwalk Parkway, Riverside, CA 92515, USA.

References

1 L L Grismer, B E Viets, L J Boyle, J Herpetol 33, 382

(1999).

2 H Ota, M Honda, M Kobayashi, S Sengoku,

T Hikida, Zool Sci 16, 659 (1999)

3 For additional plant and animal examples, see

L Guterman, Chron Higher Educ 52, A12

(21 July 2006)

Roles of CITES in Protecting New Species

IN THEIR LETTER “SCIENTIFIC DESCRIPTIONcan imperil species” (26 May, p 1137), B L

Stuart et al warn of a dilemma faced by

sci-entists who publish the first scientificdescription of a new species Revealing geo-graphical locations in the publication canguide unscrupulous collectors from theinternational pet trade to the species, whichcould lead to a rapid decline in populationsize and even extinction

To prevent this, Stuart et al suggest that

taxonomists should work closely with vant governmental agencies The problem

rele-LETTERS I BOOKS I POLICY FORUM I EDUCATION FORUM I PERSPECTIVES

919

Flowers evolve along ridges

Polymers with a difference

Memories and memory

LETTERS

edited by Etta Kavanagh

Captive Breeding and a

Threatened Gecko

IN THEIR LETTER “SCIENTIFIC DESCRIPTION CAN IMPERIL SPECIES” (26 MAY,

p 1137), B L Stuart et al warn that scientific description can draw

attention to newly described species attractive for hobbyists, which

could lead to their overexploitation or even extinction Although this

scenario sounds plausible, and taxonomists should keep in mind the

conservation impacts of their work, at least one of the three examples

given is incorrect The gecko Goniurosaurus luii from southeastern

China was heavily threatened by hunting for pet trade and local

medi-cine purposes and was probably extirpated from its type locality before

it was scientifically described The specimens of G luii obtained from

pet dealers and listed as Goniurosaurus sp were studied by Japanese

molecular phylogenetics before the official description (1) Lui, the

collector of the holotype of G luii, himself “became aware of the

exis-tence of Goniurosaurus luii and G araneus” from “individuals who

specialise in gecko collecting for commercial purposes” (2).

Stuart et al also claim that immediately after being described in

1999, G luii reached a breathtaking price of $1500 to $2000 per

indi-vidual in importing countries During the last few years, hobbyists

perfectly mastered the keeping

and breeding of G luii and closely related G araneus and

established numerous ing colonies of both species

breed-Recently, hundreds of born juveniles have beenavailable on the world pet market every year for about $40 each,which has two important conservation consequences First, there is

captive-no further demand on the imported, wild-caught animals Second, as

G luii is a species with limited range still hunted for local medicine

trade (3) and endangered by habitat damage (2), the captive

popula-tion will soon outnumber the wild one and can serve as a guaranteethat this species will survive at least in captivity with a potentialchance for re-introduction

LUKÁS KRATOCHVÍL

Department of Ecology, Faculty of Science, Charles University, Vinicná 7, 128 44 Praha 2, Czech Republic E-mail: kratoch1@natur.cuni.cz

References

1 H Ota, M Honda, M Kobayashi, S Sengoku, T Hikida, Zool Sci 16, 659 (1999).

2 L L Grismer, B E Viets, L J Boyle, J Herpetol 33, 382 (1999).

3 K S Lee, M W N Lau, B P L Chan, “Wild Animal Trade Monitoring in Selected Markets in Guangzhou and Shenzhen, South China 2000–2003” (Kadoorie Farm and Botanic Garden Corporation, Tai Po, Hong Kong SAR, 2004).

A G luii gecko

COMMENTARY

v v

18 AUGUST 2006 VOL 313 SCIENCE www.sciencemag.org916

LETTERS

with governmental agencies, however, isthat the protection is local, not global Oncethe species is illegally exported from thecountry of origin, it can be legally importedinto most other countries For example, the

snake species Bothrops insularis occurs

solely on Queimada Grande, a small island(of 43 ha) off the Brazilian coast, where itcould potentially be collected in large num-bers This species is protected by Brazilianlaw and listed as “Critically Endangered” inthe IUCN Red List However, once illegallyexported from South America, the species

is completely legal in Europe No law orconvention protects this species from thetrade there

If newly described species are to be tected from international trade, it must be at aglobal level through CITES (Convention onInternational Trade in Endangered Species ofwild fauna and flora) registration Before sci-entists publish their descriptions of newspecies, population sizes and potential vulner-ability to trade should be carefully assessedagainst the relevant criteria for amendments

pro-on the CITES list (with the CITES secretariat

in Geneva probably being the best contactpoint), and the process of listing the speciesinitiated in conjunction with the preparation

of its formal scientific description

FREEK J VONK1ANDWOLFGANG WÜSTER2

1 Department of Integrative Zoology, Institute of Biology, Leiden University, Post Office Box 9516, 2300 RA, Leiden, the Netherlands 2 School of Biological Sciences, University of Wales, Bangor LL57 2UW, Wales, UK E-mails: F.J.Vonk@umail.leidenuniv.nl; W.Wuster@ bangor.ac.uk.

A Problem in Archaeology Too

THE LETTER “SCIENTIFIC DESCRIPTION CAN

imperil species” (B L Stuart et al., 26 May,

p 1137) notes that formal publications ofnew species “advertise ‘novelties’ for hobby-ists and drive new markets.” The authorsdocument tragically increased commercialexploitation of reptiles and amphibiansfollowing publication in the literature.Ironically, this same “dual-use dilemma,” asthey term it, has also followed formal publi-cation in another discipline: archaeology.Site location data have stimulated pot-hunters and collectors who use the reports

as veritable guidebooks to further theirillegal activities This has been particularlythe case in Americanist studies, and I havelittle doubt of its foreign analogs

BERNARD W POWELL

Chuluota, FL, USA

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under license Represented by The Roger

Richman Agency, Inc., www.albert-einstein.net.

Photosynthesis in Balance

with Respiration?

AS AN ORDINARY BIOLOGIST, I ASSUMED THAT

living organisms’ impacts on atmospheric

balance,” with plant photosynthesis being

equalled by the summed respiration of plants,

animals, and soil and aquatic microbes

Thus, I find puzzling the attempt by A W

King et al (“Plant respiration in a warmer

world,” Perspectives, 28 Apr., p 536) to use

an adaptation of plant respiration to higher

temperatures as compensation for increased

temperature-stimu-lated increases in photosynthesis Surely,

temperature also affects rates of respiration

in almost all organisms that utilize

photosyn-thates for their energy source? Thus, only the

small handful of animals capable of thermal

control of body temperature could

effec-tively offset rises in body temperature to

lower respiration rates—and even those

capacities can add to respiration-derived

energy demands Why is plant adaptation by

lowering temperature-induced increases in

respiration a necessary hypothesis to offset

higher photosynthetic rates?

Surely, if we are to estimate the

temper-atures, we must also consider the impacts of

such temperatures on photosynthesis, as

well as on the rates of respiration not only of

plants, but also of all other lifeforms—from

microbes to humans How well do they

adapt their metabolic needs to persistent

temperature increases? On balance, over

eons of time, the photosynthate has more or

less been “in balance” (once the great

quan-tities of reduced carbon were sequestered in

fossil fuels, creating an oxygen-rich

atmo-sphere)—through periods of warming and

temperature-dependent responses of all

these metabolic regimes be part of any

meaningful analysis? If all reactions are

more or less equally affected by

tempera-ture, how can there be a net “problem” from

increased plant respiration?

MARY E CLARK

Professor of Biology, Emerita, San Diego State University;

Professor of Conflict Resolution, Emerita, George Mason

University; 780 Girard Court, Cottage Grove, OR 97424,

USA E-mail: meclark@efn.org

Response

CLARK’S ASSUMPTION THAT GLOBAL

PHOTO-synthesis is more or less “in balance” with

total plant and animal respiration holds as an

approximation only when those processesare not being forced from their quasi-equilib-rium by disturbance The ongoing anthro-pogenic perturbation of the atmosphere byfossil-fuel burning is a major disturbance of

Earth’s carbon cycle (1) Rising atmospheric

concur-rent increases in temperature alter thesis and respiration, but with different sen-sitivities These perturbations, combinedwith deforestation accompanying large-scaleagriculture, are large enough that the world’sterrestrial ecosystems are not in equilibrium

We did not investigate “adaptation” ofplant respiration, as suggested by Clark, butrather acclimation to higher temperatures

Acclimation commonly refers to ical and metabolic adjustments to environ-mental change, distinguishing these re-sponses from genetic adaptation Nor did weexamine “photosynthesis,” but rather tem-perature-stimulated respiration Clark asks,

physiolog-“Surely, temperature also affects rates ofrespiration in almost all organisms…?” Yes,

it does, and all rates of metabolic respiration

in our model are functions of temperature

(2, 3) Furthermore, organisms can indeed

lower respiration rates in the facing of risingtemperatures The concept of thermal accli-mation applies to respiratory rates (and rates

of other enzymatic-based processes) in

any poikilothermic organism (4, 5), which

includes plants Acclimation of plant ration to warmer temperatures is not in-cluded in global models of carbon cycleresponse and feedback to climate change It

respi-is important to understand how including ornot including it influences the simulationand interpretation of positive feedbackbetween Earth’s carbon cycle and future cli-mate change

The argument can be made that if one’spurpose is to estimate the production of

tempera-ture, then one must consider the impacts oftemperature (and temperature acclimation)not only on plant respiration, but also pho-tosynthesis and respiration of all lifeforms

The respiration of all lifeforms in the lations was modeled as a function of tem-perature, but we purposefully designed thesimulation experiments to isolate the con-tribution of acclimation of plant (leaf) res-piration to temperature Nonetheless, thedifferential effects of increases in atmo-

cellu-lar reactions could result in plants making anadditional net contribution to the imbalance

ANTHONY W KING, CARLA A GUNDERSON,

LETTERS

18 AUGUST 2006 VOL 313 SCIENCE www.sciencemag.org918

LETTERS

WILFRED M POST, DAVID J WESTON,

STAN D WULLSCHLEGER

Environmental Sciences Division, Oak Ridge National

Laboratory, Oak Ridge, TN 37831, USA.

References

1 J T Houghton et al., Eds., Climate Change 2001: The

Scientific Basis (Cambridge Univ Press, Cambridge, 2001).

2 A W King, W M Post, S D Wullschleger, Clim Change

33, 199 (1997).

3 J S Amthor et al., J Geophys Res 106, 33623 (2001).

4 A Pisek, in Temperature and Life, H Precht, J.

Christophersen, H Hensel, W Larcher, Eds

(Springer-Verlag, New York, 1973), pp 102–194.

5 K Y H Lagerspetz, J Thermal Biol 31, 332 (2006).

TECHNICAL COMMENT ABSTRACTS

COMMENT ON“Computational

Improvements Reveal Great

Bacterial Diversity and High Metal

Toxicity in Soil”

Igor Volkov, Jayanth R Banavar, Amos Maritan

Based on analysis of the reassociation kinetics of bacterial

DNA in soil, Gans et al (Reports, 26 August 2005, p 1387)

claimed that millions of microbe species existed in 10

grams of pristine soil and that 99.9% of the diversity was

lost as a result of toxic metals We show that the data do not

support these startling conclusions unambiguously

Full text at www.sciencemag.org/cgi/content/full/313/

5789/918a

RESPONSE TOCOMMENT BYVOLKOVET AL.

ON“Computational Improvements Reveal Great Bacterial Diversity and High Metal Toxicity in Soil”

Jason Gans, Murray Wolinsky, John Dunbar

Volkov et al claim that significant conclusions about the total number of species (S) cannot be made because dif-

ferent abundance models cannot be distinguished andthe sensitivity of the chi-square measure to changes in

estimates of S is low We point out that currently

avail-able data do not support these claims

Full text at www.sciencemag.org/cgi/content/full/313/

5789/918b

COMMENT ON“Computational Improvements Reveal Great Bacterial Diversity and High Metal Toxicity in Soil”

John Bunge, Slava S Epstein, Daniel G Peterson

Gans et al (Reports, 26 August 2005, p 1387) provided an

estimate of soil bacterial species richness two orders of nitude greater than previously reported values Using a re-derived mathematical model, we reanalyzed the data andfound that the statistical error exceeds the estimate by a fac-tor of 26 We also note two potential sources of error in theexperimental data collection and measurement procedures

mag-Full text at www.sciencemag.org/cgi/content/full/313/

5789/918c

RESPONSE TOCOMMENT BYBUNGEET AL.

ON“Computational Improvements Reveal Great Bacterial Diversity and High Metal Toxicity in Soil”

Jason Gans, Murray Wolinsky, John Dunbar

Bunge et al claim that we underestimated the error in

our analysis of bacterial diversity in noncontaminatedsoil However, they used an unsatisfactory model thatexhibited pathological behavior and consequently led

to an exceptionally high calculated error In contrast,the zipf distribution yielded an error estimate only 0.7

times the estimate of the total number of species (S),

and it is more biologically relevant

Full text at www.sciencemag.org/cgi/content/full/313/5789/918d

Letters to the Editor

Letters (~300 words) discuss material published

in Science in the previous 6 months or issues of

general interest They can be submitted throughthe Web (www.submit2science.org) or by regularmail (1200 New York Ave., NW, Washington, DC

20005, USA) Letters are not acknowledged uponreceipt, nor are authors generally consulted beforepublication Whether published in full or in part,letters are subject to editing for clarity and space

an enchanting book that has a broad

historical and conceptual sweep

rem-iniscent of a David Lean film It takes us on

a journey through the life of one of our

greatest neuroscientists,

inter-twining his personal

intellec-tual history with the events

that were simultaneously

occur-ring on the world stage In the

process we meet not only Eric

but his many compatriots,

who have shared the journey

with him

The fascinating read begins

with Eric’s memories of young

Erich (his German first name)

on his ninth birthday, in

Nov-ember 1938 He is playing

w i t h a m u c h - c r ave d t oy :

a battery-operated,

remote-controlled model car,

re-ceived as a birthday gift from

his parents, who owned a

small toy store Two days

later, a shattering new

mem-ory is encoded in Erich’s mind

alongside this idyllic one

Austrian Nazis invade the

small Kandel apartment,

arrest Erich’s father, and

remove the rest of the family

to a stranger’s apartment

After many anxious days, his

father is released and the

fam-ily is allowed to return home They find it

ransacked and all the valuables stolen,

including Erich’s coveted toy car The

fol-lowing months are marked by more

trau-mata, as Austrian Jews are subjected to

vicious humiliations that forebode a

danger-ous future The Kandel family finds a way to

escape to a Promised Land in New York

There Erich changes his name to Eric and

begins a new life as a young American boy

entranced by endless opportunities and

free-doms, ultimately becoming a psychiatrist, a

neuroscientist, and a Nobel laureate

This autobiography will be interesting to

both scientists and general readers for manyreasons The book provides a lucid andcomprehensive overview of developments

in neuroscience during the 20th century

Kandel consistently places his work within

the context of his sors as a reminder that he toohas stood on the shoulders ofgiants in the field The earlypages are filled with sum-maries of the contributions ofsuch figures as Santiago Ramón

predeces-y Cajal, Charles Sherrington,Edgar Adrian, Alan Hodgkinand Andrew Huxley, Bernard

Katz, Otto Loewi and Henry Dale, and JohnEccles Their findings constitute the basics

of contemporary neurophysiology, butKandel describes these giants with a fresh-ness and drama that portrays them as realpeople, identifying and struggling to answerearly crucial questions of neuroscience

The book also provides a wonderfulreminder of the importance of mentors inshaping the careers of scientists Very early

in his career, Kandel became interested inFreud, and he was encouraged to become apsychoanalyst-psychiatrist by the prominentanalysts Ernst and Marianne Kris, the par-ents of a friend Eric changed his careerinterests from history to medicine, becausethat was the pathway to becoming an ana-lyst While a medical student (like many of

us future neuroscientists), he would look atmodel brains and neuroanatomical speci-mens and wonder where thoughts arise Inhis case, the question was, Where in thebrain are the id, the ego, and the superego?

So he sought out his first mentor, HarryGrundfest of Columbia University With thehubris of youth, he animatedly explained hisvast and lofty goals Grundfest’s reply:Study the brain one cell at a time OfferingKandel his first experiences with the joys ofdoing research, Grundfest proved an inspir-ing and supportive mentor He was followed

by many others—Dominick Purpura, WadeMarshall, Stephen Kuffler, and LadislavTauc—who served as role models, taughtKandel new methods and ways of thinking,shared their excitement and questions withhim, and ultimately helped him grow into acreative independent scientist who ques-tioned and answered with his own individualvoice The author’s love, appreciation, andadmiration for his mentors pervade the

book and give it a warm andmature tone

At the heart of In Search of

Memory lies the story of how

col-leagues, and subsequently dents, became Kandel’s compan-ions in his “search for memory.”

stu-An adventurous band of friendsand students—working amidstthe kaleidoscope of new findingsthat occurred in neuroscienceand molecular biology in the sec-ond half of the 20th century—created new ideas and methods,shared them with one another,and relentlessly pursued thequestion of how memories areformed, preserved, and dis-carded Kandel’s work with the

sea hare (marine slug) Aplysia

produced ground-breaking discoveries: thatsynapses (of the gill withdrawal reflex) aremodified by learning, that the same synapsecan be modified in different ways by differ-ent forms of learning, and that long-termmemory differs from short-term memory inrequiring the use of gene expression to lead

to the growth of new synapses The bookdetails how collaborations with friendsenriched Kandel’s work and how one studentafter another made creative and originalcontributions to his laboratory The tales

of doing science will be a familiar one tomany To do high-quality, original research,Kandel continually remade himself, learnednew techniques, and adapted to advances inthe field The long and arduous road thatbegan with inserting microelectrodes into

From Austria, Through Aplysia,

Toward the Mind

Nancy C Andreasen

NEUROSCIENCE

In Search of Memory

The Emergence of aNew Science of Mind

by Eric R Kandel

Norton, New York, 2006 526

pp $29.95, C$42, £19.99

ISBN 0-393-05863-8

The reviewer is at the Department of Psychiatry, University

of Iowa Hospital and Clinics, Iowa City, IA 52242, USA

E-mail: nancy-andreasen@uiowa.edu

Ideal system for memory studies Aplysia californica offered “a simple reflex that

could be modified by learning and that was controlled by a small number of largenerve cells whose pathway from input to output could be identified.”

18 AUGUST 2006 VOL 313 SCIENCE www.sciencemag.org920

Aplysia neurons has helped move our

under-standing of the formation of memories from

behavioral conditioning to elegant

molec-ular biology

The author’s own memories help make

his account special Kandel is a confident

and persistent man with a hearty sense of

humor (As those who know him have found,

his laughter is both infectious and unique.)

But the book is marked with introspection

and is sometimes haunted by the pain of

loss—of his friends, parents, and brother

through disease and death (sometimes

cruelly premature) His connections with

Vienna and its culture—and the

near-destruction of that culture in the

Holo-caust—are very much part of his search of

his personal memories His wife, Denise, is

beside him throughout the journey,

provid-ing love and support, while his children

pro-vide corrective critiques

In short, In Search of Memory is a

must-read account of science and a life, with all

the associated joys and sorrows It provides

an insightful perspective on how first-rate

research is carried out One encounters a

fascinating and persistent person who

pur-sued the quest for his own Holy Grail (or,

more appropriately, Ark of the Covenant)

and found it

contributing correspondent who covers

human evolution for Science, offers a

wonderful, balanced, and accurate account

of the search for the oldest human ancestors

and the personages involved in this quest

Gibbons provides a revealing window into

the house of horrors that can be human

ori-gins research The descriptions of the

pro-tagonists’ personalities, which in every case

conform to my own perceptions, are

in-sightfully woven into the main fabric of the

book: the immensely engaging, and

some-times self-destructive, effort to find the

first human

At the same time, there is not a word of

gossip in this book Although the strengthsand weaknesses of various researchers aredescribed with no pulled punches, Gibbonssticks to their professional behavior anddoes not get personal This respectful de-tachment was a great relief, as I initiallyfeared the book might be a

soap opera of the type written

by some previous authors(including some people fea-tured in the book), whichwould have done a disservice

to the field Other researchersmight still feel that a disserv-ice has been done, but I dis-agree Gibbons profiles insome detail a dozen amongthe hundreds of past and present paleoan-thropologists In an even-handed manner,she presents both sides of each conflict, afew cases of which are highly acrimonious,

if not borderline criminal, in nature Somewould say she is in places a bit too kind,but that is for the reader to judge Paleo-anthropologists will understand that theconflicts and dubious activities the authordescribes are not typical of their field, andother scientists will recognize that their ownponds have a film of prima donnas some-times behaving badly that rises to the surfaceand comes to the attention of outsiders Iknew something of these battles from chatswith those involved, but reading the bookhas given me a much more detailed under-standing of what actually happened and theparticipants’ motivations Nonetheless, forthe most part paleoanthropologists do noteat their young, and we usually get alongquite well

Gibbons provides a multifaceted view ofpaleoanthropology, one that will serve as anexcellent introduction for nonspecialists

Combining science, the history of ideas, andcurrent events, her account allows the reader

to virtually live the events as they unfold

Interesting portrayals of historic luminariessuch as Eugène Dubois, Raymond Dart, andLouis Leakey accompany insightful analyses

of contemporary researchers Smoothly written,informative, and easy-to-understand asides,which focus on paleoanthropological meth-ods and theory, place everything in perspec-tive The reader should come away with asense of why the field is so important andengaging—as well as why some of its practi-tioners occasionally go mad

The book brings to mind a number ofinteresting problems How will we knowwhen we have found the earliest human (that

is, a member of the earliest population moreclosely related to humans than to chim-

panzees)? Necessarily, this fossil will mostlikely be indistinguishable from the earliestmember of the chimpanzee and bonoboclade How should we interpret the conflict(to which Gibbons devotes some attention)between molecular and morphological ap-

proaches to human origins?This issue has again come tothe attention of a broad audi-ence with the recent publica-tion of a comparative analysis

of DNA from African apesand humans that suggestschimps and humans experi-enced a lengthy and complexperiod of hybridization beforefinally going their separateways, sometime after the age of the earliest

human fossils Gibbons discusses (1) Whether

or not Sahelanthropus, Orrorin, and

Ardi-pithecus can be described as the love

chil-dren of unions between ancestral chimps andhuman ancestors remains to be seen, but thepaper raises stimulating questions about thesometimes curious mixture of African apeand human traits in all of these fossils

I have a few quibbles Molecular dates

of human origins are not so consistent asGibbons suggests They range from 3 million

to 12 million years ago (Ma), though it istrue that most converge around the 5 to 7 Marange Younger dates have been used to dis-qualify certain fossils from membership inthe human club, and older dates have beenused to nominate much older fossils I wassaddened to see Leonard Greenfield’s con-

tribution to the Ramapithecus debate again

ignored It was Greenfield who first lished a detailed rationale for the interpreta-

pub-tion that Ramapithecus is in fact a female

Sivapithecus and not a human ancestor (2);

David Pilbeam only later reached that sameconclusion Lastly, it is probably an over-statement to say that the monumental dis-covery of Lucy sealed the deal for the viewthat humans originated in Africa That viewgained wide acceptance after work in SouthAfrica by Robert Broom and John Robinson

in the 1930s and 1940s Their efforts also led

to the discovery of a “skeleton” (STS 14), soLucy was not the first

In spite of these minor complaints, readersshould enjoy Gibbons’s compelling andinformative account of recent research onhominin origins

The reviewer is at the Department of Anthropology,

University of Toronto, 100 St George Street, Toronto, ON

M5S 3G3, Canada E-mail: begun@chass.utoronto.ca

The First Human

The Race to DiscoverOur Earliest Ancestors

by Ann GIbbons

Doubleday, New York, 2006

341 pp $26, C$37 ISBN 385-51226-0

Integrity in International Stem Cell

Research Collaborations

Debra J H Mathews, 1 * Peter Donovan, 2 John Harris, 3 Robin Lovell-Badge, 4 Julian Savulescu, 5

Ruth Faden 1

SCIENCE AND LAW

em-bryonic stem cell research (hESCR)

cur-rently face ethical and policy challenges

resulting from conflicting national

regula-tions To address these challenges, we

con-vened more than 50 scientists, ethicists,

jour-nal editors, lawyers and policy-makers from

14 countries, in Hinxton, Cambridge, UK (1).

Through exploration of case studies (see

Supporting Online Material) and

delibera-tions, we came to consensus on guiding

prin-ciples (see table, page 922) for international

collaborations in hESCR (1).

Science, Society, and the Law

Society has the authority to regulate science,

and scientists have moral and legal duties to

obey the law The Hinxton Group engaged in

discussion about the power of law to facilitate

or to restrict hESCR and about the need, given

the critical contribution science makes to the

public good, for lawmakers to be circumspect

in regulating science

Even apparently well-crafted laws can

have unintended consequences as science

progresses Since enacted legislation is

diffi-cult to change, a premium should be placed

on flexible regulatory structures that can

respond to the rapid evolution of scientific

understanding To strike the best possible

bal-ance between free scientific inquiry and

social values, it is essential that lawmakers

and scientists consult with each other and

with the public

We also call for clarity in the law

Scientists and clinicians have the right to

know what is, and is not, permitted with

respect to their research, the jurisdiction of

any prohibitions, and related penalties so that

they and their research institutions can

regu-late their behavior accordingly The lack of

clarity in laws, for example, due to the

am-biguous use of technical language [e.g (2)],

may have unintended chilling effects on ence It can lead to costly and time-consum-ing legal challenges, and in the face of ambi-guity, scientists and research institutions maychoose not to pursue a particular line of investi-gation or collaboration

sci-Governments have the authority to late science according to the values and histo-ries of their nations One of the most con-tested issues the Hinxton Group dis-cussed was whether or under whatconditions governments should exertextraterritorial jurisdiction overhESCR One case study that

regu-we debated involved anItalian scientist traveling toEngland to pursue collabo-rative work in which nucleartransfer will be used to de-velop patient-specific hESClines This is legal in Englandbut illegal in Italy Because Italianlaw does not address conduct of its sci-entists outside its borders, it appears that theItalian investigator would not be violating hercountry’s laws A second case study involved

a German scientist planning travel to theUnited States to collaborate with a Californiacolleague on research involving derivation ofhESC lines from supernumerary in vitro fertil-ization (IVF) embryos This is legal inCalifornia but illegal in Germany In contrast

to Italy, Germany appears to claim torial jurisdiction, regulating conduct ofGerman scientists outside Germany

extraterri-The Hinxton Group calls on lawmakers to

be circumspect in restricting citizens’ conductextraterritorially with regard to hESCR Weagreed that if scientifically and ethicallydefensible hESCR is undertaken in a country

in which it is legal, scientists should be free toparticipate without fear of being liable toprosecution, restriction, or discrimination inanother jurisdiction There was not, however,unanimity in the group on how far this pointshould be extended For example, the apparentextraterritorial reach of German law is embed-ded in the German constitution and is not spe-cific to hESC research or scientists, but rather

applies to the conduct of federal employees,which includes most scientists Insofar as this

is a basic principle of German law, it may beinappropriate, and unrealistic, to expect thatscience should be treated as an exception

In countries with laws that restrict elements

of hESCR but that do not expressly prohibitcitizens’ participation in these practicesabroad, research institutions should neither

discriminate against nor restrict thefreedom of investigators whowant to travel to do scientifi-cally and ethically defensi-ble research For example,when the traveling Italianscientist is evaluated forpromotion, his home insti-tution should include in itsassessment any publica-tions that come from hiscollaboration in England

By contrast, the home tution of the German scien-tist, even if she is not prose-cuted, may be legally constrainedfrom including in her review any publicationsthat emerged from her work in California

insti-In some cases, scientists who are citizens

of countries with restrictive laws may wish tocollaborate with colleagues in more permis-sive countries without personally engaging inthe activities that are illegal in their homecountries Particularly for such scientists, andalso generally, journal editors should encour-age authors to include in manuscripts explicitdescriptions of their specific roles in the col-laboration that led to the published research

ing and microsatellite data) (3) publicly

avail-able Journal editors should require authors

1 Phoebe R Berman Bioethics Institute, The Johns Hopkins

University, Baltimore, MD 21205, USA 2 Stem Cell

Research Center, University of California, Irvine, CA 92697,

USA 3 Institute of Medicine, Law, and Bioethics, University

of Manchester, Manchester M13 9PL, UK 4 Division of

Developmental Genetics, Medical Research Council (MRC)

National Institute for Medical Research, London NW7 1AA,

UK 5 Oxford Uehiro Centre for Practical Ethics, University of

Oxford, Oxford OX1 1P, UK.

*Author for correspondence E-mail: dmathews@jhmi.edu

18 AUGUST 2006 VOL 313 SCIENCE www.sciencemag.org922

(i) to provide specific information about the

source of the cells used in research, (ii) to

submit data verifying the authenticity of new

hESC lines, and (iii) to explain how they have

complied with accepted standards of good

cell culture practice

Journal editors and reviewers have a

responsibility to promote ethical, as well as

scientific, integrity Journal editors should

require a statement from scientists that their

research conforms to local laws and policies

and has been approved by all applicable

oversight committees Scientists should also

be ready and willing to provide approved

protocols, consent forms, and other related

information that may bear on the ethics of

their research

The Hinxton Group is creating a public

database for the deposition of relevant

poli-cies, information provided to potential human

subjects and tissue donors, and other

docu-ments that bear on the ethics of hESCR This

site will also provide a forum for

inter-national conversation among scientists and

the broader society It should be available in

the fall of 2006 (4).

Some ethical challenges facing hESCR

can be addressed through national regulatory

mechanisms and international norms of ethics

for conduct of research involving human

sub-jects Although human materials donors in the

context of hESCR may not normally be

con-sidered research subjects, for ethical

over-sight, we believe that they should be treated as

such Currently, the status of human materialsdonors and the policies that pertain to theirparticipation as donors in hESCR variesbetween countries (see table, above)

However, many ethical challenges inhESCR fall outside the traditional humansubjects framework As the science evolves,academies of science and relevant profes-sional organizations, in consultation with thepublic, should continue to develop guidelinesfor the ethical conduct of hESC research andclinical trials Several national and inter-national bodies are currently attempting this

(5–8) The process should include concerted

efforts to engage people worldwide in honestand realistic conversations about the scienceand ethics of hESCR Research institutionsshould create opportunities for scientists andtrainees to learn about the social context andimplications of research and to engage in eth-ical discussion and reflection among them-selves and with the public Funders of hESCRmust satisfy themselves that the scientiststhey fund conduct their research ethically and

in accordance with national regulations andinternational guidance

Although we should not expect nization of international laws with respect tohESCR, we should strive to develop interna-tional consensus on ethical and scientific stan-dards and practices Stem cell scientistsshould be vigilant in anticipating comingethical challenges to ensure that the scienceproceeds in an acceptable fashion

harmo-References and Notes

1 See (www.hinxtongroup.org).

2 B Hansen, Med Law 23, 19 (2004).

3 I Wilmut et al., Science 310, 1903 (2005).

4 Public database (www.hinxtongroup.org) in design stage.

5 U.K.’s Human Fertilisation and Embryology Authority (www.hfea.gov.uk ).

6 U.S National Academy of Sciences (http://dels.nas.edu/bls/stemcells/).

7 International hESCR Guidelines Task Force of the national Society for Stem Cell Research (www.isscr.org/ scientists/guidelines.cfm).

Inter-8 International Stem Cell Forum (www.stemcellforum.org/).

9 Country-specific sources that formed the basis for the table were as follows Australia: Human Cloning Prohibition Act (2002); Research Involving Human Embryos Act (2002); National Health & Medical Research Council’s Ethical Guidelines on the Use of Assisted Reproductive Technology

in Clinical Practice and Research China: Ethical Guiding Principles for Research on Human Embryonic Stem Cells (2003); The Guidelines on Human Assisted Reproductive Technology (July 2003), promulgated by the Ministry of Health United Kingdom: Human Fertilisation and Embryology Act, Schedules 2 and 3 (1990); Human Fertilisation and Embryology (Disclosure of Information) Act (1992); Human Fertilisation and Embryology (Research Purposes) Regulations (2001) Germany: StGB (German Penal Code); Embryonenschutzgesetz—ESchG (1990); Stammzellgesetz—StZG (2002) Israel: Prohibition of Genetic Intervention (Human Cloning and Genetic Manipulation of Reproductive Cells) Law, 5759-1999 (this law was renewed, and slightly amended, in 2004, with the same sunset clause established for another 5 years); Report of the Bioethics Advisory Committee of the Israel Academy of Sciences and Humanities: The Use of Embryonic Stem Cells for Therapeutic Research (2001); Public Health Regulations (1979).

10 Supported by the Greenwall Foundation; the Wellcome Trust; the British Embassy in Washington, DC; and the Juvenile Diabetes Research Foundation.

Supporting Online Material www.sciencemag.org/cgi/content/full/313/5789/921/DC1

10.1126/science.1127990

HINXTON GROUP PRINCIPLES AND A SAMPLING OF NATIONAL POLICIES

IsraelGermany

United KingdomChina

AustraliaHinxton Group

Consultation between lawmakers, scientists, and the public.

Flexibility in hESC policy

Circumspection in exerting extraterritorial jurisdiction

Classification and protection as human research subjects.

Extensive consultation was undertaken by the Lockhart Committee — over 1000 submissions

Relevant Acts were reviewed by the Lockhart Committee in 2005 and are awaiting government response

The Guiding Principle applies to ”research activity related to [hESCs]

conducted in the territory

of the People‘s Republic

of China.”

Protections and procedures required for human subjects research.

Not addressed in the relevant policy

Licensure guidelines are broadly written, allowing flexibility in case-by-case assessment of research proposals.

An annual report from HFEA (focuses on its own activities)

Not addressed in the relevant policy

Not addressed in the relevant policy

Current law is valid only until 1 March 2009

“Existing regulations… [to be] respected, and when necessary changed.”

Public discussion and an annual report from the advisory committee (issues include medicine, science, biotech, bioethics, and law) Not addressed in the relevant policy

Informed consent for gamete donors in relation to IVF (Oocyte donation is accepted only for cases of infertility.)

Not addressed in the relevant policy

The Embryo Protection Act and the German Penal Code imply that prohibited actions are illegal—and prosecutable—regardless

of location of the transgression.

Defers to national policies for the countries where stem cell lines were derived.

Regulations extend to Northern Ireland and the Channel Islands

Implies that prohibited actions are illegal

Protections and procedures required for human subjects research.

Jurisdiction is limited to Australia

Protections and procedures required for human subjects research

The Lockhart Committee recommended that the NHMRC develop guidelines for egg donation.

Last updated 24 July 2006; for source documents, see (9) HFEA, Human Fertilisation and Embryology Authority; NHMRC, National Health and MRC.