Tạp chí khoa học số 2007-11-16

Madden Privacy Policies Take a Toll on Research, Survey Finds 1049 Robotics in Remote and Hostile Environments 1098 Panel Calls for Pilot Program for National Indicators 1051 PERSPECTIV

| science

2003 Autonomous Ocean Sampling 1042 Contact Science Network program in Monterey Bay, 1045 Random Samples California See the special section 1047 Newsmakers

‘on robotics beginning on page 1083, ape Dal erseke 1159 New Products 1160 Science Careers

Making Machines That Make Others of Their Kind 1084

Robots’ Allure: Can It Remedy What Ails Computer Science? 1086

REVIEWS

Self-Organization, Embodiment, and Biologically Inspired 1088

Robotics

R Pfeifer, M Lungarella,F lida NEWS OF THE WEEK

Mobile Robots: Motor Challenges and Materials Solutions 1094 Did Merck's Failed HIV Vaccine Cause Harm? 1048

4.0 Madden Privacy Policies Take a Toll on Research, Survey Finds 1049

Robotics in Remote and Hostile Environments 1098 Panel Calls for Pilot Program for National Indicators 1051

PERSPECTIVE New Analysis Questions Push for More Degrees 1052 Learning in and from Brain-Based Devices 4408 New Jersey Rejects Bonds for Stem Cell Institute 1053, G.M Edelman Scientists Say Continued Warming Warrants 1054 trop, 1037; Nos 1055, 1056, ond 1060; Report 1355; eee ae

prance eh ta digs cok ccs coca Robot Cockroach Tests Insect Decision-Making Behavior 1055 Robotics se 083: Report p 115:

NEWS FOCUS

1056 Inthe HIV Era, an O16 T8 Vaccine Causes 1059 New Problems

1060

‘One Another

Evidence Linking DISC1 Gene to Mental Iliness Builds 1062

MOLECULAR BIOLOGY

Orchestration of the DNA-Damage Response by the RNF8 Ubiquitin Ligase

WN K Kolas et al

‘Akey ubiquitin ligase builds polyubiquitn chains at radiation-caused DNA lesions,

hich subsequently receuit other factors necessary fr repair

10.1126iscience.1150034 MATERIALS SCIENCE

High-Performance Carbon Nanotube Fiber

K Koziol etal

‘Aeragels of carbon nanotubes can be twisted and compacted to produce fibers of

exceptional strength and stifiness

LETTERS

The Origins of Human Bipedalism 1065

1H Schwartz Response S K S Thorpe et al

Technical D.R Begun etal and, H.C tal

What's in a Name? R Baserga

The Carbon Benefits of Fuels and Forests G, Marland et al

Response R Righelato and 0 V Spracklen

Eyeing a New Network / M MacDonald et al

CORRECTIONS AND CLARIFICATIONS 1066

BOOKS £7 AL

Dynamics of Cancer incidence, Inheritance, and 1070

Evolution Steven A Frank, reviewed by O C Krakauer

Burroughs Wellcome & Co Knowledge, Tust, Profit 1071

and the Transformation ofthe British Pharmaceutical

Industry, 1880-1940 R Church and E M Tansey,

reviewed by A E Simmons

POLICY FORUM

Biobanks in Developing Countries: 1074

Needs and Feasibility

S K Sgaier etal

PERSPECTIVES

When Oxides Meet Face to Face 1076

E, Dagotto >> Research Article p, 1214

Widespread Monoallelic Expression 1077

‘The Arabidopsis Circadian Clock Incorporates a cADPR-Based Feedback Loop ALN Dodd etal

InArabidopsis cyic ADP ribose, aytoplasmic signatng molecule, modulates the ican clock, driving periodic Ca* release and boosting robustness of te oscilator

10.1126 science.1146757

CELL BIOLOGY Rev-erbcr, a Heme Sensor That Coordinates Metabolic and Circadian Pathways

L Yin etal

‘Anuclear receptors a heme sensor that coordinates cicadian and metabolic uncions by Controlting the expression ofa major clack component and the gene for generating sugar

10.1126/science.1150179 CELL BIOLOGY

Daily Watch on Metabolism

i y, J Sch

T Imaizumi, S.A Kay, J 1 Schroeder 3i64104468064150380 DNA Circuits Get Up to Speed 1078

R, Bar-Ziv >> Report p The Gene Topography of Cancer 1079 J.M Trent and} W.Touchman >> Research Article p 120

PH, Schultz >> Reportp 1225

TECHNICAL COMMENT ABSTRACTS

ANTHROPOLOGY Comment on “Origin of Human Bipedalism Asan 1066 Adaptation for Locomotion on Flexible Branches”

D.R Begun, B G Richmond, D S Strait Response to Comment on “Origin of Human Bipedalism

{As an Adaptation for Locomotion on Flexible Branches”

R.H Crompton and S K 5 Thorpe

BREVIA

ECOLOGY Hurricane Katrina's Carbon Footprint on 1107 U.S Gulf Coast Forests

1.0 Chambers etal

Hurricane Katrina killed or damaged about 320 milion large trees, representing alos of about 105 teragrams of stored carbon

RESEARCH ARTICLES MEDICINE

The Genomic Landscapes of Human Breast and 1108 Colorectal Cancers

J Ghakhatian et al

‘charge transfer from Mtn atoms in an oxide layer to Cu atoms ina superconductor layer changes the orbital configuration ofthe Cu atoms and the properties of the layered structure >> Perspective g 1076

CONTENTS cont

‘Anew theory of how photonic-crystal fibers guide light is used to

design a hydrogen-filled fiber that emits light from 325 to 2300

nanometers at low input power

CHEMISTRY

Engineering Entropy-Driven Reactions and 1121

Networks Catalyzed by DNA

D.¥ Zhang, A }.Turberfield, 8 Yurke, E Winfree

Biochemical circuits based on nucleic acids can use output strands

of oligonucleotides as catalysts for subsequent reactions to amply

small signals for use in sensors, >> Perspective p, 107

PLANETARY SCIENCE

Radar Sounding of the Medusae Fossae Formation 1125,

‘Mars: Equatorial Ice or Dry, Low-Density Deposits?

TR Watters et al

Radar sounding of equatorial hill on Mars suggests that they contain

a large subsurface feature with low density, either a large volume of

water ice or light volcanic ash >> Perspective p 108

GEOPHYSICS

Three-Dimensional Splay Fault Geometry and 1128

Implications for Tsunami Generation

GF Moore et al

Detailed seismic imaging ofa thrust faut off Japan shows that slip

along a near-vertical splay faut may explain why this prt ofthe

faultsystem generated a devastating tsunami

PALEONTOLOGY

Rise and Fall of Species Occupancy in Cenozoic = 1131

Fossil Mollusks

M Foote et al

New Zealand molluscan species, while extant, expand into diverse

habitats, yielding a brief peak, then contract toward eatinction,

following a genera pattern seen for genera

EVOLUTION

Transgenerational Plasticity Is Adaptive in the Wild 1134

LF Galloway and j.R.Etterson

Ald herb nongenetcally adapts to local light conditions and

asses the adaptation to offspring, ilustratng how sedentary

organisms cope with variable envionments

GENETICS

Widespread Monoalletic Expression on 1136

Human Autosomes

A Gimelbrant, J N Hutchinson, B R Thompson, A Chess Rather than being expressed from both the maternal and paternal

alleles, 5% of human genes surprisingly large fraction, are

CONTENTS ll

IMMUNOLOGY Promotion of Tissue Inflammation by the Immune 1141 Receptor Tim-3 Expressed on Innate immune Cells,

in Prefrontal Cortex During Sleep

D R Euston, M Tatsuno, B L McNaughton

‘Neural firing patterns that occur inthe prefrontal cortex during a complex task are replayed there during subsequent sleep at about seven times the awake rate

NEUROSCIENCE Time-Dependent Central Compensatory Mechanisms 1150

of Finger Dexterity After Spinal Cord Injury

Y, Nishimura et al

Alter suffering damage to the spinal cord, monkeys recover finger function by sequential reorganization of distinct regions of the motor and premotor cortices

BEHAVIOR Social Integration of Robots into Groups of 1155 Cockroaches to Control Self-Organized Choices

J Halloy etal

Small autonomous robots integrated into groups of cockroaches can influence collective decision making and coax the group toward an inappropriate shelter >> ews story p 105

expressed from only one allele >> Perspective p 107

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ADVANCING SCIENCE, SERVING SOCIETY AY#SS te cots ‘eatlegn ese 6254 S22 ates ———— asi ry! 85 fet as, sem tse and ee tes nage nan ates Wh ST tal ypemet ner OSL SLM pr en 0 pee os Printed on

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SCIENCE VOL318 16 NOVEMBER 2007

30% post-consumer

CONTENTS continued >>

Dental clues from an ancient ape

SCIENCENOW

vwivnsciencenow.org 0

‘Superbug Knocks Out Patient's Defense

‘Strains of MRSA found outside of hospitals destroy

hte blood cell

New Ape Fossils Found in Africa

Discovery casts doubt on notion that apes went extinct

in Africa and were replaced by others from Eurasia

Glia Stoke Morphine’s Fires

Helper cells in the brain are linked to addictive effects of opioids,

Small hearts and tong lite

SCIENCE'S STKE

wwwestke.org SIGNAL TRANSDUCTION KNOWLEDGE ENVIR

PERSPECTIVE: Adenylyl Cyclase 5—A New Clue in the

Search for the “Fountain of Youth”?

J.-A Chester and V J Watts

‘deficiency in adenylyl cyclase type S leads to a long life span

PERSPECTIVE: Entrainment of the Drosophila Circadian

Clock—More Heat Than Light

J-Y Fan M J Muskus, J L Price

Astudy now provides the first insight into the molecular

‘mechanisms by which temperature cycles synchronize

circadian cythms with the environment

‘Atechnical professional describes innovative ways of uncovering hidden tatent

US: Opportunities—The Golden Chapter

P Fiske Create your own career options by considering the direction you want to head in and then seeking opportunities to get you there, UK: A Career “Framework”—Guiding Light or Empty Words

E, Quill Wil the U.K Council for Science and Technology's recommendation fora science careers flow chart work?

US: From the Archives—Supply Without Demand

D Kennedy, C Taylor, K Urquhart, J Austin Bad estimates have become routine in the part of science policy called “ientiic manpower”

ŠCIENCEPODCAST

Download the 16 November Science Podcast to hear interviews relating to this week's special section on robotics

Topics include robotics in extreme environments, robot ethics, the social behavior of robot cockroaches, and more

vt scencemag org/aboutpodcast tt

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

eee (oe

individuals in the system

Reconstructing output oligonucleotides that are released go Equatorial Water

3 on to act as catalysts for other reactions The

The rich phase diagram of the transition metal

oxides and the recent demonstrations of pattern-

ing and tuning the interface region, which can

lead to unexpected phenomena such as the

quantum Hall effect and superconductvity, have

generated much interest in developing oxide

electronics Chakhalian et al, (p 1114, pub:

lished online 11 October; see the Perspective by

Dagotto) now report on an x-ray spectroscopy

study on the interface between high-tempera-

ture superconducting (Y,Ca)Ba,Cu,0, and metal

lic Lag gag :MnO, with surface-sensitive as well

as bulk-sensitive configurations Charge trans-

fers from the Min oxide layer to the

Cu oxide layer, but does not simply

move into the d,2_,2 orbitals of Cu in

a rigid manner Instead, orbital

reconstruction occurs that involves

population of the 3,2_,2 orbital Cal-

culations show that the orbital

reconstruction is consistent with a

scenario in which the Cu atom forms

a covalent bond with the Mn atom,

Entropy-Driven

DNA Networks

Akey aspect of electronic circuits is amplifica-

tion or gain, so that low signals can be distin-

guished from any persistent background

Zhang et al (p 1121; see the Perspective by

Bar-Ziv) show how gain can be achieved in bio:

chemical circuits They have designed complex

Catalytic networks based on DNA in which the

process is designed to be entropy driven so that the pathways for reactions are well controlled and can be modified at wil Possible applica:

tions lie in the field of catalysis, sensor devel opment, the development of enzyme-free alter:

native for the polymerase chain reaction, and the construction of nanomachines

Photonic Route to the High Notes

Excitation of microstructured optic fibers with intense femtosecond laser pulses can generate

broadband white light, and applications range from metrology to the generation of ultrafast pulses of a chosen

wavelength The princ:

ples behind white-light generation and optical

‘guidance have not been well understood, and the control ofthe loca~

tion and spectral range

of the generated light has been limited Couny et a (p 1118) devel- oped theoretical insights into the guidance of light and generation of higher-order modes in the

‘microstructured fibers that has allowed the gener- ation ofa frequency comb spanning an extremely

‘wide spectral range with modest input power The authors discuss how this approach could enable a simplified route to femto- and attosecond pulse generation and arbitrary waveform synthesis

SCIENCE VOL318 16 NOVEMBER 2007

Water on Mars is primarily locked up in the polar ice deposits Watters ef al (p 1125, published online 1 November; see the Perspec- tive by Schultz) show that comparable amounts

‘of water could be hidden at the equator in the hills of the Medusae Fossae Formation, which are believed to be formed of volcanic ash and wind-blown sediments Radar sounding with the Mars Advanced Radar for Subsurface and Jonospheric Sounding instrument aboard the

‘Mars Express spacecraft saw reflections from the underlying terrain beneath the sediments that have a dielectric signature consistent with the presence of water ice If these hills are ice rich, they must contain more dust and sand than the polar layered deposits but could host a volume of water similar to that of the south polar layered deposits

Megasplay Faults and Tsunami Production

Tsunamis often result when there is rapid uplift

of the sea bed, but their sizeis very sensitive to the local fault geometry Megasplay faults, which are long thrust faults that rise from the plate boundary megathrust and intersect the sea floor, are thought to be particularly effective in trans- ferring displacement to the surface By creating

a three-dimensional seismic view of a megasplay fault zone in the Nankai Trough off Japan,

‘Moore et al (p 1128) show hiow such a fault operates and suggest that its stip may have

Continued on page 1035

1033

2ek in Science

contributed to devastating historic tsunamis such as the 1944 Tonankai event Similarly, megasplay

geometries may affect tsunami generation in subduction zones worldwide

THE HUDSONALPHA

The maternal and paternal copies of most genes are generally thought to be expressed at comparable (VU han)

levels, but there are several examples known where this isnot the case Imprinted genes have either BIOTECHNOLOGY

the maternal or the paternal allele shut down, and in X-inactivation, one of the two X chromosomes is

leukins—are known to have one or other copy inactivated Gimelbrant etal (p.1136; see the Per

spective by Ohlsson) looked across the entire human genome and found that in 5% of analyzed loci FIRST RESIDENT

either the paternal or the maternal allele is randomly and stably inactivated This fraction is much

LÔ 10 0c)

Cancer's Mutational

Landscape

The genomes of human tumors contain many

sequence alterations, a subset of which help

drive tumor growth, Wood et al (p 1108,

published online 11 October; see Perspective

by Trent and Touchman) have now under

taken a systematic sequence analysis of

>18,000 genes in human breast and colorec:

tal tumors Depiction of the mutational data

on a topographic map indicates that each of

these tumor types contains only a few gene

“mountains” mutated at high frequency and a much larger number of gene “hills” mutated at low Open Biosystems, Ine

frequency Importantly, while a large fraction of the mutations driving tumor growth reside in the

gene hills rather than the mountains—a finding that underscores the heterogeneity of human can

er—it appears that many of the mutated genes function through cellular signaling pathvrays that SourcefF, Inc

are already well known

[To U04 sant Healthcare Systems, Inc

Laboratorie‹

The Yin-Yang of Inflammatory Responses

Inflammatory responses in the nervous system are very tightly regulated In particular, T helper 1 type SHARING THE BELIEF

T cell responses must be kept in check, and a potent negative regulator of these cells is the surface

receptor TIM3, a member of the T cell immunoglobulin and mucin family, However, Anderson et al Use dell

(p 1141) report the unexpected finding that TIM3 also promotes inflammation through expression on AND INNOVATION WILL

cells of the innate immune system—namely, dendritic cells and microglia of the brain The opposing EXPEDITE THE SHIFT FROM

roles for the same immune protein when expressed on different populations of immune cells raises

intriguing questions about the balance between the promotion and inhibition of tissue inflammation KNOWLEGE AND IDEAS TO

CC 2Q PVC, 1Á)

During sleep, hippocampal cells play back sequences of activity recorded beforehand during running

of a maze task Euston et al (p 1147) report a similar, although more compressed, form of activity

playback, but in the medial prefrontal cortex (mPFC) rather than the hippocampus The mPFC has

been implicated in memory storage and retrieval, and it receives direct inputs from hippocampus

HUDSONALPHA

Neuro-rehabilitation is based on the concept that training recruits intact neuronal systems to com- Pea Mee)

pensae for brain injury However, the neuronal basis of the underlying mechanisms is still poorly eee eet)

understood Nishimura et al (p 1150) carried out a longitudinal study in macaques using a well:

defined lesion ofthe direct cortico-motoneuronal connection at mid-cervcal segments ofthe spinal

otd, Functional recovery ater lesion ofthe corticospinal tract involved a variety of widely distributed

cortical networks The contribution of each different cortical region changed depending on the post: Soe a

operative recovery stave www.sciencemag.org SCIENCE VOL318 16NOVEMBER2007 0rsit af the HudsonAlpha Insiitte 1035

Robert} Sawyer isa

Hugo and Nebula

‘Award-winning science-

Robot Ethics

(-3PO AND R2-D2 MAY BE TWO OF THE WORLD'S MOST FAMOUS FICTIONAL ROBOTS,

‘but a quasi-robot named MQ-SBYC is perhaps more interesting just now: On 1 September 2007,

‘operators used this unmanned airborne drone to locate and drop a bomb on two individuals who appeared to be planting explosives near Qayyarah, Irag, As we make robots more intelligent and autonomous, and eventually endow them with the independent capabilit

need to consider how to govern their behavior and how much freedom to aecord them roboethies Science fiction dealt with this prospect decades ago: governments are

‘wrestling with it today Why now’? I'S not only because robots are killing people, IkSalso because they have become household consumer-electronies items and because some now look and act like humans (Honda's Asimo can even dance)

We have an instinctive reaction that a threshold has been crossed

The notion of killer robots is a mainstay of science fiction: but then agai

so is the idea of robots with builtin safeguards against that In hs 1942 story

“Runaround.” Istac Asimov offered his now-famous Three Laws of Robotics:

A robot may not injure a human being or, through inaction, allow a human

‘being to come to harm: a robot must obey orders given to it by human beings except where such orders would conflict with the First Law: and a robot ust protect its own existence as long.as such protection does not conflict

‘with the First or Second Law Most of Asimov's stories deal with things

‘going awry because these laws don’t equip robots to tackle real-world ions In his 1947 story “With Folded Hands,” Jack Williamson had robots adhere to an even simpler directive: To serve and obey and ward men from harm That, oo, had an unwelcome result totalitarian society

in which robots prohibit humans from participating in almostall activities, lest one of us be injured

Indeed all attempts to govern complex robotic behavior with coded strictures may be misguided Although the machines will execute whatever logie we program them with, the real-world results may not always be what we want

And yet, we seem unable to resist trying, and so governments are now drafiing their versions of Asimov's and Williamson's laws This year, South Korea's Ministry of Commerce, Industry,

thics Charter, which sets ethical guidelines concerning robot functions The move anticipates a time when intelligent service robots are part of daily life EURON (the European Robotics Research Network) also announced plans to develop

‘guidelines for robots in five areas: safety, security, privacy, traceability, and identifiability

Japan's Ministry of Economy, Trade, and Industry has joined in too With an aging population and robot caregivers being developed there (and elsewhere in the world), the Japanese foresee robots in many homes and have issued policies for how they should behave and be treated, The United States has yet to jump on the roboethics bandwagon That many U.S robots are created for the military and designed to harm humans may be the reason Still itis likely that the

‘most interesting litigation defining robot responsibilities and rights will emerge in the United States Forstarters, a Michigan jury awarded the family of the first human ever killed by a robot (accidentally, in 1979) $10 million, which was, at that time, the largest personal-injury award in the state's history

science fiction may be our guide as we sort out what laws, if any, to impose on robots and as we explore whether biological and artificial beings can share this world as

1c Asimov's 1954 novel The Caves of Steel describes a fully equal robotic partner

portrays what might be one

a as one day all humans and robots

or one, look forward to that time

Robert J Sawyer 10.1126%ciee.1151606

How Old Is the Canyon?

Much about the timing of formation of the Grand Canyon in Arizona remains

uncertain The process is closely tied into the history of uplift of Western North

‘America during the Cenozoic, including even recently, as well as regional climate

change One approach toward improved understanding isto date past positions of

the Colorado River as it deepened the canyon To do this, Karlstrom et al have

taken advantage of the many volcanic fields in the western part of the canyon;

some of these poured lava into the canyon during the past several million years

In fortunate cases, remnants of these flows are preserved perched on ledges or

beaches in the canyon, marking past river levels #°Ar/Ar dating of these young

flows shows that the western part of the canyon has continued to deepen by about

100 to 150 m since about 1.5 million years ago To the east, across a major fault,

the canyon has been deepening at 2 to 3 times that rate Further dates show that

this pattern of active differential uplift, facilitated by faulting, has operated over

the past 5 to 6 million years and has continued to modify the canyon even geolog-

ically recently — BH

MICROBI0L06Y

More than Skin Deep

‘kin fungi cause conditions ranging from flaky

scalps and eczema to weeping dermatitis and

invasive disease Major culprits are the

‘Matassezia spp., which are closely related to plant

pathogenic basidiomycetes, such as Ustilago

‘maydis ina proteomic-genomic study, Xu et al

discovered that when Malassezia grows on the

human scalp, it secretes over 50 proteins, which

are generally more similar to those secreted by

other skin-parasitizing fungi, such as Candida

albicans, than to those of its plant parasite

cousins The secreted proteins include allergens

responsible for atopic eczema, but the ones criti

«al for the Malassezia lifestyle are lipases; these

enzymes are required in order to harvest host

Lipids in compensation for an apparent fungal

inability to synthesize fatty acids de novo The

secteted enzymes include a distinctive arsenal of

extracellular hydrolases, another similarity to

Candida Furthermore, sequencing of the haploid

genome revealed mating type genes and a

pheromone-responsive MAP kinase module, like

www.sciencemag.org_

Geol Soc Am Bull 129, 1283 (2007)

those found in yeast It could be that sex pro-

‘motes skin colonization and the exchange of Virulence determinants — CA

Proc Nat Acad Sci USA 104, 10.1073/pnas.0706756104 (2007)

MATERIALS SCIENCE

A Matter of Coexistence Alloys such as Ge,Sb, Te, (GSD find use in non:

volatile electronic memory and as recording

‘media in DVDs because they undergo a fast and reversible transition between amorphous and caystalline phases with distinct optical and elec tronic properties It was initially assumed that the amorphous form was simply a disordered version of the metastable cubic (rock salt) form

However, experiments on quenched thin films and simulations have given a different and often conflicting picture Caravati et a used ab initio

‘molecular dynamics simulations to probe the amorphous structure, They started with meta:

stable cubic GST with Te occupying one sublattice and Ge, Sb, or vacancies randomly occupying the other For a quenched and annealed sample

EDITED BY GILBERT CHIN AND JAKE YESTON

at 300 K, the calculated x-ray scattering factor was in good agreement with experimental results from the literature The Ge and Sb atoms were mostly four-coordinate and the Te atoms mostly three-coordinate in defective octahedral-like sites, resembling cubic crystalline GST However, about one-third of the Ge atoms occupied a tetrahedral environment, absent in the crys talline phase but supportive of the large number

‘of homopolar Ge-Ge, Ge-Sb and Sb-Sb bonds that formed The authors believe the coexistence

of these two arrangements accounts for the rapid phase changes and strong optical contrast between the phases — MSL

‘Appl Phys Lett 91, 173906 (2007 VIROL06Y

Come In and Take Your Coat Off

The replication of animal viruses relies on their ability to cross a cellular membrane on their way into the host cell's cytoplasm Simian virus

40 (SV40) is a non-enveloped DNA virus that enters cells via caveolar endocytosis, followed

by vesicular transport to the endoplasmic retic:

tulum (ER)-the entry portal of the host cel’s secretory pathway-whence it crosses into the

‘cytosol en route to the nucleus Schelhaas et al wondered why the viruses follow this relatively

‘complex itinerary They found that ER-tocal:

ized enzymes that promote the isomerization of cysteines between their thiol and disulfide states were required for viral entry, and that two ER membrane proteins, Deslin-1 and Sel1L, which are known to mediate the retrotransloca:

tion of misfolded host proteins from the ER back into the cytoplasm, were also important

Specifically, the oxidoreductase ERp57 cat alyzed a rearrangement of disulfides within the

‘capsid, resulting in a loosening of the pen:

tamer-hexamer joints in the virus coat, Once in the cytosol, the reduced levels of calcium may promote viral capsid disassembly, facilitating release of the genome — SMH

elt 132, 495 (2007, Continued on page 1041

Nitrogenase enzymes use an elaborate metal

luster to catalyze the reduction of dinitrogen to

ammonia under remarkably mild conditions Two

‘questions about this process continue to puzzle

researchers: What are the elementary steps

underlying the scission of the nitrogen triple

bond, and how isthe cluster that guides these

steps assembled? Curatti et a shed light on the

latter question by reconstituting from purified

‘components a system for in vitro synthesis of the

cluster—which contains 7 Fe, 95, Mo, homoci

trate, and one as-yet unidentified light atom and

is called the FeMto cofactor Of 11 nitrogen fixa

tion (Nit) proteins previously shown to be

involved in Fetto cofactor biosynthesis, they find

that NifB, NIIEN, and NifH are key NifB assem:

bles ferrous iron, sulfide, and S-adenosyimethio

nine into the NifB cofactor (a precursor of the

FeMo cofactor) under reducing conditions; NifEN

pushes the synthesis one step further by convert

ing the NifB cofactor into the VK cluster, to which

molybdate and homocitrate are then added in a

NitH-dependent fashion The other Nif proteins

are thought to supply the relevant forms of Fe, 5,

‘and Mo under in vivo conditions and also to pro:

tect labile intermediates The catalytic compe-

tency of the synthesized Fetto cofactor (whose

structure is still unknown) was confirmed by its

Proc Natl Acad Sci U.S.A 104, 17626 (2007)

Many desirable materials properties tend to have tradeoffs For example, engineered cross-linked polymer networks can have high tensile strength, but though lighter than metals, they have much poorer extensibility —their rigidity causes them

to fail after a small increase in length Some pro teins, such as the muscle protein titin, do com bine high strength and elasticity, in part because they have a modular structure that unfolds upon deformation Kushner et al mimicked this property in their design for cross-links in a poly(n-butyl acrylate) network Side chains that could form four hydrogen bonds also carried long-chain terminal olefinic groups, which through ring-closing metathesis formed flexible covalent links between the hydrogen bonding pairs (much like the safety chain on a car trailer), providing two levels of chain cross-linking Com- pared to a control material with a poly(ethylene lycol) cross-link, the tensile strength increased

by 700% for similar elongations at a cross-link density of 6% — PDS

J Am Chem Soc 229, 10.102 00742176

Although an antibody directed against VEGF (aVEGF) can prolong life when motherapy to individuals with certain cancers, inhibiting VEGF signaling can elicit adverse side effects

and switch on alternative angiogenic mechanisms in tum

Noting that placental growth factor (PIGF, a VEGF family member)

is not required for normal development of the vasculature but has

been implicated in pathological angiogenesis, Fischer et al inves

tigated the effect on tumors of an antibody directed against PIGF

(GPIGP).In a mouse model, aPIGF by itself inhibited the growth or

metastasis of melanoma and of colon and pancreatic carcinomas,

calls

Metastases of a pancreatic tumor in mesenteric lymph nodes

and enhanced inhibition of tumor growth by the chemotherapeu:

tic agents gemcitabine and cyclophosphamide, as well as the anticancer effects of an antibody

directed against the VEGF receptor (EGFR) The processes inhibited included tumor angiogen:

esis and lymphangiogenesi

as well as the recruitment of proangiogenic macrophages On the

other hand, aPIGF did not turn on the expression of proangiogenic genes, nor did it mimic or

enhance e:VEGFR-dependent side effects; indeed, preanant mice treated with cPIGF delivered tt

ters of healthy pups Thus, the authors hope that cPIGF might representa useful addition to the

anticancer armamentarium, — EMA

www.sciencemag.org SCIENCE VOL318

aera

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Training Your Gut

I you love chocolate, you can thank—or

blame—the microorganisms in your gut

People who are hot for chocolate, researchers

say, harbor different bacteria from those who

are indifferent to the treat

Biochemists from Nestlé chocolate company

and Imperial College London spent 5 days

studying 22 healthy volunteers, half of them

avowed chocoholics, on a set diet They analyzed

urine and blood samples for the metabolic

byproducts of different types of bacteria The

results, published in the November Journal of

Proteome Research, reveal that levels of dozens

‘of these compounds in the two groups differ

The differences are “not just a product of

our genes,” says biochemist and proj

@ that indians who move to the

in gut bacteria Kochhar thinks they become attuned over time to a

S&S person's lifestyle and, in turn,

ences—sometimes in a positive direction Researchers found that

chocoholics’ blood had lower levels of bad cho:

lesterol and higher levels of albumin, a nutri-

ologist at the University of Reading, U.K., says

understanding how diet affects gut activity can

lead to the development of personalized nutri

tion plans that can nudge bacteria in the direc

United States show changes

—

can influence future prefer-

ent-carrying protein Glenn Gibson, a microbi:

tion of good health,

Phony Scoop on CO,

Global warming is actually caused by growing

numbers of CO,-emitting bacteria on the

sea floor, says a study published online on

3 November in the Journal of Geoclimatic

Studies “Those who subscribe to the [human:

«caused climate change] theory have overlooked

the primary source” of CO, emissions, write

Daniel Klein and colleagues at the University of

Arizona in Tucson

The problem is that Klein and his team

don’t exist Neither does their Department of

Climatology; Okinawa University, where the

journal is purportedly published; or its editor,

OU climatotogist Hiroko Takebe

It's a hoax designed “to expose the credulity

and scientific illiteracy of ‘climate skeptics,’ *

according to “Mark Cox,” the self-described real

author of the article, Cox says several anti~

global warming Web sites cited the paper but

hastily erased their coverage when the hoax was

revealed, Science got an e-mail from Cox after

speaking with David Thorpe, a U.K.-based science

Md

EDITED BY CONSTANCE HOLDEN

Boys in Delhi pore over a globe that atthe press of a button will show different peoples ofthe world speaking their native tongues It's part of a science exhibit on a train that will travel 15,000 kilo meters over the next 7 months, stopping in more than 55 cities throughout India The 14-car-long Science Express is chock full of multimedia exhibits covering topics such as black holes and CERN’s search for the Higgs boson, It also has a hands-on lab where children can do experiments such as mixing cement or separating chemicals with paper chromatography The $10 million indo German project is a mobile version of the Max Planck Society's long-running “Science Tunnel,”

which has been on display in Hannover, Germany, and has traveled to several cities in Asia

joumalist and Web site designer Thorpe says he Created the site but denies writing the article The paper report that algal blooms have gradually killed off “brachiopod molluscs of the genus Tetrarhynchia” and other organisms that prey on CO, producing bacteria, allowing bac teria populations to explode The paper has some clever ideas,” says geochemist Steven D'Hondt of the University of Rhode Island in Kingston, but “some fairly fundamental flaws,’

such as meaningless equations He also notes that brachiopods and

mollusks are two different phyla

A Probable

Killer?

Is Lucia de Berk, a Dutch nurse, a serial Ailler or the victim of shoddy statistics? Dutch courts sentenced De Berk to life in prison for

‘murdering seven patients and attempting

to kill three others But dozens of statisticians last week petitioned the Dutch justice department to reopen the case

Suspicions first arose in 2001 after a

SCIENCE VOL 318

De Berk shown as witchlike in cartoons

‘6-month-old girl died under murky circum stances while De Berk was on duty Prosecutors found that nine other suspicious incidents had

‘occurred during her shifts at three hospital

Although no direct evidence implicated De Berk, the courts decided that it was unlikely—only

‘one chance in 342 million, according to one wit nness—that so many deaths could have occurred accidentally while she was nearby

That conclusion is based on “every statisti

‘al mistake in the book,”

says Leiden University statistician and petition organizer Richard Gill

For instance, he says, several deaths were deemed natural and only later declared sus picious by doctors who knew De Berk had been

øn duty And fewer people died during

De Berk’s 2-year stint

at one hospital ward than during the prior

2 years “Nobody was murdered by anybody,” Gill concludes

Last month, a justice department panel rec

‘ommended that the case be reopened The decision now rests with the Supreme Court

16 NOVEMBER 2007

IBN AWN EDITED BY YUDHI]IT BHATTACHARJEE

ASECOND LOOK The gripping story of Mario Capecchi'’ childhood in wartime Italy made headlines throughout the world last month when he won the Nobel Prize in physiology or medicine (Science, 12 October, p 178) But the extra fame has triggered a new level of scrutiny that casts doubt on some details The questions arose after the Associated Press (AP) reported th:

story Capecchi has repeatedly described—surviving on the streets from

to 9 after his mother was arrested in 1941 by the Gestapo and taken to the Dachau concentration camp—ecan’t have happened that way The AP found no record of Capecchi’s mother being held at Dachau, and historians say that the Gestapo was not working in Italy then Other records suggest that Capecehi spent at least part of that time living with his father After AP showed him the new information, Capecchi released a statement saying that “what I have said and written is my most accurate recollection of my early childhood.” He has said that the stories were based on what his mother and uncle told him after the war,

A longtime collaborator, molecular biologist Kirk Thomas of the University

TROPICAL TRAINING A fledgling medical

school in Singapore has lured tropical disease

specialist Duane Gubler away from the sun and

sands of Hawaii to set up a research program in

emerging infectious diseases The school,

established by Duke University and the

National University of Singapore, opened this

summer with the goal of strengthening gradu-

ate-level medical training in the city-state

Gubler, an expert on dengue, now directs

the Asia-Pacific Institute of Tropical Medicine

and Infectious Diseases at the University of

Hawaii, Manoa He expects to assemble a team

of 10 principal investigators to do basic, clini

cal, and translational research, as well as to

train grad students and postdocs He also hopes

to knit new field labs into an emerging infec-

tious diseases regional network “Singapore is

in an ideal position to provide regional leader-

ship,” Gubler says

ON FIRMER GROUND After 2 years of

uncertainty, the leading journal of environ-

mental health has a new editor in chief Hugh

Tilson, 61, a neurotoxicologist and adminis-

trator at the Environmental Protection Agency,

will head Environmental Health Perspectives

(EHP), published by the National Institute of

Environmental Health Sciences (NIEHS) in

Research Triangle Park, North Carolina In

2005, then-NIEHS director David Schwartz

proposed privatizing the open-access journal

but later scuttled the plan after protests from

scientists, environmentalists, and Congress

Tilson filsa slot that’s been empty for the

past year He says NIEHS will restore cuts to

EHP’s budget and bring back some features He

hopes to expand the role of associate editors

of Utah in streets of Capecchi’s optimism, all survival skills

and publish more research on risk assessment

“We are confident that [Tilson] will provide sta- bility and scientific rigor to the journal,” says Jennifer Sass of the Natural Resources Defense Council in Washington, D.C

MONEY MATTERS

FOR GREATER GOOD David Heymann has spent a lifetime fighting the spread of infec- tious diseases, most recently teaming up with epidemiologists and health professionals around the world to stop SARS in its tracks Those efforts earned the 61-year-old World Health Organization expert a $250,000 prize from the Heinz Family Foundation last month, which he’s now donating to work on the global monitoring and prevention of infectious diseases

The money will go to the Emory University Global Health institute in Atlanta, Georgia, to support the training of young epidemiologists

in developing countries The initiative, to be

It Lake City, says the details of C:

“If you asked me what makes him a great scientist, I think

torn Italy probably h:

Office of Science, filling the new posi

ecchi’s story are unimportant

owing up on the something to do with it,” he says

0 focus, and ability to make tough decisions “are

‘Thomas adds,

coordinated through the International

‘Association of National Public Health Institutes (IANPHI)-—a nonprofit funded by the Bill and Melinda Gates Foundation—is “totaly consi tent with David's own dedication and passion

How could I keep

in public health,”

i - \

Vee

a this award to myself

says IANPHI president and Heymann’

longtime friend Jeffrey Koplan, who describes Heymann as

a “remarkably humble

when there are so many others working to protect the human condition,” Heymann says, citing individuals such as "Red Cross workers fighting Ebola or Marburg disease in the Congo” and “community volunteers trudging to remote villages to stop polio in Afghanistan.”

and self-effacing soul.”

< INSIDE GOVERNMENT

DOE SHAKEUP Patricia Dehmer has become the top research,

hin the Department of Energy's (DOE's) $4 billion

of deputy director of ams under Raymond Orbach Orbach, who isalso

tndersecretary for science, promoted Dehmer last month from head of basic eneray sciences to overseer of all six DOE research programs—which also encompasses high-energy physics, nuclear physics, fusion, biological and environmental sciences, and advanced computing—whose managers previ- ously reported directly to Orbach

“Pat is an extremely effective communicator,” says Michael

‘American Physical Society "She understands very, very well how to deal with members of Congress and with DOE.”

1048

AIDS RESEARCH

said “no” t0 tem collfund

Did Merckcs Failed HIV

Vaccine Cause Harm?

SEATTLE, WASHINGTON—A common cold

Virus has walloped the already aili

vaccine field

AIDS researchers, who are still stagger

ing from the unexpected failure in September

of the most promi candidate in

clinical trials, met here last week to explore

an even more alarming finding: The vaccine,

made by Merck and Co., may actually have

increased the risk of HIV infection

study participant, Working with the academic-

based HIV Vaccine Trials Ne

In the first full accounting of the trial results, Merck

researchers and their partners reported that,

as of 17 October, HIV hhad infected 83 people in the placebo-controlled

Scientists debate g60engineering

AdS antibody levels When data th

ed that this concern had been overblown,

they doubled the trial size in July 2005 to include people with high AdS immunity Most participants were men who have sex with men, although 38% were women, many of whom were sex workers

The interim analysis in September that revealed the vaccine wasn't working looked only at the low-Ad5-antibody group

When the researchers subsequently

‘examined the high AdS-antibody group, they were startled

to find 21 infeet- ions in vaccinees versus nine in the

work (HVTN) and the U.S cell alae eis

National Institutes of Health 2 50 49Vacdne Em, Typically, researchers deem a

(NIH) in Bethesda, Maryland, Š Ỹ 21 acing difference as significant if it

Merck researchers stopped the = 4 Ew has a 95% probability of not

multicountry study afteran 23 i SN being duetochance—a P value

interim analysis revealed that Ễ £ of less than 0.05 By these st

(Science, 5 Oetober p.28) § Š P value of 0.029, was signifi-

Now further analysis suggests s cant But Steven Self, HVTN'S

that the vaccine may have i seiuecoosy bead statistician at the Univer=

helped HIV infect a subset of

participants who at the trial’s

start had high levels of anti-

body to adenovirus 5 (AdS)

which causes the common cold

and is also a component of the

vaccine “This is the worst pos-

sible outcome in a vaccine

trial,” said AIDS researcher Erie Hunter of

Emory University in Atlanta, Geon

the study sites

The finding is as befuddling a

and its implications are The data presented here to some

at an HVTN meeting on 7 November found

“tend”toward what’ called “enhance- leaving investigators wondering whether the elevated number of infections in

vaceinees who had high AdS immunity was

due to chance, behavior, ora vaccine-induced

problem Despite int

how preexisting immunity to AdS could make

vaccinated people more susceptible to HIV

“The data are very complex, and trying to

Double trouble The vaccine clearly failed (lft), but in men with high AdS antibodies (ight, it may have increased their risk of infection (Women were excluded from this analysis because only one became infected during the study.)

trial, Of these, 49 were vaccinated and

34 received saltwater injections This differ- cence clearly indicates that the vaccine does not protect a

tions in and likel The discovery of possible enh the so-called Step Study also owes som

to chance The vaccine contains three HIV _genes stitched intoa modified Ad vector that

reating HIV proteins that teach the immune system how to attack the real

worried that high levels of preexisting AdS antibodies might attack the vector and cripple the vaccine So when Step began in December

2004, they enrolled 1500 people at high risk of

0.025 and 0.0025, bee study was not designed to

cause the

assess potential harm, nor did

investigators p aluate a subset ofthe study population Still, Self said rend” deserves close examination

Sev efforts to make sense of the t

UW's Juliana McElrath,

who directs HVTN’s lab program, explored

what many consider the most likely explana

tion: that people in the high-AdS-antibody

‘group were more vulnerable to HIV because

of “immune activation.” Specifically, HIV

«establishes an infection by attaching to T cells that have surface receptors known as CD4 and CCRS Natural infection with AdS creates

memory banks of these very T cells, which

expand and direct an attack if AdS shows up

same Way, creating more targets for HIV But

McElrath’s preliminary work found no evi-

dence for this

ar

Behavioral changes don’t seem to provide

an explanation: Study co-chair Susan

Buchbinder of the San Francisco Department

of Public Health said risk behaviors had

decreased across the board and more so in the

high-AdS-antibody group Buchbinder said

investigators still are sorting out many vari-

ables related to HIV transmission, including

circumeision, coinfection with oth

transmitted diseases, and genetic factors

‘One thing is clear: The monkey studies that

suggested that the vaccine could thwart the

AIDS virus, fueling much excitement, misled

trial participants if they received the vac

or the placebo A more recently study of the same vaccine in South Arica was stopped and quickly “unblinded” after learn- ing the Step results, notifying everyone of their vaccine status (Science, 2 November,

p 729) After much debate here Step’s scientific steering committee recommended unblinding, and an oversight committee con-

‘curred on 13 November

The specterof enhancement alsoafleets the AIDS vaccine field's next-best hope This NIH-made vaccine uses a similar AdŠ vector and was slated to entera $130 million trial this fall without sereening people immu-

“Steps results demand that we reexamine and redesign our stud

gator and Step collaborator Scott Hammer of Columbia University

Merck's Mark Feinberg wamed colleagues that “the whole field will come apart at the seams” if it doesn’t properly investigate and respond to the Step results “I've never seen more complicated data to emerge from a study.” Feinberg said "And thisone focuses on

as important a question as I've ever known,”

A federal rule aimed at protecting patient data

is hindering epidemiology research, adding

costsand delays without enhancing confiden-

tiality, according to a study this week in the

Journal of the American Medical Association

(JAMA) The survey responses from 1500

epidemiologists reflect the first systematic

analysis of privacy rules that researchers have

complained about for 4 years

The problems stem from the Health

Insurance Portability and Accountability Act

(HIPAA), passed by Congress II y

to make it easier for people to transfer their

health insurance A so-called Privacy Rule

that took effect in April 2003 requiring

health care providers to protect the privacy

records also affects research,

§ potential participants If that is not poss

the researchers can try to get by with a d:

set stripped of identifiers, such as name and

address, or they can seek a waiver from an

nstitutional ethics board

These requirements have had a major

impact on population-based health research,

headed by epidemi- igist Roberta Ness of the University of

Pittsburgh in Pennsylvania Survey invita

tions were e-mailed to more than 10,000

3 members of 13 epidemiology societies, and

more đifcult Enhanced confidentiality 47 rene)

Delayed time to study completion Overprotected? Arule meant to ensure the privacy of medical data jis hampering research, according to survey of epidemiologists

protocol to comply with HIPAA, two-thirds said it was much harder to recruit subjects

The results support anecdotal evidence that the Privacy Rule has slowed enrollment and threatened some studies, says Ness (Science, 9 July 2004, p 168: 17 March

2006, p 1547) For example, at the Univer- sity of Michigan, researchers were required

to obtain consent fora survey of patients with

‘married participants Ness’s survey ests that US surveillance of inf

sure what they can report Three years ago, an advisory panel urged the Department of Health and Human $

(HHS), which administers the Pri- vacy Rule, to ease the burden on researchers by revamping the rule

The agency never formally responded But HHS and other organizations commissioned the USS National Academies" Insti- tute of Medicine (TOM) to exam- ine the issue broadly: one of the results is the JAMA survey Researchers in other disciplines have told the panel of difficulties, too, For instance, clinical oncologist Richard Schilsky of the University of Chicago Med ical Center says HIPAA has been “a huge problem” for studies involy

ples, among others Ness says she and her col-

I “really are hoping” that the IOM panel will devise recommendations that pro- duce action, Its report is due by early 2009

16 NOVEMBER 2007

1049

ENVIRONMENT

Panel Calls for Pilot Program

For National Indicators

US agencies that track the health of the envi-

ronment should kick-start a pilot project to

establish a national system of environmental

indicators, a blue-ribbon review panel has rec-

‘ommended In the same Way that the gri

national product tracks the state of the econ-

‘omy, environmental inl

of wetlands, would monitor prog

meeting environmental goals The panel urged

theagencies to start now and develop a plan for

the remainderof the Bush Administration; they

recommended water quantity stored in lakes,

aquifers and snowpacksasa test-bed indicator

Observers last week voiced support fora pilot

project but stressed that users and contributors

Of data must be included in the design process

ifit isto be politically viable

Many agencies monitor aspects of the envi-

ronment, In 2004, the Govert ‘ount-

ability Office recommended that the White

House Council on Environmental Quality

(CEQ) figure out how to coordinate federal

efforts After a yearlong series of meetings

states and nongovernmental organizat-

:Q in 2006 asked an interagency team

ure out how to proceed The team’ white

ized in September, laid out several

options and recommended the creation of an

interagency council to set policy, another inter-

agency teamto manage the technical work, and

anadvisory panel The Department of the Inte-

rior (DON), one of five agencies involved, had

asked the National Academy of Public Admin-

istration to evaluate the wam’s ideas

Chaired by Hermann Habermann, former

{statistician ofthe US Census Bureau, the

month sent DOL an adva

‘mary of its final report” due out in December

The panel agreed with the overall approach but

tressed the need for immediate action,

‘What's needed at this juncture is not a new

organizational chart but concerted leadership

said project manager Don Ryan ata workshop

hheld last week by the nonprofit National Coun-

«il for Science and the Environment

A national indicator of water quantity

would be a good place to start, Ryan

explained, because this measure is relatively

straightforward—compared to water quality,

® for example—and people care about supplies

of water for drinking irigation, and wildl

3 Ultimately dozens of indicators might cover

“A Green Compass: Institutional Options for Developing a

National System of Environmental Indicators

Shrinking reservoir Water scarcity, suchas Atlanta is experiencing, could be a prototype national indicator

of the state ofthe environment

everything from air quality to biodiversity to outdoor recreation, The panel felt that the agencies should request funds for the pilot project in the 2009 budget: although it didn’t come up with a figure, Ryan

hhuge sum to get rolling.”

Reaction was mixed Although the panel recommended that indicators be usefl tohigh- level policymakers, such a “crosscutting indi- ator of water availability for the whole coun- try doesn’t make much sense,” said CEQ Ted Heintz at the workshop “Water use is loca However, he and others emphasized that the

‘main point ofa pilot program would be to help federal agencies learn to work together better, and for that, water quantity might suffice

Robin O'Malley, who heads the Heinz Center's Environmental Reporting Program in Washington, D.C.,.and others say that building broad support for a national system of indie:

tors will be especially crucial now, because the political leadership at the agencies will change

‘with the new Administration in January 2008

“The action plan has got to be about making sure it rooted in the community when there is

‘no one at the transition to save this.” O’ Malley said "You take a big risk by keeping people out.” he says

Officials at DOL and CEQ are expected to decide in the next few weeks about whether and how to proceed ERIK STOKSTAD

SCIENCE VOL318

iN ee

Texas Votes for Cancer Research

Texas researchers are looking ahead to 2009 for the first grants from a $3 billion bond measure that voters approved easily last week The project, which will fund as much as '$300 million a year for 10 years in cancer research, was championed by several promi nen Texans, including Governor Rick Perry and Lance Armstrong, the former cycling champion and cancer survivor (Science,

31 August, p 1154) John Mendelsohn of the University of Texas M D Anderson Cancer Center in Houston says he expects that “out- standing scientists, hopefully from outside the state,” will help review research proposals for the institute, ~]OCELYN KAISER

Tests on Tests Urged

‘A.group of scientific advisers wants the U.S Department of Health and Human Services

to tighten oversight of genetic tests, a growing enterprise regulated by a patchwork of federal rules Last week, the Secretary's Advisory Com mittee on Genetic, Health, and Society released

a 192-page draft report on genetic testing that called for new research to evaluate the clinical Utility of genetic tests and for the expansion of public databases of gene mutations The group also urged better proficiency testing of tabs performing genetic tests

“There's been very litle movement for-

‘ward in more aggressively regulating these tests, says Gail Javtt of the Genetics and Pub- lic Policy Center in Washington, D.C., whose director helped write the report Public com- iments are due by 21 December (wwiv4.o4.nih govloba/SACGHS/public_comments.htm)

“JENNIFER COUZIN

Europe Maintains Orbit

BERLIN—The European Space Agency (ESA) should maintain a human presence in low Earth orbit even if, as some have suggested, NASA pulls out ofthe international space station in the next decade, says ESA Director General Jean-Jacques Dordain “Iam convinced that uti- lization ofthe space station wil bring scientific progress and technological progress,” Dordain said at a press conference last week atthe nter- national Space Exploration Conference in Bertin

‘Although the space station without NASA “isa scenario that is very difficult to imagine,” he said, “itwill not be an end We will continue to offer capability in low Earth orbit.” ESA will unveil

a formal proposal forthe project next summer, Dordain says Any decision about plans will come next November at a meeting of ministers from ESAmember states ~GRETCHEN VOGEL

i NEWS OF THE WEEK

1052

SCIENTIFIC WORK FORCE

New Analysis Questions Push for More Degrees

Academics, business leaders, and politicians

have warned repeatedly that the United

States risks losing its economic edge unless

it produces more scientists and engineers

also say that the country’s system of nce and math education is not up to

snuff, But a new study” questions two basic

tenets of t argument, concluding that

work force data do not support claims of a

looming labor shortage and that test scores

indicate U.S students are doing at least as

well in science and math as their inter-

national counterparts are

The supposedly sorry state of STEM (sei-

ence, technology engineering, and mathe-

matics) education was a driving force behind

enactment this summer of the America

COMPETES Act, which authorizes $44 bil-

lion for a cornucopia of research and educa

tion programs across several federal agencies

(Science, 10 August, p 736) The bill drew

heavily on a 2005 U.S National Academies’

report, the title of which, Rising Above the

Gathering Storm, refers to the impending

economic crisis facing the United States

unless it bolsters STEM education (Seience,

21 October 2005

But sociologist Harold Salzman of the

Urban Institute and demographer B, Lindsay

Lowell of Georgetown University, both in

Washington, D.C., say that the academies’

report paints a misleading picture and that

its assumptions are leading to flawed STEM

education policies They note that the

annual US production of bachelor's, mas-

ter’s, and doctoral degrees in STEM fields

‘Against the grain Harold Salzman (center) told Congress last week thatthe United States produces enough technical workers

for the economy

16 NOVEMBER 2007 VOL318 SCIENCE

has averaged three times the annual growth

of science and engineering jobs between

1985 and 2000 They also point out that fewer than one-third of the 15.7 million workers with at least one STEM degree at

ny level hold jobs that require such train ing Given those numbers, says Salzman, expanding our production of scientists and engineers just defies market reality.” Last week, Salzman made his case twice on the same day, at a talk at the Urban Institute titled “Houston, Do We Really Have a Prob- lem Here?” and in a hearing before the House Committee on Science and Technol- ogy on how globalization affects the U.S

science and engineering work force

The authors also say that US students are keaming more than critics give them credit for

For example, they note National Assessment of Educational Progress, (NAEP) for students in eighth grade rose

15 points from 1973 to 2004 And contrary to popular belief that they trail the pack, says Salzman, U.S, students rank in the middle tier

of countries on an international assessment of

5-year-olds in math and science

Norman Augustine, former CEO of Lockheed Martin and chair of the panel that produced the Gathering Storm report, does not buy their arguments In an e-mail to other members of the panel, Augustine notes, that “what the [new analysis] does not observe is that an undergraduate degree in {science or] engineering isa prized creden- tial for those who wish to attend business school, law school, medical school or [20 to] a number of other fields{.] If the Gathering Storm repor is incorrect, we Will end up having devoted additional dollars to

Those who argue for strengthening

US science education say that NAEP is not the right yardstick for measuring what today’s students need to know “In a global economy with a global labor pool it is insufficient to compare American students past performance to American students’ current performance.” says Bill Bates of the Council on Competitiveness, one of sev- eral groups that lobbied heavily for the COMPETES Act, Salzman and Lowell say that they are not arguing for the status quo but rather that any new policies should address the real problems in STEM educa- tion, ary and secondary schools, they call for more resources for the lowest performing students, many of whom are minorities And within higher education, they say that scholarships should be based

on market demand for workers trained in individual disciplines rather than across- the-board support Salzman also recom- mends that universities put greater emphasis

on teachi tions and teamwork skills.“ -ess has had more to

do with its creative design rather than its

he say istine says Salzman and Lowell have important issues but that he is worried their criticism could undermine efforts to boost the research and training budgets of federal research agencies slated for growth in the COMPETES Act However,

David Goldston, the top staffer on the House Science Committee before he retired from the government last year, doesn’t think their paper will weaken the case for greater investments in science and ering “It’s worthwhile

te what the nature of tments should be what part of the social scale they should be targeted toward, and what competitive- ness really comes from,” he says Ifthe new study sparks those discussions, Goldston adds, “that’s all to the good:

a3

U.S STATE ELECTIONS

Bond slayer Steven Lonegan (ổn necktie) pumped up Vot

9 defeat tem celLinitia

New Jersey Rejects Bonds

For Stem Cell Institute

A proposal to ratchet up stem cell research in

New Jersey was defeated last week by an

array of hard-working opponents and a sense

of overconfidence by supporters Despite

recent polls showing that the $450 million

bond issue would be approved the state's vot-

ers last week rejected it by a margin of 53% to

47%, “[We] were a little bit too confident”

and didn’t shift into high gear until too late,

's Martin Grumet, director of the W M

Keck Center for Collaborative Neuroscience

at Rutgers University in New Brunswick

The bond measure, which was on a ballot

featuring contests for various local and state

offices, would have supplied an additional

$45 million a year for stem cell research over

the next 10 years to researchers at both public

and private entities in New Fersey Itwas backed

by a succession of New Jersey governors: the

$150,000 of his own money to th

passed Last year, Corzine signed into law

allocation of $270 million—New Jersey'sshare

‘ofa national tobacco settlement—for new stem

cell research facilities OF this, $150 million is

for the Stem Cell Institute of New Jersey

in New Brunswick, for whi

broken last month

As recently as October, polls were predict

le win But a combination of

fort to get it

ground was ing a comforta

religious and fiscal conservatives carried the

§ day Catholic churches showed a video dis-

= paraging embryonic stem cell research, and

§ Bishop John M Smith of Trenton sent out a

B letter on 7 October urging Catholies—who

§ make up 43% of New Jerseyites—to pray

© against the referendum, Antiabortion groups

8 nicknamed the measure “Loan to Clone

‘The measure also drew the ire of a

for Prosperity that wants to

củrh 'overnment spending Steven Lonegan, former mayor of Bogota, New Jersey, who heads the group's state chapter, says the issue caught fire in the past few months, “ 1ed more people on the groun

in the state ina long tim, Citing the state Shigh tax rates and $30 billion debi, the group offered voters a simple mes- sige about three fiseal proposals before them:

“Vote No on All Ballot Measures.”

Rutgers neuroscientist Wise Young,

co-founder of the stem cell institute, says

that the referendum was fatally hurt by the

record-low turnout of 26,6% of eligible vor-

ers Participation was lowest in counties

where support for stem cell research was highest, he added

Corzine says he will continue to press for

more money for stem cell research, both

from public funds and the private sector

New Jersey, the first state to direct funds to stem cell research, has spent $15.2 million since 2005, according to the New Jerse

Supporters regard the defeat as an expres~

sion of taxpayer frustration rather than

CONSTANCE HOLDEN

New Limits on Defense Grants

U.S lawmakers last week put the squeeze on Universities that receive basic-research grants from the military by tightening the amount of money that universities can be reimbursed for the cost of facilitating that research The new language limits overhead costs to 35% of the total amount of the grant That's the equivalent of a 54% indi rect cost rate, and many schools won't notice the difference because their rates do not exceed that amount

But Barry Toiv of the Association of Amer can Universities says at least 40 universities could be affected by the decision, and lobby

ists fear that Congress might eventually apply the same formula to the government's entire research portfolio “A cap on reimbursement is

a first step down a potentially slippery slope,”

says Toiv “Preventing universities from reim:

bursing all the real and necessary costs of conducting research will discourage them from applying for defense grants.”

~YUDHIIT BHATTACHARJEE

Moonstruck

India and Russia have signed an agreement

to jointly explore the moon As a first joint venture, India envisages using one of its rockets to launch a crewless mission in

2011 called Chandrayaan-I (a second moon mission for India) Together, Russia and India will develop a robotic rover that will be deployed from a lunar

orbiter to probe the moon's surface for geological data and took for helium-3, a potential fuel for fusion reactors The collaboration

is “an area of great prom:

ise” for the two countries, said Indian Prime Minister Manmohan Singh at a meeting in Moscow this week with Russian Presi dent Vladimir Putin The predecessor to this mission is India’s Chandrayaan-I, a resource-mapping project that India plans to launch on its PSLV rocket (above) in April 2008 It will carty two Ameri:

can research payloads and involves no Russ ian participation However, India and Russia have collaborated on space projects for decades: India’s only astronaut, Rakesh Sharma, lifted off in @ Russian Soyuz rocket in

1984, and Russia supplied the cryogenic engines that have carried India’s heavy com munications satellites into space

~PALLAVA BAGLA

1053

i NEWS OF THE WEEK

1054

Chilling conclusion Rapid arctic

metting ha stimulated interest in

Perr?

CLIMATE CHANGE

Scientists Say Continued Warming

Warrants Closer Look at Drastic Fixes

CAMBRIDGE, MASSACHUSETTS—Should sci-

entists study novel ways to alter Earth’s cli-

mate to counteract global warming? Last

week, a group of prominent research;

who gathered here gave a qualified “yes”

after ag hat the road to understand-

ing the science is fraught with booby traps

and that deliberately tinkering with the cli-

mate could make the problem worse Some

even admitted to being surprised by their

affirmative

“My objective going [into the meeting]

\was to stop people from doing something stu-

pid” says climate modeler David Battisti of

the University of Washington, Seattle, But

rising temperatures and carbon emissions,

combined with little meaningful action by

politicians, convin

that it was time for mainstre: edhim and his colleagues

ence to look more closely at g

Even so, Battisti suspects that the partici-

pants share the hope of many of those who

took part in the Manhattan Project to build

the atom bomb: that society would never

they provided “It

have to use the knowle,

would be incomprehensible th

this,” Battisti says, emphasizing the greater

need to cut carbon emissions

Organized by the University of Calgary

and Harvard University, the event allowed

50 elite climate, energy, and economics

researcher

to explore and debate geoengi-

the subject has been ges of science fic-

‘by Nobelist

mostly confined to the p;

tion and unfunded by rẻ

4 2006 paper in Climatic Chang

16 NOVEMBER 2007 VOL318 SCIENCE

20 October 2006, wabler” to drive dis-

Paul Crutzen (Science

p 401) served as an cussion among scientists of the once-taboo topic says Harvard environmental chemist Scot Martin, Harvard geochemist Daniel Schrag and physicist David Keith of the Uni versity of Calgary in Canada then decided to

“The very best would be if emissions of the greenhouse gasses could be reduced so much that the [geoengineering] experiment would

have dreamed up schemes to f

by blocking sunl ant spa

or by creating sea clouds to albedo of the ocean In 1997, physicist and Star Wars stalwart Lowell Wood and col- leagues affiliated with Livermore Berkeley National Laboratory suggested usi

One of Wood's central points is that the aerosol method is cheap In 1992, recalls Harvard physicist Robert Frosch, a National Academies’ panel on climate resisted his restion to include the cost of

2 Earth’s surface "Nobody wanted to put the geoengineering line on the figure because it looked too [economically]

option could be deployed for a few billion

dollars a year That amount could make geo- engineering attractive to politicians looking for radical fixes ina warming world “The decision on whether to do this will not be made by this group.” Schrag told his col- leagues sitting in the wood-paneled premises

of the American Academy of Arts and Sci-

ences But what scientists can do,

he said, is offset the input of

‘oups driven by profit or ideol-

‘ogy with solid research on the pos sible side effects of various geo- engineeri

And to certl

echniques

et started, the group ested plenty of side effects Atmospheric dynami- acked the few modeling

as preliminary.) Ecolog pointed out that artificial coolin;

lowers Earth’s temperature wouldn't address

the problem of the steadily acidifying ocean,

Modeler Raymond Pierrehumbert of the

University of Chicago in Illinois warned that

eoen 1g could become a global addic-

tion, ‘ually work on geoengineer-

don't

ing.” he told the group “But now that the

e nie's out of the bottle, I feel Ihave to.” Inone

unpublished experiment, Pierrehumbert simu-

lated a future scenario, presumably in the next

century, in which the amount of atmospheric

CO, had quadrupled but Earth was kept cool

bya yearly dose of geoengineering His model

showed that a halt in the

effort—"by, sa

result in an 7°C temperature jump in the trop-

iesin 30 years That rise, he says, would trigger

unimaginable ecological effects

Sallie Chisholm, an MIT biological

oceanographer, urged caution, She told

Science that her colleagues are downplaying

the dif how “inher-

ently unpredictable” biospheric feedbacks

will react to “turning the temperature

knob We the biosphere’

response to an intentional reduction in global

temperature through geoengineering.”

Other scientists were more willing to

entertain the idea of studying climate manip-

ulation but warned about a likely public back-

lash, Political scientist Thomas Homer-Dixon

of the University of Toronto in Canada talked

bout street protests "Some people may con-

sider geoengineering to be an act of ultimate

hubris.” he says “ItS going to provoke fear,

anger, guilt, and despair.”

Others, however, viewed public alarm

about geoengineering as a potentially positive

effect “If they see us talking about this as a

last-ditch effort, itmight inerease their alarm”

and drive them to cut emissions, explained

Harvard t Peter Huybers

during one of the By the end of the

2-day event, participants were stunned that

they had come so far “In this room, we've

reached a remarkable consensus that there

should be research on this.” announced climate

‘modeler Chris Bretherton of the University of

Washington, Seattle, Nobody dissented

Mixed in with his new sense of “responsi

bility?” Batt is dismay that the climate

problem has grown so serious ato drive scien

tists to contemplate steps that, in theory, might

lead to more serious problems than continued

warming Afr speaking on the phone with his

\wife from his hotel room, B:

told her this meeting is terri

(For a discussion of the topic with some

of the meeting participants, go to www

BEHAVIOR

NEWS OF THE WEEK L

Robot Cockroach Tests Insect Decision-Making Behavior

cience-fiction writers have long envi- sioned societies in which the boundaries between humans and lifelike droids blurand

‘man and machine freely intermingle José Halloy has taken the first steps toward creat- ing that world, at least for insects His tiny, autonomous robots lack legs wings, and antennae, but they nonetheless pass muster with cockroaches Indeed, these wheeled machines are so well accepted by the house~

hold pests that the robots become part of the insects’ collective decision-making process, Halloy, a theoretical biologist at the Fre University of Bru

colleagues report on pas The robots persuaded many of their insect “peers” to hide in

‘with animals on their own, “In many ways, {the work] isa big step in the study of collec- tive behavior in animals.” says animal behav- iorist Stephen Pratt of Arizona State Univer- sity in Tempe

Halloy and his Brussels colleague Grégory Sempo picked cockroaches for these robot experiments in part because they had earlier found that cockroaches typically sel-organize:

within a few hours, for example, they setle together in one place, preferring darker spots when available, For those experiments, and the later ones with the robots, Hallay Sempo, and their colleagues built a L-meter-diameter arena with two “shelters.” the roofs of which made of plastic dises covered by red

By adding layers of filters, Halloy Sempo can make one shelter darker than the other

Based on observations of insects in this arena, Halley and his colleagues developed a

‘mathematical mode! that predicts which shel- tera cockroach should pick depending on the

SCIENCE VOL 318

level of darkness of the shelter and the num- berand activity ofits fellow roaches Halloy’s group then used this model to program robots designed by him and Francesco Mondada and

at the Ecole Polytechnique Fédérale de Lausanne, Switzerland,

The roaches usually ran away from the robots but not if the machines smelled like the insects, For the experiments, Halloy and Sempo covered the robots with a filter paper containing the pheromone equivalent

of one cockroach

Halloy initially programmed the robots to have the same darkness preference as the cockroaches, and they joined the cockroaches

at whatever shelter the majority chose to rest in, Next, Halloy programmed the robots to prefer the lighter shel- ter About 60% of the time, the robots tipped the group's preference

in favor of the light shelter “This is a true example of automated leader- ship.” says David

‘Sumpter of Uppsala University in Sweden

“Instead of the robots rounding up the cock- roaches like sheepdogs, they lead through social attraction

But Coby Schal, an urban entomologist at North Carolina State University in Raleigh, has reservations about the effectiveness of the pheromone guise in convincing the roaches that the robot is just like them, He

‘wonders if the physical presence of the robots made the lighter shelter more attractive sim- ply by increasing the structural complex this hiding place “In my view, the jury is still out” on whether the robots became part of the decision-making, says Schal

Nonetheless, roboticist Daniela Rus of the Massachusetts Institute of Technology in Cambridge calls the idea that robots can influence biological group behavior “very powerful.” She speculates that the work could have many applications, such as robots that aid pest control by luring insects into traps or that help herd livestock

“ELIZABETH PENNISI

1056

NEWSFOCUS

24/24

[UP 10071717377 1117)//17173))07c7-Í by thousands of: i[Bmeters of fiber~

optiểfấfffpoýe,cab[Ss điim fo retolutionize oceanography, But will

Set 2cieficð-0f0jectS also hamstring the future of ocean research?

ca SEATTLE,WASHINGTON—Whhen John Delaney

first started using ships and submersibles to

explore the underwater voleanoes off the

coast of Washington state back in the early

1980s, the experience, he says, was exhilaral-

ing Delaney was part of the team that in 1984

discovered the Endeavour vent, a 70-kilometer

Jong volcanic ridge where magma from

Earth’s mantle wells up between a pair of

earch

tectonic plates As exciting as thos

trips were, they were equally exasperati

nographer at the Uni-

on (UW), Seattle, who looks every inch the bearded sea captain and

is fond of reciting T S Eliot, Ralph Waldo

Emerson, a

says Delaney, an oc

versity of Washin

\d Robert Frost “They offered

snapshots” he says “We would get ship and

sub for a couple of weeks, come home, pub-

lish our results, and then write another set of

nts We woul

2 id see something inter-

esting But it was or3 years before we could

come back and see what was going on That

became very frustrating”

Delaney’s frustration convinced him that

there had to be a better way

up a sustained research presence in the ocean, means to set

Ocean buoys outfitted with sensors of course

have continuously monitored conditions

suchas sea-surface temperatures for decades

But that was harder to do 1000 meters or

16 NOVEMBER 2007 VOL318 SCIENCE

more below the ocean’s surface, and deep- water devices suffered from weak power sup- plies and either could transmit only small amounts of data back to shore or had to be retrieved after months of data collection

In 1987, Delaney hatched the idea of

using underwater telecommunications cables

to wire the sea floor Such cables already crisscrossed the ocean carrying phone calls and computer data between continents If

re archers could tap into those cables, per-

haps they could use them as both a power source and a conduit to link to a new

tion of sensors, robots, and autonomous vehi- cles The idea lay dormant for a few years but

slowly started 1 twas like a

snowball goi ” Delaney says

“People sail “If ;oing to do that, then

1 can hook into it to look at fish stocks, tsunamis, pollution, and so on:

1998, Delaney successfully pitched the idea for a feasibility study to the National Oceanographic Partnership Program, which fosters collaborations among US federal

he says In

universities, and companies to pro

issues At about the same time, researchers at other major oce §eraphic institutions such as the Scripps Institution of Oceanography (SIO) in San Diego Califor- nia, and the Woods Hole Oceanographic

University (OSU) in Corvallis plan to string

cables to sites scattered around an entire

the Juan de Fuca Plate off

on and Washi

continental plate- the coasts of Or ure, p 105

on state (see fi ) Cable was recently laid for

Canadian arm of the project as well as for a deep-water cabled-observatory test bed off the coast of Monterey, California Early next year, the European Union will link instruments to three separate cables cur- rently

trino observatories, g used to Wire up underwater neu-

nd its members are considering further dedicated cable systems down the road And Japan and Taiwan have recently installed cabled systems, largely for seismic research

“Its really a dawning of a new age of how humans can explore the oceans,” Delaney Ship-based oceanography began in the 1870s, when the British ship Challenger conducted the first-ever prolonged oceanographic cruise,

High definition, Cabled observatories will scrutinize

ocean hot spots such as these black smokers

global reach about 100 years later, “What we're

looking at now is a third phase.” Delaney says

Iv’s one in which continuous power and data

channels offer researchers the ability todevelop

a new array of instruments that can

the DNA of under-

\water organisms on the spot and shipping the

data back to researchers continuously Until

now, the ocean has been close to a black box:

says Marcia McNutt, president and

CEO of the Monterey Bay Aquar-

ium Research Institute (MBARD

in Moss Landing, California “I

will be very surprised if we do not

make startling new discoveries,

cause we will be there 24/7 and

can study the ocean on our terms,”

MeNut says

But although proponents of

the system are quick to liken the

Utility of the new cabled observa

tories to the revolution sat

lites provided to oceanography, detrac-

{ors Say a more apt comparison is,

the international space station: a

money sink that provides se

tific value to relatively few

researchers The concern, they

say, is that the cabled observato-

ries will be so expensive to main-

tain and operate that they will

inevitably siphon money from

other area

s of ocean sciences

“Ocean scientists are always of

one mind when it comes to ships,”

says Peter Niiler, a physical

oceanographer who retired this

summer from SIO “We are usu-

ally of one mind when it comes to

satellites We are not of one mind

on this”

Growing appetite

While Delaney has sper

complete his vision of a cabled underwater

himoutofthe

observatory, others have bea

gate, In 1992, researchers led by physical

oceanographer Scott Glenn of Rutgers Uni-

versity in New Brunswick, New Jersey,

launched a near-coast cabled observatory

called LEO-15, which was built off the coast

just north of Atlantic City, New Jerse

‘water 15 meters deep and thus could be serv-

iced and maintained by scuba divers “It

really whetted the appetite of the science

Š community to do more.” McNutt says

wwwsciencemag.org

Wired Oceanographers plan

Researchers in Hawaii took the next step

in 1998, when they we doned undersea telephone cable that runs from the Hawaiian island of Oahu to Califor- nia They made it the backbone of the first deep-water cabled monitoring system, known

as the Hawaii-2 Observatory Below 5000 meters of water, researchers inserted a jun tion box with eight ports for tapping into the cable's power supply and hooked up a variety

of seismometers, pressure sensors, and a hydrophone The network operated for only 5 years but helped persuade oceanographers to push for purpose-built cabled observatories

iven use ofan aban-

ity to get data back to shore in real time That's fabulous,” says MeNutt Oc:

instruments including buoys at the surface and seismometers and other sensors on the sea floor—have traditionally worked with very limited power, supplied either by bater-

ies or by small wave-powered generators and the like Therefore, they typically haven't been able to record or transmit larg

of data, That has tended to limit them to tak- ing periodic measurements that were either sent back to shore by a low-bandwidth satel-

researchers the first glimpse of oceanogra- phy’s future Of California s coast, th kilometer Monterey Accelerated Research System cable—about the width of

hose—will carry fiber and 10,000 volts of electricity to

reduce the voltage and sit alon

side eight ports Instruments will connect directly to the ports or be linked to them by underwater extension cords

The instruments vary widely

, called the Eye in the Sea,

On will use a video camera that nplifies stray photons to in deep-water bioluminescent organisms Another, a robotic

n floor taking measurements effort to sort out the long- mystery of just how

ine which organisms are pres-

from above and reaches the deep ocean floor,

Because the

such experiments are power-hungry and typically operate continu

it, “Td love to have cabled observatories all over the sea floor.” Smith says

Vigorous discussion Despite their obvious upside, cabled obser- vatories have long proven a tough sell The issue, Niiler says, stems from the wide

1057

Bie

1058

WSFOCUS,

diversity of disciplines in the ocean sci-

ences, including geologists and geophysi-

cists interested in understanding plate t

tonics, fisheries biolo;

ish stocks, and physical oceanographers inter-

ested in tracking how earbon dioxide

moves between the atmosphere and the

oceans “Oceanography is not one sei

says Niiler

ne for scientists that

In the United States, however, those com-

munities essentially compete for one pot of

money as the lion's share of funding for basic

nces research comes from the ence Foundation (NSF) This year, Congress gave NSF $5 million to begin

nstruction of the $331 million Ocean

Observatories Initiative (OL); NSF hopes

fora big funding spike in 2009-11 to finish

the job The largest portion of funds

estimated to be about $170 million—will go

to build the deep-water cabled observatory

offthe Oregon and Washington coasts When

the idea for this expensive observatory first

began to gain traction several years ago, the

broader oceanography community balked

until additional components—a few buoys

designed to operate at high latitudes a net-

work of instruments off the Oregon coast, and

a cyberinfrastructure component to handle

the expected surge of data—were added “In

order to get community buy-in to the OOL

idea, there were some compromises made?

MeNutt says

However, although Congress agreed to pay

for the new infrastructure, it didn’t provide any

exirt money to run or maintain OOT's cables

and instruments That money—expected to

total about $50 million a year—will have to

come out of NSF's general budget of about

$300 million a year for ocean sciences Niiler

and other critics angue that because the cabled

‘observatories are fixed in place on the ocean

floor, they will primarily benefit underwater

16NOVEMBER 2007 VOL318 SCIENCE

Cerner Oot new đe robots

TT orcs Ínstrument

th

geologists and geophysicists Ye, because the operations and maintenance funding will come from the ocean-sciences community asa whole, the high price tag could force cuts in other areas, “I worry that small, individual principal investigator-driven science will be harmed in its breadth and depth by

much for these observatories

However, he and others point out that geolo-

$120 million ship for arctic research,

$100 million for a new drilling ship, submersibles, and a global oc

network

“Now w new capability that will not appeal to everyone As an organization, we have to find a balance Schultz says Julie Morris, director of NSF'S

in sciences division, adds that if Con- ress and President George W Bush con- tinue their push to double spending on phys- ical sciences research and development, that could obviate much of the funding concems

For his part, Delaney is quick to deny that deep-water cabled observatories are of little

an float

Creeper This robotic rover will track how much T

‘organic carbon reaches the sea floor

ime

est to anyone but geologists.“ Matly dis-

“he ‘There is a tremendous

agre ays

amount of oceanographic science to be done

in the waters overlying the Juan de Fuca Plate.” Niiler acknowledges that a cabled

observatory offers advantages for studying

‘ocean vents and the chemistry and onganisms

the ocean and atmosphere affeets climate change, he says, the cabled observatory has far less rele hey just don’t go together, ‘To pretend they do is just not

Critics also fear that once major new observatories are built, future research grants

” says the anonymous U.S.-based nographer “It’s exactly like the finter- national] space station,” adds Russ Davis,

another oceanographer recently retired from

to grips with the facilities “It’s a vigorous discussion, as it should be.” he says Christoph Waldmann, a member of the

European Sea Floor Observatory Net- work steer

k der way in Europe and else- where is much the same But he and others repeat that proponents of cabled observatories are not out to do away with anyone else’s earch but rather seek to open dra- matie new possibili-

‘The science commu

ties to ocean research

nity ing this is a capability we need to have,” says Robert Detrick Jr.,a marine geol- ogist at WHOI who chaired a recent National Research Council report that favored build- ing cabled observatories “They provide a new capability for the community and approach ocean sciences in a different way.”

PUBLIC HEALTH

In the HIV Era, an Old TB Vaccine

Causes New Problems

The only TB vaccine available can be deadly for HIV-infected children That puts public

health officials in a difficult dilemma

It's well-known that HIV and tuberculosis

(TB) form dual, deadly epidemies that fuel

each other, More than 13 million people, most

of them in sub-Saharan Africa, are infected

with the pathogens that cause both diseases

Recently, researchers have found that HIV-

infected chikiren—who need protection from

TB more than anyone else—are also much

more susceptible to side effects of a widely

used anti-TB vaccine The live vaccine, devel-

‘oped more th 1d known as

Bacille Calmette-Guerin (BCG), can lead to a

generalized infection that may be fatal in as

many as 75% of cases Based on these data, experts,

baby with HIV should be vace

TB But that’s easier said than doi

infected infants isn’t feasible in many countries

with high HIV rates What’ more, researchers

worry that discussing these side effects could

give the vaccine a bad name and lead to a drop

in overall vaccination rates, “It really aterrible

dilemma,” says pediatrician Elizabeth Talbot of

the Dartmouth-Hitehcock Medical Center in

Lebanon, New Hampshire

As vaccines go, BCG was always a mixed

blessing, Researchersat the Pasteur Institute in

Paris developed it by weakening a strain of

Mycobacterium bovis, a cousin of M, tuber

cculosis, the agent that causes human TB (The

process was inspired by vaccinia, the smallpox

vaccine most likely derived from cowpox.)

BCG doesn’t appear to do much for adults, but

it protects children from the most serious

forms of TB during the first

parts of the worl

BCG isthe only TB vaccine that exist

almost every country in the world uses it

Recently, many Western countries have

started limiting their use to high-risk groups,

such as immigrants from endemic counties,

cause dropping TB rates have made the vac~

cine less cost-effective But in regions with

high TB rates, it's still an important line of

defense In Africa, most children are vac

nated right after birth Some studies have even

shown that BCG reduces mortality from

‘causes other than TB as well, perhaps because

it boosts the immune system

Researchers have long known that BCG

WHERE !

TB AVI nERE

Double-edged sword

Experts stress that to prevent TB—which has infected this Nairobi gir—

BCG use should continue in Hiv-negative children

consuming process—and then using a poly merase chain reaction test to determine that they are M ovis, not M tuberculosis:

Sowhen Anneke Hesseling of the Desmond

‘Tutu TB Centre of Stellenbosch University near

e Town, South Africa, started looking care- fully ina hospital in the Western Cape province,

500 times the risk for healthy children

A new, unpublished study based on better surveillance in more hospitals suggests that the risk for HIV-infected children may be two times higher still, she adds The concems about BCG are corroborated by an as-yet-unpublished study in Argentina, presented at 2005 meeting

by Aurelia Fallo of Children’s Hospital Ricardo Gutiérrez in Buenos Aires

The solution sounds easy: Children bom to HIV-infected mothers should be tested and if HIV-positive, should not get BCG But in many African countries, mothers aren’t tested for

HIV to begin with What’s more

mother-to-child transmission of HIV occurs mostly around birth, so tests can't be reliably done until at least 6 weeks later That would mean postpor

vaccinate HI during that period

The Western Cape is consider-

n1o do just that, says

major undertaking, she says, and post- poning vaccination carries the risk that some ofthe children will never come back Even in counties with high HIV rates, a large major children are HIV-negative

points out; if they missed the cine because ofa policy chang would be a disaster

ion (WHO) for

after reports from two expert panels, WHO began advising against vaccinat- ing HIV-positive babies But th

mendations are “not all that helpful Hesseling In an e-mail to Science communications officer said that “there is concern that recommendations might become counter-productive if BCG use ceases or is discontinued in HIV-endemie population WHO continues to recommend using BCG

if nothing is known about a child’s HIV status

The agency is in a difficult position, Doherty says as it will be blamed if overall tion rates drop “In situations like this,

Robotic Cars Tackle Crosstown

Traffic—and Not One Another

In DARPA's Urban Challenge, cars that drive themselves face off in a strange, soulless

rush hour Are human drivers about to go the way of the buggy whip?

VICTORVILLE, CALIFORNIA—The Land Rover

nical por- neer at the y

bristles with sensors like a me

cupine, John Leonard, an

Massachusetts Institute of Technolo

(MIT) in Cambridge, ticks off the robo

features On the roof spins a conical laser

range finder called a lidar that sees in three

dimensions A dozen lidars that see in one

direction, 15 radars and six di

look out every which way Computers fill

the back of the truck, and a generator sup-

plies the 3.5 kilowatts of power they need

It's impressive But all this so the truck can

turn left across traffic by itself?

The robot is one of nearly three dozen

vying in the Urban Challenge a competition

sponsored by the U.S Def

Advanced Research Projects

Agency (DARPA) It’s the third

‘and most demanding in a series

that aims to spur the developme:

of autonomous vehicles, which

the U.S military hopes to press

into service by 2015 In 2004 and

2005, robots raced one at a time

across open terrain This time,

they must navigate the streets of

an abandoned air base here in the

Mojave Desert without colliding,

with one another or with humal

‘guided vehicles

The competition showcases

some of the world’s best talent in

robotics “We were drawn to the

Urban Challenge because it requires real-time

decision-making in a dynamic environment

and in the presence of uncertainty.” Leonard

says Italso serves the higher purpose of try-

to save lives, as worldwide, 1.2 million

people die each year in traffic accidents that

robotic cars might help avoid

‘And yet the Urban Challenge is at le

slightly absurd It looks a bit like a real race

Engineers wear bright shirts emblazoned

with the logos of sponsors—GM, Ford, Intel,

Google Teams have hauled in tractor trailers

full of equipment and plastered their robots

with decals Besides the $2 million first prize,

the appeal of the challenge is obvious I's

hard, and by pitting idea against id

technology against technology,

mines what technical DNA moves to the next generation” in the evolution of autonomous vehicles says roboticist William “Red”

Whittaker of Carnegie Mellon University in Pittsburgh, Pennsylvania

Still, the task the robots will attempt seems so ordinary They must obey the Ca fornia traffic laws (although if two collide, they won't have to exchange insurance infor- mation as human drivers are required to do)

We're all here to wateh traffic But we won't see with our own eyes Instead, we'll have to watch iton television, Ir'snot even clear what DARPA gets out of this well-crafted media circus The competition is meant to stimulate the development of cars that drive them-

Go ahead, bend the rules

At the decaying fighter ba:

road from the new federal prison here in Victorville, 11 teams have made the final competition Three years ago, not one robot traversed more than a dozen kilometers of the 230-kilometer off-road course A year later, four completed a similar course And this year’s robots are far more capable than last year’s crop, possessing better sensors, more powerful computers, and, most important,

‘more sophisticated programming “Driving is

a software problem, not a hardware problem,

Stanford, we can’t build a better

‘can make a smarter ear.”

Computationally, this year’s challenge is much more difficult than the first two researchers say In the desert races, the robots had only to identify obstacles in a static land- scape and plot a safe path around them, This time, the vehicles will have to avoid other cars, including other robots, while at the same time obeying the relatively a

laws To do that, each robot’s computer must calculate the likely trajectories of all the objects around it and plan to miss them, Of course, a robot cannot know exactly where another car will go, so the machines generally employ layers of probabilistic algorithms to decide their next moves,

MIT has decked its robot, Talos, with the most sensors The radars see distant objects, the lidars see at an intermediate range and the

‘cameras spot things close by explains David Barrett, a team member from the Franklin W, Olin College of Engineering in Needham, Massachusetts Talos depends mainly on its sensors to nav Barrett says Tha because the team assumed, incorrectly itturns

‘out, that DARPA would not let robots use sig- nals from the satellite-based Global Position- ing System (GPS) all over the course

Researchers from Stanford, who won the

2005 competition, say that they focus on the algorithms programmed into their robot Merely encoding the traffic laws can leave the robot stymied, says Stanford computer scien- tist Sebastian Thrun For example, when two robots arrive at a four-way stop simultane-

‘ously, each may try to yield to the other end- lessly To avoid such deadlock, the team lets its robot skirt the laws, “Ourcar hasa hierarchy it follows,” Thrun says “At the top, it obeys strict rules, And ifit gets stuck, it ignores more and more rules.” Fair enough Why expect more from a robot than a human?

Team AnnieWAY, one of two German squads in the final, has taken a minimalist approach to guiding its Volkswage

The team relies almost entirely on the

$75,000 three-dimensional (3D) lidar, which Bruce Hall and colleagues at Velodyne Acousties Ine in Morgan Hill, California, developed to compete in the 2005 DARPA challenge The sensor may be all you need, says Séren Kammel ofthe Karlsruhe Institute

of Technology in Germany “I think some teams have a lot of sensors because they have alot of sponsors, and everybody wants their sensor on the ear” he says

Even that one sensor is beyond the means

‘of Donald Harperand his six teammates from 16NOVEMBER 2007 VOL318 SCIENCE www.sciencemag.org

of Central Florida in Ork

“ve outfitted Knight Rider, a 1996

aru Outback that belonged to Harper's wife

and has 99,257 miles (159,705 km) on it, with

just enough gizmos to get around the

course—they hope Instead of the spinning

3D lidar, they use two lidars that see in one

direction and rock them back and forth “If

just one wire falls off, something essential is

not going to work.” Harper says Still, the

team made the final having invested only

Robots, start your engines!

Race day usually brings the intoxicating

smell of high-octane fuel and the electri-

fying scream of engines But not here At

8:00 a.m., the robots leave the startin;

area, one by one, like rental cars leaving a

lot There's a glitch Interference from a

jumbo TV sereen knocks out the GPS

of first qualifier, Boss, Carne;

Mellon's Chevy Tahoe The team replat

the unit and has to wait 30 minutes to

Odin, a Ford hnic Institute ersity in Blacksbu Junior, Stanford's Volkswagen Passat: and

the others head out, hesitating and swerv-

ing as if driven by octogenarians After a

half-hour, all 11 robots—plus their chase

cars and 37 other cars—are on the road

There's only one curve from which to

glimpse the robots, so DARPA has hired a

the event on three huge sereens ina vast tent, Jamie Hyneman and

3 Grant Imahara of the geeky cable-television

§ reality show Mythbusters provide commen-

5 tary Its like watching hybrid ofa NASCAR

space in alot, traversing an off-road passage,

or navigating between two places After each mission, the robots return to the start area to download the specifications for the next, and each machine must travel 60 miles (97 kilo- meters) in less than 6 hours

At first, the action comes fast and heavy,

An hour into the race, TerraMax, the hulking, vehicle entered by military contractor Oshkosh Truck Corp in Wisconsin, turns toward a pillar and gets stuck staring at it Forty-five minutes later, Central Florida runs straight toward a house Caroline, the robot from Team CarOLO the other German squad, collides with MIT's Talos and loses sensors

By 11:00 a.m five robots have either failed

or been disqualified Then things settle down, The remaining robots’ “personalities” emerge Carnegie Mellon’s Boss zooms confidently away from

MIT's Talos is ie—it also clips Cornell's Chevy Tahoe, Skynet—but skittish off-road, stopping and starting like a cat creeping downa steep slope

Around 1:30 p.m., three teams have nearly completed their missions, and spectators swarm back tothe grandstands, At 1:42, Stan- ford cruises across the finish line, followed a minute and a half later by Carnegie Mellon, Upstart Virginia Tech cruises home third even without the 3D lidar “We knew we were

SCIENCE VOL 318

Junior and Virginia

“Tech's Odin negotiate

an intersection

good” says Virginia Tech's Alfred Wicks “We'd done our home- work.” The University of Pennsyl- vania’s Toyota Prius, Little Ben, straggles in an hour later Some- time past 3:30 p.m., MIT slips in just before Comell

The outcome seems obvious

Carnegie Mellon spotted Stan- ford and Virginia Tech a 20- minute head start and made up almost all of it It seems the v tory should be theirs DARPA officials will make the final call, however And, some participants grumble, DARPA never fully explains its judgments,

Make it out to

But the next morning brings

no surprises Carnegie Mellon walks off with the win, Stanford takes second and $1,000,000, Virginia Tech takes third and $500,000 “There's tremen- dous satisfaction in what the whole field accomplished” Whittaker says “That was a day that stunned the world.” DARPA Dit tor Anthony Tether also gushes “Quite frankly, I watched these things and I forgot after a while that there wasn’t anybody in

to come Reinholtz | and an engine

bits and pieces,

\der of the Virginia Tech team

at Embry-Riddle Aeronauti- cal University in Daytona Beach, Florida

Ironically the success of the Urban Chal- lenge could reduce the chances that DARPA will stage another competition “DARPA never finishes anything.” Tether says “All we doisshow that itcan be done” in the hope that industry takes over and pushes further devel- opment Clearly, when it comes to making robotic cars, the Urban Challenge has shown that itis possible

Stil, many engineers are eager foranother competition Their robots aren’t nearly ready for the open road, they say, and many already know what they would like to see in the next challenge: a contest for autonomous cars that must communicate and work together Sud- denly, that doesn’t seem quite so absurd

ADRIAN CHO

Evidence Linking DISC1 Gene to

Mental Illness Builds

Animal studies add weight to the view that an important gene for brain development

plays a role in diseases such as schizophrenia and depression

Every clan has its misfits, but an extended

family in northern Scotland is extraordinary

More than half have suffered from schizo-

phren ther form of mental illness

A group of Scottish researchers reported in

1990 that the affected people all carried the

same genetic anomaly—a translocation, or

swap, of two stretches of DNA on the lo

arms of chromosomes | and 11 With mod-

esty, the investigators wrote that this “may be

4 promising area to examine” for genes that

predispose people to mental illness

The area turned out to be very promising

indeed By the year 2000, it had led

researchers to a gene called DISC/ which

may be a key player in the chain of events

Jeading to mental illness The circumstantial

evidence for assigning a major role to

DISCI (Disrupted-in-Schizophrenia 1) is

strong Several studies have linked the gene

to schizophrenia, major depression, bipolar

disorder, and autism; recent findings on

DISC1’s biological function appear to sup-

port the hypothesis,

Animal studies have shown that the gene

is needed for normal brain development

both in the embryo and later in life and that

malities in brain structure resembling those

sn in patients with schizophrenia The pro-

tein encoded by the gene also turns out to be

part of a nerve cell signaling pathway

involved in learning, memory, and mood “I

its function produces subtle a

16NOVEMBER 2007 VOL318 SCIENCE

think this gene is really the first big break- through in schizophrenia and other men- tal diseases,” says Christopher Ross of Johns Hopkins University School of Medicine in Baltimore, Maryland

Afier decades of following false leads, researchers are cautiously optimistic that they are on the right track with /2/SC/, Bút the evi- dence isn’t airtight, Except

in the Scottish family

researchers haven't cons tently linked any particular DISC] variant to a mental

cautions psychia-

trist Daniel Weinberger of the National Institute of Mental Health in Bethesda, Maryland But ifthe connec tion of DISC/ to mental dis- orders holds up,

to better therapies for treat-

g the conditions—espe cially schizophrenia, a dev- astating disease that is now poorly controlled at best

disorders mainly because the diseases are complex,

Held in place An RNAi that blocks DISC2 synthesis prevents migration of neurons (green) to the upper layer of the cortex in mice (ight micrographs); controls are on the let

meaning that sẽ as well as envi ronmental factors, contribute to their devel-

‘opment That's why the Scottish family proved to be such a boon The 1990 study, which was conducted by a team including David St Clair, Douglas Blackwood, and Walter Muir of the University of Edinburgh,

ion disrupted by the translocation seen in affected members of the Scottish fi

anomaly, Attention has focused on the first DISCI which normally produces a large pro-

n the structure of which su:

interacts with other proteins

Shortly after identifi follow-up study by the Edinbur buttressed a causative role for the

as you could get.” Porteous

‘nvironmental influences may

considered good In this close to causalit

says Even so,

still be important, asa few members carry the translocation but remain unaffected

The Scoitish family is unusual because so many members develop bipolar disorder and depression, as well as schizophrenia, and no

‘one has detected a similar DISCI abnormality

in other families In 2003, however, Leena

Peltonen of the National Public Health Institute in Helsinki, Finland, and her colleagues reported a link- age between a particu

variants (single-nucleotide polymorphisms) in D/SC1 and schizophrenia in a group of 438 Finnish fami- lies “Thisis the first genetic evidence that DISC/ has something to do with the more common garden

Research on DISC/’S normal function has

strengthened the case that it is involved in

mental disease For starters, the gene is

expressed in many tissues, but particularly in

brain areas such as the hippocampusand cere-

bral cortex that are affected in schizophrenia

That puts the gene’s protein product in the

of the mental disease

In addition, as predicted from DISCI’s

structure, researchers have unmasked numer-

‘ous binding partners for the protein, The

rent count stands at about 50, Porteous says,

including “10 or 12 where the interaction

influences function.” Several ofthese partners

estarole for DISC in brain development

and cognition

For example, about 5 years ago, three inde-

pendent groups, those of Porteous, Akira Sawa

of Johns Hopkins University School of

ine, and Christopher Austin at Merck

Research Laboratory in West Point, Pennsylva-

nia, found that DISCT binds toa protein called

NUDEL (for NudE-lke) that is needed for the

neuronal migrations that occur during brain

development Several other partners of DISCI,

including FEZ 1, LISI, dynein, and tubulin, are

also involved in nerve-cell migrations

That suggests that brain development

might go awry if DISC/’S function is altered

or missing Evidence supporting that idea

includes the demonstration about 3 years ago

by the Sawa team that inhibiting DISCT syn-

thesis in mouse embryos with small interfer-

ing RNAs causes abnormal migration of neu-

rons to the cerebral cortex

More evidence comes from animal models

developed in the past year This fall, two Johns

Hopkins groups, one led by Sawa and the

‘other by Mikhail Pletnikov, published reports

‘on two similar mouse models produced by

introducing a truncated version of the DISCI

gene into mice Both lines showed similar

changes “The brain is superficially normal

but isn’t wired correctly.” says Ross, a: mem-

ber of the Pletnikov team

Outgrowth of neuronal projections called

neurites, which help guide neuronal mig

tions, was reduced In addition, interior brain

spaces called ventricles were larger than nor-

mal—an alteration also seen in people with

schizophrenia, And although it’s not possible

to diagnose mice as “schizophrenic.” the ani

mals showed certain behavioral changes seen

in human patients, such as hyperactivity

and cognitive impairment (The

team’ results were published online 3 At

in the Proceedings of the National Academy of

Sciences: those of the Pletnikov team

appeared online in Molecular Psychiatry on

cd rather than decreased, and neurons migrated farther than normal “If you disrupt DISC/ function, everything goes faster.”

Cento tant

Brain disruption Putting a mutant human DJSC†

gene in mice produces enlarged lateral ventricles similar to those of human schizophrenia patients

researchers have long thought that schizo- phrenia is the result of aberrant brain develop-

‘ment, and the results with these models but- tress the case that irregularities in DISCT function contribute to that,

AcAMP connection Although it may not be possible to help patients by correcting abnormalities in brain development, work by Porteous and Millar, in collaboration with Miles Houslay of the Uni versity of Glasgow, U.K., suggests another tack to take Two years ago, this group identi- fied an enzyme called phosphodiesterase 4B (PDE4B)as one of DISCI’s many binding partners This enzyme is a key regulator of cyclic adenosine monophosphate (cAMP), which transmits nerve signals into cellular responses, including those needed for mem- ory formation,

The PDE4B enzyme breaks down cAMP after it has done its job in the cell, and further work by the Edinburgh group indicates that

Additional evidence that disrupting the DISCI-PDEAB interaction can affect mental states comes from work on mouse models developed by Steven Clapeote and John Roder of Mount Sinai Hospital in Toronto, Canada, and their colleagues in collaboration with the Porteous team, (The results appeared

on 3 May in Neuron.) By screening, library of mutant mice at the RIKEN research institute

in Japan, the researchers identified two lines oftmice, each witha different DISC/ mutation that reduces DISC binding to PDE4B, Behavioral studies further showed that mice with one mutation display symptoms construed as schizophrenia-like including hyperactivity and impaired learning and

‘memory Those symptoms were reduced by treatment with the drug rolipram, a PDE4B

inhibitor, and also by treatment with two drugs used to treat human schizophrenia, The other mouse strain, Porteous says had more depression-like symptoms For example,

‘when placed in water, the animals quickly gave up trying to escape and simply floated These animals responded to treatment with antidepressant drugs Developing drugs to

an enzyme such ay PDEAB might lead to better ways of treating schizophrenia and other mental disorders

The fact that DISC/ associates with so many different proteins might help explain the diversity of conditions to which it has been linked “It seems that DISC/ acts as a scaffold around which other proteins cluster’

Porteous says Thus, the symptoms that develop in a given individual might depend

on which interaction is altered by a genetic tion in DISC] And conversely varia- any of DISCI’s pariners could also

tion, Geneticists have begun hunting for link- ages between these other proteins and various mental disorders

Neurobiologists are heartened by what they've learned so far about DISCI At the very least, the work has tapped into what could bea very important or regulat- ing brain neuron activities As Ross puts it,

‘the findings support the idea that schizophre- nia isa brain disease and can be studied the same way as degenerative diseases.”

“JEAN MARX

LETTERS | BOOKS |

LETTERS

POLICY FORUM

edited by Jennifer Sills

The Origins of Human Bipedalism

THE REPORT BY S K S THORPE ET AL ON HAND-ASSISTED ARBOREAL

bipedalism in orangutans certainly deserves attention (“Ot f

human bipedalism asan adaptation for locomotion on flexible branches?

1 June, p 1328) But does the discovery of orangutans en;

human-like straight-leg bipedalism actually mean that "

bipedalism is

h]uman less an innovation than an exploitation of a locomotor

behavior retained from the common great ape ai Altho

embraced by P O'Higgins and S Elton in their accompanying

Perspective (“Walking on trees.” | June, p 1292), this interpretation

embodies the Lamarckian ust disuse expectation that the poste

features unique to humans and their fossil relatives would have emerged

because a common human-ape ancestor had originally stood bipedally

But no known ape—fossil or extant—possesses the posteranial features

associated with human-like bipedalism, and to anticipate that any num-

JEFFREY H SCHWARTZ Departments of Anthropology and History and Philosophy of Science, Univesity of Pittsburgh, Pitsburgh, PA 15260, USA

Reference

1 C0 Lovejoy, M.) Cohn, TD White, Proc Nal Acad Sci USA 96, 13247 (1999)

Response

SCHWARTZ IS INCORRECT TO CLAIM THAT OUR

proposal is Lamarckian We refer to selection

and the main contribution of our

paper is to identify a selective pressure that

could have favored the adoption of upright,

ed bipedality some of the posteranial features such posture may be controlled bya limited number of developmental genes

(2) is interesting, but unless Schwartz is pro-

posing that natural selection cannot operate

‘on such genes, itis not relevant to an assess-

ment of our paper

The most striking feature of modern

human bipedalism compared with that

of other vertebrates is that we walk with

extended hips and knees (2) permitt

substantial energy savings by exch:

of potential and kinetic energies In th

facultative bipedalism, untrained captive

Because the common ancestor of crown hominoids is likely to have had a similar niche

to orangutans—that is, to have been a ripe- fruit eater exploiting the peripheral canopy of

showing orangutan-like features of the hand (6)], and there is strong evidence for highly and habitually extended hips

in the much later, partially or wholly arboreal crown hominoid Orrorin (7)

These adaptations would certainly facil- itate the adoption of habitual terrestrial bipedality by early hominins Terrestrial bipedalism would then be expected to select for features of the hominin post- cranium that enhance the effectiv

of human (terrestrial) bipedalism (7)

€.g., adaptations limiting abduction of the thigh on the trunk (such as a short ilium) and a talocrural joint that favors tal motion of the legs over the stance

foot, also at the expense of abduction—as

first in Australopithecus anamensis (8)

Such selective forces eventually lead to the

modern form of the human foot and pelvis,

although thismay not have been in place even

References

1 €.0 Lovejoy M.} Cohn, T.O White, Proc Not Acad Sci USA.96, 13247 0999),

2 RMeN Alexander) Anat 204, 321 2009)

3 RLM Crompton 115 2003) et a, Cour Forsch, inst Senchenb, 243,

4, D Pilbeam, in The Primate a (Cambridge Univ ress, Cambridge, 2002), Fossil Record, W.C Hartwig,

pp 303-310

5 CV Ward, in Hondbook of Poleoanthopology ‘Primate Evolution and Harmon Origins, W Henle, L Wo 2:

Tatesal, Es Springer, Heidelberg, Germany, 2007),

pp 1011-1030,

6 Š.Aimedj, D M ba, S,Nojô-Sd, Me, Proc Soc tondon Ser B 214, 2315 (200)

2 B Senut, in Human Origins ond Environmental ‘Backgrounds, M\hida, RH Tl, M Pickford,

N Ogihara, M Nakatsukasa, Eds (Springer, Heidelbers, Germany, 2008), pp 199-208

8 CV Ward M Leakey, A Walker, Hum Evol 4, 235 2001)

16 NOVEMBER 2007

1065

Ẵ LETTERS

1066

What's in a Name?

IF THE NAME LUPA FOR THE EUROPEAN DOG

genome studly was chosen afierthe Roman she-

wolf (“Europe going to the dogs.” E Pennisi,

News Focus 21 September p 1670), the

choice is not a f

legend was dismissed even by the Roman

historian Titus Livius, who explained that the

‘mother of Romulus and Remus was a certain

Acca Laurentia,a very prosperous sex worker

(to use a Dutch expression) —so prosperous

that she left a lot of money to the city founded

by herons In popular Latin, lupa meant s

wolf, but it also meant whore Even today, in

certain languages, we speak of brothelsas lupa-

nari (in Ialian; the French havea similar word)

Obviously, no one wants to have a whore on

their

legend came about Tam affaid that our Euro-

pean colleagues made the same mistake as

Mussolini, who called the preschool Italian

children Figli della Lupa, hus sendingacollec-

tive insult to Italian mothers Ifthe LUPA con-

sortium were to change their name, I suggest

JASPER, the name of my German shepherd,

who is, of course, the best specimen of the best

of all possible breeds,

RENATO BASERGA Department of Cancer Biology, Thomas Jtferson Univesity,

Philadelphia, PA 29107, USA,

The Carbon Benefits of

Fuels and Forests

THE POLICY FORUM “CARBON MITIGATION BY

biofuels orby saving and restoring forests?” by

R Righelato and D V Spracklen (17 August,

902) provides limited perspective a a result

relatively short time horizon and a limited consideration of the options available

Righelato and Spracklen conclude thatthe

bon sequestered by saving or restoring forest

greater than the emissionsavoidedby the use of

the liquid biofuels Although they may be cor-

rect given current technology, the case studies

they analyzed, and a 30-year time horizon, their

conclusion is dependent on site technology

and time, and it does not apply to biomass used

for direct combustion or gasification, Marland

and Schlamadinger (/) showed that the carbon

balance between restoring forests and proxue-

Isis site-specific and depends on bio- mass productivity, the efficiency with which

harvested material is used, the initial state of the

surface vegetation, and the fossil fuel to be dis-

placed, When forest products are used eff

ciently to displace carbon-intensive fossil fuel,

and when productivity is high, sustainable

ieitous one The she-wolf'

andards, and that show the she-wolf'

CORRECTIONS AND CLARIFICATIONS [News of the Week: “CDC director's message on risk runs afoul of White House ets" by E Kitsch (2 November, p 726) The photo caption should not have said that White House science adviser John Marburger wanted to remove parts of pro- posed testimony by CDC Director Julie Geberding onthe public health effects of global warming Marburger raised ques tions about portions of her testimony but didnot suggest any cuts

TECHNICAL COMMENT ABSTRACTS:

Comment on “Origin of Human Bipedalism As an Adaptation for Locomotion on Flexible Branches”

David R Begun, Brian G Richmond, David S Strait Thorpe et al (Reports, 1 June 2007, p 1328) concluded that human bipedalism evolved from a type of bipedal posture they observed in extant orangutans with seemingly human-like extended knees However, humans share knuckle- walking characters wit Arian apes that are absent in orangutans These are mast parsimonious explained by positing

‘a knuckle-walking recurso to human bipedalism, Ful text at wunsciencemag,oro/cgicontentfull3 18/585 3/1066d

Response To COMMENT ON “Origin of Human Bipedalism As an Adaptation for

Locomotion on Flexible Branches”

Robin H Crompton and Susannah K S Thorpe

‘Begun eta purport to present technical concerns regarding our case fr an arboreal origin or terestialbipedalsm in early hominins, but merely reiterate their knuckle-walking hypothesis, which lacks support rom the fossil record and is highly unparsimonious The technical concerns ae refuted by published studies cited in our study and thus do not affect,

‘ur original conclusions, Ful text at wunesciencemag,oro/cgicontentfull318/585 3/1066 harvest yields the greater carbon benefit, espe- cially over a longer time period Current- technology liquid biofuels represent low- efficiency conversion of harvest to energy, but direct combustion or gasification is more eff cient at displacing carbon from fossil fuels

Righelato and Spracklen show that, over 30 years, even producing diesel fuel from woody biomass can begin to look “compatible” to reforesting temperate cropland As we wrote in

1997, “there is not a one-size-fts-all strategy for optimal management of all land available for forest management to mitigate CO, emis-

sions” (J) However, in many circumstance:

biomass can produce greater carbon bene!

than saving or restoring forests

GREGG MARLAND, *? MICHAEL OBERSTEINER,*

BERNHARD SCHLAMADINGER®

‘untenational institute for Applied Systems Analysis,

‘42361 Lovebug, Asta "Ervitonmertal Sciences Dison, (Oak Ridge National Laboratory, Oak Ridge, TN 37831-6335,

USA Joanneum Research, A-8010 Graz, Aust Reference

1 G.Marlan, 8, Sclamadinge, Biomass Bioenergy 13, 389 1997)

Response

IN OUR POLICY FORUM (17 AUGUST, P 902),

‘we explicitly considered only liquid biofuel hich substitute for petrol and diesel La scale replacement of fossil fuels in transporta- tion isa more intransigent problem than the substitution of fossil carbon for heat and power considered by Marland and Schlamadinger

to develop and implement carbon-free transport-fite! technology On this

the current biofuels reduce carbon dioxide emissions less effectively than restoration

of forests As Marland, Obersteiner and Schlamadinger indicate, there may be net carbon benefits from biofuels if longer time periods and new technology are considered However, these avoided emissions would be too small and too late to meet ta

more reduction in emissions by 2050

We noted in our Policy Forum that under some circumstances, fuel use of woody bio- mass may be compatible with retention of for- est carbon stocks and may provide net carbon benefits similar to forest restoration in temper- ate zones This is consistent with the model of Marland and Schlamadinger (/) However, land resources for arable substitution of tra port fuels on the scale required are not avail- able without further extensive deforestation, which would cause massive carbon dioxide emissions Further demand for forest land to provide biomass for burning or gasification

‘would need to be on a similarly lange scale to meet emissions reductions targets Itis becom= ing increasingly clear that the risks associated with these land-use changes may outweigh any benefits In our view, biofuels cannot providea

www.sciencemag.org

Ẵ LETTERS

solution to our energy needs, but by appearing

to be a “quick fix.” they may distract us from

developing effective, long-term, carbon-free

solutions inthe time window available to us

RENTON RIGHELATO® AND DOMINICK V SPRACKLEN?

‘World and Trust, Halesnorth, Sufok, IP19 8A8, UK

2chool of Earth and the Environment, University of Leeds,

1G Marland, 8 Schlamadingr, 389 (1997 Biomass Boeneray 13,

Eyeing a New Network

| S KOHANE AND HIS COLLEAGUES’ POLICY

Forum (11 May, p 836) on *Reestablishing

the researcher-patient compact” should evoke

a response from clinical researchers, Health-

care organizations are keen to use large data-

bases of information that have accumulated

through record-keeping for clinical care

delivery Unfortunately, the consent process

did not necessarily allow the freedom to con-

tact patients as research subjects The authors

propose a prospective approach in developi

formed cohorts, with linked medical and

In 2003, the National E:

vened a broadly representati siona National Genotypi ited eye diseases with two goal resource for ophthalmic research in inherited ocular disorders, and to allow access to geno- typing for patients and their doctors A ne Work of certified laboratories (7) was orga- nized with a coordinating center to which a secure Web-based database was linked In September 2006, the eveGENE™ Network received its first sample (2) Phenotypic infor~

‘mation was entered by the patients doctor with the understanding that the patient

heritable ocular conditions The Network has not encountered any issues related to breaches

in patient confidentiality or concerns about

‘employment or insurance discrimination This research project has been enthusiastically received by the ophthalmic and optometric

‘community and stands as an example of how

‘genomic research can be translated to patients,

IAN M, MACDONALD, BRIAN P BROOKS,

PAULA SIEVING National ye insttute, NIH, Bethesda, MD 20892-1860, USA

References and Notes

1 Laborateries Laberatery improvement Amendments (CL were certified according tothe Clink

2 The National Ophthalmic Disease Genotyping Network, _eeGENE™ (nnn neiih govlesourceseyegene 25)

Letters to the Editor

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1070

MEDICINE

The Universal Darwinism of Disease

David C Krakauer

ost remember the title

Mei bassin sot jonary book, On the

Origin of Species by Means of

Natural Selection, but then for-

get the subtitle, Or, the Preser

vation of Favoured Races in the

Struggle for Life Whereas the

former pertains to change and

Variation, the latter relates to sta~

bility and uniformity The math

matical theory of evolution has

sought to explore the cons

quences of mutation and vari

tion on change and those con-

straints and evolved mechanisms

that confer robusiness on 0

robustness mi

to the prevention and elimination of disea

Evolutionary theory is the right framework

toadopt when we are seeking to

account forthe sources and con-

straints of variation in mutable

lineages within large popula-

appropriate, the application of

Darwinism toa stunning range

of phenomena, from the

the pro- gression of disease, and the

processes of speciation to the

licenses,

eC dynamics of genom

DỊ origin of language Incachcase, iW

we are dealing with random

develop- ment, replication, drift, and

selection But the effectiveness of the theory as

for all powerful scientific theories, turns on the

subtleties of quantitative rigor

In The Dynamies of Cancer evolutionary

biologist Steven Frank (Un

fornia, Irvine) explores a theoretical immunol-

y perspective on cancer—seeki

abundant data on coarse-pr

Evolution processes of variatio

selection dynamics The core macroscopic

focus of the book is the age incidence curve

of cancer, and the microscopic explanation

ression

-e records the number

of cancer cases per year for a particular

The reviewer is atthe Santa Fe Institute, 1399 Hyde Park

Road, Santa Fe, NM 87501, USA, E-mail: krakauer@

Spectral karyotype Multicolored painting probes reveal chromo

somal rearrangements in an oral cancer cel

group divided by the number of people in that ige group When representing age against inci- dence on a double logarithmic plot, one fre- quently observesa straight line that canbe fit by

function of the form = ct, where / is the incidence, ¢ the

age, and n the number of stages

through which the cancer pro-

esses The constant ¢ varies

according to a number of differ cent det hic and disease factors Different cancers and different

females, for example) tend to show very different patterns of

oups (males versus

ae incidence Moreover, the slopes

n depart from ind their gradients (accelera- tion) carry important information It is these patterns—incidence and acceleration—that Frank seeks to explain, as he sees them as the primary quantitative signatures of cancer The key to understanding incidence acceleration is a multistage progre describes a sequence of mutational events through which a tissue must transit on its path toward cancer, These mutations can be classi- fied according to their impact on the b

cell birth and cell death Mutations in involved in programmed cell death abro the ability of cells to kill themselves when detecting damage Mutations in tumor suppres- sors remove key constraints on cellular prolif eration, and mutations in oncogenes typi stimulate cell division Mutations in DNA repair pathways can lead to hypermutation and chromosomal instability, accelerating the rate

‘of mutation toward cancer, Lastly, mutations in

certa n-genes cause tumors to promote the

‘growth of blood vessels required for tumor sur- vival The mutational spectrum is vast, but the underlying logic is often fairly simple Important contributions of the bookare the two theory chapters in which Frank develops a

series of simple mutation-selection models Building on pioneering work of Knudson, Armitage, Doll, and others, he aims to capture how variation in the sequential accumulation of

mutations can generate the panoply of age inc dence curves

Frank's forte in the book is his search for the simplicity that is often masked by the com- plexities of cancer With his mathematical

eration of melanoma versus the rapid

tion of pancreatic cancer Frank par- simony-based approach to theory leads hin to stress comparative analysis rather than curve- fitting The comparisons follow a hypothetico- deductive model, whereby differences in progression are used to hypothesize differ- ences in the a

A pervasive theme in the book concerns the lamentable, growing distance between molec-

and the kind of macroscopic the- ory Frank favors As our measurement tech-

Kingdom The firm was the first in the coun-

try to adopt many industry characteristics,

stich as the establishment of research labora-

toriesand the use of detail men, andit was also

a leader in product innovation and ethical

advertising In Burroughs Welleome

historians Roy Chureh and Tilli Tansey pro-

vide a detailed, profusely illustrated account

of the company’s first 60 years

‘The reviewer sat the Department of the History of Scence,

Technology, and Medicine, The Open Univesity, Walton Hall, Milton Keynes MK7 6AA, UK E-mail: a simmons@

‘openacuk

Burroughs Wellcome was established in London in 1880 by two American pharmacist Silas Mainville Burroughs and Henry Solomon Wellcome Both brought key skill to the part- nership: Burroughs contributed initial capital and innovation, foundations that Wellcome then built on The firm soon expanded its business

‘overseas and introduced detail m products directly to medical practitioner

| druggists In its first decade, the company underwent a tran-

sition from trading to man- facture, which culminated

in the 1889 opening of its main factory in

Kent, and established itself

as a leader in the British pharmaceutical industry

The themes of knowl edge, trust, and profit are central to understanding the firm’ development

Trust provides a particularly interesting per- spective highlighting both strengths and weak- nesses in the business operation Despite the many achievements, Burroughs and Welk distrusted one another to the extent tha

However these personnel problems did not affect customers’ trust in the firm, A reputation

for high-quality products and ethical advertising was central to itsrelations with both physicians and pharmacists This trustwor- thy reputation was enhanced by Henry Welleome’s objective to advance medical knowledge through the creation of research laboratories, whose scientists could publish freely and pursue independent lines of research

uch an ethos undoubtedly

1876 Cruelty to Animals Act That achieve-

‘ment—which the authors describe as “possibly

Thousands of Products Hundreds of Techniques Infinite Possibilities

self, request a copy of our new Cell Biology Application

‘cReom

the most important conitibu-

tion Wellcome made to med-

ical research in Britain”

allowed the firm to carry out

the animal testing required

for the production of anti-

toxins and set a precedent

for the registration of other

Jaboratories associated with

‘commercial manufacturers,

While recognizing the

worth of trust and knowl-

edge in pharmaceutical

manufacturing, Henry Well-

‘come also understood com-

mercial demands, and he

‘emphasized the importance

‘of “quality for profit” In the years leading up

to the First World War, net profits grew steadily

to just over £80,000, This growth did not con-

ined sharply between the 1920s and 1930s,

g the business in the context of wider

Church and Tansey provide a

more nerpretation of the problems

Burroughs Wellcome en- countered than have pre- vious histories Holdin ick from directly ap- pealing to consumers through the mass media and remaining loyal to individual retail chemists, (rather than discounting Prices for multiple-outlet wholesalers such as Boots), the company was

le behind by cru

‘developments in pharma- ceutical retailing, De- spite ts history of research ellence it launched only oneimportant innovative product (Digoxin,

a substitute for digitalis) during the 1930s, while it also failed to diversify and develop new lines of general goods Knowledge, trust, and profit, the authors argue, are also cen- tral to understanding the difficulties the

as Burroughs Wellcome inadvertently supplied many of its rivals with ready-trained

' By 1940, Boots, May & Baker, axo, and British Drug Houses all employed research directors who had previously worked for Burroughs Wellcome These influences have continued The Welleome Trust is the largest private funder of medical research in Britain and, with the recent opening of the

‘come Collection in London, brings F Wellcome’ legacy to a much wider audien (The Trust also provided “generous funding support” forthe book.) Much more than a com=

pany history, this attractively presented and comprehensively researched book shows how one firm transformed the pharmaceutical industry in Britain

10.11264ience.1147950

Detailed Pathways Proven Expertise Unlimited Opportunities

Guide toda

www.millipore.com/OneBook ADVANCING LIFE SCIENCE TOGETHER™

Research Development Production

ation of Upstate® and Millipore brings together al

ew Cell Signaling Application

upstate

1074

PUBLIC HEALTH

Biobanks in Developing Countries:

Needs and Feasibi

S.K Sui

One in developing coun-

tries, yet only 10% of globa

lity

'* Jha,'†.Mony2A Kurpad? V Lakshmi R Kumar,‘N K Ganguly®

Technological advances coupled with use

of existing resources can be used to create biological repositories that may lead to better health in developing countries

wide due to HIV/AIDS, tuber- culosis.or malaria are in devel- oping countries Even inf

keted drugs were for tropical | 98 (40-69 0) (-s240) * No smokingandtuberculosis (5)

diseases and tuberculosis (J) stnian Genome <A miont 525mMMeE — ye No Genetic or undiscovered Repositories of biological Piet (3250) copathogens may help ex- samples linked with medical Keane decode 25000 $22milon Yes, No plain the unprecedented in-

banks) are infrastructures [or Kadooie study of Chronic 500.000 $22 milion Yes some and southern Africa, Natural sustained research on the bio- _ DSeass in China 5-74) (550) resistance to HIV appears to logical determinants of dis: thedesc Cty 160000 = 5 be evolving among select

ease and promise to acceler- Prospective Study (5+ y0 Morante X4 populations (6) that are con-

ate the discovery of vaccines, TheGambianNatlonal $0.6 million! esl stantly being challenged by

ever, the distribution and TheldanNalawal focusofeurrentbiobanks suz- | BESSA ~2-3mllớU 20-830 milion 8x) cống Yes Yes_—_the immune systems have so evolve fo Fight thoke Intec:

gests that their discoveries

will not sufficiently benefit

those living in developing

- Innovative use of :chnological advan- sting infrastructure platforms make biobanks cost-effective and feasible in devel-

The Human Genome Project, annotation

of millions of single-nucleotide polymor-

phisms (SNPs) within the genome, develop-

ment of ultrahigh-throughput genotyp-

ing, small-molecule detection methods, and

powerful software to analyze the mass of

data that is generated, now make possible the

discovery of the allelic and biological va

ants that underlie complex d

centre fr Global Health Reseach, t Michael's Hospital

(USKUKRO), Univesity of Toronto, Toronto, ON, MSBICS,

Canada, 25 John’s Research Institue, Bangalore 560034, India ?Nizam’s Institute of Medical Sciences, Hyderabad,

500082, india ‘School of Public Health, Post Graduate

institute of Medical Education and Research, Chandigarh,

160022, India Sndian Council of Medical Research, New

Delhi, 110029,1ndia

“Present address: Howard Hughes Medical institute, Beth

Israel Deaconess Medical Center and Harvard Medical

School, Boston, MA 02115, USA

‘Author for correspondence Email: Prabhatjha@

Wtort.ca

16NOVEMBER 2007 VOL318 SCIENCE

'#sinxie IS đolà, {sis 75% othe Estranpoptin fora pl poet of 10,00 paicpants ‘aml kage uses ae posite rhe wo Bans nd geet

‘etnks Bet Mor he ests years fond to doe contac nnksal T andr malas rd te ADS, wh has iow pelea The Gambia sPesenly at the cegn age

as cardiovascular diseases, cancer, diabetes,

tuberculosis, and AIDS) Common genetic variants likely involve moderate effects,

such asa relative risk of 1.2 Reliable assess-

ment of these variants in different popula-

tions (including documenting any interac

tions between genes and other risk factors) requires studies with thousand

of thousands, of cases and controls,

A few biobanks have already been estab- lished in developing countries such as the Chinese Kadoorie study (2), the Mexican biobank (3) and the Gambian national DNA bank (4) (see table, above) The Chinese and Mexican biobanks were designed primarily

to discover correlates of noncommunicable diseases in adults over age 35 years, and the Gambian study is relatively small These studies are not sufficiently representative of the major causes of death and disability in developing countries or of the age groups at which disease strikes In particular, HIV AIDS, tuberculosis, and malaria require larger studies in diverse popu!

ation esr posible fr a tions can enable new drugs

and vaccines Focused biol ical research on the genetic and other biological corre lates of infectious dis

is under way, most notably by the Grand Challenges in Global Health (7) These need

to be complemented by more open-ended platforms for unpredictable discoveries, as is possible with larger biological repositories linked to medical data,

Developing countries, unlike most developed countries, suffer from the dual burdens of chronic (chiefly noncommuni- cable) diseases and infectious diseases (3) Already, four out of five chronic disease deaths occur in developing countries The genetic and environmental variations that contribute to complex chronic diseases are

sarily the same in geographically segregated populations Indeed, common

‘onic diseases can have surprising cor-

ly low, as well as those with exces-

siv sively high, body mass even after adjusting

for smoking and blood pressure (9) Two

small studies in India (/0) and in Iraq (//)

found that low body mass and diabetes were correlated with tuberculosis history

and a positive tuberculin test, respectively

www.sciencemag.org

.A Way Forward

Typieal biobanks are

expensive partially

because the serum

samples that they col-

lect and keep must be

keptcold continuously

Dried blood spots

(DBS), in contrast,

do not require reftis

eration during col-

lection or transport

(2) DBS simplescan

be easily collected

and safely transported

by regular mail The

higher acceptability

by participants of -

DBS versus whole-

blood collection, lower

costs, and ease of handling also enable

much larger sample sizes to be achieved

within a

Despite their small volume, DBS samples

have been increasingly used for molecular,

enzymatic | biochemical,

and hematopoietic analyses SNPS within the

\whole genome can now be reliably assessed

from DBSs (/3) The continuous decline in

the sample volume and the cost of SNPs and

the development of high-throughput analyses,

mean that biobanks based on DBSs are

becoming economical, as well as scienti

cally practicable The major roadblock is get-

ting reliable epidemiological evidence

about the relevance of variables measured to

the development of d Appropriately

large-scale epidemiological fieldwork in

developing countries to acquire blood sam-

ples systematically linked to relevant me:

ures of disability and future mortality is eru-

cial Biobanks in Westem countries use their

national health systems, with physi

collecting samples and medical data for

their patients In developing countries, how-

ever, fewer people have access to medical

and linkage to routine health care is,

not yet possible

Several developing countries have

established disease and mortality surveil-

lance systems, which could be cost-effe

tive platforms for biobanks A good exam-

ple is the antenatal clinic HIV surveillance

system recommended by the World Health

Organization to track changes in HIV

prevalence among pregnant women in 132

countries This widely implemented sys-

tem is not used adequately to understand

the transmission and correlates of HIV

infection, primarily because collected

samples are usually discarded after HIV

I correlates of HIV Other examples lished surveillance systems include surveys of malaria parasites and the INDEPTH network of 37 demographic surveillance sites—26 of which are in Africa (14)

of disease in India The MDS is unique because it collects data that will allow both family-based genetic studies and case-con- trol association studies The design and seale should ensure that for each complex disease of interest, several thousand cases and controls (efficiently tested through

“nested” case-control design) will be avai able for association studies with sufficient statistical power to detect modest but med- ally relevant associations,

We are exploring methodolo logistical issues of build biobank in Indi

alcohol use, other variables, and DBSs were

collected in household surveys in 2006 from

2700 adults aged 18 years or older in six dis triets in three states (see figure left) Only 5% of the people interviewed refused to give DBSs, in contrast to refusal rates of nearly 40% in a similar study collecting a serum

Toward a Global Consortium

of Biobanks National or regional biobanks are a first step Others have called for a global con- sortium of biobanks to address common ethical issues, data ownership, and data sharing (17, 78) We see these consortia arising for two reasons First, joint analy- ses of important, but uncommon, gene variants will be needed to generate more definitive results than can be generated from individual (and likely underpow- ered) studies Second, reasonable expee- tations from funders and beneficiaries will push toward collaboration, as has pened with the Human Genome Project (19) and the Global HIV Vaccine Enter- prise (20) The promise is enormous:

cessible and affordable studies in diverse populations to permit imaginative search for common and rare genetic and other biological correlates of global diseases,

References and Notes

2 Peller eta, Lancet 359, 2188 (202

2 2.Cheneta ft -Epdemiok 34, 1243 2005)

3 RlapiaConyere al, nt Epdemiol 35, 283 e006

4, G.Siugoet ol, Nat Geet 36,785 (2008

5 V Goji & Peto, 15, Kana, ha Lancet 362, 507 (2003)

6 Le Heney AG Dag, RA Wes, Since 323, 462 (2006)

7 H.Varmuset al, Science 302, 398 2003)

8 CO Mather, Loner, PS 3, e442 (2008)

9 2 Gheneta, it} Epidemil 35,181 2008)

0 H.Shety,M.Sherko, Ma, D'Sou, nt aber ‘ung D's 10, 802008)

11, W.ALKubasy AA Dutayme 0.5, Hashim, Eos Medier: Heath 9, 675 2003

22 K, Stenberg et ol, Epidemiology 13, 246 2089

1B, RLA Payer etal, Cancer Epidenial Biomarkers Pree 15,2533 (2006)

14, INDEPTH Network, wm indepth etn ogi roils, sitesi

1, Phvet ol, Pas ed 3, 182006, 16 Prospective Urban and Ral Eidenilogial Sty, mccmemasttapureide

17 WE Hagen, | Cred Due, Hot ed 10, 668 0000,

18 A.Cambon Thomsen, Not Re Genet 5, 8662009

19 Human Genome Proje, worn govsiechesouces! Human_Gerameshome shtml

20 Global HV Vaccine Enterprise, wm hinacineentepie S8

10.1126 ence.1149157

1075

1076

PHYSICS

When Oxides Meet Face to Face

Elbio Dagotto

tilayer structures have

Ms ssearch topic now that

atomically precise methods for

preparing them are available, In

particular, researchers expect that

‘oxide multilayers may lead to

interesting artificial mate

with novel properties (see the fi

everal of the oxides used in

er systems belong,

of compounds with strongly correlated electrons The

exotic properties of these oxides

include high-transition tempera-

ture (7) superconductivity, with

critical temperatures far higher

than in standard superconductors,

and colossal magnetore

(CMR), where the app!

magnetic fields of a few tests

report x-ray analysis and calculations of the

interface between two such oxides

These authors prepared a heterostructure

with layers of (¥.Ca)Ba,Cu,O, (YBCO) and

La,,Ca,Mn0, (LCMO) and observed a

transfer of charge from the Mn oxide to the Cu

oxide This induces important modifications in

‘tronic orbitals of the atoms atthe inter-

‘or example, the orbitals designated

dy (2) are considered irrelevant in bulk

cuprates because they are fully occupied and

cannot act as bridges for current flow At the

interface, however, they become partially

‘occupied and can move electrons between the

‘wvo oxides The interfacial orbitals undergo

“reconstruction” —that is, they are deformed

shape so that the electronic structures of the two different oxides can blend,

Most ofthe oxides under consideration forhet-

cerostructures are very Sensitive to reconstru

tion, something that must be considered in all

future designs of artificial oxide multilayers,

High-7, superconductivity and CMR are

examples of “emergent” phenomena—new

properties that cannot be anticipated from the

The author isin the Department of Physic, University of Tennessee, Knosvile, TN 37996, USA, and the Materials

Science and Technology Division, Oak Ridge National

Laboratory, Oak Ridge, TN 37831, USA E-mall:edagotto@

utkedu

16NOVEMBER 2007 VOL318 SCIENCE

Oxide interfaces Models of heterostructures of lanthanum alumi- nate between strontium titanate layers The atoms are represented

by colored spheres (oxygen, white; lanthanum, orange; aluminum, yellow, strontium, large blue; and titanium, small dark blue)

‘Although the materials alone are insulating, the electrical conductiv- ity ofthe bottom interface (purple spheres, brighter onthe Left ini Cating higher conductivity) can be tuned due to coupling withthe top interface (12)

local interact ions among the electron:

between electrons and the lattice, Many recent and

investigations ha led the complex nature of these materials in bulk These hard ceramic materials seem to hide a “Soft” elec- tronic component that produces nonlinear responses to small perturbations, as well as emergent behavior (3, 4)

Antficial thin-film oxide structures could thus make the already complex individual properties of bulk strongly correlated oxides even more interesting The oxides used in these structures could have different bulk properties but they all have similar lattice constants (i distances between atoms), allowing fora good

‘mateh at the interfaces The number of combi- nations of these oxides is enormous, and the potential for novel behavior is a strong motiva tion for these investigation

If interfaces of semiconductors—which are rather featureless materials with a non-

‘magnetic rigid lattice—can nonetheless lead

to fascinating physies such as the quantum Hall effect, imagine what could be done with oxides A variety of exotic two-dimensional electronic systems could be stabilized at the oxide interfaces, exploiting spin, charge, and orbital interactions as well as lattice vibra- tions Recent investigations have already shown that both a metal (5) and a superco

ductor (6) can be induced at the interface of

tự Is, and the number of surprises will surely continue to grow

Charge transfer at oxide interfaces (1 7) produces novel two-dimensional phases, as well as charge doping without the typical disorder caused by chemical doping Thus interfaces provide an interesting venue for doping oxide perovskites (such as the high-T materials) with carriers (8) Technological applications are also possible For example, several groups are working on composition- ally graded interfaces made from mang: with the hope of achieving high-performance etic tun junctions (9)

‘oxide electronics” i fast (/0) although achieving the mobility levels and purity ‘miconductor heterostructu ains a challenge The

issues is what makes oxide heterostructures so interesting: This area of research is located at the intersection between fundamental science investigations and technological applications

Previous studies of oxide heterostructures, were framed in terms of “lattice reconstruc: tion.” That is, because interfacial ions are sub- {ject to forces different from those in bulk, th atoms can change position And the mere trans- fer of charge at interfaces can lead to “elee- tronic reconstruction” (7, 11) In this case, the different electronic density atthe interface rela- tive to the bulk is the origin of the exotic prop- erties Chakhalian er ai have now introduced orbital reconstruction as a third process Although the ds orbital is widely thought to

be unimportant in bulk cuprates, itis known to becrucial nites As cluster calcu- lations suggest (/), the reported strong Cu-O-

Mn bond that leads to the orbital reconstruction

is precisely caused by the dy,

Despite recent activity the

interfaces remains virtually unexplored What might happen if we could mix materials with vasily different properties such as ferromag- antiferromagnets, superconductors, fer- roelectries, multiferroies, geometrically frus- trated spin systems, heavy fermions, and oth- ers? Considering this enormous number of combinations, theoretical guidance is needed But for theory to be usefil, the calculations must be reliable, at least qualitatively Powerful techniquesare needed to study inter-

www.sciencemag.org.

faces of strongly correlated electronic sys-

tems Reliable procedures to calculate and

measure work functions of individual mat

re also needed to predict the direction of

transfer at interfaces The collective

als

cha

responses and nonlinearities of models for

oxide interfaces must be carefully analyzed

By this multilevel effort, the potential new

functionalities and exotic phases of the oxide

‘combinations under scrutiny will hopefully be

revealed Lattice, electronic, and now orbital

References and Notes

1 J Ghathaian eo, Science 318, 1114 2007); published online 11 October 2007 (10.1126écence

6, NeReyren eo, Science 317, 1196 (2007); published ‘online 1 August 2007 (10.2126/science 1146008)

$ Okamoto, A Mil, Nature 428,630 (200) 5 Yunok eta, Phys Re B76, 064532 2007)

9 Yamada el, Science 308, 66 (2008), and references therein,

10 A.P.Ramicez, Science 325, 1377 (2007)

11, ML Huijpen eta, Mot Mater 5,556 (2006)

12 Supported by NSF grant ONRO7 06020 and bythe Division of Materials Sciences and Engineering, US Department of Energy, under contract with U-Batlle, LC

‘ost eukaryotic cells have two copies

ing) chromosomes Although both

copies (alleles) of individual genesare usually

expressed in each diploid cell, one of the alle-

Jes is inactivated in a subset of genes (/) Itis

Of profound interest that monoallelic expres~

sion in somatic cells does not simply represent

a rheostat control for gene expression Rather,

it often operates in some selective function,

such as determining the repertoire of odorant

receptors or T cell receptors that are expressed

(2, 3) Moreover, the parental alleles of some

mouse genes, such as those that encode

cytokines, are expressed in random patterns,

in which either, neither, or both alleles are

inactivated, potentially influencing the selec

tion and expansion of particular on T cells (4),

Onpage 1136inthis issue, Gimelbrantetal,

(5) report that the mammalian genome em-

ploys random, monoallelic expression more

tersively than thought This may be to gener-

ate diversity in expression patterns on an un=

precedented scale, which has important impli-

cations for the ontogeny of human diseases

nelbrant et al determined the propor-

tion of human be expressed

‘monoallelically in patterns that are epigenet

cally stable (for example, chemical modifica

tions of DNA, such as cytosine methylation,

that do not alter the sequence but are heritable

within cell populations) They identified

expressed alleles in cloned cell populations of

human B lymphocytes by taking advantage of

polymorphie sequences, or single-nucleotide

‘The author isin the Department of Development and Genetics, Uppsala University, Norbyvigen 18A, 5-752 36

Uppsala, Sweden E-mail: rol ohlsson@ebc.wu.se

‘monoallelically expressed

in epigenetically stable pat- tems in at least one popu tion of cells derived from

a single B cell clone, Al- though most of these genes

‘were also found to be biallelically expressed in some other B cell populations, up to 20 could be consistently expressed from one of the parental alleles in some B cell clones Thus, each cell population displays a vast hetero- geneity in patterns of mono- and biallelic gene expression, providing numerous combinator- ial patterns of gene expression (see the figure) Although other patterns of monoallel expression have been described in human cells (6, 7), Gimelbrant et al go much further

in two important respects Fist, they analyze large number of genes, thereby increasing the generality of their conclusions Indeed, based

on their findings, the authors argue that more

The surprisingly high prevalence of random allele inactivation in human cells can generate diversity in gene expression that affects cell fate and physiology

Generating diversity Alleles are ran- domly inactivated on a pair of chromo- somes in a human somatic cell The various patterns of inactivation in progeny cells are then stabilized (epi- genetically) This can generate diverse cellular and physiological outcomes

than 1000 genes in the human genome can potentially be mono- allelically expressed at any given

cell diversity and cell fate (8)

Second, Gimelbrant et al hint at the fascinating possibility that the same set of genes can be monoallelically expressed at certain stages of development in

a subset of tissue cells and/or perhaps in only some individ

It is unclear, though, how random monoal- Jelic expression is established in somatic cells, Unlike the acquisition of imprinted, methy- fated marks on DNA from the parental germ lines-so-called genomic imprinting, which inactivates either a matemal or paternal allele during gamete development (/)—random inactivation of nonimprinted autosomal alleles

‘occurs in somatic cells Gimelbrant etal, show that many of the monoallelically expressed genes are highly expressed, apparently ruling

i PERSPECTIVES

1078

out concerns about stochastic monoallelic

transcription events postulated to occur at low

levels of transcription (/), Perhaps both alleles

are in different transcriptional environments

within the nucleus Indeed, alleles that display

asynchronous replication, a hallmark of many

monoallelically expre: es (2), can

‘occupy different positions within the nucleus

(9).Ltmay also be that limitingamounts of pro-

tein complexes that remodel chromatin (the

DNA and protein constituents of

somes) could randomly inactivate alleles

Finally, differentially modified (methylated)

DNA regions that are adjacent, far apart, or

even on different chromosomes might interact

and modulate allele-specific epigenetic states

and transcription (/0) Such possible explana-

tions can now be tested

‘The data fiom Gimelbrant er al could fun-

damentally influence current views on the

‘mechanisms of some pathological conditions uch as haploinsufficiency (having only one functional allele, which produces insufficient amounts of product) or the loss of function of tumor suppressor genes In both cases, the loss

of one allele might lead to a dramatie eff

if the remaining allele already carries epig netic marks that render it inactive (I1), Consequently, anyone unfortunate enough to possess the “wrong” set of monoallelically expressed genes might be susceptible to the earlier onset of a complex disease such Alzheimer’s disease The interplay among genotype epigenotype, and gene inactivation will now become more important for under- standing developmental mechanisms, pene- trance of diseases, and responses to medi atments in an individual,

References and Notes

1 R Ohisson 8 Tek, C Sapienza, lends Genet 14, 435 (1998)

2 BLM, Shykind, Hum Mol Genet 14 pec no 1), R33 (205)

3 M Golémit,¥ Bergman, immuno Rev 200, 197 (2008),

4 BLL Kally, RM Locksley, Immunol 165, 2982 (2000)

5 A Gimelbant, JN Hutchinson, Chess, Science 318, 1136 (2007) 8 RThompson, A

6 PL Pant etal, Genome Res 16, 31 (2006)

1 1.Pastnen eto, Physiol Genomics 16, 184 (2004)

8 5 sum eto, Wot Genet 37, 171 (2008)

9 PK Yang Kuroda, Cell 128,777 (2007)

10 R Ohlsson, A Gondor, Cur Opin Cel Bil 39, 321 0007)

11, H.Raslow eta, J Clin Invest, 124, 77 (2004)

112 Supported by rants fram the European Union (HEROIC), Swedish Cancer Research Foundation, and Snedish Research Counc,

shown that DNA can be programmed into

higher-order structures and used to

encode mathematical computation (/-3)

Many attempts have been made to crea

DNA-based devices and machines of

mechanical and computational nature (3-5)

Yet DNA nanotechnologists still face substan-

tial challenges in passing fiom proof-of-prin-

ciple demonstrations to functional devices

that are reliable, quick, and extendable On

page 1121 of this issue, Zhang et al (6) report

an important step toward this goal,

In contrast to solid-state devices, DNA-

based systems operate at the nanometer scale

in an aqueous environment, where thermal

motions render molecular interactions impr

se Hence, in seeking programmable bio-

ical functions, scientists must invent

ns that are hierarchical and resilient to

spurious interactions and signal degradation,

Living organisms rely on genetie biochem-

-al networks to regulate complex functions

such as sensing, adaptation, timing, and

ultimately— reproduetion These networks

have evolved in noisy environments and are

hence inherently robust, often endowed with

high-fidelity capabilities They are composed

Of genes and their respective RNA and protei

T the past three decades, scientists have

The author & in the Department of Materials and Interfaces, Weizmann Institute of Science, Rehovot 76100,

Israel E-mail ry.bar-ziv@veizmann.acit

16NOVEMBER 2007 VOL318 SCIENCE

ate’s 3, inducing two branch migrations and releasing the output

strand, a waste complex, and the catalyst for another turnover

products and exhibit a variety of dynamie pat- terns Key players in these biochemical [unc- tions are enzymes that can pick up even faint chemical signals, amplify th lì the oreanism, and relay them rapidly for sub- sequent processin;

Ati chemi try may one day play an analogous role in human-made systems, Imagine circuits that control DNA- based motors and sensors, similar to electrie circuits controlling electromechanical devices, For example, a recent report described DNA circuits (4) in which the input and output sig- nals, as well as the logic gates, were rep!

2 Computations were per-

formed by hooking up and cascading gates and signals

in a manner similar to ele tric circuits However, adding more components incurred long response time and signal loss, thereby forming a bottl neck for nontrivial computa- tion, Hence, a fast and modu- lar amplification mechanism

is essential

Zhang et al now propose

an elegant solution to this nal amplification bottleneck

In essence, they emulate the concept of the biochemical enzyme, but with DNA strands only The

ism alters no covalent bonds and is driven by entropy (rather than

most biological catalysis) The desi

on the separation of binding energy s making it easy to understand, robust, modular, and potentially usef\

The basic species are six short, singh stranded DNA domains that interac Watson-Crick base pairing Strands com- posed of these domains make up all the play- ers in the reaction: substrate, fuel, output nals, catalyst, and waste (see the figure) The

core domains of the substrate (domains 2, 3,

Signat

and 4) are paired to the signal and output

strands, whose domains 1 and 6 are unpaired,

as is the substrate’s dangling end domain, 5

The goal is to release the signal and output

strands Naively, in the absence of a catalyst,

this can be done solely by the fuel—a strand

composed of domains 2, 3, and 4—which

replaces the two strands The signal and output

strands are then released to solution along

with a waste by-product composed of the sub-

strate core and the fuel In this catalyst-free

exchange reaction, the same domains are

base-paired in the initial and final states so

there is no net change of binding energy

However, the overall configurational entropy

ses in passing from two to three free

s The reaction is thus thermody

ly favorable Yet a lange kinetic barrier

is incurred because the catalyst-free exchange

reaction must proceed by unzipping the sub-

strate one base afier another—a highly

improbable sequence of events that would

takea very long time

To push forward the reaction, Zhang et a

troduce a catalyst composed of domains 4

and 5 The catalysts dom: now pair

with the substrate’s domain § to trigger the

rapid displacement of the signal by a proc

called branch migration The catalyst thus

reduces the kinetic barrier and stabilizs

Zhang et al demonstrate two applications

of amplification using their catalytic scheme

First, a two-stage cascade was constructed

by introducing an upstream catalyst system whose output acts as the catalyst to another system The circuit amplifies the initial eata- lyst by a factor of 900 Second, an autocat- lytic circuit was constructed by encoding the catalyst asa part of the output, such that reac- tion closes a loop on itself, displaying expo- nential growth kinetics

Why Embedded in a biochemical logic circuit, it can be used to amplify weak signals and thus

4 and 6) never appear in single-stranded form, Molecules can interact only via the

PERSPECTIVES L

short, weakly binding “tochold” domains (3 and 5) This separation of energy scales renders the design extendable and tractable

Catalytic DNA citeuits of the kind de- seribed by Zhang ef al could be coupled to various biochemical reactions to analyze heterogeneous macromolecular mixtures, detect weak biochemical signals, and control nnoscale devices Combining such enzyme- free DNA circuits with biosynthetic reactions may get us closer to understanding nature’

design principles DNA circuits could also be integrated into materials platforms, such

as gels, polymers, and surfaces, to generate ive programmable systems (4, 7-10)

References

NC Seeman, Theor Bol 99,237 (1982) LM Adleman, Science 266, 1023 (1994),

LC Seeman, rends Bachem Sc, 30,119 (2005)

- G Selig, Ð.%lovechit, D.Y.Zhang, € Wire, Science 314, 1585 (2008)

5 BLK Rothemund, Noture 440,297 (2006)

6 0.¥-Zhang, A.J Tuber, Burke, Winfree, Science 318, 1121 (2007)

7 Ve Moiteau,R BarZiy, A Libchabe, Proc Sci USA 100, 12672 (2003) Not Aco

8 M Ieln, C (emele,L Serano,Plo§ Bo 3, 488 (2008),

9 W.U Dittmer, 5 Kemptr, JO Raley, FC Simmel, Small, 709 (2005)

10 A Busboim etal, Small 3, $00 2007)

10.1126/xience:1150200

CANCER

The Gene Topography of Cancer

Jeffrey M Trent and Jeffrey W Touchman

here are three key questionsany cancer

Ts cn wie saftey hinge her diagnosis: What type of cancer do 1

have? What is my outlook? What can be done

about it? Increasingly, the answers are coming

from DNA-based sequence information

Decades ago, sciemtists discovered that de-

use eancer (1, 2), thereby hing a paradigm for tumor biology

and providing an important motivation for

embarking on the Human Genome Project

Yet this remarkable sequencing achievement

marked only the beginning of the quest to fully

understand the biology of cancer With the

complete sequence of nucleotide bases in

normal human DNA available, scientists now

classify the wide array of human genes

ording to their involvement in tumorigene-

sis On page 1108 of this issue, Wood et a (3)

The authors are at the Translational Genomics Research Insitute, Phoenix, AZ 85004, USA E-mail jrent@tgen.org_

www sciencemag.org

advance this endeavor by describing tional spectrum of nearly every well-anno- tated human gene [18,191 distinct genes from the Reference Sequence (RefSeq) resource] in

11 breast and 11 colorectal tumors through systematic sequencing of coding exons

The resulting sequence “landscape’

these tumor genomes is striking The authors

ering of five well-studied genes commonly mutated (which they call

‘mountains”), as well over 200 genes mutated

a lower frequency (“hills”) in these two can- cers For the first time, there is evidence that most of the mutations that drive cancer may not occur in such gene mountains, but rather are spread across heterogeneous gene hills

These findings are generating some interesting opinions Viewpoints differ as to the value and timeliness of using current established technologies (e.g., polymerase chain reaction and Sanger sequencing) to define the mutational landscape of cancer,

versus waiting for the “certain” promise of next-generation, whole-genome sequencing approaches In the 1990s, the argument for waiting for technology improvement was

‘one of expense and throughput as well as the limited expectations of identifying med- ally useful information To some extent, that is the argument again today as new tech- nologies will likely be less expensive pro- ide haploid resolution (that is, differentiate the maternal from the paternal contribution

to the genome), and hold the possibility

of much more complete genome-wide sequence coverage Even granting that tech- nological progress in genomic sequencing

at hand, the question remains how much more we will see What is clear is that by

technology, anchored to expert insights into cancer biology and clin-

al therapeutics, Wood eral have revealed a previously unrecognized view of the genetic landscape of human cancer