Tạp chí khoa học số 2005-12-09

“There have been many nail-biting moments, but 2005 has been a great year for European space science,” says ESA science director David Southwood.. government announced on 1 December that

9 December 2005

Pages 1569–1724 $10

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D EPARTMENTS

1579 S CIENCEONLINE

1581 THISWEEK INS CIENCE

1585 EDITORIALby Hubert S Markl

Battle for the Brains?

NASA Starts Squeezing to Fit Missions

Into Tight Budget

Europe Trumpets Successes

on Mars and Titan

Universities May Have to Pay

More in Support of Graduate Training

Young Scientists Get a Helping Hand

1602 INDIANOCEANTSUNAMI

Girding for the Next Killer Wave

A Dead Spot for the Tsunami Network?

In the Wake: Looking for Keys to

Posttraumatic Stress

1606 INFECTIOUSDISEASES

Will a Preemptive Strike Against

Malaria Pay Off?

Cracks in the First Line of Defense

Calls Rise for More Research on

Toxicology of Nanomaterials

For Nuclear Fusion, Could Two Lasers

Be Better Than One?

1612 RANDOMSAMPLES

1615 Support for the Human Cancer Genome Project

H Varmus and B Stillman Attribution of Disaster

Losses R A Pielke Jr Response E Mills Bilateral Action for Right Whales J S Sayles and D M Green.

Response S D Kraus et al.

1618 Corrections and Clarifications

1619 EVOLUTION

The Plausibility of Life Resolving Darwin’s Dilemma

M W Kirschner and J C Gerhart, reviewed by

B Charlesworth

1620 PHYSICS

The Pendulum A Case Study in Physics

G L Baker and J A Blackburn, reviewed by A G Rojo

1621 AGRICULTURELosing the Links Between Livestock and Land

R Naylor et al.

1623 MATERIALSSCIENCEMetallurgy in the Age of Silicon

D C Chrzan related Report page 1665

1624 NEUROSCIENCEEmotion and Reason in Making Decisions

A Rustichini related Report page 1680

1625 ATMOSPHERICSCIENCELand Use and Climate Change

R A Pielke Sr.

related Report page 1674

1626 NEUROSCIENCESynaptic Membranes Bend to the Will of a Neurotoxin

J Zimmerberg and L V Chernomordik related Report page 1678

1602

Serono is attracted, we bet you are too.

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S CIENCE E XPRESS www.sciencexpress.org

VIROLOGY:Herpesviral Protein Networks and Their Interaction with the

Human Proteome

P Uetz, Y.-A Dong, C Zeretzke, C Atzler, A Baiker, B Berger, S Rajagopala,

M Roupelieva, D Rose, E Fossum, J Haas

Upon infection of a host cell, the protein interaction networks of herpesviruses change so that they

more closely resemble those of the host cells

CHEMISTRY:Asymmetric Hydrogenation of Unfunctionalized,

Purely Alkyl-Substituted Olefins

S Bell, B Wüstenberg, S Kaiser, F Menges, T Netscher, A Pfaltz

An iridium catalyst accomplishes the longstanding goal of adding hydrogen across alkyl-substituted

carbon double bonds to generate homochiral products, a common reaction in organic synthesis

ASTRONOMY:The Distance to the Perseus Spiral Arm in the Milky Way

Y Xu, M J Reid, X W Zheng, K M Menten

Radio parallax measurements provide an accurate distance to a star cluster in the Perseus spiral arm and

show that this cluster is rotating differently than expected for the Milky Way

1618 HISTORY OFSCIENCE

Comment on “How Science Survived: Medieval Manuscripts’ ‘Demography’ and

Classic Texts’ Extinction”

G Declercq

full text at www.sciencemag.org/cgi/content/full/310/5754/1618b

Response to Comment on “How Science Survived: Medieval Manuscripts’ ‘Demography’ and

Classic Texts’ Extinction”

J L Cisne

full text at www.sciencemag.org/cgi/content/full/310/5754/1618c

1641 MEDICINE:Increase in Activity During Calorie Restriction Requires Sirt1

D Chen, A D Steele, S Lindquist, L Guarente

Mice usually increase their physical activity when fed a calorie-deficient diet, but not when they have a mutation

A key phosphorylating enzyme in the liver, which is required for the action of a diabetes drug, regulates

glucose synthesis and blood levels

1646 CELLSIGNALING:A Systems Model of Signaling Identifies a Molecular Basis Set for

Cytokine-Induced Apoptosis

K A Janes, J G Albeck, S Gaudet, P K Sorger, D A Lauffenburger, M B Yaffe

A model of the interactions among cellular signaling components predicts previously unknown regulatory

pathways for cell death

1653 PHYSICS:Mach-Zehnder Interferometry in a Strongly Driven Superconducting Qubit

W D Oliver, Y Yu, J C Lee, K K Berggren, L S Levitov, T P Orlando

A superconducting circuit can split a qubit state like a light beam, send each half on a separate path, and

recombine them to produce quantum interference patterns

1658 BIOCHEMISTRY:Evidence for Macromolecular Protein Rings in the Absence of Bulk Water

B T Ruotolo, K Giles, I Campuzano, A M Sandercock, R H Bateman, C V Robinson

Protein-protein assemblies and protein-ligand complexes retain their overall structures during mass

spectrometry, suggesting a new tool for structural determinations

1671

Contents continued

1653

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Table 1—Invitrogen’s kinase portfolio offers more choice than the

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Distinct, wild type, human protein kinases 237 206

Protein kinases validated with FA platforms 201 80

Protein kinases addressed by RNAi platform ALL <100

1661 CHEMISTRY:Rapid Chiral Assembly of Rigid DNA Building Blocks for Molecular Nanofabrication

R P Goodman, I A T Schaap, C F Tardin, C M Erben, R M Berry, C F Schmidt, A J Turberfield

Four single strands of DNA can be coaxed to self-assemble in seconds to form a rigid tetrahedron with defined

stereochemistry, providing a module or template

1665 MATERIALSSCIENCE:The Chemistry of Deformation: How Solutes Soften Pure Metals

D R Trinkle and C Woodward

Simulations show that impurities soften some body-centered cubic metals by making it easier for dislocations

to move.related Perspective page 1623

1668 GEOLOGY:Rapid Glacial Erosion at 1.8 Ma Revealed by 4He/3He Thermochronometry

D L Shuster, T A Ehlers, M E Rusmore, K A Farley

Glaciation increased the rate of incision of a Canadian alpine valley by at least a factor of six around 1.8 million

years ago

1671 PLANETARYSCIENCE:Hf-W Chronometry of Lunar Metals and the Age and Early Differentiation

of the Moon

T Kleine, H Palme, K Mezger, A N Halliday

The abundance of tungsten-182 in lunar metals implies that an extensive magma ocean on the moon solidified

about 45 million years after formation of the solar system

1674 ATMOSPHERICSCIENCE:The Importance of Land-Cover Change in Simulating Future Climates

J J Feddema, K W Oleson, G B Bonan, L O Mearns, L E Buja, G A Meehl, W M Washington

Climate models show that expansion of agriculture into forests in the tropics or mid-latitudes could either

enhance or retard warming regionally related Perspective page 1625

1678 NEUROSCIENCE:Equivalent Effects of Snake PLA2 Neurotoxins and Lysophospholipid–

Fatty Acid Mixtures

M Rigoni, P Caccin, S Gschmeissner, G Koster, A D Postle, O Rossetto, G Schiavo,

C Montecucco

The paralytic effects of a snake venom on neuromuscular synapses are mimicked by a mixture of fatty

acids and lipids, suggesting its mechanism of action.related Perspective page 1626

1680 NEUROSCIENCE:Neural Systems Responding to Degrees of Uncertainty in Human

Decision-Making

M Hsu, M Bhatt, R Adolphs, D Tranel, C F Camerer

People prefer choices with defined risk to those with ambiguous risk, but damage to the emotion-processing

areas of the brain eliminates this preference.related Perspective page 1624

1683 CELLBIOLOGY:A Conserved Checkpoint Monitors Meiotic Chromosome Synapsis in

Caenorhabditis elegans

N Bhalla and A F Dernburg

In nematodes, a newly recognized checkpoint prevents meiosis unless the homologous chromosomes are

paired, and a second checkpoint validates proper recombination

1686 STRUCTURALBIOLOGY:Snapshot of Activated G Proteins at the Membrane:

The Gαq-GRK2-Gβγ Complex

V M Tesmer, T Kawano, A Shankaranarayanan, T Kozasa, J J G Tesmer

After hormonal stimulation, one of three subunits of a membrane-bound signaling protein dissociates and

interacts with a target protein to activate it

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Contents continued

1683

1686

(…) individual dopaminergic midbrain neurons, involved in disease patterns such as drug addiction,

Schizophrenia and Parkinson’s disease Single-cell gene expression analysis techniques including the

Leica Microdissection system are crucial for our research.”

Prof Dr Birgit Liss, Department of Normal and Pathological Physiology, Institute of Molecular Neurobiology,

Philipps University Marburg, Germany

“My research focuses on identifying functional

and molecular differences between (…)”

@ www.leica-microsystems.com

sciencenow www.sciencenow.org DAILYNEWSCOVERAGE

Faulty “Emotional Mirror” May Help Explain Autism

Autistic kids have less activity in brain region associated with empathy

Love Is an Open Wound

When married couples argue, their physical injuries take longer to heal

Bees Recognize Human Faces

Complex ability may not require complex brain

science’s next wave www.nextwave.org CAREERRESOURCES FORYOUNGSCIENTISTS

US: What’s Wrong with American Science? B Benderly

A new National Academies report calls for more scientists for the United States to remain competitive

M I S CI N ET: Piecing Together the Past R Arnette

Physical anthropologist Rachel Watkins examines human skeletons in search of cultural clues

An Italian entrepreneur, now a Silicon Valley executive, describes how he ran with a good idea

The German Research Foundation’s Emmy Nother Programme strives to give researchers scientific independence at a relatively young age

US: Making the Most of Career Fairs G Fowler

Before you attend a career fair, ask yourself what kind of scientific career you are looking for

science’s sage ke www.sageke.org SCIENCE OFAGINGKNOWLEDGEENVIRONMENT

P ERSPECTIVE: Living Longer and Paying the Price? J Q Trojanowski, M K Jedrziewski, D A Asch

Conference featured discussion of health care costs and longevity in America

N EWS F OCUS: Tapping into Renewal M Leslie

Compound that boosts cell division slows Huntington’s disease in mice

science’s stke www.stke.org SIGNALTRANSDUCTIONKNOWLEDGEENVIRONMENT

More scientists needed?

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Not only does SciFinder provide access to more proteins and nucleic acids than anypublicly available source, but they’re a single click away from their referencing patentsand original research.

Coverage includes everything from the U.S National Library of Medicine’s (NLM) MEDLINE®andmuch more In fact, SciFinder is the only single source of patents and journals worldwide.Once you’ve found relevant literature, you can use SciFinder’s powerful refinement tools to focus on aspecific research area, for example: biological studies such as target organisms or diseases; expressionmicroarrays; or analytical studies such as immunoassays, fluorescence, or PCR analysis From each reference,you can link to the electronic full text of the original paper or patent, plus use citation tools to track howthe research has evolved and been applied

Visualization tools help you understand results at a glance You can categorize topics and substances,identify relationships between areas of study, and see areas that haven’t been explored at all.Comprehensive, intuitive, seamless—SciFinder directs you It’s part of the process To find out more, call

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What if moving from one particular protein to the most relevant journal and patent literature were as easy

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Restoring the Forests

Deforestation in the tropics has had seriously adverse

conse-quences for biodiversity, ecosystem services, and the human

inhabitants of the tropical forest In recent years, projects have

been set in motion to restore degraded forest lands in some

countries Lambet al (p 1628) review the range of approaches

to restoration and assess the extent to which these approaches

might be successful in achieving their aims, particularly with

respect to human well-being

Superconducting

Qubit Interferometry

Mach-Zehnder

interferome-try is a powerful technique

to probe quantum optical

ef-fects Such interferometers

contain two beam splitters

The first sends two beams

of photons along separate

paths The acquired path or

phase difference the two

beams may acquire creates

interference fringes after the

second beam splitter

recom-bines the two beams Oliver

et al (p 1653, published

on-line 10 November) show that

a two-level superconducting

qubit can also be made to

exhibit similar interference

fringes In this case, the

anti-crossing between the ground

and excited states acts as

the beam splitter, and the

energy level splitting

be-tween them corresponds to the optical path difference

Multi-ple photon transitions (up to 20) can be induced, thus

illustrat-ing a potentially useful route for the manipulation of

supercon-ducting qubits in quantum computing schemes

Going Softer

Whether added deliberately or by accident, impurities or solutes

have long been used to strengthen metals A more recent discovery

was that impurities can soften some metals, but the underlying

rea-sons have not been fully understood Using simulations, Trinkle and

Woodward (p 1665; see the

Perspective by Chrzan) show

that for molybdenum, certaintransition metal solutes caninfluence the energy barriersfor dislocation motion, and insome cases, these changeslead to a softening of the metal

By reducing the strength, andthus the tendency to fractureabruptly, these modified met-als may find expanded use instructural components

Rapid Glacial Erosion

Determining the relative importance of incision by rivers and ciers in the creation of alpine valleys is often hampered by difficul-

gla-ties in quantifying rates of glacial erosion Shusteret al (p 1668;

see the cover) assessed the timing and rate of glacial erosion by

4He/3He thermochronometry Using an example from the CoastMountains of British Columbia, Canada, they determined erosionrates both before and during alpine glaciation The Klinaklini Valleydeepened rapidly by 2 kilometers or more around 1.8 million years

ago when it became glaciated, at least sixtimes as fast as during its preglacial state

Moon Magma

A giant impact into the early Earth isthought to have ejected a hugeamount of debris into orbit thatcoalesced to form the Moon Heatfrom the impact also apparentlymelted much of the Moon and cre-ated a huge ocean of magma One means

of dating these processes is by detecting

182W, the daughter product of a lived isotope,182Hf Differences in theabundances of 182W are producedwhen magma, rocks, and crystalsseparate while 182Hf is still present

short-Klieneet al (p 1671; published

online 24 November) report curate measurements of tungstenisotopes by analyzing metals re-turned in Apollo samples (metalsprovide the most accurate meas-ure) The data imply that the giantimpact occurred about 30 millionyears after the formation of thesolar system and that the magma ocean had solidified by about

ac-50 million years

Protein Interaction in the Gaseous Phase

The identification of transient or readily reversible interactionsbetween proteins is a difficult problem that has been addressed

with a variety of methods Ruotolo et al (p 1658; published

online 17 November) have now applied mass spectrometry tothe problem in order to exploit its advantages of sensitivity andspeed They show that the trp RNA-binding attenuator protein(TRAP) maintains its 11-membered ringlike structure in the gasphase and that binding of RNA and tryptophan influences theshape and stability of the ring in a fashion consistent with itsknown behavior in aqueous solution

The Liver and the Control of Glucose Metabolism

The protein kinase and tumor suppressor LKB1 is a potential vator of the adenosine monophosphate−activated protein kinase(AMPK), a kinase that senses cellular energy levels by binding the

acti-metabolite AMP Shaw et al (p 1642; published online 24 November)

DNA Twisted into Tetrahedra

One strategy for building molecularnanostructures in three dimensions

is to exploit the connectivity forded by nucleic acid structures

af-In many cases, the steps needed toselect particular base pairing to cre-ate structures such as cubes lead to

long, multistep syntheses Goodmanet al.

(p 1661) have developed a rapid assembly process that creates DNAtetrahedra that have 10 to 30 basepairs on each edge Four single strandsthat contain the complementary se-quences for six edges anneal in sec-onds in 95% yield, and single di-astereomeric products are formed

self-The authors also present atomicforce microscopy studies of thecompression of a single DNAtetrahedron

edited by Stella Hurtley and Phil Szuromi

This product is a Licensed Probe Its use with an Authorized Core Kit and

research and development under the 5' nuclease patents and basic PCR patents

of Roche Molecular Systems, Inc and F Hoffmann-La Roche Ltd No real-time

Corporation, and no rights for any other application, including any in vitro

diagnostic application under patents owned by Roche Molecular Systems, Inc.

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PROBELIBRARY is a registered trademark of Exiqon A/S, Vedbaek, Denmark

Other brands or product names are trademarks of their respective holders

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engineered mice so that LKB1 expression could be acutely blocked only in the liver;

they found that its expression plays a critical role in the control of metabolism in the

liver and in glucose homeostasis In the absence of LKB1, AMPK was almost

com-pletely inactive Animals lacking LKB1 in the liver showed hyperglycemia and increased

expression of genes encoding enzymes of gluconeogenesis and lipogenesis

Predicting Responses on the Death Pathway

Multiple signaling pathways can influence whether a cell

commits to the cell death program known as

apopto-sis For many years, it has been possible to categorize

signals as contributing to the “gas” or to the “brakes.”

However, predicting the biological outcome of multiple

signals that apply some gas here, and a stomp on the

brakes there, has remained a challenge Janes et al.

(p 1646) applied a systems-level approach to this

prob-lem and created a model to analyze coupling between

almost 8000 measurements of signaling parameters in

cul-tured cells with about 1500 measures of the various stages of

apoptosis in cells treated with various combinations of cytokines The model allows the

cellular apoptotic response to be correctly predicted under a variety of conditions

Land-Use Effects on Climate

Climate models are still only rather crude representations of real climate systems, and

one class of important feedbacks not adequately realized in them is that of land

processes Fedemma et al (p 1674; see the Perspective by Pielke) investigate the role

of biogeophysical land processes, which directly affect the absorption and distribution

of energy at the Earth’s surface, by integrating them into a global climate model

In-creases in atmospheric CO2concentrations during the next century and associated

greenhouse gas−induced warming led to significant regional impacts directly

associat-ed with land cover, mostly in mid-latitude and tropical areas However, global average

temperature was not affected much by land cover change because regional variations

that led to more or less warming tended to cancel out

Lipids and Neurotoxins

The venom of certain snakes includes neurotoxins capable of paralyzing their victims

Upon intoxication, snake presynaptic phospholipase A2 neurotoxins (SPANs) cause

mo-tor nerve terminals in the neuromuscular junction to enlarge and induce exocytosis of

neurotransmitters from synaptic vesicles Rigoni et al (p 1678; see the Perspective by

Zimmerberg and Chernomordik) now find that a mixture of lysophospholipids and

fatty acids, which are released by SPANs acting on phospholipids, closely mimics all of

the biological effects of SPANs Thus, at the presynaptic membrane, lysophospholipids

and fatty acids help to generate a membrane conformation that promotes vesicle

exo-cytosis and also inhibits synaptic vesicle retrieval

Ambiguity Averse

In a 2002 news briefing, U.S Secretary of Defense Donald Rumsfeld famously

distin-guished between known knowns, known unknowns, and unknown unknowns The last

group remains difficult to discuss, but neuroscientists and economists have joined forces

to examine the distinctions between the first two Hsuet al (p 1680; see the Perspective

by Rustichini) challenged subjects to choose between risky and ambiguous payoffs, where

the former type of choice contains outcomes with known probabilities and the latter type

features the same outcomes but with unknown probabilities Even under conditions where

the expected payoffs are equal, normal humans prefer risk over ambiguity, and

brain-imag-ing results suggest that the amygdala and orbitofrontal cortex (OFC), which both become

more active with ambiguity, modulate a third area of the brain, the striatum Notably,

patients bearing lesions in the OFC did not exhibit an aversion to ambiguity

 

   

        

       !"  

C ONTINUED FROM 1581T HIS W EEK IN

E DITORIAL

Scientific talent is always attracted to the heights of excellence, and those can often reside in world locales

other than where the talent burgeoned in the first place The result has been a global mixing of minds thathas nurtured many splendid contributions to human knowledge based on expertise from all corners ofthe world So it is disturbing to hear politicians, economists, and academicians frequently bemoan acountry’s loss of young talent, describing a “brain drain” that could damage national self-interest This is

an unfortunate description, leaving the impression that a society should not encourage its people to learnand work in countries that offer an opportunity for further intellectual and social growth on many levels However, this

is exactly what societies should do if we are to be successful in solving the world’s frightening problems such as

climate change, sustainable energy supplies, water management, and epidemic infectious diseases What we need is

the most talented scientific minds, whatever their origins, for a battle of—not for—brains

The past few decades have seen the development of internationally organized programs in astronomy,climate, biodiversity and global ecology, and the health sciences By bringing together scientists,

economists, and politicians from different countries, significant accomplishments have been

made that would have been impossible without some concentration of human resources in

particular places That can’t happen without some drainage in others

The participation of its best and brightest talents in these international efforts tosolve humankind’s common problems constitutes a future guarantee for every

nation, which then becomes part of the self-organizing network of international

cooperation And the contribution yields benefits when their nationals return

home (either temporarily or permanently) to strengthen their country’s own

innovative capacity, economy, and social capital When politicians complain

about losses from a brain drain, it conjures a view of scientific talent as

some kind of national heritage or even property They describe a “loss” of

intellectual talent as a threat to competitiveness and say that the depletion

of intellectual human resources must be reversed But these human

resources are individuals who should be able to decide for themselves

where to settle, to learn, and to work, either for a period or permanently

There are many different and often personal reasons for scientific

emigration; no single attribute of a particular destination explains why it occurs

According to the German Research Council, about two-thirds of all German postdoctoral fellows who go abroad(including more than 70% in the natural sciences, biosciences, and engineering) spend their training period in the

United States, as compared to some 15% in member states of the European Union Of the approximately 15 to 20%

that remain abroad, only 40% do so in the United States (and about the same proportion in the European Union)

Decades of experience have convinced me that the 85% of the German scientists who return from the United States

bring improved expertise, knowledge of other languages and cultures, and many excellent connections with scholars

from all over the world I cannot think of a better way in which to link my country with leading developments in

science, humanities, and technology in the rest of the world

Science as a global social enterprise needs continuous stimulation through diversity of cultural traditions, languagesand literatures, styles of education, gender, and giftedness The United States alone receives many thousands of young

foreigners every year in its higher educational system, which is often perceived as a one-way street The United States

should encourage its own rising talents to go abroad, expose themselves to foreign cultural influences and languages,

and even risk being more permanently attached to those other societies Although some of the highest ground in certain

disciplines may be found at home, that won’t be true for all; some U.S scientists who have ventured abroad have

become their own foci of attention At the Max Planck Society, more than one-quarter of the 278 scientific directors are

foreigners, many of whom are American

So let’s worry less about brain drain and instead strengthen scientific ties by encouraging drainage in both directions

“Mind swapping” across the ocean unites intellectual forces for the common pursuit of knowledge, and that, after all,

is the better part of the “pursuit of happiness” for scientists Let’s focus on gathering together to confront the troubling

challenges that await scientists who now serve a global society

Hubert S Markl

Hubert S Markl is a retired professor of Biology, University of Konstanz, Konstanz, Germany, and past president of the Max Planck

Society, Munich, Germany

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B I O C H E M I S T R Y

Ribosomal Logic

The recently acquired

apprecia-tion of metabolic and regulatory

pathways as an immensely

complicated wiring diagram

has been accompanied by

attempts to reroute and

rede-fine these circuits by adding

and subtracting switches and

connectors One challenge, of

course, is to maintain cell

via-bility while tinkering with

macromolecular components

whose interactions may not

yet be completely specified

Rackham and Chin have

devel-oped an orthogonal

approach—building a parallel

metabolism within a cell—by

selecting for modified

Shine-Dalgarno sequences that bind

to correspondingly modified

16S ribosomal RNAs (rRNAs)

and that no longer bind to

wild-type 16S rRNAs

Amazingly, these orthogonal

16S rRNAs still assemble into

competent ribosomes, and

placing the cognate

Shine-Dalgarno sequence in front of a

reporter gene results in faithful

translation of an active enzyme

independently of the

endoge-nous protein synthesis ery Introducing several pairs oforthogonal messenger RNAsand rRNAs allows for the con-struction of AND and OR gateswithin otherwise unperturbedEscherichia coli — GJC

machin-J Am Chem Soc 10.1021/ja055338d (2005); Nat Chem Biol 1, 159 (2005).

C E L L B I O L O G Y

A Good Amyloid

Amyloids are an insolublefibrous form of protein aggre-gates and are generally associ-ated with a variety of neurode-generative disease states

Fowler et al.find that in

melanocytes, intracellularamyloid is not a pathologicalaberration but instead plays aproductive role in melanin for-mation Melanin is a tyrosine-based polymer that protectsorganisms from some toxinsand ultraviolet radiation Inmammalian melanocytes,melanin is produced withinmembrane-bound organellesknown as melanosomes, withthe aid of the protein Pmel17

During this process, it appearsthat Pmel17 adopts an amy-loid-like structure that provides

a template for the assembly ofmelanin precursors, and recom-binant Pmel17 amyloid wasobserved to accelerate melaninproduction in vitro.Within thecell, the Pmel17-containing

amyloid could also serve tosequester highly reactive inter-mediates in melanin biosyn-thesis — SMH

PLoS Biol 4, e6 (2006).

S U R F A C E S C I E N C E

Subsurface Manipulation

The movement of hydrogeninto and out of the bulkregions of metals is important

in hydrogen storage, metal

embrittlement, and fuel cell

reactions Sykes et al.used

voltage pulses delivered via ascanning tunneling micro-scope tip to manipulate sub-surface hydrogen atoms Theyapplied bias pulses of

>0.5 V to a Pd(111)surface held at 4 Kthat had had hydrogenremoved from its near-surface region by oxy-gen treatment Thesebias pulses were able

to excite residualhydrogen atoms in thebulk (which has a pop-ulation of one H atomper 2000 Pd atoms) andallowed these atoms to moveinto more energetically favor-able subsurface sites The sub-surface hydride depleted thesurface Pd atoms of chargeand caused an outward surfacerelaxation of Pd atoms of 0.1

to 0.6 Å Surface hydrogen alsotended to move away fromthese regions to leave behindordered arrays of overlayervacancies — PDS

Proc Natl Acad Sci U.S.A 10.1073/pnas.0506657102 (2005).

H I G H L I G H T S O F T H E R E C E N T L I T E R A T U R E

edited by Gilbert Chin

Pmel17 fibers (left), melanosomes (right), and the melanin-producing reaction (center).

Emulsifying the Crust

Not quite 2 billion years ago, a large asteroid stuckitself into what is now eastern central Ontario, formingthe Sudbury impact crater The energy of the impactmelted a large amount of the continental crust,producing a thick melt sheet that was initially about1700°C, well above the liquidus for norite (~56% sil-ica) and for granophyre (~70% silica)

Zieg and Marsh describe the subsequent tion and cooling of this molten body as a naturalexperiment that can be compared to the formation

evolu-of magma bodies in igneous intrusions such asthose underlying volcanoes The superheated Sudbury melt sheet began as an emulsion containing droplets of silica-rich and

silica-poor magma; the less dense, silica-rich drops separated within months and coalesced into an upper melt sheet Vigorous

convection in both sheets occurred until they cooled to the liquidus, at which time crystals began to form and convection

ceased The combined melt layers solidified from the top and bottom Aside from the initial separation of the two liquids, the

solidified sheet shows little compositional gradations Early formed crystals are dispersed throughout, and layers are not apparent

These textures contrast with those of many igneous magma bodies, suggesting that the latter may not have originated as large

hot chambers at an instant in time — BH

Geol Soc Am Bull 177, 1427 (2005).

Crust Target Superheated Emulsion Separate Layers

The early stages of emulsification and separation (norite, black

blobs; granophyre, red blobs).

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C H E M I S T R Y

All in the Dope

Cadmium selenide nanoparticles are used

in light-emitting diodes, lasers, and sensors

and for biological labeling However, the

tox-icity of cadmium is a major concern Zinc

chalcogenides, such as ZnSe, doped with

transition metal ions may offer as much

flexibility and dynamic range as CdSe,

but it has been difficult to dope particles

uniformly Recent success in separating the

nucleation and growth phases in making

high-quality nanoparticles prompted

Pradhan et al.to consider whether efficient

and controlled doping could be introduced

For growth-stage doping, seed ZnSe

parti-cles were quenched, and copper was then

added as a dopant Overgrowth with

addi-tional ZnSe shifted the photoluminescence

(PL) toward the red wavelengths For the

nucleation strategy, Mn was added to shiftthe PL even further toward the red.Thenanoparticle syntheses were performed asone-pot reactions so control of the dopingrelative to the nucleation or growth could

be achieved by varying the reactivity of theprecursors and the temperature — MSL

J Am Chem Soc 10.1021/ja055557z (2005).

E C O L O G Y

Fisheries Failures

Some collapsed fisheries fail to recovereven when harvesting has stopped for morethan a decade Fishing usually targets thelargest, oldest, and fastest-growing individ-uals and hence favors the survival ofsmaller, younger, and slower-growing fish

Walsh et al.have chosen the Atlantic

silver-side, a commercially exploited fish with anannual life cycle, for harvesting experimentsunder a variety of regimens.They foundthat selecting out the largest individualsaffected multiple traits in subsequent gen-erations, with significant reductions in ver-tebral number, egg size and subsequent via-bility; rates of growth and growth effi-ciency; and foraging and fecundity It is stillnot clear why some fish stocks fail torecover and others are more resilient,although duration and intensity of exploita-tion may be a factor.The authors are con-tinuing to monitor rates of recovery of theexperimental silverside populations — CAEcol Lett 8, 10.1111/j.1461-0248.2005.00858.x (2005).

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Six (of 96) markers in pairwise comparison for strains B6 and 129

C ONTINUED FROM 1587 E DITORS ’ C HOICE

Remember That Gradient?

During early development, morphogen gradients instruct thedifferentiation of distinct cell types in proper spatial order

Exposure of cells to a specific concentration of morphogen canspecify cell fate, but the exposure does not need to last for the several hours needed to

complete execution of the gene expression program that drives the cell’s response

Jullien and Gurdon explored how cells remember a brief exposure to morphogen by

studying responses of Xenopus embryo cells to activin Exposure for 10 min resulted in

changes in gene expression several hours later This response appeared to require

continuous receptor signaling, because it could be inhibited at later stages by a

phar-macological inhibitor of kinase activity of the activin receptor Continued signaling

also appeared to require receptor internalization, because a dominant-negative form

of dynamin that prevents internalization of receptors from the plasma membrane

inhibited activin-dependent gene expression when injected into embryonic cells

Expression of mutant Rab proteins that increase trafficking of membrane proteins

through the lysosomal pathway (and thus increase the rate at which they are

degraded) did not affect the memory of the activin signal, and the authors concluded

that the signaling receptors have not yet entered the degradation pathway Rather, it

seems that the persistence of vesicles as they move from the plasma membrane to the

lysosome accounts for the signal, and the authors propose that receptors activated by

brief exposure to activin provide a prolonged signal — LBR

9 DECEMBER 2005 VOL 310 SCIENCE www.sciencemag.org1590

John I Brauman, Chair, Stanford Univ.

Richard Losick,Harvard Univ.

Robert May,Univ of Oxford

Marcia McNutt, Monterey Bay Aquarium Research Inst.

Linda Partridge, Univ College London

Vera C Rubin, Carnegie Institution of Washington

Christopher R Somerville, Carnegie Institution

George M Whitesides, Harvard University

R McNeill Alexander, Leeds Univ.

Richard Amasino, Univ of Wisconsin, Madison

Meinrat O Andreae, Max Planck Inst., Mainz

Kristi S Anseth, Univ of Colorado

Cornelia I Bargmann, Rockefeller Univ.

Brenda Bass, Univ of Utah

Ray H Baughman, Univ of Texas, Dallas

Stephen J Benkovic, Pennsylvania St Univ.

Michael J Bevan, Univ of Washington

Ton Bisseling, Wageningen Univ.

Mina Bissell, Lawrence Berkeley National Lab

Peer Bork, EMBL

Dennis Bray, Univ of Cambridge

Stephen Buratowski, Harvard Medical School

Jillian M Buriak, Univ of Alberta

Joseph A Burns, Cornell Univ.

William P Butz, Population Reference Bureau

Doreen Cantrell, Univ of Dundee

Peter Carmeliet, Univ of Leuven, VIB

Gerbrand Ceder, MIT

Mildred Cho, Stanford Univ.

David Clapham, Children’s Hospital, Boston

David Clary, Oxford University

Jonathan D Cohen, Princeton Univ.

Robert Colwell, Univ of Connecticut

Peter Crane, Royal Botanic Gardens, Kew

F Fleming Crim, Univ of Wisconsin William Cumberland, UCLA Caroline Dean, John Innes Centre Judy DeLoache, Univ of Virginia Edward DeLong, MIT Robert Desimone, MIT John Diffley, Cancer Research UK Dennis Discher, Univ of Pennsylvania Julian Downward, Cancer Research UK Denis Duboule, Univ of Geneva Christopher Dye, WHO Richard Ellis, Cal Tech Gerhard Ertl, Fritz-Haber-Institut, Berlin Douglas H Erwin, Smithsonian Institution Barry Everitt, Univ of Cambridge Paul G Falkowski, Rutgers Univ.

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

R Gadagkar, Indian Inst of Science Mary E Galvin, Univ of Delaware Don Ganem, Univ of California, SF John Gearhart, Johns Hopkins Univ.

Jennifer M Graves, Australian National Univ.

Christian Haass, Ludwig Maximilians Univ.

Dennis L Hartmann, Univ of Washington Chris Hawkesworth, Univ of Bristol Martin Heimann, Max Planck Inst., Jena James A Hendler, Univ of Maryland Ary A Hoffmann, La Trobe Univ.

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

Bernhard Keimer, Max Planck Inst., Stuttgart Alan B Krueger, Princeton Univ.

Antonio Lanzavecchia, Inst of Res in Biomedicine Anthony J Leggett, Univ of Illinois, Urbana-Champaign Michael J Lenardo, NIAID, NIH

Norman L Letvin, Beth Israel Deaconess Medical Center Richard Losick, Harvard Univ.

Andrew P MacKenzie, Univ of St Andrews Raul Madariaga, École Normale Supérieure, Paris Rick Maizels, Univ of Edinburgh

Eve Marder, Brandeis Univ.

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

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

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

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

Erin O’Shea, Univ of California, SF Malcolm Parker, Imperial College John Pendry, Imperial College Philippe Poulin, CNRS Mary Power, Univ of California, Berkeley David J Read, Univ of Sheffield Colin Renfrew, Univ of Cambridge Trevor Robbins, Univ of Cambridge Nancy Ross, Virginia Tech Edward M Rubin, Lawrence Berkeley National Labs David G Russell, Cornell Univ.

Gary Ruvkun, Mass General Hospital

J Roy Sambles, Univ of Exeter Philippe Sansonetti, Institut Pasteur David S Schimel, National Center for Atmospheric Research Dan Schrag, Harvard Univ.

Georg Schulz, Albert-Ludwigs-Universität Paul Schulze-Lefert, Max Planck Inst., Cologne Terrence J Sejnowski, The Salk Institute

George Somero, Stanford Univ.

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

Edward I Stiefel, Princeton Univ.

Thomas Stocker, Univ of Bern Jerome Strauss, Univ of Pennsylvania Med Center Tomoyuki Takahashi, Univ of Tokyo Glenn Telling, Univ of Kentucky Marc Tessier-Lavigne, Genentech Craig B Thompson, Univ of Pennsylvania Michiel van der Klis, Astronomical Inst of Amsterdam Derek van der Kooy, Univ of Toronto

Bert Vogelstein, Johns Hopkins Christopher A Walsh, Harvard Medical School Christopher T Walsh, Harvard Medical School Graham Warren, Yale Univ School of Med Fiona Watt, Imperial Cancer Research Fund Julia R Weertman, Northwestern Univ.

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

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

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

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

David Bloom, Harvard Univ.

Londa Schiebinger, Stanford Univ.

Richard Shweder, Univ of Chicago Robert Solow, MIT

Ed Wasserman, DuPont Lewis Wolpert, Univ College, London

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Clickable Chemistry

Cracking this virtual chemistry text

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electro-chemistry or help readers soak up

the properties of water Retired

chemistry professor Stephen Lower of Simon Fraser University in

Burnaby, Canada, wrote the virtual primer in part to offer an

alternative to “commercial textbooks which in my view possess

far too much sameness and shallowness.” Eleven chapters cover

fundamentals such as measurement, chemical equilibrium, and

bonding A new section tackles atomic structure, explaining

concepts such as why electrons don’t plunge into the positively

charged nucleus (above) For students who want more, the book’s

tutorials dig deeper into particular topics

www.chem1.com/acad/webtext/virtualtextbook.html

C O M M U N I T Y S I T E

Social Studies

Social psychologists investigate topics as varied as the

tech-niques of propaganda, group dynamics, and facial expressions A

gathering place for students and researchers in this diverse field

is the Social Psychology Network, managed by Scott Plous of

Wesleyan University in Middletown, Connecticut For users who

need a tutorial on persuasion and influence or want to locate an

online experiment their classes can participate in, the network’s

archive holds links to more than 12,000 resources on other Web

sites Separate discussion forums let students and professionals

sound off If you’d like to team up with a researcher who works

on, say, conflict resolution and personality, check the directory

with profiles of 1100 or so social psychologists There are also

links to relevant stories in the media

www.socialpsychology.org

I M A G E S

Truly Heaven Sent?

The man who bought this glossy, 19-kilogram orb (below) wascertain he’d nabbed a genuine space rock—and for only

$10 To his dismay, lunar geochemist RandyKorotev of Washington University in St

Louis, Missouri, recognized that it wasnot a meteorite but a coal ball, acompacted glob of peat To avoidmaking the same mistake, visitKorotev’s A Photo Gallery ofMeteorwrongs, which showcasesmore than 100 objects misidenti-fied as meteorites Korotev andcolleagues have either examinedthe finds or studied photographs

of them Captions explain why eachspecimen probably isn’t a meteoriteand indicate its likely identity Forinstance, the coal ball’s nearly sphericalshape is a giveaway, as is the presence

of calcite, a mineral meteorites lack Thesite also illustrates criteria for recognizing space stones, includ-ing the presence of a fusion crust, a glassy coating formed whenthe outer layer melts and then solidifies during descent

M a s s a c h u s e t t s – b a s e dcompany Cell SignalingTechnology Users enterthe name of a mouse orhuman protein, and the site pin-points which amino acids pick upphosphates The output often speci-fies how modifications at differentpositions alter the protein’s function.Data gleaned from the literature are free,but access to the company’s experimen-tal findings may require a subscription

This collection from the University of

California, Santa Barbara, presses the

fast-forward button on gradually

unfolding geological processes By

cue-ing the more than 20 animations,

undergradu-ates can follow the filling of San Francisco Bay as sea

levels rose at the end of the last ice age or observe how the

colli-sion between California and Baja California forced up the mountains

north of Los Angeles (above) Although emphasizing California geology, the

site also includes examples from other parts of the globe, such as a sequence that

tracks the formation of the South Atlantic Ocean as Africa and South America

pushed apart Educational users can download the animations for free

emvc.geol.ucsb.edu/downloads.php

9 DECEMBER 2005 VOL 310 SCIENCE www.sciencemag.org1594

N EWS P A G E 1 5 9 7 1 5 9 8 Europe’s

Titanic missions

Cambridge’s patent debate

Th i s We e k

While the public is focused on NASA’s

attempts to prepare the still-grounded space

shuttles for a mid-2006 launch, the agency’s

science program is also in the midst of a

painful, though less visible, overhaul In the

past few weeks, NASA managers have

decided to delay by 2 years the flight of a new

space telescope and halted work on an asteroid

mission that is nearly on the

launch pad, and they are

recon-sidering plans to revive a

mis-sion to Jupiter’s moon Europa

“We’ve got to get everything

under control,” says Mary

Cleave, NASA’s new science

chief “We’re overcommitted.”

Meanwhile, another part

of the agency has begun to

cancel a slew of life sciences

experiments slated for the

international space station,

despite a National Academies’

report released 28 November

that criticized NASA’s

scal-ing back of research on the

orbiting base “We’re

refo-cusing on near-term needs,”

explains NASA exploration

chief Scott Horowitz The

agency intends to slice in half

the roughly $1 billion it spends

annually on biological and

physical sciences research; the

other half will be devoted primarily to

ensur-ing the health of astronauts on lunar and Mars

missions, which are the centerpiece of

Presi-dent George W Bush’s plan to return humans

to the moon and send them on to Mars The

vast majority of exploration funding will be

devoted to building new launchers

NASA managers laid out their plans and

problems at a meeting last week of the newly

reconstituted NASA Advisory Council,

which gathered in Washington, D.C., for the

first time since Administrator Michael

Grif-fin took over the agency this spring NASA’s

$5.5 billion science budget grew slightly in

2006 and is likely to win a modest increase in

the president’s upcoming 2007 request to

Congress But that budget can’t keep up with

rapidly rising costs for science projects such

as the James Webb Space Telescope (JWST),the successor to the Hubble Space Telescope

A technical and scientific review this fallmanaged to reduce significantly the $1 billion

overrun on the $3.5 billion JWST (Science,

2 September, p 1472) Still, a host of lems, including delays in winning U.S gov-ernment approval for a European launch and

prob-difficulties in ment design, forcedCleave last month topostpone the launchdate from 2014 to

instru-2016 That delay, inturn, ate up the savings from the fall review

“The cost is still $4.5 billion,” says JWSTproject scientist Eric Smith The additional

funding, Cleave told Science, must be found

within the agency’s already-strained omy and astrophysics budget

astron-The fate of a proposed mission toEuropa—already canceled twice because ofits high cost—is now again in question Plan-etary scientists are eager to return to themoon, and a 2002 National Academies’ panelrated it the top planetary priority in its decadal

plan Griffin promised shortly after taking thejob last spring that he would press for a con-ventional mission following cancellation ofplans for a nuclear-powered spacecraft thatwould orbit Jupiter’s moons Cleave told thecouncil, however, that budget pressures mightyet again delay the probe

“We wouldn’t necessarily say our nextouter planet mission is to Europa,” Cleave

later told Science Instead, she would prefer to

hold a competition to see if scientific interest

in the mission has shifted since the decadalreport But given the stresses on the existingscience budget, other agency officials andoutside scientists say privately that it would be

difficult to start an expensive newouter planets mission before 2008 Even NASA projects nearingtheir launch dates are gettingextra scrutiny Cleave recently

h a l t e d a l l wo r k o n D aw n , a

$373 million spacecraft set toblast off next summer on a mis-sion to examine two large bodies

in the asteroid belt Technicaland managerial troubles and aresulting spike in costs attractedthe attention of NASA headquar-ters’ managers this fall, andCleave ordered the Jet Propul-sion Laboratory in Pasadena,California, to cease work pend-

ing a detailed pendent assessment

inde-to be completednext month Ironi-cally, the project ispart of the Discov-ery program that isintended to launchmissions relativelycheaply and quickly

Probes already aloftalso face a squeeze On

6 December, NASAshut down the UpperAtmospheric Research Satellite launched in

1991 that measures ozone, winds, and ature In October, it abandoned the EarthRadiation Budget satellite after more than 2decades in orbit NASA and outside review-ers are considering the fate of a host of plan-etary and astrophysics spacecraft as well Inaddition, a 6-month delay in launching theEarth probes CloudSat and CALIPSO willcost at least $15 million Cleave has alsoordered cuts to the future Mars program

temper-Lunar research, however, is almost

NASA Starts Squeezing to Fit

Missions Into Tight Budget

S P A C E S C I E N C E

Dawn breaks? NASA has stopped work

on Dawn and its ion-propulsion system

to reach two asteroids

1 6 0 2 1 6 0 6 1 6 1 0

A year after

the tsunami

Fusion with less brute force?

Preventing malaria

F o c u s

certain to receive more funding in coming

years, given the White House focus on the

moon Horowitz’s office will launch a lunar

orbiter in 2008 to reconnoiter for possible

landing sites, and Cleave hopes to include a

bevy of scientific instruments on the flight

She told the council that supporting any

more lunar research, however, would leave

less for other areas of science

Although Cleave is an ecologist by

train-ing, she has no oversight of NASA’s biological

and physical sciences That portfolio belongs

to Horowitz, who is drastically reducing

fund-ing for a host of experiments designed for the

space station He’s already canceled at least

half of NASA’s current life sciences grants and

contracts Much of the research planned for the

station has little connection with Bush’s plan to

return astronauts to the moon and continue to

Mars, Horowitz told Science.

That view is at odds with a new report

from the National Academies, which warns

that abandoning fundamental biological

and physical research “is likely to limit or

impede” research into the impact of the

space environment on astronauts The panel

notes that “once lost, neither the necessary

research infrastructures nor the necessary

communities of scientific investigators can

survive or be easily replaced.” The panel

argues that NASA needs a detailed plan to

use the station for a host of research ors, including studies on the effects of radi-ation on biological systems, loss of boneand muscle mass during space flight, firesafety, and flow and heat-transfer issues

endeav-Several Democratic lawmakers are critical

of the cuts in life sciences research, butstaffers and lobbyists say that their voicesare unlikely to rescue the projects

Even if Horowitz were to reverse hisdecision, NASA’s plans to halt shuttleflights by 2010 would make it difficult tocarry out some research on the space sta-tion William Gerstenmaier, head of NASA’sspace flight efforts, told the agency’s advi-sory council that the shuttle is needed toreturn experiments and materials to Earth.Without those flights, he says, “you wouldhave to do more in situ research.” Thatresearch, in turn, would require more com-plex equipment and crew time

NASA needs an additional $1.4 billion toredesign space station parts and buy spares

so that the station can keep operating out the shuttle, Gerstenmaier added Thatmoney is part of an estimated $6 billion inadditional funding for space flight that is notyet included in NASA’s future budgets Ontop of that long-term fiscal crisis, the agencyexpects to receive from Congress less thanhalf of the $760 million in damages its facil-ities suffered from Hurricane Katrina Con-gress may also impose an across-the-boardcut to all agency budgets to cover hurricanecosts, although that didn’t stop it frominserting nearly $300 million in pork-barrelprojects into NASA’s $16.46 billion budget.Such external pressures spell additionaltrouble for a science effort already sufferingfrom its own excesses –ANDREWLAWLER

with-Stretched thin NASA’s Mary Cleave says space

science is “overcommitted.”

Landmark Paper Has an Image Problem

New questions about scientific validity are

dogging South Korean cloning researcher

Woo-Suk Hwang and his colleagues On

4 December, Hwang notified Science

edi-tors that a f igure in online material that

accompanies his group’s heralded 2005

paper on the derivation of stem cells from

cloned human embryos contained duplicate

images The problem follows close on the

heels of Hwang’s admission that, despite his

previous denials, two members of his lab

had donated oocytes for his group’s

experi-ments and others had been paid for their

donations (Science, 2 December, p 1402).

Katrina Kelner, Science deputy editor

for life sciences, says it appeared that the

duplicate panels were not part of the

origi-nal submission but had been sent in

response to a request for high-resolution

images after the paper had been received

“From the information that we have so far,

it seems that it was an honest mistake,” she

says “We have no evidence that there wasany intent to deceive.”

In May 2005, Hwang and his colleaguesreported that they had produced 11 newhuman embryonic stem (ES) cell lines thatcarried the genetic signature of patients withdiabetes, spinal cord injury, or a genetic blood

disorder (Science, 20 May, p 1096) The

paper not only seemed to validate the group’sclaim a year earlier that it had created a singlecell line from a cloned human embryo, but italso reported a huge increase in efficiency forthe technique In the first paper, researcherssaid they produced one cell line from

230 tries, but in the second, they claimed theyproduced a cell line in about one of 15 attempts

The f igure in question is supposed toshow patterns of expression for a range of

ES cell markers in the 11 cell lines But it tains four pairs of apparently duplicatedimages, even though they are labeled asshowing different cell lines Gerald Schatten

con-of the University con-of Pittsburgh in nia, who was the corresponding author on thepaper and provided the high-resolution

Pennsylva-images to Science, declined to comment A

university spokesperson said that the sity’s office of research integrity had begun

univer-an investigation Schatten univer-and his lab bers are cooperating, she said, “and are care-fully going through the data we have access to

mem-to determine how it could have happened.”She said Schatten would not comment duringthe investigation, which might last 6 months.Rudolf Jaenisch of the Whitehead Insti-tute for Biomedical Research in Cambridge,Massachusetts, says he still has confidence

in the reported results “This is an extremelyimportant study, and I have no reason what-soever to question any of the publisheddata,” he says

Kelner says the journal will issue a tion once the editors are satisfied they under-stand what had happened –GRETCHENVOGEL

Powerful Protein Expression

FuGENE is a registered trademark of Fugent, L.L.C., USA.

Other brands or product names are trademarks of their respective holders.

© 2005 Roche Diagnostics GmbH All rights reserved

Roche Diagnostics GmbHRoche Applied Science

68298 Mannheim Germany

reagent suitable for transfection of animal and insect cells for protein expression The combination of a rapid protocol, activity in up to 100% serum, and effectiveness with many cell lines commonly used for protein expression makes it the product of choice for this application.

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I Minimize cytotoxicity or changes in morphology by transfecting cells at high densities.

I Save time by eliminating the need to change media; the reagent functions exceptionally well in up to 100% serum.

I Employ a reagent that is free of animal- or human-derived

Figure 1: GFP expression in HEK-293 EBNA cells

HEK-293 EBNA suspension-adapted cells were

trans-fected with plasmid DNA for GFP following the

recom-mended protocol, using ratios of 7:2, 6:2, 5:2, 4:2, and

3:2 (μl FuGENE®HD Transfection Reagent:μg plasmid

DNA) The percentage of cells transfected (a) was

determined 28 hours post transfection and quantity of

GFP protein (b) was estimated from the Coomassie

Blue-stained gel at 72 hours post transfection

Gifts With Broad Impacts

Not many scientific institutes score

$100 million gifts, much less twice TheBroad Institute in Cambridge, Massachu-setts, tasked to turn genetic data intomedical advances, last week received itssecond windfall from Eli and EdytheBroad in less than 2 years

The Broads stipulated with their firstgrant that the collaboration between theMassachusetts Institute of Technologyand Harvard University must spend

$10 million a year; the second gift meansthat the institute will be required tospend $20 million The institute, whichwill move into new digs opposite MIT inthe spring, has an annual budget of about

$100 million, most of which comes fromgovernment grants –ANDREWLAWLER

Neuroscientists Without Borders

The Karolinska Institute in Stockholm hasbeen chosen to host a new center to helpneuroscientists manage and share theirdata, organizers announced last week inParis Founded by six European countriesand the United States, the $1.2-million-per-year International NeuroinformaticsCoordinating Facility will foster inter-national collaboration in maintainingdatabases and analyzing the torrent ofdata generated by brain scanners andother modern tools.The center will alsofund projects to create neuroscience data-bases and develop computational tools fordata analysis and modeling brain function

–GREGMILLER

Collider Coming Together

Particle physicists settled this week onthe basic specs for the International Lin-ear Collider, a multibillion-dollar particlesmasher they hope governments inEurope, Asia, and North America willagree to build sometime in the nextdecade Researchers in Frascati, Italy,finalized a document that sets generalparameters, such as the strength of theparticle-accelerating electric fields in the40-kilometer-long tunnels Over the nextyear, physicists will design the many parts

of the machine, which would collide trons and positrons “Before [this docu-ment], it wasn’t clear that we were alldesigning the same thing,” says BarryBarish of the California Institute of Tech-nology in Pasadena, who leads the designeffort Researchers will also calculate thecost; previous estimates have run as high

ScienceScope

Anderson would like to be free to patent his

own inventions and make private deals, even

though he’s a university employee The last

thing he wants is “bureaucrats” getting in his

way So far he’s been lucky: He works for the

University of Cambridge, which has given

him and other staff members tremendous

leeway—even permitting them 100%

owner-ship of some patents

Very few other sities allow such lati-tude But this week,Cambridge is pushing

univer-a new policy thuniver-atwould curtail some ofthat independence and

require all inventors on staff to let the university

own and more actively manage staff patents

Anderson, spokesperson for a group

called the Campaign for Cambridge

Free-doms (CCF),*sees the new rules as

intru-sive He and allies such as molecular

biolo-gist Mike Clark, whose income from

mono-clonal antibody discoveries is a major

rev-enue source for the university, are fighting

to retain some of the old ways of doing

busi-ness A campus-wide vote this month will

determine which side prevails

The university has been advancing its

claims on intellectual property (IP) for

sev-eral years, prompting fierce debates at every

turn It is setting up a management group

called Cambridge Enterprise and wants

rules that apply consistently across the

board, says university deputy vice

chancel-lor Anthony Minson So this week, the versity sent out ballots to roughly 4000 eli-gible academic voters to get their approvalfor its IP rules Academics will also get tovote on an opposing scheme from CCF thatwould block some aspects of the university’splans For example, the dissenters do notwant the university to be able to assertownership of privately sponsored researchthat is not restricted by the donor And theirplan could prevent the university from inter-vening in some intramural IP disputes

uni-A lot of money is at stake, but both sidesstress lofty principles “This is not primarilyabout money,” says Minson, a virologist whohelped draw up the university’s proposal

“It’s about accountability” to taxpayers who

help fund the facilities where theresearch takes place The goal, hesaid in an e-mail, is “to achieve fair-ness by equal treatment of all staffregardless of funding source … and

to ensure that the university hasthe information” it may need to

“resolve potential conflicts”

among staff and students

In contrast, Anderson says thebattle is really about academicfreedom and creativity Cam-bridge is “the last university in theU.K where the academics own[their own patents],” he says “Ifthe university locks down IP, it willbecome much more difficult for academics tospin out” ideas into commercial ventures

Minson disagrees The university haspromised its staff what he believes are

“more generous terms than any other versity in the U.K.” Although the adminis-tration intends to claim ownership, it will letindependent-minded inventors such asAnderson and Clark do the patenting andnegotiate deals themselves if they want to

uni-And he says a sliding-scale formula wouldreturn most income to the inventor: 90% below

£100,000 a year, dropping to around 30% at

£200,000 Because the scheme is flexible,Minson says, “I just don’t accept” the argumentthat a “bureaucracy will sit heavily” on Cam-bridge’s creative spirits

The referendum is expected to drawabout 1500 votes Anderson says 84 academ-ics have publicly endorsed the CCF amend-ments, and he believes there are another

“several hundred” solid supporters But versity leaders have been selling their planaggressively within the ranks The dissentersconcede that they’re facing an uphill battle

uni-–ELIOTMARSHALL

Cambridge University Reins In

Faculty Patents

I N T E L L E C T U A L P R O P E R T Y

Hands off Ross Anderson doesn’t want Cambridge

University to own his inventions

*CCF and university statements, respectively:

www.freecambridge.org and www.admin.cam

ac.uk/reporter/2004-05/weekly/6001.17.html

9 DECEMBER 2005 VOL 310 SCIENCE www.sciencemag.org1598

P ARIS —Less than a week before it has to

per-suade European governments to approve its

budget for the next several years, the

Euro-pean Space Agency (ESA) has been

parad-ing some of its achievements in 2005 These

include the first batch of published results

from the Huygens probe to Saturn’s

enig-matic satellite Titan (the most distant

land-ing ever accomplished) and tantalizland-ing

glimpses of underground water from the

Mars Express mission’s ground-penetrating

radar—the first subsurface view of another

world “There have been many nail-biting

moments, but 2005 has been a great year for

European space science,” says ESA science

director David Southwood

On 14 January, after hitching a 7-year

ride on NASA’s Cassini spacecraft bound

for Saturn, Huygens descended through

Titan’s murky atmosphere and landed on an

alien but weirdly familiar world in which

the rocks are made of water ice and

mon-soons of liquid methane rain down from the

orange sky Many of Huygens’s results have

already been released (Science, 21 January,

p 330; 28 January, p 496; 13 May, p 969;

23 September, p 1985), but the first

com-prehensive set of scientif ic papers,

pub-lished last week on Nature’s Web site, fills

in the details They indicate that Titan—

which is larger than the planet Mercury—is

a frigid world sculpted by intermittent

downpours of methane that carve out

val-leys and leave tarlike puddles of

hydro-carbon goo Huygens also found evidence

for ammonia-spewing cr yovolcanoes,

detected bolts of lightning, measured wind

patterns in the atmosphere, and analyzed the

organic-rich airborne dust particles, as well

as the reddish surface material

At a 30 November press conferencehere, Jonathan Lunine of the University ofArizona’s Lunar and Planetary Laboratory

in Tucson also presented a detailed ison of small-scale Huygens descent imagesand wide-angle Cassini radar maps,obtained during the orbiter’s Titan flyby on

compar-28 October “We’ve now been able to point the Huygens landing site to within afew kilometers,” he says It’s “kind of sur-prising,” Lunine adds, that the dark, hydro-carbon-rich areas in the Huygens images arealso dark in the radar maps, indicating asmooth terrain—very different from the icycobbles seen by Huygens at its landing site

pin-Unfortunately, Cassini won’t have anotheropportunity to radar-map the landing siteuntil 2008, says Lunine

In the other ESA success story, anotherradar instrument, Italy’s Mars AdvancedRadar for Subsurface and IonosphericSounding (MARSIS) on board MarsExpress, has provided scientists with a first

peek beneath the martian surface (Science

Express, 30 November 2005, www.sciencemag

org/cgi/content/abstract/1122165) AlthoughMars Express arrived at the Red Planet 2 yearsago, MARSIS was not deployed until lastsummer because of concerns that unfurlingthe long radar booms might damage thespacecraft So far, team member Jeffrey Plaut

of NASA’s Jet Propulsion Laboratory inPasadena, California, says he’s “absolutelythrilled by its performance.” For instance,MARSIS was able to detect radar reflectionsfrom the subsurface base of the ice layerclose to the planet’s north pole, indicatingthat the deposit is about 1.8 kilometers thick,

it contains less than 2% dust, and the lying crust must be very strong

under-Ice-rich material may also f ill a kilometer-wide buried crater found inChryse Planitia at Mars’s midnorthern lati-tudes “The find of subsurface craters is initself not surprising,” says planetary geolo-gist Michael H Carr of the U.S GeologicalSurvey in Menlo Park, California, “but ifthey are filled with ice, that would be a veryinteresting discovery, since we don’t knowwhere the water went that was present onMars in its early history.” The search forsubsurface liquid water may have to waituntil next spring, when Mars Express is in abetter orbit for detailed radar observations

250-of the planet’s low-lying Hellas Basin,where water may be closer to the surface.France’s OMEGA instrument, whichmaps martian minerals from orbit, has con-firmed that the Red Planet must have beenwet for extended periods in the distant geo-

logic past In last week’s issue of Nature,

OMEGA principal investigator Jean-PierreBibring of the Institute of Space Astrophysics

in Orsay, France, and his colleagues describehow the device found claylike mineralsknown as phyllosilicates in locations whereerosion has exposed very ancient terrain.They date back to an era when liquid waterwas abundant, some 3.8 billion years ago

“These spots are the most favorable to havehosted the possible emergence of life,” saysBibring “I hope the future European Exo-Mars astrobiology lander will go there.”Gerhard Neukum of the Free University inBerlin, who heads the camera team of MarsExpress, agrees that the planet went dry glob-ally about 3.5 billion years ago “But locallyand regionally, there has been glacial andfluvial activity every few hundred million years

or so, maybe until the present time,” he says.New images from the High-Resolution StereoCamera show clear evidence of young glaciers

in Deuteronilus Mensae and recent lava flows

on the flanks of the Olympus Mons shieldvolcano Says Neukum: “Mars is not dead.”Whereas the Huygens mission was overwithin a few hours of touchdown (its batterieswere only designed to last a short time), ESArecently extended the Mars Express missionuntil November 2007 But according to proj-ect scientist Agustín Chicarro of ESA’s R&Dcenter in Noordwijk, the Netherlands, thecraft’s solar-charged batteries will last for atleast five more years, and there’s enoughonboard propellant for another 2 decades

“ESA has never shut down any missionbecause of money constraints,” says Chicarro

“Let’s hope they’ll continue the tradition.”

–GOVERTSCHILLING

G ove r t S c h i l l i n g i s a n a s t ro n o my w ri t e r i nAmersfoort, the Netherlands

Alien world Peaks and dark plains on the surface

of Titan were snapped by Huygens during itsdescent on 14 January 2005

N E W S O F T H E WE E K

Europe Trumpets Successes on

Mars and Titan

S P A C E S C I E N C E

Nuclear Pact at Issue

Three Western nuclear powers are hopingthat five former Soviet states will listen totheir concerns before inking an agreementthat would establish a Central Asia Nuclear-Weapon-Free Zone.The problem is languagedeferring to a 1992 collective securityagreement that Russia interprets as allow-ing for the possible deployment of nuclearweapons in Central Asia during a crisis

The Central Asia zone would increasenuclear safeguards in Kazakhstan,Kyrgyzstan, Tajikistan, Turkmenistan, andUzbekistan and fight trafficking of nuclearmaterials from Russia A tentative agree-ment to create the zone, the world’s fifth,was reached in September after 8 years oftalks But in a démarche the next month,the United States, the United Kingdom,and France stated that they “cannot beexpected to support the treaty … if theobligations of existing internationaltreaties take precedence over the obliga-tions of the proposed” nuclear-free pact.Their concerns have so far blockedfinal adoption of the treaty In earliernegotiations, the three powers had an ally

in Uzbekistan, which had pushed for anuclear-free pact to take precedence overthe 1992 Tashkent treaty But a recentdownturn in U.S.-Uzbek relations maychange Uzbekistan’s stance

The Office of Portfolio Analysis andStrategic Initiatives (OPASI) is a response

to complaints that NIH’s 27 institutes andcenters have become too unwieldy, aswell as a way to plot NIH’s future NIHDirector Elias Zerhouni eventually wants

to put as much as 5% of each institute’sbudget into a fund for crosscutting initia-tives But NIH Deputy Director RaynardKington assured NIH’s advisory councillast week that the 1.7% share going tothe prototype for this effort, the NIHRoadmap, in 2008 won’t grow unless NIHreceives budget increases that at leastmatch rising costs Funds will be disbursed

by institutions, not OPASI, reassuring medical research advocates “There’s a lot

bio-of support” for the bio-office’s analytical role

as well, says David Moore of the tion of American Medical Colleges

Associa-–JOCELYNKAISER

Heeding war nings that it risks falling

behind, the U.K government announced on

1 December that it will increase its funding

of stem cell research from £50 million to

£100 million ($85 million to $170 million)

over the next 2 years But even more is

needed if the country is to compete with

places such as California, which pledged

$3 billion over the next decade, says a new

report by the government-appointed U.K

Stem Cell Initiative

“It’s very encouraging,” panel chair

John Pattison, a former Department of

Health director, says about the

govern-ment’s commitment However, like the

panel, which recommends the United

King-dom spend at least £600 million ($1 billion)

between 2006 and 2015, he urges the

gov-ernment to do more

The United Kingdom is already well

positioned, the panel notes It has been

home to several impor tant stem cell

advances, including the first cloned

mam-mal Dolly the sheep and the world’s firststem cell bank And it has a strict but facili-tating regulatory environment “The U.K

has enthusiastically supported growth of theemerging areas of both embryonic and adultstem cells,” says stem cell biologist RogerPedersen of the University of Cambridge

Both he and the panel emphasize that term investment is needed to keep talentedresearchers from going to the United States,Singapore, or South Korea

long-Funding is also needed to reduce the lagbetween scientific advances and develop-ment of medical treatments Funding agen-cies give this sort of translational researchlower priority, Pattison says The report rec-ommends that the government establish apublic-private partnership to develop stemcell tools for testing the toxicity of drugs

“We have made a good start here in theU.K.,” Pattison says, “but additional fund-ing is needed to capitalize on that earlyinvestment.” –MICHAELSCHIRBER

U.K Doubles Stem Cell Funding

B I O M E D I C A L P O L I C Y

ERC Moves Forward Despite Budget Impasse

European Research Council

(ERC) now has three veteran

science chiefs to guide the

agency through its birth

ERC, designed to fund

basic science across Europe, is

supposed to award its f irst

grants in 2007 However,

high-level disagreements over the

E.U budget have kept scientists

guessing about how hard a hit

the fledgling body’s proposed

€1.5 billion yearly budget

might have to absorb

Uncer-tainty notwithstanding, ERC’s

scientific council last week

elected Fotis Kafatos as chair Kafatos, a

molec-ular entomologist at Imperial College London

led the European Molecular Biology

Labora-tory from 1993 to 2005 and is credited with

revitalizing one of Europe’s top research

institu-tions Rounding out the triumvirate are

vice-chairs Helga Nowotny, an expert on science and

society at the Wissenschaftszentrum in Vienna,

and physicist Daniel Esteve of the French

Com-mission for Atomic Energy CEA Saclay

The three, along with the rest of the

sci-ence council, are well equipped to fend off

political attempts to divert ERC funds to

par-ticular fields or countries, says Frank

Gan-non, president of the European Molecular

Biology Organization in Heidelberg “All

signs are that the process is working the waythe scientific community wants it to,” he says

In the meantime, U.K Prime MinisterTony Blair put forward a budget proposal

on 5 December that did nothing to easeresearchers’ fears Earlier this year, E.U offi-cials proposed doubling the overall researchbudget, to just over€10 billion ($12 billion) peryear But as political disagreements escalated,those proposals took a hit; Blair’s compromisewould scale back the research budget to closer

to€6 billion yearly Both Kafatos and Nowotnysay that to be viable, the ERC will need at least

€1 billion per year European heads of state willmeet next week to try again to seal a deal

–GRETCHENVOGEL

E U R O P E A N R E S E A R C H

This big? Fotis Kafatos, chair of the European Research Council

scientific council, hopes political wrangling won’t shrink the newagency’s budget

Supporters: The British Consulate General — Chicago & UK Trade & Investment Glenn Medical Research Foundation

Merck Research Laboratories Merck/AAAS Undergraduate Science Research Program

Prologue Ventures

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National Institutes of Health (NIH) officials

regularly say that training the next generation

of biomedical scientists is a high priority for

the $28 billion agency But last week at a town

hall–style meeting in Bethesda, Maryland,

they conveyed a different message to

univer-sities: Pony up more of your own resources to

shoulder the costs of training, or face a

decline in the number of graduate students

and postdocs that NIH supports

The meeting explored a fiscal crunch

fac-ing the Ruth Kirschstein National Research

Service Award (NRSA) program, which

sup-ports more than 17,000 Ph.D students and

postdocs, primarily through institutional

train-ing grants NIH currently provides the major

share of trainees’ tuition, paying the first

$3000 plus 60% of the remainder, and covers a

share of each trainee’s health insurance But

faced with steadily rising tuition and health

care costs, along with a flat budget, NIH says it

must transfer more of the burden to universities

or reduce the number of NRSA trainees If the

program’s funding doesn’t grow, the current

formula would result in a loss of “4000 slots by

2015,” says NIH deputy director Norka Ruiz

Bravo (see graphic)

To ease the problem, the agency is

consid-ering three options The first would retain the

existing formula but cap the reimbursable

amount at $16,000 to $18,000, roughly the

current average subsidy The second option

would provide a f ixed allowance—againcapped at $16,000 to $18,000 The last wouldcontinue the current policy, staying on budget

by squeezing both the number of institutionalgrants and the number of trainees per grant

Some call for NIH to shift funds intoNRSA from other areas The choices on the

table reflect the lack of “an appropriate bution and management of training and edu-cational funds” within the NIH budget,believes Glen Gaulton of the University ofPennsylvania School of Medicine in Philadel-

distri-phia “All three are lousy options,” saysRobert Simoni, head of biological sciences atStanford University in California, who never-theless supports the status quo

NIH officials defend flat-lining their ment in training “Prudent policy requires anappropriate balance between training budgetsand the funds available for research support,”says Ruiz Bravo But she acknowledges that

invest-“an annual loss in training positions wouldthreaten the stability of ongoing programs andimpede consideration of training programs innew and emerging scientific fields.”

The proposed ceiling ontuition would force universi-ties to shift funds “away frominvestment in new investiga-tors and research equipment,”complains Linda Dykstra ofthe University of North Car-olina, Chapel Hill Speaking

on behalf of the Association ofAmerican Universities, whose

62 members are a mix of lic and private institutions,Dykstra favored retaining thecurrent formula and reducingthe number of trainees Mostparticipants from public uni-versities, however, came out insupport of a cap, a change thatpresumably would affect themless than the most-expensiveprivate schools Based on those who spoke,the audience on the NIH campus appearedevenly divided among the three options

pub-NIH expects to make a decision on NRSA’sfuture by spring –YUDHIJITBHATTACHARJEE

Universities May Have to Pay More

In Support of Graduate Training

N I H T R A I N I N G G R A N T S

–4000 –3000 –2000 –1000 0 +1000

Emptying Out the Lab

2005 2007 2009 2011 2013 2015

Year

Fewer trainees NIH projects a loss of 4000 NRSA awards over

10 years if spending remains level

N E W S O F T H E W E E K

Young Scientists Get a Helping Hand

Getting that first faculty job represents the

end of one arduous journey for a biomedical

scientist—and, given the difficulties and

cost of establishing a new lab, the start of

another Last week, the National Institutes

of Health (NIH) rolled out three initiatives

intended to smooth that transition to

becom-ing an independent researcher

One of them, expected to be finalized by

spring, is a 5-year award for postdocs that will

provide initial salary support and then convert

to a full-fledged research grant once the

sci-entist gains a faculty position The other two

are already being tested: an independent

investigator grant program that does not

require applicants to submit preliminary data

and a process to speed up the resubmission of

R01 grant applications by new investigators

who fail on their first attempt NIH

offi-cials hope that the three initiatives will help

young scientists get their labs up and running

more quickly—a goal agency Director Elias

Zerhouni calls his “number one priority.”

At $250,000 a year, the new transitionawards will be more than three times largerthan a typical career development award, andthey come with an equal amount of institu-tional overhead compared to the 8% indirectcost rate allowed by the career awards Thegoal is to give universities an added incentive

to recruit young investigators and providenewly hired faculty members with somebreathing room before applying for their firstmajor grant, says Story Landis, director of theNational Institute of Neurological Disordersand Stroke in Bethesda, Maryland

“If you came with this kind of dowry,”

Landis says, “deans, even in troubled times,should be willing to take a chance [on you].”

Biologist Thomas Cech, president of theHoward Hughes Medical Institute in ChevyChase, Maryland, and chair of a recentNational Research Council (NRC) report onfostering independence among young bio-

medical researchers, calls the award “a derful move forward.” Landis won’t say howmany awards NIH plans to give, althoughCech says it should be at least 100

won-The NRC report inspired another of the tiatives: a new grant competition at the NationalInstitute of Environmental Health Sciences(NIEHS) for investigators lacking enough pre-liminary data for a full-fledged NIH proposal.NIEHS plans to give out six such grants nextyear, and other institutes may join in

ini-A third effort, by the Center for ScientificReview, the NIH unit that evaluates grantapplications, aims to speed up the turnaroundtime for new investigators so they can resub-mit a revised application by the next triyearlydeadline Beginning in February, 40 study sec-tions will meet earlier than usual to review sub-missions from first-time applicants and pro-vide written evaluations within a week Appli-cants will also receive 20 extra days to file aresubmission –YUDHIJITBHATTTACHARJEE

N I H C A R E E R AW A R D S

B ANGKOK —At 10:42 p.m on Sunday, 24 July,

a strong undersea earthquake rattled the

Nicobar Islands, 660 kilometers west of

Thailand Minutes after the 7.3-magnitude

quake struck, Thailand’s National Disaster

Warning Center (NDWC) swung into action

Director Plodprasop Suraswadi appeared on

national television to issue the country’s

first-ever tsunami watch: If the quake

gener-ated a tsunami, he warned, the wave would

hit the resort island of Phuket at 12:12 a.m

The advisory, broadcast on all Thai

chan-nels, was not an evacuation order But with

memories of the devastating 26 December

2004 Indian Ocean tsunami still fresh,

hun-dreds of people on Phuket and along the

Andaman Sea coast of the Malay Peninsula

grabbed what they could and fled to higher

ground A crucial piece of data came in

just before midnight: Off the Similan Islands,

50 kilometers from the Andaman coast, a tide

gauge measuring sea level had barely bobbed

There would be no tsunami Suraswadi took

to the airwaves to sound the all clear

If the NDWC had been operational lastyear, thousands of lives might have beenspared The Indian Ocean tsunami killed

5396 people in Thailand; another 2951 peopleare still listed as missing Warnings couldhave saved countless lives elsewhere Some230,000 people died in a dozen nations,including 168,000 in Indonesia’s Acehprovince at the tip of the island of Sumatra

The lesson in ill-preparedness hassparked a mad dash to create a tsunami warn-ing system for the Indian Ocean As the firstanniversary of the disaster approaches, analarm network is beginning to emerge—aloose web of deep ocean sensors, tidegauges, and seismic stations operated byindividual countries, along with mechanismsfor sharing data and disseminating public

warnings Last month, for example, sia, the country deemed most vulnerable tothe next big Indian Ocean tsunami, deployedtwo sea-floor pressure sensors and associ-ated buoys, the vanguard of a 10-sensor net-work “We want to show the world that weare ready,” says Jan Sopaheluwakan, deputychair of earth sciences at the IndonesianInstitute of Sciences in Jakarta

Indone-By establishing warning centers, Thailandand other countries have begun to fill a lethalvoid They will issue tsunami advisories moreoften, and in most instances the resulting wavewill be puny or nonexistent—ratcheting upanxiety and prompting people to flee the sea-side needlessly “People are going to have to

be understanding about this,” says NDWC’sCherdsak Virapat, director of Thailand’s Inter-national Ocean Institute in Bangkok

Asleep at the wheel

The Indian Ocean tsunami last Decembercaught governments woefully off-guard.The trigger was a monster earthquake at amagnitude of 9.3, centered west of Aceh, onthe northwestern tip of Sumatra The quakestruck at 7:59 a.m Indonesia time, andwithin 40 minutes a wave, the first of threedestructive moving mounds of seawater,had inundated the city of Banda Aceh.Nearly 2 hours after the earthquake, the firstwave barreled into Phuket and neighboringseaside provinces of Thailand It was a Sun-day morning; most government off iceswere closed Staff in a meteorological office

in northern Thailand saw the seismic reportbut had no idea that a tsunami might beimminent, says Virapat “Every year, some-one would ask, ‘What should we do if there

is a tsunami?’ ” The possibility seemedremote, he says

Minutes later, the Nicobar Islands, ing an Indian Air Force base at Car Nicobar,were pummeled It took another 90 minutesfor the tsunami to travel across the Bay ofBengal But no one sounded the alarm, and thewaves claimed 15,000 in India and 31,000 inSri Lanka

includ-9 DECEMBER 2005 VOL 310 SCIENCE www.sciencemag.org1602

A year after the Indian Ocean tsunami, nations along the coast have

created the framework for a regionwide warning system

Girding for the Next

Big heave.The 26 December 2004 quake exposed coral off Simeulue Island in Aceh province Dudi Prayudi

of the Indonesian Institute of Sciences and Aron Meltzner of Caltech measure the uplift at 1.2 meters

Stunned by the realization that the human

toll need not have been so high,

representa-tives of Indian Ocean nations met in Bangkok

last January to begin planning for a tsunami

alert system Discussions bogged down over

who would host a regional warning center By

spring it was clear that each country would

establish its own center, although the

Inter-governmental Oceanographic Commission

of UNESCO was invited to coordinate an

Indian Ocean Tsunami Warning and

Mitiga-tion System, the subject of an IOC meeting

next week in Hyderabad, India It is expected

to cost $200 million to bring the system

online over the next few years

IOC is counting on f ive nations—

Australia, India, Indonesia, Malaysia, and

Thailand—to cover the entire Indian Ocean,

with other nations enhancing the coverage

“No single nation can protect itself or

pro-vide protection to others alone,” says IOC

executive secretary Patricio Bernal

Real-time data will stream into one or more

“sub-regional centers,” he says, where it will be

rapidly processed and fed back to national

warning centers, which would decide on

their own whether to issue tsunami

advi-sories to their citizens India continues to

resist sharing real-time seismic and tidal

data, out of concern that certain information

could compromise its nuclear weapons

pro-gram (see sidebar, p 1604) Nevertheless, a

basic Indian Ocean–wide system is expected

to be in place by July 2006, says physical

oceanographer William Erb, head of IOC’s

off ice in West Perth, Australia More

advanced assets, such as the deep-ocean

tsunameters, will come later

A hazardous way ahead

As governments gear up to cope with the next

tsunami, scientists have pieced together a

vivid picture of the shattered Sunda fault off

the island of Sumatra—and an idea of what

could be in store for the region

The December quake’s

1300-kilometer-long offshore rupture shunted stress

south-ward beneath the sea floor, prompting

seis-mologists to warn that the section of fault

adjacent to Sumatra could be the next to fail

No one knew how close to failure that

seg-ment was, but geophysicists John McCloskey,

Suleyman Nalbant, and Sandy Steacy of the

University of Ulster in Coleraine, Northern

Ireland, warned in the 17 March issue of

Nature that the fault had not broken since

1861 That was enough time to build up

energy for a sizable earthquake On 28 March,

it struck at a hefty magnitude 8.7

As in December, the region was

unpre-pared The U.S National Oceanic and

Atmos-pheric Administration’s (NOAA’s) Pacific

Tsunami Warning Center (PTWC) in Ewa

Beach, Hawaii, registered the earthquake

8 minutes after it occurred and issued a

tsunami bulletin 11 minutes later Withoutany deep ocean sensors or tide gauges offIndonesia, “it took hours to determine if, infact, [the earthquake had] created a tsunami,”

notes David Johnson, director of NOAA’sNational Weather Service The bang endedwith a whimper: The wave recorded at CocosIsland was just 23 centimeters The tsunamiwas trivial in large part because the quake hadheaved the sea floor upward beneath islandsand surrounding shallow waters, not in deepwaters where motions can spawn massive

waves (Science, 15 April, p 341).

Now the Ulster group, joined by mologist Kerry Sieh of the California Institute

paleoseis-of Technology in Pasadena, is warning that therisk is moving southward The next section offault down the line—from 1°S to 5°S, off-shore of the Sumatran city of Padang—couldwell be poised for disaster This segment lastfailed in 1833; the accumulated stress coulddrive a quake larger than magnitude 8.5 Asubsequent tsunami would threaten a millionpeople along 500 kilometers of low-lyingIndonesian coast

New findings underscore the risk Earlierthis week, at the fall meeting of the AmericanGeophysical Union (AGU) in San Francisco,California, the Ulster group, with colleagues

at the National Institute of Geophysics andVolcanology in Rome, reported preliminary

computer simulations of possible southSumatra tsunamis They first modeled a range

of possible earthquakes of magnitude 8.0 to9.0 and then used the resulting sea-floormovement to drive a model of tsunami wavegeneration Initial results show that the coastfrom Padang south could be devastated

Elsewhere around the Indian Ocean, thetsunami risk from a massive quake off Padang

is relatively low The new simulations suggestthat farther from Sumatra, most wave energywould be dissipated in the vast emptiness ofthe ocean Here, the fault bends along thesouthward-facing Indonesian archipelago in away that a far-traveling tsunami would bedirected away from December’s hard-hit tar-gets: Thailand, India, and Sri Lanka

Other stretches of the deep-sea Sundafault are less worrisome At the AGU meet-ing, seismologists Emile Okal and Seth Stein

To catch a wave Last month, the first two of

10 pressure sensors were deployed off Sumatra

DART buoys will also listen in on the SundaTrench and other seismic danger zones

Acoustic modems

Sea-floorsensor

Buoy

Datacenter

GPS reference &

data collection

Differentialpressure sensor

Absolutepressuresensor

N E W S FO C U S

of Northwestern University in Evanston,

Illi-nois, reported that, based on the behavior of

similar faults around the Pacific, the

contin-uation of the fault to the south off the

Indone-sian island of Java is not likely to generate a

devastating magnitude-9 quake And to the

north of last December’s break, the fault

hasn’t even produced magnitude 7s “Our

guess would be you’re not going to have big,

thrusting earthquakes there” of the sort that

generate a tsunami, says Stein Instead of thetectonic plate thrusting down into the mantleand shoving up the sea floor to generate atsunami, he says, to the north the plates prob-ably slide by each other San Andreas–style,without triggering tsunamis

vari-veys and satellite imagery (Science, 10 June,

p 1596) His team is now modeling inundationscenarios in the Padang region

Indonesia is taking the threat seriously.Padang’s vulnerability is “bitter news” forthe local population, says Sopaheluwakan

“To prevent Padang from becoming the nextdisaster,” he says, the government is workingwith local authorities to develop a compre-hensive evacuation plan If an earthquake ofmagnitude 6 or larger occurs in the SundaTrench, an immediate evacuation order will

be broadcast for any coastal area that a wavewould strike within 30 minutes of the quake,Sopaheluwakan says

Indonesia won’t rely solely on seismic nals in making a call on a tsunami Lastmonth, scientists deployed the first two sea-floor sensors of the German IndonesianTsunami Early Warning System The devices,whose development was spearheaded by theNational Research Centre for Geosciences inPotsdam and the Leibniz Institute of MarineSciences in Kiel, measure sea-floor vibrationsand pressure changes in the water column.Data are transmitted by acoustic modem to abuoy linked by satellite to Jakarta The system

sig-is designed to alert Jakarta within tens of onds of an oncoming tsunami

sec-After the crew on the Sonne, a German

research ship, positioned the first sensor andbuoy on the Sunda Trench southwest ofPadang on 20 November, they made a portcall in Padang If a tsunami were headingthere, the area would be tough to evacuate

“Only three streets lead out of the city tohigher ground On a normal day, those threestreets are usually full to overflowing withtraffic,” expedition scientist Ernst Flüh, ageophysicist at the Leibniz institute, noted in

a Web log on the Deutsche Welle Web site.

Locals he met were placing high hopes in theGerman sensors “Over and over again wehad to explain that one or two buoys do notmake an early warning system,” he wrote.The second buoy and sensor set wasdeployed northwest of Padang on 24 Novem-ber The system won’t be operational untilanother eight are installed over the next 2 years.They will run in a line off the coast fromBanda Aceh to Bali, each separated by at most

200 kilometers The German government isfooting the system’s € 45 million bill

A network of deep ocean tsunami buoysoperated by other countries will monitor therest of the Indian Ocean The U.S.-madeDeep-Ocean Assessment and Reporting of CREDIT

A Dead Spot for the Tsunami Network?

N EW D ELHI —The budding regional tsunami warning system in the Indian Ocean may get little

useful information from one key partner: India The Indian government insists it will not

release seismic recordings in real time, because if it were to resume nuclear testing, the

detailed seismic signatures would immediately be broadcast to the world Officials have also

told Science they will not share online tide-gauge data, out of concern that such information

could aid an aggressor attempting an invasion by sea Delays in pinpointing an earthquake’s

location or confirming wave propagation could delay a tsunami warning

India’s status as data holdout contrasts with its commitment to creating the region’s

most ambitious warning center for tsunamis and cyclone-generated storm surges Under a

$30 million plan, India will increase the number of its tide gauges fivefold and more than

triple its seismic stations from 51 to 170 The first of 17 new broadband seismic stations

came online at Port Blair, capital of the Andaman and Nicobar Islands, last May And India

plans to deploy up to 12 tsunameters—Deep-Ocean Assessment and Reporting of Tsunamis

(DART) buoys and sea-floor sensors that detect pressure changes in the water column—

although it is not expected to share these readings in real time either Data will feed into a

nerve center in Hyderabad, planned to be operating by September 2007

Indian scientists predict that the new tools, coupled with inundation models under

develop-ment at the National Institute of Oceanography in Goa, should reduce the time required to

assess tsunami risk after an earthquake from 40 minutes to 10.To minimize false alarms, Indian

officials say that a tsunami warning will be issued after a major quake only if a significant

pres-sure increase is registered by a DART, oncethese are in place in the Bay of Bengal, theArabian Sea, and the southern Indian Ocean

India’s reluctance to share data couldcome back to haunt it India has refused tohook up its vaunted array of seismometers tothe Global Seismographic Network, 128 sta-tions that record temblors and listen forsignatures of nuclear detonations to helpverify compliance with the ComprehensiveTest Ban Treaty, which India has not joined

The seismic network is crucial to quicklypinpointing a quake’s magnitude and loca-tion—and for analyzing tsunami threats

Some Indian officials acknowledge arisk “Our existing policy of not sharingonline seismic data has to change,” saysValangiman Subramanian Ramamurthy,

a nuclear scientist and secretary of theDepartment of Science and Technology He says India is reassessing its relationship with

international networks, and India may agree to divulge data on earthquakes greater than 5 on

the Richter scale in “near–real time.”That would help, but near–real time equates to a roughly

40-minute lag as Indian experts process data before releasing it

Earlier this year, some tsunami experts were highly critical of India’s policy (Science, 28

Jan-uary, p 503) But concerns have been eased by ongoing efforts to bolster seismic stations

elsewhere in the region and by the prospect of DARTs managed by other countries “I am less

pessimistic now,” says Costas Synolakis of the University of Southern California in Los Angeles

“India’s [seismic] recordings are not as essential for early warning, particularly for sources ‘far’

from India,” he says Maybe not—if a killer wave doesn’t come before the rest of the Indian

Ocean states bring their new instrumentation on line –PALLAVABAGLA

Sharper hearing India has fired up its first new

broadband seismometer, in Port Blair

Tsunamis tsunameters—each a buoy and an

associated bottom pressure sensor—already

serve as sentinels for the PTWC in Hawaii

It’s the only such device that’s been “tried

and tested,” notes IOC’s Erb At a price tag

of $250,000 per buoy and a design life of

1 year, the network won’t come cheap, nor

will it come quickly: The U.S factory that

produces the buoys was inundated by

Hurri-cane Katrina, so production is lagging,

sources say Thailand plans to buy two and

have them in place in the Andaman Sea by

early 2007 India expects to deploy up to a

dozen, and Malaysia will place three more in

the Straits of Malacca, the South China Sea,

and the Sulu Sea

Some experts contend that investing

heav-ily in high-tech tsunameters such as these, the

sexiest and costliest components of the

warn-ing systems, is overkill They say

seismo-graphs and tide gauges, coupled with

height-ened vigilance, are sufficient for most

coun-tries But everyone wants new technology

Indian Ocean nations meanwhile are

upgrading or adding seismic stations and

sharpening their ability to map earthquake

hazards and analyze data Thailand, for

exam-ple, plans to triple the number of its digital

stations to 45 by the end of 2008 Countries

are also installing digital tide gauges Before

the tsunami, Malaysia’s shore-hugging

gauges could not transmit data in real time It

is now installing six gauges on far-flungislands that will transmit data to KualaLumpur by satellite and increase warningtimes by minutes Through IOC, the UnitedStates is kicking in $16.6 million over 2 yearsfor these efforts, primarily in India, Indone-sia, the Maldives, Sri Lanka, and Thailand

The most valuable legacy of the 26 ember 2004 tsunami may be the nationaldisaster centers that countries are setting up

Dec-to moniDec-tor and act on the data that will bepouring in India plans to have its tsunamiearly warning center in Hyderabad up andrunning by fall 2007 Thailand’s NDWC,opened on 30 May, features a 24-hour oper-ations room with live feeds of seismic, tidegauge, and other data from around theIndian Ocean and from Japan and theUnited States, banks of televisions tuned tonews stations, and clusters of desks whereanalysts are primed to sound the alarm

“Now we have all the information we need

to forecast tsunamis,” says NDWC gist Passkorn Kunthasap

geolo-With input from PTWC experts, NDWCscientists have designed a simple schematicfor making snap decisions For offshoreearthquakes registering 7.0 to 7.7 on theRichter scale, the center will issue a tsunamiwatch A stronger earthquake will trigger a

warning and immediate evacuation order.Thailand has recently erected three warningsiren towers on Phuket and the peninsula,with plans for 62 more next year

An open question is whether the nationalcenters “will have the resources and stamina

to stay active and alert for what amounts tofrom now to eternity,” says Costas Synolakis,director of USC’s Tsunami Research Center

If the centers are devoted solely to their raisond’être—watching for a tsunami that may notcome for generations—political and financialsupport could melt away “In several years,people would forget and get lax,” says Erb.IOC has been urging nations to broaden theirmission to a number of natural hazards

Thai officials have taken that to heart.They hope NDWC will stimulate a morerapid response to flooding, which each yearclaims dozens of lives and inflicts about

$750 million in economic losses, roughlyequal to the damage to infrastructure and losttourism revenue from last December’stsunami But as the first anniversary of thedeadly wave approaches, NDWC and its sis-ter centers will at least have a palliative effect

“We’re on watch 24 hours,” says AdmiralThaweesak Daengchai, NDWC’s executivemanager “And we’re not afraid anymore.”

–RICHARDSTONE ANDRICHARDA KERR

With reporting by Pallava Bagla in New Delhi

and anguished survivors Thousands of victims in the region are

thought to suffer from posttraumatic stress disorder (PTSD), whose

symptoms include flashbacks, panic attacks, amnesia, and

out-of-body sensations Now, in what’s billed as the largest study of its kind,

Thai researchers have embarked on a hunt for genes that may leave

people vulnerable to PTSD

Most previous PTSD studies involved victims who had endured

trau-mas of varying duration and intensity: witnessing torture, for example,

or experiencing a bomb blast This work has not nailed vulnerability

genes as yet, although it has found candidates An advantage of the

Thai government–funded study, organized by the Thailand Center of

Excellence for Life Sciences(TCELS), is that most victimsshare a common geneticheritage and were exposed

at the same time to thesame stimulus, namely the tsunami wave A pharmacoge-netic component of the study aims to assess whether anindividual’s response to drug therapy depends on his or hergenetic makeup It’s “a highly novel and potentiallyunprecedented approach,” says Robert Malison, a psychi-atric researcher at Yale University

Beginning in February, psychiatric epidemiologist NantikaThavichachart of Chulalongkorn University and colleaguesinterviewed more than 3000 adults on the coast “Victimswere committing suicide more than 3 months after thetsunami,” says TCELS president Thongchai Thavichachart.About 600 were diagnosed with chronic PTSD Researchers drew bloodfrom victims, healthy siblings, and unrelated individuals

In the $3 million study’s next phase, to begin in early 2006,researchers will create “immortalized” cell lines from each blood sam-ple and then fish for gene variations, or alleles, that may underlie sus-ceptibility to PTSD A team led by geneticist Verayuth Praphanphoj ofThailand’s Department of Mental Health will target about 20 genes byzeroing in on DNA markers called single-nucleotide polymorphisms.His group will also take a second tack, trawling for genetic signals in awhole-genome association study of a few hundred individuals

Experts suspect that several genes are involved in susceptibility toPTSD, considering the constellation and variability of symptoms,some of which overlap with those of anxiety disorder and depression.Preliminary results are due in late 2006 Yale’s Joel Gelernter, for one,has high expectations “There’s a very good chance” that the studywill pinpoint more candidate PTSD genes, he says –R.S

Compounding the tragedy.

Anguish over loved ones lost

in the December tsunamiwas one trigger for PTSD

The fight against malaria is famously

frus-trating A vaccine is still years away, drug

resistance is on the rise, and

mosquito-thwarting bed nets, although effective, have

proved difficult to get to the people who

need them Now researchers are testing a

bold new strategy aimed directly at

protect-ing malaria’s most likely victims: infants

and young children Akin to a preemptive

strike, the strategy involves giving

anti-malaria drugs routinely to infants

regard-less of whether they are infected with

malaria parasites

Treating hundreds of millions of children

for a disease they might not have flies in

the face of standard public health practice

But evidence so far suggests that this simple

and inexpensive treatment, called IPT for

intermittent preventative treatment, may

signif icantly slash the disease burden in

young children Nearly 1 million children

die each year of the disease

There is some precedent for the strategy

The World Health Organization (WHO)

already recommends that all pregnant women

in malaria-affected regions receive IPT The

agency says that whether an expectant mother

is infected or not, she should receive one dose

of malaria medicine in the second trimester

and another in the third But some malaria

experts question whether the costs and benefits

were weighed carefully enough before thepractice became official policy In particular,some worry that such large-scale interven-tions could backf ire by promoting drugresistance “We can do better” to ensure that

an investment in IPT in infants will pay off interms of lives saved, and that it will alsoavoid causing harm, says David Schellenberg

of the Ifakara Health Research and ment Centre in Kilombero, Tanzania

Develop-In an effort to weigh the costs and benefits

as quickly as possible, researchers in

2003 formed the IPTi consortium (The ‘i’ isfor infants.) The group, which includes WHO,UNICEF, and scientists from 14 institutions

in 11 countries, received $28 million infunding from the Bill and Melinda GatesFoundation By coordinating trials andsharing data, the consortium hopes tohave enough hard evidence to be able torecommend a policy for whether and how

to implement IPTi by the end of 2006 At ameeting*of malaria researchers last month inYaounde, Cameroon, IPTi was high on theagenda, as consortium members presentednew results from one of the half-dozen trialsunder way across Africa

Prevention on the cheap?

One of the key advantages of IPT forexpectant mothers is that it can piggyback

on existing public health programs bytreating women when they visit healthclinics for routine antenatal checkups.Several studies have shown that just twotreatments with a standard malaria drugpair called sulfadoxine-pyrimethamine (SP)

is as effective at preventing malaria cations such as maternal anemia and lowbirth weight as is more frequent prophylaxis,though much cheaper and easier to admin-ister The hope is that infants, who wouldreceive antimalaria drugs at the same timethey receive vaccinations against polio,diphtheria, and measles, would also benefitfrom routine intermittent treatment

compli-The first data on IPT in infants—whichhelped inspire the formation of the consor-tium—were remarkable In 2001, Schellenbergand his colleagues reported that in a study

of 700 babies in Tanzania, IPTi cut rates ofclinical malaria by almost 60% comparedwith rates in infants who received aplacebo Another Tanzanian study in 2003showed that IPTi reduced malarial fevers by65% in the first year of life

But more recent studies suggest that suchdramatic results can’t be expected every-where In a trial of nearly 1500 infants in

Ghana, described in October in the British

Medical Journal, treatment cut malaria

episodes by just 25% compared to a placebo.Hospital admissions for anemia, one of themost dangerous malaria complications,were 35% lower in the treatment group One explanation for the different findingsmay be the patterns of disease transmission

in the two study areas, says Brian Greenwood

of the London School of Hygiene andTropical Medicine, who helped lead theGhana trial At the Tanzanian study site,malaria spreads at a relatively low rate year-round At the site in Ghana, the disease istransmitted during the 6-month rainy season,when residents face about 10 times the rate ofinfective mosquito bites as faced by those inthe Tanzanian study Greenwood notes thatfor a subset of Ghanan babies who receivedtheir first two doses during the rainy season,results were nearly as good as those inTanzania; it reduced clinical cases of malaria

by 52% and anemia by 72%

But mosquito bite rates and differingseasons of infection can’t explain all thedifferences seen in IPTi trials Results from

a trial in Mozambique, first reported last

I n f e c t i o u s D i s e a s e s

Piggyback If the IPT strategy works, antimalaria

drugs could be delivered to infants at the sametime they receive vaccinations for childhooddiseases

*Fourth Multilateral Initiative on Malaria African Malaria Conference, Yaounde, Cameroon,13–18 November

Pan-Will a Preemptive Strike Against

Malaria Pay Off?

Researchers are trying to determine whether routinely treating children for malaria

before they contract it will save lives without promoting drug resistance

month in Yaounde, “are not as exciting as

we’d hoped for,” admits Andrea Egan of

the University of Barcelona in Spain, who

coordinates the IPTi consortium A study

of 1500 infants, also living in an area of

moderate year-round transmission, showed

a 22% reduction in clinical malaria rates

compared to rates in babies who received a

placebo but no difference in anemia rates

Egan suspects differences in both bed net

use and nutrition contributed to the smaller

effect More than half the population in the

Tanzanian trial slept under bed nets, she says,

whereas in Mozambique, bed net use was

almost nil In addition, in both Ghana and

Tanzania, the treatment and control groups

received a routine iron supplement, whereas

babies in Mozambique did not Egan

specu-lates that babies in Mozambique might have

had such high baseline rates of anemia that

protecting them from malaria didn’t make a

noticeable dent Consortium members

expect to know more soon Three studies

nearing completion, one in Gabon and two in

Ghana, are in part designed to elucidate how

environment and epidemiology affect IPTi,

says Peter Kremsner of the University of

Tübingen in Germany, who is helping direct

the trial in Lambaréné, Gabon

First, do no harm

Perhaps the biggest concern about IPTi,

however, is whether it could backf ire by

increasing the malaria parasite’s resistance

to medications Drug resistance is one of the

most serious problems in the fight against

malaria, rendering many of the cheapest and

safest drugs ineffective in curing the disease

Indeed, this week researchers reported in

The Lancet the first evidence for resistance

to artemisinin-based drugs, the newest

therapy against parasites that can evade

other drugs (see sidebar)

In many areas, resistance to the drug

combination SP is already well

estab-lished Cheap and safe, SP remains a

first-line defense against the disease It is also

the first choice for IPTi Giving the drug

to otherwise healthy children might not

necessarily increase SP resistance, notes

Egan If the approach succeeds in

reduc-ing clinical malaria rates, she says, overall

use of the drug might also decline, and

resistance rates could even fall Answers

should come from a consortium-sponsored

trial involving 12,000 infants in Tanzania

that is monitoring rates of resistance as

IPTi is introduced

Some researchers are also worried that

IPTi might leave infants more vulnerable

to malaria later in their lives For children

living in malaria-endemic areas, early

infections are something of a mixed blessing

Although they can be deadly, infections

seem to confer some immunity, protecting

the babies who survive from becomingseriously ill when infected later If thatprocess is interrupted, the disease might bedelayed but not prevented

Researchers watching for the so-calledrebound effect have reported mixed results

Schellenberg and his colleagues reported in

April in The Lancet that children in Tanzania

who had received IPT as infants still hadsignificantly lower rates of malaria throughage 2 The researchers suggest that IPTmight actually be helping boost the body’snatural defenses against the disease by givingchildren a head start in fighting off mildinfections But in Ghana, again, the resultsare less encouraging Overall rates of malaria

went up slightly among IPT-treated childrenbetween ages 16 and 24 months, althoughepisodes of cerebral malaria, the most seri-ous form of the disease, decreased

Nevertheless, consortium members arelargely optimistic that studies will supportexpanding IPT to infants Reported sideeffects have been minimal, and even the22% reduction in malaria among infants inMozambique is “still very positive,” Egansays Says Kremsner, “If there are soon sixand seven studies showing protection, thatcounts If that goes along with considerablesafety and good tolerability, the policy deci-sion becomes fairly straightforward.”

as the last best hope against parasites that can already elude other treatments So far, theevidence comes just from lab tests of parasites isolated from infected people; no patient hasdied of artemisinin-resistant malaria But researchers say the observation is an urgentreminder that the compound and its relatives, just beginning to be employed widely aroundthe world, could fail if not used carefully

Based on extracts from the sweet wormwood plant Artemisia annua, used for centuries in

Chinese traditional medicine, artemisinin and its derivatives such as artesunate andartemether had seemed almost invincible Even in areas where multidrug-resistant parasitesrender most other malaria medications useless, treatments containing artemisinins routinelycure 90% of patients within days

Because the compounds are powerful and fast-acting, scientists had hoped that theymight pack such a wallop that resistant strains would be slow to appear To be doubly safe,officials have stressed the importance of using the compounds only in tandem with otherdrugs, an approach called artemisinin combination therapy (ACT)

The importance of that ACT strategy is highlighted in the 3 December issue of The Lancet,

in which Ronan Jambou and his colleagues at the Institut Pasteur in Dakar, Senegal, comparedthe effects of various drugs on malaria parasites from three

different parts of the world In an effort to develop an warning system for signs of resistance, the researchers tookblood samples from 530 malaria patients in Cambodia,French Guiana, and Senegal In samples from Cambodia,where use of artemisinin-based drugs has beentightly regulated as part of ACT therapy, theyfound no evidence of resistance But insamples from Senegal and French Guiana,where artemisinins are either unregulated

early-or approved fearly-or use without other drugs,lab tests revealed the presence of parasitesthat could survive the drug In addition, theyidentified several mutations that are likely to conferthe resistance “This is the first step toward treatmentfailure with this drug,” Jambou says

“When you use drugs in monotherapy, sooner or later you willdevelop drug resistance,” says Pascal Ringwald of the World HealthOrganization But he says the news comes several years sooner thanmost people expected

Even so, Jambou says, if countries heed the early warning and crack down on stricted use of the drugs, there is a good chance they can preserve artemisinin’s usefulness

unre-He notes that it took 40 years for public health experts and governments to withdrawchloroquine from regular use after the first treatment failures: “If we use these compoundscarefully, we still have time.”

–G.V

N E W S FO C U S