Table Of ContentVolume 436 Number 7047 pp1-150
In this issue (7 July 2005) • Essay
• News and Views
• Editorials • Brief Communications
• Research Highlights • Mars: News and Views
• News • Mars: Analysis
• News Features • Mars: Articles
• Business • Mars: Letters
• Correspondence • Articles
• Books and Arts • Letters
• Naturejobs
• Futures
Editorials
Climate of distrust p1
Six months into President George W. Bush's second term of office, partisan politics continues to widen
the gulf between researchers and the administration.
Rules of engagement p2
Biologists may soon have little option but to sign up to codes of conduct.
Playing the name game p2
Stem-cell biologists should not try to change the definition of the word 'embryo'.
Research Highlights
Research highlights p4
News
Flu officials pull back from raising global alert level p6
Conflicting results from Vietnam cause concern.
Declan Butler
Climate change: is the US Congress bullying experts? p7
Climate chief Rajendra Pachauri responds to US demands for information.
Parasite infiltrates fruitfly research p8
Geneticists fear Drosophila results skewed by unnoticed bacterium.
Claire Ainsworth
Stem-cell 'heroes' celebrate a series of breakthroughs p9
With fresh initiatives and funding the future is bright, say researchers.
Erika Check
Sidelines p10
Scientists finally get their hands on Kennewick man p10
Bone studies and DNA tests will help determine the origins of the 9,000-year-old skeleton.
Rex Dalton
US willing to pay for Russia's help in space p11
Anti-Iran legislation set to be loosened for fresh deal on space station services.
Tony Reichhardt
Genetic patent singles out Jewish women p12
European ruling on test for breast cancer gene slammed as discriminatory.
Alison Abbott
News in brief p13
News Features
Conservation biology: Is this any way to save a species? p14
Thanks to the influence of a powerful US senator, more than $120 million has been pumped into research
on Alaska's endangered Steller sea lions in just four years. Rex Dalton asks what we've learned.
Neuroscience: Deep in thought p18
Electrodes implanted in the brain could transform the lives of psychiatric patients. Alison Abbott watched
an operation to release a man from his obsessive thoughts.
I
Electronic notebooks: A new leaf p20
Record-keeping in the lab has stayed unchanged for hundreds of years, but today's experiments are putting
huge pressure on the old ways. Declan Butler weighs up the pros and cons of electronic alternatives to
that dog-eared notebook.
Business
Computer hardware: Silicon down to the wire p22
Microchip-makers are starting to look beyond silicon, and what they see, reports Colin Macilwain, is a
semiconductor industry of a very different complexion — but not for some time yet.
In brief p23
Market watch p23
Correspondence
Call for openness about farm-animal experiments p24
Ian G. Colditz
Plagiarism criteria ignore the way research evolves p24
Bent Sørensen
Six-word rule could turn description into plagiarism p24
Beverly E. Barton
Penalties plus high-quality review to fight plagiarism p24
Klaus Wittmaack
Editor's note p24
Books and Arts
The race for the bomb p25
How close was Nazi Germany to developing atomic weapons?
Dieter Hoffmann reviews Hitlers Bombe: Die Geheime Geschichte der Deutschen Kernwaffenversuche by Rainer
Karlsch
A happy gathering p26
Dylan Evans reviews Happiness: Lessons From a New Science by Richard Layard and Making Happy People: The
Nature of Happiness and its Origins in Childhood by Paul Martin and Happiness: The Science Behind Your
Smile by Daniel Nettle
Exhibition: Apollo in the lab p27
New in paperback p27
Essay
Concept
The mental Universe p29
The only reality is mind and observations, but observations are not of things. To see the Universe as
it really is, we must abandon our tendency to conceptualize observations as things.
Richard Conn Henry
News and Views
Neuroscience: A home for the nicotine habit p31
Nicotine is extremely addictive, but it can also improve cognitive performance. Attempts to unravel the
complex pathways underlying these effects pinpoint a single type of receptor in just one brain region.
Julie A. Kauer
Solid-state physics: Doping the undopable p32
Impurities that increase the number of electron carriers are essential in most bulk semiconductors.
Introducing such foreign atoms into semiconductor nanocrystals is fiddly, and requires exact knowledge
of the material's surface.
Giulia Galli
Cancer biology: The weakest link? p33
Cellular lineages are defined by master regulatory proteins that dictate their fate and ensure their
survival. The dependence on such factors of tumours that are resistant to treatment may prove to be their
Achilles' heel.
Glenn Merlino
Conservation biology: Where slugs may safely graze p35
Grazing animals mow meadows to useful effect. From the results of experiments on newly established
grassland, one such grazer, the little-considered slug, evidently has a big and beneficial influence on
plant diversity.
Peter D. Moore
50 and 100 years ago p36
II
Nonlinear dynamics: When instability makes sense p36
Mathematical models that use instabilities to describe changes of weather patterns or spacecraft
trajectories are well established. Could such principles apply to the sense of smell, and to other aspects
of neural computation?
Peter Ashwin and Marc Timme
Correction p37
Brief Communications
Acoustics: The vocal tract and the sound of a didgeridoo p39
Acoustic measurements show how a player can extract a range of timbres from this primitive instrument.
Alex Tarnopolsky, Neville Fletcher, Lloyd Hollenberg, Benjamin Lange, John Smith and Joe Wolfe
Palaeoclimatology: The record for marine isotopic stage 11 p39
Dominique Raynaud, Jean-Marc Barnola, Roland Souchez, Reginald Lorrain, Jean-Robert Petit, Paul Duval
and Vladimir Y. Lipenkov
Mars: News and Views
Mars: Twin studies on Mars p42
The twin Mars Exploration Rovers don't themselves range widely, but the observations they make do.
Information on partial solar eclipses, salty rocks and magnetic dust are among the latest highlights of
the rovers' findings.
David C. Catling
Mars: Analysis
Assessment of Mars Exploration Rover landing site predictions p44
M. P. Golombek, R. E. Arvidson, J. F. Bell, III, P. R. Christensen, J. A. Crisp, L. S. Crumpler, B. L.
Ehlmann, R. L. Fergason, J. A. Grant, R. Greeley, A. F. C. Haldemann, D. M. Kass, T. J. Parker, J. T.
Schofield, S. W. Squyres and R. W. Zurek
Mars: Articles
An integrated view of the chemistry and mineralogy of martian soils p49
Albert S. Yen, Ralf Gellert, Christian Schröder, Richard V. Morris, James F. Bell, III, Amy T. Knudson,
Benton C. Clark, Douglas W. Ming, Joy A. Crisp, Raymond E. Arvidson, Diana Blaney, Johannes Brückner,
Philip R. Christensen, David J. DesMarais, Paulo A. de Souza, Jr, Thanasis E. Economou, Amitabha Ghosh,
Brian C. Hahn, Kenneth E. Herkenhoff, Larry A. Haskin, Joel A. Hurowitz, Bradley L. Joliff, Jeffrey R.
Johnson, Göstar Klingelhöfer, Morten Bo Madsen, Scott M. McLennan, Harry Y. McSween, Lutz Richter, Rudi
Rieder, Daniel Rodionov, Larry Soderblom, Steven W. Squyres, Nicholas J. Tosca, Alian Wang, Michael Wyatt
and Jutta Zipfel
Mars: Letters
Solar eclipses of Phobos and Deimos observed from the surface of Mars p55
J. F. Bell, III, M. T. Lemmon, T. C. Duxbury, M. Y. H. Hubbard, M. J. Wolff, S. W. Squyres, L. Craig and J.
M. Ludwinski
Aeolian processes at the Mars Exploration Rover Meridiani Planum landing site p58
R. Sullivan, D. Banfield, J. F. Bell, III, W. Calvin, D. Fike, M. Golombek, R. Greeley, J. Grotzinger,
K. Herkenhoff, D. Jerolmack, M. Malin, D. Ming, L. A. Soderblom, S. W. Squyres, S. Thompson, W. A. Watters,
C. M. Weitz and A. Yen
Indication of drier periods on Mars from the chemistry and mineralogy of atmospheric dust
p62
Walter Goetz, Preben Bertelsen, Charlotte S. Binau, Haraldur P. Gunnlaugsson, Stubbe F. Hviid, Kjartan
M. Kinch, Daniel E. Madsen, Morten B. Madsen, Malte Olsen, Ralf Gellert, Göstar Klingelhöfer, Douglas
W. Ming, Richard V. Morris, Rudolf Rieder, Daniel S. Rodionov, Paulo A. de Souza, Jr, Christian Schröder,
Steve W. Squyres, Tom Wdowiak and Albert Yen
Water alteration of rocks and soils on Mars at the Spirit rover site in Gusev crater p66
Larry A. Haskin, Alian Wang, Bradley L. Jolliff, Harry Y. McSween, Benton C. Clark, David J. Des Marais,
Scott M. McLennan, Nicholas J. Tosca, Joel A. Hurowitz, Jack D. Farmer, Albert Yen, Steve W. Squyres,
Raymond E. Arvidson, Göstar Klingelhöfer, Christian Schröder, Paulo A. de Souza, Jr, Douglas W. Ming,
Ralf Gellert, Jutta Zipfel, Johannes Brückner, James F. Bell, III, Kenneth Herkenhoff, Phil R. Christensen,
Steve Ruff, Diana Blaney, Steven Gorevan, Nathalie A. Cabrol, Larry Crumpler, John Grant and Lawrence
Soderblom
Articles
Dynamic predictive coding by the retina p71
Toshihiko Hosoya, Stephen A. Baccus and Markus Meister
Genome-wide analysis of human kinases in clathrin- and caveolae/raft-mediated
endocytosis p78
Lucas Pelkmans, Eugenio Fava, Hannes Grabner, Michael Hannus, Bianca Habermann, Eberhard Krausz and Marino
Zerial
Letters
Photon blockade in an optical cavity with one trapped atom p87
K. M. Birnbaum, A. Boca, R. Miller, A. D. Boozer, T. E. Northup and H. J. Kimble
III
Doping semiconductor nanocrystals p91
Steven C. Erwin, Lijun Zu, Michael I. Haftel, Alexander L. Efros, Thomas A. Kennedy and David J. Norris
Breaking of Henry's law for noble gas and CO solubility in silicate melt under pressure p95
2
Philippe Sarda and Bertrand Guillot
Generation time and temporal scaling of bird population dynamics p99
Bernt-Erik Sæther, Russell Lande, Steinar Engen, Henri Weimerskirch, Magnar Lillegård, Res Altwegg, Peter
H. Becker, Thomas Bregnballe, Jon E. Brommer, Robin H. McCleery, Juha Merilä, Erik Nyholm, Wallace Rendell,
Raleigh R. Robertson, Piotr Tryjanowski and Marcel E. Visser
Nicotine reinforcement and cognition restored by targeted expression of nicotinic
receptors p103
U. Maskos, B. E. Molles, S. Pons, M. Besson, B. P. Guiard, J.-P. Guilloux, A. Evrard, P. Cazala, A. Cormier,
M. Mameli-Engvall, N. Dufour, I. Cloëz-Tayarani, A.-P. Bemelmans, J. Mallet, A. M. Gardier, V. David,
P. Faure, S. Granon and J.-P. Changeux
ATP is a mediator of chemosensory transduction in the central nervous system p108
Alexander V. Gourine, Enrique Llaudet, Nicholas Dale and K. Michael Spyer
Angiotensin-converting enzyme 2 protects from severe acute lung failure p112
Yumiko Imai, Keiji Kuba, Shuan Rao, Yi Huan, Feng Guo, Bin Guan, Peng Yang, Renu Sarao, Teiji Wada, Howard
Leong-Poi, Michael A. Crackower, Akiyoshi Fukamizu, Chi-Chung Hui, Lutz Hein, Stefan Uhlig, Arthur S.
Slutsky, Chengyu Jiang and Josef M. Penninger
Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in
malignant melanoma p117
Levi A. Garraway, Hans R. Widlund, Mark A. Rubin, Gad Getz, Aaron J. Berger, Sridhar Ramaswamy, Rameen
Beroukhim, Danny A. Milner, Scott R. Granter, Jinyan Du, Charles Lee, Stephan N. Wagner, Cheng Li, Todd
R. Golub, David L. Rimm, Matthew L. Meyerson, David E. Fisher and William R. Sellers
Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability
p123
Derek C. Radisky, Dinah D. Levy, Laurie E. Littlepage, Hong Liu, Celeste M. Nelson, Jimmie E. Fata, Devin
Leake, Elizabeth L. Godden, Donna G. Albertson, M. Angela Nieto, Zena Werb and Mina J. Bissell
Kinase-regulated quantal assemblies and kiss-and-run recycling of caveolae p128
Lucas Pelkmans and Marino Zerial
Molecular basis of photoprotection and control of photosynthetic light-harvesting p134
Andrew A. Pascal, Zhenfeng Liu, Koen Broess, Bart van Oort, Herbert van Amerongen, Chao Wang, Peter Horton,
Bruno Robert, Wenrui Chang and Alexander Ruban
X-ray structure of a tetranucleosome and its implications for the chromatin fibre p138
Thomas Schalch, Sylwia Duda, David F. Sargent and Timothy J. Richmond
Naturejobs
Prospect
They'll see you now p143
Seeking feedback, whatever the setting, can help you plan for the next stage of your career.
Paul Smaglik
Region
Golden opportunities p144
No longer rivals, Oxford, Cambridge and London are now working towards a common goal — ensuring the 'golden
triangle' becomes a global science hub.
Paul Smaglik
Spotlight
Spotlight on UK Golden Triangle
Futures
What's expected of us p150
It's a tough choice...
Ted Chiang
IV
7.7 Editorial 005 MH 5/7/05 3:03 PM Page 1
www.nature.com/nature Vol 436 | Issue no. 7047 | 7 July 2005
Climate of distrust
Six months into President George W. Bush’s second term of office, partisan politics continues to widen
the gulf between researchers and the administration.
T
he story has become so familiar that new twists in the plot cease questioning and overthrowing of currently accepted ideas, and the
to outrage. Time after time, in agency after agency, political fac- detail of Mann and colleagues’ work has itself been debated within
tors have prevented US science from serving its time-honoured the climate community. Barton, in contrast, has chosen to cherry-
role in informing government decisions. pick selected information on the hockey-stick work, using an article
In one of the latest examples, Congressman Joe Barton (Republi- from The Wall Street Journalas his scientific guide.
can, Texas) has asked three climate researchers, along with the heads Even President George Bush, in widely reported comments last
of the National Science Foundation and the Intergovernmental weekend, now accepts that humans are contributing to climate
Panel on Climate Change (IPCC), for background information on change. But by requesting infor-
“Congressman Barton
certain palaeoclimate research. On the surface, such a request seems mation on research that does
natural. The congressman heads the House of Representatives’ not fit his world view, Barton has chosen to cherry-pick
Committee on Energy and Commerce, which deals with environ- seems determined to use his selected information,
mental matters, among other topics. political influence to put pres-
using an article from
But dig a little deeper and you find Joe Barton is not known as a sure on the scientific process.
The Wall Street Journal
friend of the environment. His home town’s newspaper, The Dallas Questions remain over how
as his guide.”
Morning News, nicknamed him ‘Smokey Joe’ for his efforts to exempt this might affect scientists’
cement plants in his district from stricter anti-smog rules. This spring contributions to the next IPCC
he helped the House pass an energy bill that contains no measures at report, due out in 2007 but being written now. Climate researchers
all to limit greenhouse-gas emissions. will recall the case of Benjamin Santer, an IPCC contributor who
took a beating from climate sceptics over allegedly altering the 1995
Flaws and errors IPCC report to play up the anthropogenic influence on climate.
As a congressman, Barton is well within his rights to request infor- Some wonder whether Mann, whose work played a prominent role
mation from researchers funded by US taxpayers. His letters to the in the 2001 report, may be facing pressure for similar reasons.
climate scientists are not a subpoena and do not legally require a Rajendra Pachauri, chairman of the IPCC, may be correct that,
response. But their tone leaves no doubt as to his agenda. overall, Barton’s letters are not a threat to the scientific community
“Questions have been raised, according to a February 14, 2005 or the integrity of the IPCC review process (see page 7), but there is
article in The Wall Street Journal,” he writes, “about the significance no room for complacency. After all, other areas of US science have
of methodological flaws and data errors in your studies of the his- not been so lucky. Federal reports on climate research have been
torical record of temperatures and climate change… We open this altered, in part by former oil and gas lobbyists, to play down human
review because this dispute surrounding your studies bears directly effects on climate. Officials at the Environmental Protection Agency
on important questions about the federally funded work upon which have been busy removing key portions from reports or altering con-
climate studies rely and the quality and transparency of analyses clusions on the orders of political appointees. And a recent survey of
used to support the IPCC assessment process.” National Oceanic and Atmospheric Administration scientists
The letters request information on the scientists’ professional revealed that nearly a third felt they could not do their jobs properly
background, financial backing, accessibility of their data and com- in the face of interference from non-scientist administrators.
puter codes, relationship to the IPCC, and more. The requests have
their genesis in a 1998 Naturearticle (M. E. Mann et al.Nature392, Roughed up
779–787; 1998), which showed that temperatures in the Northern Although Jack Marburger, President Bush’s science adviser and
Hemisphere rose sharply in the twentieth century, in a graphical director of the White House Office of Science and Technology Pol-
upswing dubbed the ‘hockey stick’. Michael Mann of the University icy, continues to defend the administration’s record, some US con-
of Virginia, Raymond Bradley of the University of Massachusetts, gressmen have taken up the banner of science. Representative Henry
and Malcolm Hughes of the University of Arizona have spent the Waxman (Democrat, California) has asked Barton to withdraw the
past few years responding to queries about this work from Canadian letters and instead hold a hearing on climate change, perhaps invit-
researchers Steve McIntyre, who worked in the mining industry, and ing the letters’recipients as witnesses.
Ross McKitrick, an economist at the University of Guelph, Ontario. The politicization of science in the United States has deepened
Subsequent studies have supported the observation that unprece- since last November’s election. But the US research community
dented warming occurred in the 20th century, while multiple lines cannot simply wait for things to improve in three and a half years’
of evidence support the notion that anthropogenic influences are time. They must speak out on each contentious issue and ensure that
contributing to it. Science is, by its very nature, a process open to the the genuine voices of science are heard. ■
1
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7.7 Editorial 005 MH 5/7/05 3:03 PM Page 2
EDITORIALS NATURE|Vol 436|7 July 2005
Rules of engagement
was to all but accept that genies cannot be kept in bottles, and to
focus instead on developing a ‘culture of responsibility’ in research
institutions, journals and, especially, among individuals (see Nature
Biologists may soon have little option but to sign up
435, 860; 2005). Engineers and medics are imbued with a culture
to codes of conduct. that, if ignored, can lead to professional prohibition. For most basic
W
hy don’t people resent driving licences? After all, most researchers, codes of behaviour, although taken for granted where
drivers don’t intend to go out and kill people and they safety and human or animal experimentation are concerned, are
don’t like their freedom to roam restricted. But road vehi- alien when it comes to broader professional practice.
cles can be turned into a means of destruction, whether through Consider the phrase ‘do no
“If codes are to carry any
carelessness, mischief or malice. People accept, therefore, a licence harm’. Deceptively simple, a
that reinforces rules designed to help keep people safe. trite piece of motherhood and weight they will need to
Substitute ‘organisms’ for ‘road vehicles’ and ‘researchers’ for apple pie, and yet, as one med- be backed by certification,
‘drivers’ and you have a case for the licensing of biologists. And how- ical researcher at the meeting
and institutions will have
ever outrageous Nature readers may consider it, politicians and said, this fundamental principle
to extend their means of
policy-makers are taking codes of conduct and licensing in research had provided him with signifi-
assuring compliance.”
seriously. This much was clear from last week’s inaugural meeting of cant help when faced with some
the US National Science Advisory Board for Biosecurity (NSABB). critical professional decisions.
Just a US problem? Applicable only to defence labs? Think again. As Rappert highlighted, many codes for biologists have been drafted,
Any biologists whose work could be misused (and they are many) ranging from such statements of aspiration to enforceable codes of
face growing pressure to reassure their fellow citizens. This would practice (see www.projects.ex.ac.uk/codesofconduct).
also pre-empt excessive regulation by a willingness to declare explic- If they are to carry any weight, they will need to be backed up by
itly just how responsible they intend to be. certification, and research institutions will need to extend their often
Most researchers would wonder what planet such proposals come flimsy means of assuring compliance. Less demandingly, good
from. Speaking at the NSABB meeting, a social scientist, Brian behaviour can be encouraged by education, as illustrated at the
Rappert of Exeter University, UK, described discussions with 600 meeting by Nobel laureate Phillip Sharp with examples of courses on
biologists in the United Kingdom, most of whom were blissfully science ethics and best practice at the Massachusetts Institute of
unaware of issues of ‘dual use’ that learned societies, biological Technology.
weapons convention negotiators and others have been fretting about Codes of practice have so far attracted little attention in the biol-
for years. Speakers from the intelligence services and weapons ogy community. But in a world threatened by terrorism, govern-
inspectorates emphasized, however, the active interest in the harm- ments are taking more interest in such codes, and scientists would
ful uses of biology they have encountered among a malevolent few. do well to engage in a constructive discussion about what role they
The approach favoured at the NSABB’s preliminary discussions might play. ■
Playing the name game
issues by changing the terms of the debate.
At the equivalent meeting last year, the society decided to formally
Stem-cell biologists should not try to change the adopt the term ‘somatic cell nuclear transfer’ to describe the proce-
definition of the word ‘embryo’. dure in which an adult cell nucleus is transplanted into an egg to
produce embryonic stem cells. This procedure had been called ‘ther-
L
ast month’s meeting of the International Society for Stem Cell apeutic cloning’ to distinguish it from ‘reproductive cloning’, which
Research in San Francisco witnessed a bizarre semantic debate. would use the same technique in an attempt to make a baby.
Delegates discussed a proposal to refrain from using the term But the work is far from yielding any therapies, and scientists real-
‘embryo’ when referring to the blastocysts from which human ized that the word ‘cloning’ was generating public concern. So they
embryonic stem cells are harvested. The scientists involved reject decided to adopt a more technical term less likely to stir up strong
the accusation that they are creating and destroying human lives, emotions. At least that re-branding had the positive effect of toning
and fear that the word ‘embryo’ is a lightning rod that attracts down the hype surrounding therapeutic cloning.
negative scrutiny. The name change debated at last month’s meeting would be a step
It is true that embryo is an emotive term, but there is little too far, however. In the future, researchers may isolate pluripotent
scientific justification for redefining it. Whether taken from a fertil- stem cells from biological entities that do not have the same devel-
ity clinic or made through cloning, a blastocyst embryo has the opmental potential as embryos. This may justify the creation of a
potential to become a fully functional organism. And appearing new set of words. Until then, stem-cell biologists should stick to
to deny that fact will not fool die-hard opponents of this research. debating the merits and ethics of their work using clear and simple
If anything, it will simply open up scientists to the accusation language. They have a strong case to make that will not be helped by
that they are trying to distance themselves from difficult moral playing semantic games in an effort to evade scrutiny. ■
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7.7 Res Highlights MH NEW 4/7/05 12:19 PM Page 4
Vol 436|7 July 2005
RESEARCH HIGHLIGHTS
Light as a feather AGES
M
Y I
T
T
Phys. Rev. E(in the press) GE
The drab brown of male peacocks’ KI/
WS
tail feathers has been shown to arise A
R
from the same kind of structures that MU
produce the vibrant colours D. A
of the ‘eye’.
Photonic crystals give colour to
many insects, butterflies and birds.
The crystals have a periodic structure,
often created by repeating patterns of
tiny holes, that usually only reflects a
narrow range of wavelengths of light.
Researchers from Fudan University
in Shanghai, headed by Xiaohan Liu
and Jian Zi, have now proved that a
subtle arrangement of melanin rods
and air spaces can also reflect the mix
of colours needed to produce brown.
The structure may inspire designs for
artificial photonic crystals.
DRUG DISCOVERY proposals for quantum computers. But different substrates, researchers led by Wei
Screen for promiscuity Zaanen’s team shows that spontaneous Yang at the National Institutes of Health,
fluctuations destroy quantum coherence in a Bethesda, have described the structure of
Nature Chem. Biol. doi: 10.1038/nchembio718 (2005) time period that depends on the size and RNaseH bound to a DNA–RNA hybrid.
Two new drug-screening techniques temperature of the system. For macroscopic RNaseH acts on molecules that contain
could reduce the amount of time that bodies this can take centuries, but at the both DNA and RNA, but cuts only the RNA
pharmaceutical companies waste ‘mesoscale’ of hundreds of nanometres, it can chain. The structure shows that two metal
exploring the biological properties of happen in seconds. Fortunately, proposals for ions are involved in catalysing cleavage of the
‘promiscuous inhibitors’. quantum computers don’t tend to invoke RNA strand. Nucleases related to RNaseH
Such molecules seem promising as mesoscale bits, so they are not undermined. also use two metal ions to make cuts, but the
potential drugs when tested in a high- geometric arrangement of the ions in these
throughput fashion, as they inhibit the MOLECULAR BIOLOGY nucleases is different.
activity of a target enzyme. But they often Enlightened proteins
have this effect by forming aggregrates that SOLID-STATE PHYSICS
sequester the enzymes, rather than binding Chem. Biol. 12,685–693 (2005) Bendy legs
to the enzyme’s active site. So promiscuous Light can act as a powerful switch to set off
inhibitors can rarely be developed into drugs. chemical reactions. Harnessing this effect, Nano Lett.doi:10.1021/nl051064g (2005)
Researchers led by Brian Shoichet and Kip researchers led by Timothy Dore of the The first investigation of the electrical
Guy, both from the University of California, University of Georgia in Athens, and Erin properties of semiconductor tetrapods
San Francisco, have developed high- Schuman of the California Institute of (pictured), has revealed a behaviour that is
throughput screens that use detergents (to Technology, Pasadena, have developed a as intriguing as these four-legged
disrupt aggregates) and dynamic light system that could be used to inhibit protein crystals’ shape.
scattering (to detect aggregates). When synthesis in cells in a controlled way. Paul Alivisatos’s group at the
applied to 1,030 drug-like molecules, both They bound an antibiotic compound that University of California,
techniques identified promiscuous inhibitors. hampers protein formation to a light- Berkeley, studied how electrons
sensitive molecule called a chromophore. were transported between two
QUANTUM PHYSICS The antibiotic is released, and thereby branches of a tetrapod-shaped
Time’s up activated, when the compound is exposed crystal, while it sat with three
to ultraviolet light. legs on a flat electrode.
Phys. Rev. Lett. 94, 230401 (2005) Each branch was
UP
There is a fundamental limit to how long STRUCTURAL BIOLOGY O
R
G
quantum coherence can last, say Jan Zaanen All in the ions OS
and his colleagues at the University of Leiden, AT
the Netherlands. Cell 121,1005–1016 (2005) ALIVIS
Coherence, which allows many particles The enzyme RNaseH is a member of the P.
to share the same quantum state, underpins nuclease family of enzymes that cut strands
phenomena ranging from superfluidity to of DNA and RNA. In work that may help to
quantum teleportation. It is also key to explain how the various nucleases target
4
© 2005 Nature PublishingGroup
7.7 Res Highlights MH NEW 4/7/05 12:19 PM Page 5
NATURE|Vol 436|7 July 2005 RESEARCH HIGHLIGHTS
150nanometres long. Depending on how bent University of California, have implicated the JOURNAL CLUB
the branches had become when the tetrapod pathway’s activator, IKK(cid:1), in chemically
stuck to the electrode surface, electrons either induced liver cancer. Tony Pawson
behaved in a quantum way and hopped across Mice injected with a chemical Samuel Lunenfeld Research
the central junction, or a simple current carcinogen were more prone to cancer Institute, Mount Sinai Hospital,
flowed. This unexpected complexity could be when IKK(cid:1)was deleted from their Toronto, Canada
put to use in nanoscale circuits, where the hepatocyte liver cells. But if the enzyme
Signalling proteins have taught
tetrapod’s branches act as interconnects. was deleted from both hepatocytes and
this week’s writer that cells can
Kupffer cells — a type of immune cell in
add one and one to get three.
IMMUNOLOGY the liver — the animals were less likely to
On the defensive develop cancer. Karin’s lab conclude that The thought that one might
carcinogenesis depends on ‘crosstalk’ understand mechanistically how
J. Clin. Invest.115,1806–1815 (2005) between damaged hepatocytes and Kupffer cells work has always struck me as
Tissues attacked by bacteria can defend cells, mediated by IKK(cid:1). heady stuff. Yet, although we know
themselves by increasing levels of certain a great deal about the pathways
molecules, such as nitric oxide, that kill MY that orchestrate cells’ responses to
A
microbes. A protein called hypoxia-inducible AL internal and external signals, and
factor 1 is already known to control this KEL / about regulatory systems such as
response in tissues that lack oxygen — a WIN the cell cycle, more complex
typical sign that they are under attack. Now, CK cellular functions largely await
increased production of this protein by white BLI explanation.
blood cells has been directly linked to the One exciting possibility is that
presence of bacteria by Randall Johnson and cells are displaying emergent
and Victor Nizet of the University of properties. My own research is
California, San Diego, and their colleagues. focused on signalling proteins,
Johnson’s team also showed that mice were which govern the dynamic
more susceptible to infection if they lacked behaviour of cells, and I am
the protein. But the researchers’ suggestion enthusiastic about the notion that
that therapies that enhance production of the signalling proteins might interact to
protein could boost a patient’s immune yield an activity that is more than
system, although shown in vitro,remains to the sum of its parts.
be tested in vivo. Recently, Kevan Shokat and
colleagues demonstrated such
DEVELOPMENTAL BIOLOGY emergent behaviour for two protein
Uncertain destiny kinase enzymes in the yeast
Saccharomyces cerevisiae(C.Kung et
J. Exp. Med. doi: 10.1084/jem.20050146 (2005) al. Proc. Natl Acad. Sci.USA102,
A single type of precursor cell found in the 3587–3592; 2005). By analysing
thymus can develop into a T cell, B cell or gene expression, they examined the
dendritic cell, a study finds. effects of inhibiting either kinase
The precursor cells migrate from the bone alone, or both together.
marrow to the thymus before maturing into ANIMAL BEHAVIOUR They found that one set of genes
these immune cells. To pinpoint the moment Smart settlers was affected by inhibition of the
when the cells’ fates are sealed, Claudia Benz Cdk1 enzyme, which controls
and Conrad Bleul from Freiburg’s Max- Proc. R. Soc. Lond. Bdoi:10.1098/rspb.2005.3099 aspects of the cell cycle, and
Planck Institute for Immunology monitored (2005) another was regulated by Pho85,
the expression of a receptor protein that Birds with bigger brains are less likely to fly which is involved in phosphate
marks an early stage of T-cell development. south for the winter, a survey of the habits of metabolism. The key experiments
The researchers identified a threshold of 134 species has shown. This supports the showed that simultaneously
expression in the most immature precursors theory that migration evolved in birds that inhibiting both kinases also
that marks an important branching point in weren’t smart enough to survive cold weather. regulated a third set of genes,
the cell hierarchy. Beyond this threshold, the Daniel Sol from the Autonomous which participate in cell budding.
cells were incapable of turning into B cells. University of Barcelona and his colleagues These findings are clinically
analysed existing data on birds living in important because the inhibitors
CANCER temperate regions of Europe, Scandinavia used to treat diseases such as
Liver trouble and western Russia. In addition to finding cancer tend to affect multiple
that non-migratory birds have larger brains kinases. Such non-specificity was
Cell 121, 977–990 (2005) relative to their body size than species that initially viewed as a failing, but
One link between inflammation and cancer migrate, they also discovered that non- Shokat’s data suggest that
is known to involve the NF-kB pathway, migratory birds, such as the blackbird inactivating more than one kinase
which regulates gene expression. Now (Turdus merula, pictured), are more flexible may be advantageous, or even
Michael Karin and his colleagues at the in their feeding habits. critical, for a therapeutic effect.
5
© 2005 Nature PublishingGroup
7.7 News 6-7 MH 5/7/05 2:53 PM Page 6
Vol 436|7 July 2005
NEWS
Flu officials pull back from
raising global alert level
The world last week seemed to edge closer to spread (see Nature435,391; 2005).
the brink of a flu pandemic. On 30 June, offi- Concern mounted in subsequent weeks as
cials at the World Health Organization (WHO) several international groups investigated the
revealed that they recently considered raising clusters using different methods, including the
the threat level of a global pandemic, from the polymerase chain reaction (PCR), which
current 3 on a six-point scale, to 4 or even 5. amplifies DNA sequences, and western blots,
The scare was triggered a few weeks ago which use antibodies to detect proteins.
when several research groups visiting Vietnam Despite using different tests, each of the teams
filed preliminary reports that many people reported that “substantial proportions” of the
with mild cases of influenza — and those in hundreds of people it had tested seemed to be
contact with them — were testing positive for infected with H5N1.
the deadly avian flu strain H5N1. This sug- That led the WHO to consider upgrading
gested that there was widespread human-to- the pandemic threat level to 4 (small, localized
human transmission of the virus. clusters of human infection) or 5 (large clus-
Subsequent tests have so far failed to con- ters of infection) — just one step away from a
firm this, and WHO spokesman Dick Thomp- full-blown global pandemic. But first it asked
son is keen to play down the incident. “It was an international team of experts, including Close to danger? A young boy feeds ducks, a
just unpublished information provided to us Masato Tashiro, a virologist at the National source of the H5N1 flu virus, in Vietnam.
in preliminary form that spurred an investiga- Institute of Infectious Diseases in Tokyo, to
tion,” he says. “We thought about upgrading retest many of the samples and some new conclusion is expected by the end of the month.
the alert. We looked at it fast and strongly, and ones, using the WHO’s own PCR tests. In the meantime, the WHO is holding off
based on that decided not to upgrade.” They found no evidence of clusters of human- raising the alarm. “Because of the consequences
But take a closer look, and the picture in to-human transmission. “This is good news,” of such a change, the WHO is following a cau-
Vietnam is one of confusion rather than reas- Tashiro says, relieved that his worst suspicions tious approach,” it said in a statement last week.
surance. The first signs of trouble came in May, weren’t confirmed. But it remains unclear why Pushing the level to 4 for the first time would
with reports of small clusters of human cases the various groups got different results. mean deploying the international stockpile of
of H5N1, including a rise in the infection of Samples have now been sent to a WHO lab- antiviral drugs to try to contain or stamp out the
older people and an increase in milder cases — oratory in Hong Kong for the last word in con- spread, and would probably result in countries
all signs consistent with the possibility that firmation: antibody neutralization assays. restricting travel to Vietnam.
the virus had mutated to achieve improved, These take time as they involve growing large But Tashiro remains concerned that he and
although still inefficient, human-to-human amounts of the virus for analysis, but a firm his colleagues didn’t have enough time to check
Infected birds poised to take flu virus south
Thousands of migratory birds 6,000 birds of five different species distinguishable from the strains at the lake, which could be acting
infected with H5N1 avian flu virus had died at the breeding site. seen in Vietnam and Thailand, and as carriers. More than 100,000
at Qinghai Lake in western China Late last month, the Chinese more closely related to variants birds will fly home from the lake
pose a serious risk of spreading the government finally allowed 17 isolated from poultry in China or in the next few months, and the
disease to southeast Asia, India, experts from the World Health Hong Kong. Experimental infection officials urged China to implement
Siberia, Australia and New Zealand Organization (WHO) to visit part of mice and chickens also showed large-scale testing along with a
when they fly home this of the quarantined area. Although that the new variant is highly control strategy, possibly involving
September, scientists are warning. their movements were restricted virulent2— comparable to the mass culling or vaccination of wild
The outbreak first hit the and they were unable to meet or Vietnamese and Thai strains that birds, before September. Experts
headlines in May (see Nature435, interview any local people, the have caused fatal human cases. are also still waiting for clearance
542–543; 2005). Before then, scientists were allowed to take It is unclear how China will cope from China to visit three
deaths from H5N1 in migratory birds virus samples for testing. with such a huge outbreak. At a subsequent outbreaks of the H5N1
were limited, and many suspected DNA sequences of those press conference in Beijing on virus in migratory birds in Xinjiang
they were dead-end hosts that samples by scientists from Hong 28 June, WHO officials province, west of Qinghai. D.B.
occasionally picked up infection Kong, China and the United States complained that China had tested
from poultry. But the virus seemed are published this week1,2. They only a handful of birds from the five 1. Chen, H. et al. Naturedoi:10.1038/
nature03974 (2005).
to have mutated into a more virulent confirm that the virus is a new affected species, and none at all
2. Liu, J. et al. Sciencedoi:10.1126/
form, and within weeks more than form of H5N1, clearly from the other 184 species present science.1115273 (2005).
6
© 2005 Nature PublishingGroup
