Hot off the presses! Dec 24 Nature

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Latest Articles Include:

• A clean slate
  - Nature 462(7276):957 (2009)
  Nature is pleased to name physicist Steven Chu, Nobel laureate and the US Secretary of Energy, as its Newsmaker of the Year.
• After Copenhagen
  - Nature 462(7276):957 (2009)
  The agreement reached last week lends fresh urgency to challenges in science and communication.
• Palaeontology: Not from chimps
  - Nature 462(7276):960 (2009)
  
• Atmospheric science: Stealth ozone destroyer
  - Nature 462(7276):960 (2009)
  
• Stem cells: Protein reprogramming
  - Nature 462(7276):960 (2009)
  
• Neuroscience: Signal source questioned
  - Nature 462(7276):960 (2009)
  
• Genomics: Digging out a diabetes gene
  - Nature 462(7276):960 (2009)
  
• Immunology: Breaking into the brain
  - Nature 462(7276):961 (2009)
  
• Biochemistry: Changing bases
  - Nature 462(7276):961 (2009)
  
• Materials chemistry: Marvellous metal–organics
  - Nature 462(7276):961 (2009)
  
• Climate change: What's up with sea levels?
  - Nature 462(7276):961 (2009)
  
• Cancer drug development: Targeted tumour take-out
  - Nature 462(7276):961 (2009)
  
• News 2009
  - Nature 462(7276):962 (2009)
  The year in which … These stories are best viewed in a PDF. L. SENG SIN/AP PHOTO The first influenza pandemic in 40 years propelled the globe onto a roller coaster of panic and complacency. In March, a new H1N1 virus — a mongrel containing genes from swine, bird and human flu viruses — emerged in North America and spread rapidly, sparking fears of a severe pandemic. The new virus was particularly dangerous for younger adults and those with underlying diseases, but most patients had mild symptoms. The low severity cut the world some slack, as a vaccine took months to produce and some manufacturers fell behind schedule; the United States, Australia and Europe didn't start vaccination programmes until October, and poorer nations months after that, if at all. As of mid-December the flu was continuing to intensify across central and eastern Europe and parts of Asia, but its second wave had peaked in North America and parts of Europe. More than 10,580 people have died. The high-energy physics crown has passed from the United States to Europe. On 30 November the Large Hadron Collider (LHC) near Geneva, Switzerland, became the highest-energy accelerator in the world, breaking the record long held by the Tevatron at Fermilab in Batavia, Illinois. Europe's proton-pummelling behemoth had spent most of the year in recovery after an electrical failure during its first run in September 2008 caused massive damage. By December 2009, head-on collisions at the LHC had reached 2.36 teraelectronvolts; physicists plan to begin science at this energy level in 2010, with the hope of finding evidence of the long-sought Higgs boson and dark matter. In what climate-change sceptics are calling the scandal of the decade — and many climate scientists are calling a meaningless nuisance — more than 1,000 e-mails between top researchers were hacked from the Climatic Research Unit (CRU) at the University of East Anglia, UK, just weeks before the Copenhagen climate summit began. Some of the e-mails revealed frustration with data and a cavalier attitude towards sceptics, but they did not discredit the solid body of evidence showing that the world is getting warmer, probably at the hands of humans. The e-mails did, however, embolden sceptics, who interpreted them as evidence of a global conspiracy. CRU director Phil Jones, who composed most of the more controversial e-mails, has stepped aside while an independent panel investigates. A decades-long debate has been resolved: water ice can accumulate in frigid craters on the Moon. On 9 October the rocket booster of NASA's Lunar Crater Observation and Sensing Satellite (LCROSS) slammed into a lunar crater that receives no sunlight, kicking up a plume of dust that was disappointing to spectators but exciting for scientists. Just before LCROSS crashed, its instruments detected water in the dust, suggesting that vapour had frozen into the crater floor. Other spectra hinted at other molecules, such as carbon dioxide, mercury and methane. Researchers hope to explore the ice for clues about the Solar System's history. NASA/MSFC "We will restore science to its rightful place," said US President Barack Obama in his inaugural address in January. On 9 March, Obama signed a memo supporting scientific integrity in federal decision-making and an executive order lifting the prior administration's limits on human embryonic stem-cell research. The latter move greatly expanded the number of cell lines eligible for federal funding for research, and by mid-December, 40 such lines had been approved. Obama has also appointed top scientists to key positions, including physicist Steven Chu as Secretary of Energy (see page 978), physicist and climate expert John Holdren as science adviser and marine ecologist Jane Lubchenco as administrator of the National Oceanic and Atmospheric Administration. The global economic downturn forced tough choices on research funding. Crashing endowments struck top institutions such as Harvard University in Cambridge, Massachusetts, which halted construction on a new science complex, and California's formidable budget deficit drove its state university system to force faculty members to take unpaid leave. But some governments, seeing research as a driver of the economy, made significant efforts to bolster basic science. The US Congress awarded $21 billion in stimulus funding to research. German chancellor Angela Merkel signed off on €18 billion (US$26 billion) over the next decade to universities and research organizations. French president Nicolas Sarkozy promised to spend €19 billion on research and higher education. And Japan allocated ¥1.6 trillion ($18 billion) for low-carbon technologies. But rich countries looked out for their own: much of African science is hurting after foreign investment and donor funding were slashed. Japan's first new government in five decades jolted scientists to attention. In November, a cabinet-level working group chaired by Prime Minister Yukio Hatoyama recommended slashing funding for many prominent science projects, including the SPring-8 synchrotron in Harima, the country's deep-sea-drilling programme and a supercomputer at RIKEN, which would become the world's fastest. Leading Japanese researchers and Nobel laureates rallied the scientific community and appealed to Hatoyama, and in December the country's highest science-policy-making body proposed continued support for the projects. Final budget decisions will be announced by the end of the year. The warmest decade on record concluded with the United Nations climate summit in Copenhagen, where international climate negotiators failed to craft a treaty to succeed the 1997 Kyoto Protocol (see page 966). Deep fissures remained between developing nations, which will probably be affected most by global warming, and developed nations, which have historically emitted the lion's share of greenhouse gases. However, both sides offered some concessions. Rich nations pledged to speed up the delivery of clean-energy technology to the developing world, and developing nations such as Mexico, Indonesia, South Korea and South Africa promised major emissions cuts. A series of Nature investigations uncovered plagiarism in papers co-authored by high-level officials in Iran. Science minister Kamran Daneshjou, who oversaw the disputed June presidential election, and transport minister Hamid Behbahani, among others, were co-authors on multiple plagiarized papers, most of which have now been retracted by the journals involved. MCNAMEE/GETTY NASA may have to lower its ambitions. A commission headed by former aerospace executive Norman Augustine concluded that the US human-space-flight programme has nowhere near sufficient resources to meet the goals laid out by former US President George W. Bush, including returning to the Moon by 2020 using the next-generation Ares rocket (pictured). Under the agency's current budget, the panel said, astronauts won't even make it beyond low Earth orbit. The report suggested tabling the Moon mission, increasing the role of the private sector and extending the life of the International Space Station, which NASA had planned to abandon in 2015. President Barack Obama met with NASA administrator Charles Bolden on 16 December to discuss the agency's goals, and is expected to announce a decision soon. "It's sort of sad isn't it that you criticize government policy and you get sacked?" Psychopharmacologist David Nutt after being dismissed from the UK Advisory Council on the Misuse of Drugs. He had advised that alcohol is more harmful than both ecstasy and cannabis. Source: Nature News "I think the population is losing half of the human brain power by not encouraging women to go into the sciences." Chemistry Nobel prizewinner Ada Yonath, in what turned out to be a record year for women winning the prize: five took the award. Source: AFP "I have two passions. Space exploration and hip hop." Buzz Aldrin, who made the hip hop video Rocket Experience in the year of the 40th anniversary of the Apollo Moon landings. Source: http://buzzaldrin.com "In England there has been almost a fashion recently for suing scientists for libel." Journalist Simon Singh, who was sued for libel by the British Chiropractic Association, has become the focus of a campaign to keep UK libel law from stifling scientific debate. Source: Australian Broadcasting Corporation "A high level of serious hysteria." Physicist Gordon Kane describes a workshop on a mysterious dark-matter signal (see page 967). The signal was "inconclusive, sadly". Source: New York Times "The bird escaped unharmed but lost its bread." CERN statement after the Large Hadron Collider had an electrical short circuit when a bird dropped a bit of baguette. Source: CERN "I don't want to use a word like 'breakthrough', but I don't think there's any doubt that this is a very important result." Director of the US National Institute of Allergy and Infectious Diseases Anthony Fauci on a clinical trial that combined two failed HIV vaccine candidates to produce a moderate result. Source: New York Times "I'd like to go back to studying cancer epidemiology and aetiology. They're my thing." Health researcher and former prostitute Brooke Magnanti discusses her future after 'outing' herself as author of the famous sex blog Belle de Jour. Source: Times Online "We didn't pay 37 million zlotys ($11 million) for the largest elephant house in Europe to have a gay elephant live there." Michal Grzes, a councillor in Poznań, Poland, protests that 'Ninio the gay elephant' will not help the zoo's breeding programme. Source: Reuters "Darwin was wrong." This cover line in New Scientist magazine, in an issue marking the 200th anniversary of Darwin's birth, caused much ire. "I'm not going to answer that question. I am a Christian, and I don't think anybody asking a question about my religion is appropriate." Gary Goodyear, Canada's minister of state for science and technology, declining to answer the question 'do you believe in evolution?'. His rationale triggered much criticism. Source: Globe and Mail There are currently no comments.
• News briefing: 24/31 December 2009
  - Nature 462(7276):964 (2009)
  The week in science This article is best viewed as a PDF. Policy|Business|Events|Research|Funding|The week ahead|Number crunch|Sound bites The funding body that distributes the bulk of UK research money for large-scale physics and astronomy announced drastic cuts on 16 December, in a bid to solve its £40-million (US$64-million) budget gap (see Nature 462, 396; 2009). Researchers responded with disappointment and anger after the Science and Technologies Facilities Council announced a 10% across-the-board cut to grants and a gradual 25% reduction in the number of students and researchers — at present about 280 — that it directly supports with fellowships. A five-year plan also calls for a "managed withdrawal" from more than two dozen individual projects, and £71 million in cuts to ongoing projects. See go.nature.com/1mn2zW for more. Member states of the European Space Agency (ESA) have formally agreed to team up with NASA to explore Mars in the latter half of the next decade. At an agency council meeting on 16–17 December in Paris, France, ESA's council gave the go-ahead to contribute €850 million (US$1.2 billion) to two missions in the joint-agency 'ExoMars' programme (see Nature 460, 675; 2009). The first is an orbiter to detect trace gases, allied with a small lander, to be launched in 2016, the second consists of two larger planetary rovers to be launched in 2018. Hungary has become the fourteenth country to join the Scandinavian-led consortium to build the European Spallation Source (ESS) in Lund, Sweden. The €1.5-billion (US$2.2-billion) ESS will generate high-power neutron beams by firing protons at a heavy-metal target. Hungary had promoted its own rival site for the neutron facility, but earlier this year several key nations threw their support behind the Lund site (see Nature 459, 626; 2009). Spain, another rival bid, joined the Swedish project in June. Colin Carlile, director of the ESS project, says the next stage — a three-year design review — will begin in 2010. The European Institute of Innovation & Technology last week named the clusters of European centres that will host its first three 'knowledge innovation communities' (KICs). The scheme is meant to foster greater research collaboration between academia and industry across Europe. Focusing on climate change, sustainable energy and information technology, each of the three KICs will get €3 million (US$4.3 million) in start-up funding and will try to win more support from national and European funding programmes, and private sources. Solyndra, a photovoltaics manufacturer based in Fremont, California, filed with the US Securities and Exchange Commission on 18 December for an initial public offering. The firm wants to raise up to US$300 million. Founded in 2005, Solyndra makes thin-film cylindrical modules for use in solar arrays on commercial roof-tops. In March 2009, it was granted a $535-million loan guarantee from the US government to expand manufacturing capacity. Reacting to the climate accord announced in Copenhagen (see page 966), prices for permits to emit a tonne of carbon dioxide (for delivery in 2010) closed at a 6-month low of €12.45 (US$17.78) on the European Climate Exchange on 21 December. This is well down on prices that were solidly above €14 in the week before the conference. Traders think that the uncertainty associated with the accord will see transaction volumes and prices continue to slide. Julie Gerberding, who was director of the US Centers for Disease Control and Prevention in Atlanta, Georgia, during 2002–09, has been hired to head the vaccines unit of pharmaceutical giant Merck & Co. She stepped down from the health agency when US President Barack Obama took office on 20 January 2009. Click to enlargeSOURCE: OECD Preliminary data from US stock markets suggest that companies have already reduced their investments in research and development (R&D) following the economic crisis. More than 2,000 companies that filed quarterly reports with the US Securities and Exchange Commission reported an average reduction of 6.6% in their planned R&D spending in the first quarter of 2009. The data are contained in the Organisation for Economic Co-operation and Development's OECD Science, Technology and Industry Scoreboard 2009, officially released on 14 December. Vincenzo Spiezia, a senior economist at the OECD, says actual spending may drop even lower. Historically, R&D spending lags behind gross domestic product (GDP; see chart). Spiezia thinks that the lowest point for R&D has not yet been reached, and notes that only a small proportion of the economic-stimulus packages went directly to bolster research. The OECD also noted a huge drop in venture-capital investment in the United States — another! indicator of dulled R&D prospects. NOAA/NSF Footage of a volcanic eruption nearly 1,200 metres under the sea was unveiled on 17 December at a meeting of the American Geophysical Union (AGU) in San Francisco, California. The high-definition film of the West Mata volcano in the western Pacific is one of the first times that lava has been caught flowing on the deep sea floor. Jason, the remotely operated vehicle that took the pictures, "actually reached into the molten lava and pulled out a gob" of freshly erupted rocks, says lead researcher Joseph Resing of the Pacific Marine Environmental Laboratory in Seattle, Washington. See go.nature.com/sc837n for more, and go.nature.com/Q2ZovD for all of Nature's reports from the AGU meeting. The human embryonic stem-cell lines in wide use among researchers are strikingly lacking in population diversity, according to a report published last week (J. T. Mosher et al. N. Engl. J. Med. doi:10.1056/NEJMc0910371; 2009). University of Michigan scientists analysed the genetic ancestry of 47 commonly used lines — including 22 approved for US government funding earlier this month. They found that 31 were of exclusively northern and western European origin, 2 were Asian, and the rest had elements of southern European or Middle Eastern ancestry, or both. None was of African origin. A Swiss court on 21 December cleared geologist Markus Häring of any wrongdoing relating to small earthquakes caused by an innovative geothermal drilling project in Basel, Switzerland, which he had led with the Geopower Basel consortium. He had not played down any risks and acted in accordance with the state of scientific knowledge at the time, the court said. The project was shut down on 10 December following a government study into the economic damage it had caused (see also Nature 462, 848–849; 2009). NASA/C. THOMAS A decade behind schedule, the Stratospheric Observatory for Infrared Astronomy (SOFIA) has finally been unshuttered. On 18 December, a door in the side of the Boeing 747 that houses the telescope was opened during a flight (pictured) — exposing the 2.5-metre telescope to the atmosphere for two minutes. An audit earlier this year (see Nature 458, 693; 2009) found that costs of the project had more than tripled from the original estimate of US$265 million. NASA, which funds SOFIA together with the German Aerospace Center, says scientists' first opportunity to use the telescope could come in spring 2010. The prevalence of autism in the United States has grown dramatically, to 1 in 110 children, according to an 18 December report by the US Centers for Disease Control and Prevention in Atlanta, Georgia. The numbers, published in Morbidity and Mortality Weekly Report, reflect a 57% surge in cases of autism spectrum disorder (ASD) in 8-year-olds between 2002, the last survey year, and 2006. "Although improved ascertainment accounts for some of the prevalence increases documented … a true increase in the risk for children to develop ASD symptoms cannot be ruled out," the authors wrote. Spending on research and development into neglected diseases "ground to a standstill" in 2008, according to the second edition of the report Global Funding of Innovation for Neglected Diseases, published by the George Institute for International Health in Sydney, Australia. Donors, governments and industry combined spent US$2.96 billion on new products for these diseases. Although that was around 4% up on 2007, most of this rise was due to funds from the Bill & Melinda Gates Foundation, based in Seattle, Washington, which increased its spending by 36.5% to $617 million. This masked an overall trend of freezes or slight falls in support from rich countries and most donors. Spain assumes a six-month presidency of the European Union. The American Astronomical Society meets in Washington DC. → http://aas.org/meetings/aas215 The Society for Integrative and Comparative Biology meets in Seattle, Washington. → www.sicb.org/meetings/2010 The contribution of aircraft vapour trails to warming in the Arctic since temperature records began. Source: Mark Jacobson, Stanford University, Palo Alto, California. American Geophysical Union meeting in San Francisco, California. See go.nature.com/Txwdhf for more. US President Barack Obama puts a positive face on the Copenhagen accord. See page 966 for more. There are currently no comments.
• World looks ahead post-Copenhagen
  - Nature 462(7276):966 (2009)
  A weak international climate agreement leaves room for science to shape the next round of negotiations. The Copenhagen accord was blasted by environmental activists and leaders of developing nations.A. Kisbenedek/AFP/Getty Two lines of evidence nearly brought down the last-minute climate agreement brokered last week in Copenhagen by US President Barack Obama: studies indicating that the impacts of global warming could be more severe than previously thought, and that rich countries could do more to counter the problem without breaking the bank. Now, negotiators are seeing whether they can strengthen a deal nearly universally acknowledged as weak — or whether even the mounting scientific evidence on the most dire effects of climate change will be enough to forge a more meaningful deal. The Copenhagen accord, drawn up as a multilateral political agreement between the United States, China, India, Brazil and South Africa, provides a non-binding framework for capturing national commitments that are already on record. Many environmentalists and a number of developing countries criticized it immediately, saying that current climate commitments would not meet the common goal of limiting the increase in global average temperatures to 1.5–2 °C. Indeed, an analysis by the US modelling consortium Climate Interactive estimated that the commitments would result in a temperature rise of 3.9 °C by the year 2100. For its part, the European Union elected in Copenhagen not to increase to 30% its conditional offer of a 20% cut in 1990 emissions levels by 2020. The overall goal remains to hammer out a treaty to replace the 1997 Kyoto Protocol on Climate Change while incorporating climate commitments from developing countries and the United States, which has not ratified the Kyoto agreement. Negotiations will continue over the coming year, and many observers hope for a stronger deal when the parties to the United Nations Framework Convention on Climate Change meet in Mexico in late November 2010. Obama's announcement on the last day of the Copenhagen talks fractured the G77 group of developing countries. Lumumba Stanislaus Di-Aping, Sudan's fiery chief negotiator and chairman of the G77, claimed that the deal would do nothing less than "destroy" Africa. He was joined by countries including Tuvalu, Bolivia and Venezuela during an all-night debate that included the occasional tirade against capitalism but also focused on how poor nations would be affected disproportionately by climate change (see 'Growing agricultural benefits for climate'), and how rich countries should be paying more. For instance, scientists at the Copenhagen meeting had enlisted the star power of Al Gore in releasing a pair of reports on the accelerated loss of glaciers and ice sheets in Greenland and Antarctica; melting ice sheets in particular, they concluded, could increase sea level by at least 1 metre by 2100. Easy targets Still, an economic analysis by the International Institute for Applied Systems Analysis (IIASA) in Laxenberg, Austria, found that the pre-Copenhagen commitments by industrialized countries would reduce 2020 emissions by 11–22%. Taking into account cost savings due to efficiency and other factors, the cost of achieving that goal would be just 0.15% of gross domestic product, the analysis revealed. Markus Amann, who heads the IIASA's greenhouse-gas initiative, fears that such easy targets will translate into low carbon prices and end up delaying the innovation needed to make deep cuts in decades to come. Delegates worked through the night to reach an agreement.I. Kalnins/Reuters Yet most developing countries ultimately defended the Copenhagen accord — with reservations — because without it there would have been nothing to show for the largest environmental conference in history. "This is not what we have been seeking, but it is a beginning," said Mohamed Nasheed, president of the Maldives, which is a member of the Alliance of Small Island States that has been pushing for a commitment to limit warming to 1.5 °C. "I beg all nations to please back this document and do not let these talks collapse." "The most important thing to get done at this moment is to get moving," adds John Holdren, Obama's chief science adviser. "Let's not argue for the next five years what the perfect goal is. Let's get going in the right direction." For the first time under the new framework, both developing and developed countries — including the United States, which is gearing up for a legislative battle over climate in the Senate this spring — will be bound under a single agreement. Rich countries would be required to meet their promised reductions; developing countries would be required to audit and report the activities they undertake to reduce emissions, as well as open their books to international verification for any projects funded with international aid. In exchange, the agreement offers financing, valued at US$30 billion by 2012, to help developing countries prepare for a warmer world and to push forward with sustainable development goals. Developed countries committed to spending upwards of $100 billion annually by 2020, although the agreement offers no details as to where that money will come from. The World Bank has estimated that developing countries will need about that amount, but developing countries and many scientists say that number could be far too low. Martin Parry of Imperial College London, a former co-chair of the Intergovernmental Panel on Climate Change (IPCC) working group on impacts, adaptation and vulnerability, has developed a way to portray 'unavoided impacts' in which mitigation fails and there isn't enough money to help people cope with the consequences. Assuming that all countries fulfil their pledges, the agreement in Copenhagen still leaves a gap of 1.5 °C, he says. In other words, funding for adaptation could cover impacts associated with about 1.5 °C of warming, but temperatures are likely to rise by at least 3 °C. "Even the toughest and most robust measures will not achieve 2 °C," Parry says. "We should hope for 2 °C but realistically expect 3–3.5 °C, and then plan for 4 °C." ADVERTISEMENT The Copenhagen accord includes a goal of limiting temperature rise to 2 °C, but one target that was notably dropped was that for reducing global greenhouse-gas emissions by 2050. Small-island states successfully pushed for language requiring consideration of a target of 1.5 °C during the first review of implementation and commitments in 2015, one year after the IPCC is scheduled to finalize its fifth assessment report. Climate modelling for the next IPCC assessment is under way, and the panel will accept nominations and then appoint lead authors for the various chapters this spring. Sitting in his office overlooking the main hall of the Bella Center in Copenhagen last week, IPCC chair Rajendra Pachauri said that he was encouraged by the fact that so many world leaders chose to attend, even if a commitment to act falls short. "There's a certain inertia that will resist it. There are mindsets that will resist it. There are vested interests that will resist it — let's not minimize their effectiveness," Pachauri says. "This is something that politically one had to anticipate."
• 'Dark-matter' events spotted
  - Nature 462(7276):967 (2009)
  Signals may be first evidence of elusive particles. Two sightings in Minnesota have set physicists buzzing about whether the first direct detection of dark matter has been made. If confirmed, it would mark the end of a decades-long search for the mysterious particles thought to make up as much as 85% of matter in the Universe. But most agree that the signals are not statistically significant enough to be attributed to dark matter rather than to conventional particles. The two events were caught in 2007 in super-cooled crystals of germanium and silicon in the underground Cryogenic Dark Matter Search II (CDMSII) experiment in the Soudan Mine in Minnesota. Last week, CDMSII scientists announced that they have seen candidates for the dark-matter particles known as weakly interacting massive particles (WIMPs), each with a mass of 30–60 gigaelectronvolts — roughly 30–60 times that of a proton. But from the analysis, team scientists think that there is a 25% chance that both events might be false-positives caused by background radiation. Those odds are not good enough to claim a definitive detection of WIMPs, says Timothy Sumner, a physicist at Imperial College London. "Statistically, it's not compelling," he says. "The best we could call it is a hint," adds John Ellis, a theoretical physicist at CERN, Europe's high-energy physics lab near Geneva, Switzerland. "An interesting hint." ADVERTISEMENT The possible detection is the latest in a series of potential dark-matter sightings. In August 2008, an Italian-led satellite-based experiment known as PAMELA reported an excess of antielectrons (positrons) that could have stemmed from the annihilation of dark-matter particles. And in October 2009, NASA's Fermi Gamma-ray Space Telescope saw a haze of high-energy light in the centre of our Galaxy that could be a dark-matter signature. The CDMSII result will now spur physicists at the Large Hadron Collider (LHC) at CERN to try to generate WIMPs in their collisions. "The LHC would see this very easily and relatively quickly," says Ellis — and could potentially produce a detectable WIMP signal by the end of next year. There are currently no comments.
• Tsunami watch
  - Nature 462(7276):968 (2009)
  Five years after the Indian Ocean disaster, the technology is in place, but local preparedness is less advanced. Early warnings saved lives in a 2009 tsunami in Samoa.NEW ZEALAND DEFENCE FORCE, NZ HERALD/AP PHOTO On the morning of 29 September, Mase Akapo knew exactly what to do. At 6:48 a.m., on the island of Tutuila in American Samoa, he had felt the ground shake harder than he ever had before. Ten minutes later Akapo, a meteorologist, was in his office, issuing an alert for the tsunami he knew was probably on its way. Tsunami warnings are a way of life for coastal communities, but five years ago they took on a new layer of meaning. On 26 December 2004, a magnitude-9.0 quake off the Indonesian island of Sumatra generated a series of tsunamis that drowned some 230,000 people around the Indian Ocean. Most of them had no idea it was coming. Memory of the disaster remains relatively fresh in many coastal communities, even in the South Pacific, where American Samoa and other nations have used it to brush up on their preparedness plans. "What we learned from that tsunami really helped us," says Akapo, whose 2009 warnings helped entire villages to reach safety before a massive wave struck Tutuila. UNESCO, 2008 Experts say that much work remains, however. In all the world's major oceans — although not the Mediterranean Sea, where some still see a risk — sophisticated tsunami-sensing instruments are now on alert, from the extensive Pacific network first set up in 1965 to the brand-new system deployed across the Indian Ocean in the wake of the 2004 disaster (see graphic). Such systems rely on a network of seismic stations to detect the earthquake, and deep-ocean and coastal gauges to detect resulting changes in sea level. But the best instrumentation in the world cannot guarantee that crucial communication takes place where it is needed: at the waterfront, before the wave strikes, and in terms that local communities can understand and heed. "In the Indian Ocean region there is a tremendous amount of work yet to be done," says Costas Synolakis, director of the University of Southern California's Tsunami Research Center in Los Angeles. "It is urgent work, because when it comes to tsunamis, bad information kills." Before 2004, most people associated tsunamis with the Pacific Ocean, where the waves have repeatedly struck Japan and Hawaii. Few worried about such hazards in the Indian Ocean. Only 4% of all known tsunamis in the twentieth century occurred there — and none had struck in living memory in countries such as Thailand, India and Sri Lanka. Palaeorecords of ancient tsunamis suggest that the 2004 event was the biggest in that region in more than 600 years1,2. At the time, the Indian Ocean had no tsunami warning system. By 2005, the Japan Meteorological Agency in Tokyo and the Pacific Tsunami Warning Center in Honolulu, Hawaii, had started issuing warnings as well as they could for the Indian Ocean with the instruments they had set up for the Pacific. And by the end of March 2010, the new Indian Ocean Tsunami Warning and Mitigation System will be fully operational. It includes 120 seismic stations, more than 60 coastal tide-gauge stations, 24 early-detection buoys and 20 deep-ocean 'tsunameters'. The effort, which cost more than US$100 million, is being paid for by various countries, with Germany, Indonesia and India assuming the largest shares. The 28 countries that are connected to the system are each responsible for collecting and feeding in their data to regional tsunami watch centres in Australia, India and Indonesia. If the data suggest a real threat, the centres will immediately send an alert back to national tsunami focal points, which in turn disseminate warnings to local communities and emergency services. "People in the region are safer than they were in 2004," says Keith Alverson, project-office director with the Global Ocean Observing System of the United Nations Educational, Scientific and Cultural Organization (UNESCO) in Paris. "The challenge is to tailor technology to local cultures and make the system sustainable in the long term," he says. Hidden dangers A tsunami that struck Java on 17 July 2006, killing more than 600 people, highlighted the limits of any warning system, no matter how technologically advanced. The tsunami arrived about 30 minutes after the earthquake, and survivors have reported that no warnings were issued. Lifeguards also failed to recognize the initial recession of water that typically precedes a tsunami, because it was masked by large, wind-driven waves breaking on the shore3. "When it comes to tsunamis, bad information kills." The earthquake itself might have raised the alarm. "For people living close to a fault line, the only effective tsunami warning, alas, is the quake itself," says Harald Spahn, a geologist with the German Technical Cooperation who helps authorities in Sumatra, Java and Bali to improve tsunami warning capacities at the local level. But before the Java tsunami little or no ground-shaking was felt, which is typical for the 'slow' earthquakes that are common in the region. Community-based public education and evacuation drills are essential to save lives in any tsunami, even if evacuation begins just minutes before the wave arrives. Regular drills are now conducted in some Javanese communities, but not all Indonesian coastlines are sufficiently prepared, says Spahn. There have been some success stories in improving the communication of warnings down the critical 'last mile', he adds. For example, loudspeakers on mosques that normally call people for prayer are also an efficient way of broadcasting a tsunami warning, and have been used for this purpose in Sumatra and Java. ADVERTISEMENT Similar public-education efforts paid off in saving lives in Samoa and American Samoa three months ago, says Bruce Jaffe, a coastal-hazards researcher at the US Geological Survey in Santa Cruz, California. "Many people knew what to do," he says; they hurried on foot to higher ground. The 2004 Indian Ocean tsunami, he says, provided "the wake-up call" to reinvigorate overall preparedness efforts for coastal communities around the world. But as more years pass since nearly a quarter of a million million people died, Jaffe worries that people's awareness will start to drop off again. "We can't let that happen," he says. "We've got to, if anything, step up the efforts." Quirin Schiermeier, with additional reporting by Alexandra Witze * References * Jankaew, K.et al. Nature455, 1228-1231 (2008). * Monecke, K.et al. Nature455, 1232-1234 (2008). * Fritz, H. M.et al. Geophys. Res. Lett.34, L12602 (2007). There are currently no comments.
• Extortion attempt involved retracted papers
  - Nature 462(7276):969 (2009)
  Two papers retracted in the past few months have been linked to an extortion attempt. Both papers originated from the laboratory of Peter Schultz, a prominent chemist at the Scripps Research Institute in La Jolla, California. There are currently no comments.
• Fraud rocks protein community
  - Nature 462(7276):970 (2009)
  The finding by a university misconduct investigation that a crystallographer "more likely than not" faked almost a dozen protein structures has left the field in shock. The fraud is the largest ever in protein crystallography.
• 2009 Gallery: Images of the year
  - Nature 462(7276):972 (2009)
  Take a tour through the images that defined 2009, from the murkiest depths of the oceans, where warring worms pepper their enemies with glowing bombs, to the spectacular swirling rainbows thousands of light years away at the heart of the Milky Way. This year has provided a pictorial panoply, with dust-filled volcanic eruptions captured on film by luck, the tiniest of toads at risk of being lost forever and humankind's outpost in space picked out in detail as it passes in front of the Sun. Click here for the image slideshow Download a PDF of this story here. There are currently no comments.
• Newsmaker of the year: The power player
  - Nature 462(7276):978 (2009)
  As a physicist, he found a way to capture atoms and won a Nobel prize. Now he is marshalling scientists and engineers to transform the world's biggest energy economy. Eric Hand profiles the US energy secretary, Nature's Newsmaker of the Year. Download a PDF of this story is heading home on a bright day in October. His motorcade of government cars powers up the slope of Cyclotron Road, past the fragrant stands of eucalyptus and through the guard station at the entrance of Lawrence Berkeley National Laboratory. The vehicles continue along Chu Road and come to a stop near the top of the hill. The man after whom the road is named heads into Building 50, which housed his office for the five years that he ran this laboratory overlooking the University of California, Berkeley. Inside an auditorium, 225 former colleagues await his arrival. Some wear suits; others slouch in hooded sweatshirts and sandals. There is an eager anticipation in the air, and moments before Chu arrives, the crowd grows quiet. Orange-vested security guards, armed with walkie-talkies, open the doors, and Chu walks down to the podium, his entourage trailing. "It's very good to be back here," he says, flipping open his computer. "You people know I do my own PowerPoints. That has not changed." He launches headlong into a fast-paced and scattered talk that leaps across dozens of topics, all under the banner of climate change. He clicks ahead to the crucial slide — the one that shows actual measurements of rising global temperatures outpacing what would be expected without all the carbon dioxide that humans have spewed into the atmosphere. "Here's the evidence," he says. "I have to play this over and over again." Such is his task back in Washington DC, where Chu now works as Secretary of the Department of Energy (DOE) and a member of President Barack Obama's cabinet — the first Nobel-prizewinning scientist to hold such a high office in the US government. "Necessity is the mother of invention and this is the mother of all necessities." Steven Chu He is charged with transforming the world's biggest energy economy, and he has assumed the role of persuader-in-chief, trotting before Congress to explain the science of climate change and his plans for combating it. Meeting regularly with representatives and senators, he targets sceptics and walks them through the data. "I say, 'Come to my office and we'll talk about it'," he explains. "At the very least you can put a little doubt in their minds. If they're so sure it's natural causes, they may be less sure." It helps to have a Nobel prize, he adds. In confronting what he sees as the most pressing problem facing the world today, Chu looks back in time to chart a way forwards. The Berkeley lab he once ran is the descendant of the Radiation Laboratory, where the physicist Ernest Lawrence helped find ways to enrich uranium for the Manhattan Project. Chemist Glenn Seaborg's team discovered plutonium there, and theoretical physicist Robert Oppenheimer worked just down the hill before heading into the New Mexico mountains to build the first nuclear bombs. Chu plans to tackle climate change by reviving the scientific and technological urgency of the Manhattan Project — enlisting some of the nation's best minds to find a way to power the world without ruining it. His plans start at home, where he is trying to push the ponderous DOE to support riskier research that could yield huge dividends. With a budget of US$27 billion, the department runs 17 national laboratories, oversees America's nuclear stockpile and manages the environmental clean-up after the early nuclear age. It is the largest source of funds for physical-science research in the United States, and this year Chu had a much bigger pot to dole out. Just one month into his tenure, Congress gave the agency $37 billion in economic stimulus money — funds that Chu is steering towards renewable energy, nuclear power, carbon-sequestration pilot plants and projects to modernize the electric grid, all of which should help to solve the climate problem. "They say that necessity is the mother of invention and this is the mother of all necessities," he says. "So we're going to get the mother of all inventions. And it's not going to be just one, it has to be many." Hands-on manager In the 1980s, Chu made his name scientifically by trapping atoms using lasers tuned with the utmost precision. Now he is applying that same mastery of detail to a vastly more complex system: an agency of 100,000 people working on all aspects of energy and nuclear issues. Some Washington veterans have questioned whether Chu's research talent and hands-on style of management will serve him well, both at the DOE and amid the harsh political environment of the nation's capital. He has made some mistakes, notably in his dealings with Congress. But nearly a year into his tenure, Chu has proved that he is a quick learner. He has established himself as a voice that can be trusted by politicians of various stripes. He has helped to bridge international divides, particularly between the United States and China. And he has lured some top scientists from industry and universities to join him at the DOE in his quest. Carol Browner, Obama's climate tsar, works often with Chu as part of the president's 'green cabinet', a group of senior officials who oversee environmental matters. "I think he's going to turn out to be the best energy secretary ever," she says. Praise also flows from some Republican politicians. Samuel Bodman, who led the DOE for former president George W. Bush, says that Chu has "shown skills as a manager. I think it was an inspired choice by the president to pick him." Growing up in a New York suburb during the 1950s, Chu and his two brothers learned quickly that academic excellence — and competition — were family traditions. The boys would watch College Bowl, a 1960s television quiz show, and "the three of us would shout out answers and try to beat the contestants", recalls Morgan Chu, the youngest brother and a high-profile lawyer in California. Clockwise from top left: the Nobel call, biking to work this year and time at Bell Labs.L. DEMATTEIS/REUTERS; A. WONG/GETTY; DOE Chu's father and mother fled China during the Second World War and both did graduate work at the Massachusetts Institute of Technology (MIT) in Cambridge. The eldest son, Gilbert, followed the path of academic prestige — accumulating science degrees from Princeton University in New Jersey and MIT before gaining an MD from Harvard University in Cambridge, Massachusetts. Morgan did a PhD in social science before heading to Harvard Law School. Steven, on the other hand, was the A-minus student who favoured tinkering over schoolwork. In a family of Ivy Leaguers, he says he was the "academic black sheep", who settled for the University of Rochester in New York, where he studied mathematics and physics. Family pressures, he says, drove him — and frustrated him — early on, but once at Rochester, his facility for science flourished. "All of a sudden, the things they wanted me to do were very natural," he says. On entering graduate school at Berkeley in 1970, Chu began a love affair with lasers. The work that was once a chore became the focus of an obsessive energy. "I've never been that good at apportioning time," he says. "When I got really excited about something, I would dig into it. It turns out that is a quality that the best researchers have." Another Berkeley graduate student, Phil Bucksbaum, recalled nearly getting into a fist fight with Chu because he was being "bossy about the lasers", until a third student, who had studied with Chu at Rochester, explained to Bucksbaum: "It's the way he always has been. Focused and brusque," says Bucksbaum. Chu's graduate work using polarized light to probe atomic transitions was good enough for him to get a job at Bell Labs in New Jersey, then a utopia for basic research. Chu thrived there, but he also made sacrifices. As his work progressed, he spent more time away from home, says his ex-wife, Lisa Chu-Thielbar. Sometimes, she would smuggle his first son, Geoffrey, under her overcoat onto the laboratory campus to catch some time with his father. "He was always a scientist first and a father second," says Chu's second son, Michael, who doesn't fault his father for the singular focus that allowed him to achieve so much. "The ambition was all intellectual and scientific. Steve never cared about money. He didn't even care about advancement," says Chu-Thielbar. After seven years at Bell Labs, Chu had a key insight in 1985 into how to trap atoms. He crossed six lasers to form what he called "optical molasses", a goo of photons. It slowed atoms nearly to a standstill, making them sluggish enough to be held by the electromagnetic forces of an additional laser. A year later, in the winter of 1986, Chu glimpsed the foundation of his Nobel prize through the windows of a vacuum chamber. Sodium atoms, cooled in optical molasses to 240 millionths of a degree above absolute zero, grew bright orange as they fell, one by one, into a trap the size of a sand grain. A colour photo, the first ever published in Physical Review Letters, provided the proof of his success (S. Chu, J. E. Bjorkholm, A. Ashkin and A. Cable Phys. Rev. Lett. 57, 314–317; 1986). The work would spawn applications across several disciplines. It provided biologists with 'optical tweezers' — ways to manipulate individual biomolecules, such as DNA. And it gave other atomic scientists the tools to create Bose–Einstein condensates, the super-cooled states of matter that can trap light and bring photons to a standstill, in a reversal of Chu's original technique. "Steve never cared about money. He didn't even care about advancement." Lisa Chu-Thielbar By 1987, Chu was ready to move back to academia. He had offers at Harvard and Berkeley, but was intrigued at the idea of helping to build up a less-celebrated physics department at Stanford University in Palo Alto, California. It was a good plan. Stanford soon became a powerhouse; beginning in 1995, physicists there would win four Nobel prizes in a row, including Chu in 1997. While at Stanford, Chu started to push off in new directions, personally and professionally. He divorced Chu-Thielbar and married Jean Fetter, a physicist and former dean of admissions at Stanford. He took on graduate students with interests in biology and helped to convince the Stanford administration to build a $150-million biophysics centre. But in 2004, just after that centre was completed, the Lawrence Berkeley National Laboratory (LBNL) came calling. Chu, who had never managed anything bigger than a physics department, was ready to make the leap to running the laboratory, which now has 4,000 employees and a $650-million budget. He showed his mettle early on, pushing the University of California system, which manages the LBNL, to use its debt service in an unprecedented way to finance new buildings for the lab, and fighting to save employee pension plans. Chu personally argued on behalf of his employees with the president of the University of California system until he relented, says Graham Fleming, a chemist at Berkeley and Chu's deputy at the time. "If one argument didn't work, he'd try another," he adds. The climate crusader Chu says that there was no one moment when he decided to devote himself full time to climate and energy puzzles. He had been digesting the science for years, reading reports of the Intergovernmental Panel on Climate Change. And he had pursued energy efficiency in his own life with his customary precision, complaining when workers skimped on insulation in his Stanford home. But soon after arriving at the LBNL, he decided that the time was ripe to resurrect an energy-research programme that had lain largely dormant since the fuel crisis of the 1970s. The lab was ready to revive those efforts, but it needed Chu's energy and vision, says Paul Alivisatos, who succeeded Chu as the head of the LBNL. "It's a bit like a supersaturated solution that you drop a seed crystal into," he says. "Steve was the seed crystal." Chu was sworn in the day after President Obama.O. MUHAMMAD/THE NEW YORK TIMES/REDUX/EYEVINE Chu gave the sprawling lab a purpose and convinced many scientists to make the switch, as he had, into energy research. He attracted large infusions of funding from the DOE and from the energy company BP. The lab launched major initiatives in biofuels and photovoltaics, but Chu also got involved in the little stuff. Alivisatos recalls Chu's interest in revamping a system of old, lumbering shuttle buses that circle the heights of the Berkeley Hills. Chu would stand on the balcony of the director's office and keep tallies of riders at a bus stop. "He thinks at an incredibly high level, but he also delves down into the finest detail," says Alivisatos. "And one of his abilities is to find the salient detail that matters enormously to the big picture and to show you how those connect." But some thought that Chu went too far by micromanaging lab operations. "He doesn't see the necessity to get other people involved," says one scientist who knows him well but did not want to be identified as criticizing an official who controls so much research funding. "His whole career has been founded on his fantastic ability to worry about all the details himself. And that makes it hard for him to empower an effective staff." Obama's election, and his campaign pledges to revamp the US energy system, created new opportunities for Chu. A few weeks after the election, Chu flew to Chicago to meet with the president-elect. "A lot of people are telling me you're the person for the DOE," said Obama, according to Chu. Rarely at a loss for words, Chu could only think to quip, "Who are these former friends of mine?" Inspired by a sense of service, Chu planned to accept the job, but he did have a demand. He had seen the energy department hamstrung in the past by ineffectual people placed in posts to satisfy political obligations, so he wanted control over senior appointments. "There was a reasonable shot I could attract the right people. There are a whole bunch of people that have to lift this load," Chu says. Obama agreed, and Chu has recruited top talent such as Steven Koonin, former chief scientist of BP and provost of the California Institute of Technology in Pasadena, who is now undersecretary for science. "One of his abilities is to find the salient detail that matters enormously in the big picture." Paul Alivisatos On the top floor of the energy department, portraits of secretaries past preside over the long, carpeted hallway leading from the elevators to the secretary's office. Most are of career politicians, with a few exceptions: Charles Duncan, who ran his family's coffee company, Donald Hodel, who would go on to lead two Christian evangelical groups, and James Edwards, a dentist. Bodman, Chu's predecessor, has an engineering degree from MIT. But Chu is the first scientist to lead an agency that has such an important role in physical-science research. On an end table in his waiting room lie some recent biophysics papers on which Chu is a co-author. Chu puts the papers out to make a point — to visitors and himself — that he is still a working scientist. During his time at the LBNL, he kept a small research group of Stanford and Berkeley students, holding group meetings on Friday nights and on weekends. Even now, he says, he finds a little time for research during plane flights. Although Chu's October visit to the LBNL was his first lab-wide talk, he had visited before to check in with postdocs and meet new, young scientists — trips that Alivisatos calls Chu's "science vacations". During an interview at his office, Chu settles into the centre of a couch, his back to an expansive view of Washington DC's mall and the Smithsonian Castle. At 61, Chu is resolutely trim. Although he no longer commutes to work by bike, as he often did at Berkeley, he manages long weekend rides and regularly climbs the seven flights of stairs to his office. Chu leans back when he listens, which is often, and leans forward when making a point. He is quick to crack a joke and eager to please. At least, he's that way with politicians (and reporters). With scientists, he can be impatient. "He does not suffer fools," says Michael Levi, an astrophysicist at the LBNL. Chu retains a scientist's candour — and that can sometimes get him into trouble. At his confirmation hearing, some senators jumped on Chu for calling coal "his worst nightmare" in a 2007 talk. (Chu says that the United States, China and India are unlikely to turn their backs on their huge coal reserves and that underscores the need to find clean ways to use the fuel.) A month after taking office, Chu slipped when he told reporters that it was "not in his domain" whether the Organization of the Petroleum Exporting Countries (OPEC) should cut oil production, an impolitic statement. He acknowledges that he was surprised at how his words have been magnified by the press. Yet his inability to mince words is also an asset, especially in the floors below him in the DOE's headquarters, a fortress on concrete stilts. The DOE national labs have been characterized as inefficient, but that is in part because past safety and security lapses have led to a culture that stresses caution over aggressive research. When, during his talk at the LBNL, Chu mentions his desire to return to the original spirit of the labs, GOCO — government owned, but contractor operated — he gets a hearty round of applause. Chu says that the risk-averse culture, at both headquarters and the labs, must be changed. "The best way to protect yourself from something bad happening is to not do much." Chu has already made headway. When he found out that billions of dollars in loans for energy projects that had been authorized in 2005 had not progressed, he insisted that they be pushed out in months, with the first one going to a solar-power company. It has helped to get involved personally, he says. Before closing on a $5.9-billion loan with Ford Motors, Chu says he was talking to the firm's chief executive every third day — an example that sent a clear message to his subordinates to act. "In certain areas, I'm not going away," he says. "The pressure is not going to let up."[ image 4 right]To encourage more adventurous research, he has pushed to develop the Advanced Research Projects Agency-Energy, known as ARPA-E, which draws its inspiration from DARPA, the celebrated research programme run by the Department of Defense that had an important role in creating the Internet. ARPA-E is designed to pursue high-risk, high-reward research on new forms of energy and conservation (see 'Blue sky, green tech'). The programme preceded Chu, but it's a pet of his, not least because he recommended it as a co-author on an influential study by the National Academies entitled Rising Above the Gathering Storm, which in 2005 warned of declining American competitiveness. The ARPA-E concept will work, says Chu, only if the smartest reviewers are enlisted to pick out the most innovative ideas — otherwise incremental research is rewarded. "I unfortunately can't review all of the proposals myself," he told a group of clean-energy businesspeople in October, only half-jokingly. So Chu wrote a letter to the presidents of top research universities asking them to nominate their best researchers as ARPA-E reviewers. Five hundred responded to the call for duty. Chu himself spent about two hours with the final set of proposals. Fleming, Chu's former LBNL deputy, says this sort of task suits his old boss. "I've never known anyone able to go away and come back 10 minutes later knowing so much about a new topic." And on the day that he visited the LBNL, Chu announced the 37 winning proposals, which would use $151 million of an initial $400 million given to the programme. Chu's most ambitious idea has been to create eight focused and independent energy labs, modelled after the Manhattan Project, to develop technologies such as next-generation batteries and advanced nuclear power (see 'Chu's innovation factories'). But this is where he has run into the most trouble, and it exposes the limitations of the do-it-all-yourself approach. As Congress debated whether to fund Chu's new labs in fiscal year 2010, staffers found that they couldn't get the details on what, exactly, the DOE wanted. Would they be virtual labs, or permanent facilities? How many years would they be funded for? What mix of basic and applied science would be supported? "The hubs were just dropped on Congress," says one congressional staffer who adds that Chu's office did not provide consistent or timely information. The communication problems with the Hill were on display at a hearing of a congressional appropriations committee in May. Senator Diane Feinstein (Democrat, California), a friend of Chu's, had a complaint. She had wanted to talk privately with him about some solar projects, but she had not been able to make an appointment to see Chu via his staff. "I'm a little bit surprised if you asked to see me and my staff said no," Chu replied. "We just haven't gotten a response, that's sort of the way it's done," said Feinstein in an apparent attempt to educate the secretary on Washington customs. But Chu, who likes to deal with issues himself, did not seem to understand. "I'm still surprised," he said. "You actually have my private number." In the end, when Congress doled out money to the DOE, Chu lost some battles. Money that he had proposed cutting from hydrogen research was reinstated. A $115-million education programme he had championed received nothing. Worst of all, for Chu, only three of his eight energy hubs were funded. Chu's critics say that more attention to Congress could have alleviated the problems, but nearly a year into his tenure, he has not appointed an assistant secretary to head up his legislative-affairs office. Chu says the vacant position was not the problem. The issue was that he hadn't followed through himself. "The failure was on my part," he says, "because I wasn't communicating what the real vision was." Energy ambassador On a cold day in early December, Chu was preparing to travel to the United Nations' climate-change conference in Copenhagen. Before the trip, one of the last public events on his schedule was to appear with Secretary of Commerce, Gary Locke, to talk about speeding up the process for granting patents on green technologies. In July, the two secretaries went to Beijing together to meet with Chinese energy ministers. Locke, a prominent politician of Chinese descent, was greeted warmly. But Chu, with his Nobel-prize pedigree, was a rock star in a culture that reveres education. "He was like a Michael Jordan," says an administration official. "Everybody knew this guy." Busy schedule: Chu likes to take care of many details on his own.C. OMMANNEY/GETTY Chu has taken a particular interest in China not because of his ancestry, he says, but because it emits more carbon dioxide than any other nation and it is also spending billions of dollars on clean-energy research. During the trip, Chu and Locke announced that the United States and China would jointly pursue research in areas such as energy efficiency and capturing carbon dioxide from coal-plant exhaust. In his trip to Denmark, Chu reprised his role as energy ambassador. He announced plans to hold a conference next year with foreign energy ministers and pledged $85 million in US aid for renewable-energy projects in the developing world. For Chu, the summit served as a prelude to the fight next year, when he will use his main weapons — knowledge and powers of persuasion — to try to convince members of Congress to vote for a climate bill that would for the first time cap US emissions of greenhouse gases. Chu says that when he ends his time as energy secretary, he will measure his success by two criteria: whether he aided adoption of a climate bill, and how much he changed the way that the DOE supports science. Those metrics would have seemed odd to a young scientist at Bell Labs in the 1980s who spent his days fretting over the precision of laser beams. Chu didn't plan on working his way to the upper echelons of the US government, where he is the first scientist since the cold war to play such an active part. "It just sort of happened," he says. "I followed the path first from going and doing the science, to getting very concerned about some issues that affect us all as a society, to finally saying, I can't sit idly by and occasionally give a talk on this. I really have to get proactive and put my money where my mouth is and do a career shift because it is that important." ADVERTISEMENT But looking back, it's possible that the call to public service may have been whispering to Chu even during his graduate-school days at Berkeley, where the memories of the war effort remained fresh in the physics department. When Chu briefly took up sculpting at Berkeley, he chose to make a bust of Oppenheimer, the physicist-turned-manager who oversaw all details of the Manhattan Project. Chu is now looking to another Berkeley star for inspiration. Lately, he has been reading the journals of Seaborg, who led the war-time team racing to extract plutonium for a bomb. Seaborg recounts how his group required fast-working Geiger counters that were not available at the time. So he pushed his crew to invent the needed detectors. For Chu, that sense of urgency in the face of a great threat stands out in Seaborg's work: "He kept saying: 'This isn't university research. We've got to move much faster'." There are currently no comments.
• Goodbye to Darwin from a contemporary with vision
  - Nature 462(7276):984 (2009)
  One night some 40 years ago, I was working late and alone in the library at the Marine Biology Laboratory at Woods Hole (in those days, the library never really closed), searching for something in the 1882 volume of Archiv für Protistenkunde. As I opened it, out fell a folded page from the magazine The Nation (still publishing today), dated 27 April 1882.
• Global Darwin: long kept under wraps in Pakistan
  - Nature 462(7276):984 (2009)
  Marwa Elshakry's Opinion article (Nature 461, 1200–1201; 2009, and see http://go.nature.com/97zlyr
• Global Darwin: ideas blurred in early eastern translations
  - Nature 462(7276):984 (2009)
  The early diffusion of Darwin's ideas into China resulted in multiple interpretations, imperfect translations and unsatisfactory terminology, as James Pusey notes in his Opinion article (Nature 462, 162–163; 2009). However, he inadvertently implies that it was the Chinese scholar Yan Fu who translated 'evolution' as jinhualun, which means 'theory of progressive change'.
• Don't forget the artists when studying perception of art
  - Nature 462(7276):984 (2009)
  Martin Kemp in Books & Arts (Nature 461, 882–883; 2009) suggests using functional neuroimaging to study the viewing and reception of artworks. But such direct measures of brain activity allow only for correlations between brain responses and the task of the viewer.
• How much are we willing to pay for a fossil?
  - Nature 462(7276):984 (2009)
  The outrage expressed by Elwyn Simons and others over the sale of a 47-million-year-old fossil for an enormous sum (Nature 460, 456; 2009) may not be altogether justified.A fossil's intrinsic value relates to its preservation, rarity, scientific interest and completeness.
• 'Snow joke as festive season gives rise to a blizzard of fake flakes
  - Nature 462(7276):985 (2009)
  Parts of the world are once again knee-deep in images of snow crystals for the Christmas and New Year festivities. Unfortunately, the grand diversity of naturally occurring snow crystals is commonly corrupted by incorrect 'designer' versions — as illustrated by the faux octagonal snowflakes depicted in a Nature online subscription advertisement and, ironically, captioned "...for anyone who loves science".
• Rewilding can cause rather than solve ecological problems
  - Nature 462(7276):985 (2009)
  Prehistoric-restoration schemes such as those described in your News Feature (Nature462, 30–32; 2009) are highly unusual. Introducing a mix of native and exotic ungulates into former agricultural land could constitute a risky conservation strategy.
• A toast to Mendeleev, who merits more than periodic honour
  - Nature 462(7276):985 (2009)
  Before the year is out, let's raise a glass to the great Russian chemist Dmitrii Mendeleev, to celebrate the 140th anniversary of his periodic table of the elements. Russia has commemorated this, and the 175th anniversary of Mendeleev's birth, with a postage stamp (pictured) and a two-rouble silver coin.
• Timely tale of avian flu
  - Nature 462(7276):986 (2009)
  A gripping account of the spread of the bird flu virus across southeast Asia holds lessons for the global management of pandemics such as swine flu, explains Ab Osterhaus.
• Johannes Kepler on Christmas
  - Nature 462(7276):987 (2009)
  Kepler's interpretation of the supernova of 1604, De Stella Nova, interwove the science of astronomy with astrology and theology in an attempt to determine the correct birthdate of Jesus, explains Martin Kemp.
• Personal favourites of 2009
  - Nature 462(7276):988 (2009)
  Nature invited some of its regular reviewers to name their pick of this year's book publications.
• Ageing: Diet and longevity in the balance
  - Nature 462(7276):989 (2009)
  Dietary restriction promotes longevity but impairs fecundity in many organisms. When the amino acids in a diet are fine-tuned, however, lifespan can be increased without loss of fecundity — at least in fruitflies.
• Applied physics: Bubbly but quiet
  - Nature 462(7276):990 (2009)
  An array of air bubbles in a rubber-like material can be made to block the transmission of sound. This finding might help in the design of soundproof walls for music rooms and urban apartments.
• Astrophysics: Stellar revival in old clusters
  - Nature 462(7276):991 (2009)
  Observations of star clusters in the Milky Way show that collisions between stars as well as mass flow within binary systems can explain how the peculiar family of blue straggler stars came to be born.
• Hangovers: Uncongenial congeners
  - Nature 462(7276):992 (2009)
  Abstract
• Structural biology: Translocation chamber's secrets
  - Nature 462(7276):992 (2009)
  DNA transfer across membranes is a fundamental life process. The structure of part of a protein channel that performs this task offers insight into the mechanism of DNA passage through bacterial cell envelopes.
• 50 & 100 years ago
  - Nature 462(7276):994 (2009)
  The Way Things Are. By Prof. P.
• Nanotechnology: Molecular transistors scrutinized
  - Nature 462(7276):994 (2009)
  Transistors have been made from single molecules, where the flow of electrons is controlled by modulating the energy of the molecular orbitals. Insight from such systems could aid the development of future electronic devices.
• Word of the Year
  - Nature 462(7276):995 (2009)
  The News & Views WotY for 2009 is 'critical'. But this is not an accolade.
• Obituary: Vitaly Ginzburg (1916–2009)
  - Nature 462(7276):996 (2009)
  Nobel-prizewinning success in physics achieved in the Soviet system.
• The first decade of science with Chandra and XMM-Newton
  - Nature 462(7276):997 (2009)
  NASA's Chandra X-ray Observatory and the ESA's X-ray Multi-Mirror Mission (XMM-Newton) made their first observations ten years ago. The complementary capabilities of these observatories allow us to make high-resolution images and precisely measure the energy of cosmic X-rays. Less than 50 years after the first detection of an extrasolar X-ray source, these observatories have achieved an increase in sensitivity comparable to going from naked-eye observations to the most powerful optical telescopes over the past 400 years. We highlight some of the many discoveries made by Chandra and XMM-Newton that have transformed twenty-first century astronomy.
• Complex landscapes of somatic rearrangement in human breast cancer genomes
  - Nature 462(7276):1005 (2009)
  Multiple somatic rearrangements are often found in cancer genomes; however, the underlying processes of rearrangement and their contribution to cancer development are poorly characterized. Here we use a paired-end sequencing strategy to identify somatic rearrangements in breast cancer genomes. There are more rearrangements in some breast cancers than previously appreciated. Rearrangements are more frequent over gene footprints and most are intrachromosomal. Multiple rearrangement architectures are present, but tandem duplications are particularly common in some cancers, perhaps reflecting a specific defect in DNA maintenance. Short overlapping sequences at most rearrangement junctions indicate that these have been mediated by non-homologous end-joining DNA repair, although varying sequence patterns indicate that multiple processes of this type are operative. Several expressed in-frame fusion genes were identified but none was recurrent. The study provides a new perspec! tive on cancer genomes, highlighting the diversity of somatic rearrangements and their potential contribution to cancer development.
• Structure of the outer membrane complex of a type IV secretion system
  Chandran V Fronzes R Duquerroy S Cronin N Navaza J Waksman G - Nature 462(7276):1011 (2009)
  Type IV secretion systems are secretion nanomachines spanning the two membranes of Gram-negative bacteria. Three proteins, VirB7, VirB9 and VirB10, assemble into a 1.05 megadalton (MDa) core spanning the inner and outer membranes. This core consists of 14 copies of each of the proteins and forms two layers, the I and O layers, inserting in the inner and outer membrane, respectively. Here we present the crystal structure of a ~0.6 MDa outer-membrane complex containing the entire O layer. This structure is the largest determined for an outer-membrane channel and is unprecedented in being composed of three proteins. Unexpectedly, this structure identifies VirB10 as the outer-membrane channel with a unique hydrophobic double-helical transmembrane region. This structure establishes VirB10 as the only known protein crossing both membranes of Gram-negative bacteria. Comparison of the cryo-electron microscopy (cryo-EM) and crystallographic structures points to conformational! changes regulating channel opening and closing.
• The chromatin remodeller ACF acts as a dimeric motor to space nucleosomes
  - Nature 462(7276):1016 (2009)
  Evenly spaced nucleosomes directly correlate with condensed chromatin and gene silencing. The ATP-dependent chromatin assembly factor (ACF) forms such structures in vitro and is required for silencing in vivo. ACF generates and maintains nucleosome spacing by constantly moving a nucleosome towards the longer flanking DNA faster than the shorter flanking DNA. How the enzyme rapidly moves back and forth between both sides of a nucleosome to accomplish bidirectional movement is unknown. Here we show that nucleosome movement depends cooperatively on two ACF molecules, indicating that ACF functions as a dimer of ATPases. Further, the nucleotide state determines whether the dimer closely engages one or both sides of the nucleosome. Three-dimensional reconstruction by single-particle electron microscopy of the ATPase–nucleosome complex in an activated ATP state reveals a dimer architecture in which the two ATPases face each other. Our results indicate a model in which the t! wo ATPases work in a coordinated manner, taking turns to engage either side of a nucleosome, thereby allowing processive bidirectional movement. This novel dimeric motor mechanism differs from that of dimeric motors such as kinesin and dimeric helicases that processively translocate unidirectionally and reflects the unique challenges faced by motors that move nucleosomes.
• Dynamics of nucleosome remodelling by individual ACF complexes
  - Nature 462(7276):1022 (2009)
  The ATP-dependent chromatin assembly and remodelling factor (ACF) functions to generate regularly spaced nucleosomes, which are required for heritable gene silencing. The mechanism by which ACF mobilizes nucleosomes remains poorly understood. Here we report a single-molecule FRET study that monitors the remodelling of individual nucleosomes by ACF in real time, revealing previously unknown remodelling intermediates and dynamics. In the presence of ACF and ATP, the nucleosomes exhibit gradual translocation along DNA interrupted by well-defined kinetic pauses that occurred after approximately seven or three to four base pairs of translocation. The binding of ACF, translocation of DNA and exiting of translocation pauses are all ATP-dependent, revealing three distinct functional roles of ATP during remodelling. At equilibrium, a continuously bound ACF complex can move the nucleosome back-and-forth many times before dissociation, indicating that ACF is a highly processive a! nd bidirectional nucleosome translocase.
• Two distinct sequences of blue straggler stars in the globular cluster M 30
  - Nature 462(7276):1028 (2009)
  Stars in globular clusters are generally believed to have all formed at the same time, early in the Galaxy's history1. 'Blue stragglers' are stars massive enough2 that they should have evolved into white dwarfs long ago. Two possible mechanisms have been proposed for their formation: mass transfer between binary companions3 and stellar mergers resulting from direct collisions between two stars4. Recently the binary explanation was claimed to be dominant5. Here we report that there are two distinct parallel sequences of blue stragglers in M 30. This globular cluster is thought to have undergone 'core collapse', during which both the collision rate and the mass transfer activity in binary systems would have been enhanced6. We suggest that the two observed sequences are a consequence of cluster core collapse, with the bluer population arising from direct stellar collisions and the redder one arising from the evolution of close binaries that are probably still ! experiencing an active phase of mass transfer.
• A binary star fraction of 76 per cent and unusual orbit parameters for the blue stragglers of NGC 188
  - Nature 462(7276):1032 (2009)
  Blue straggler stars lie on or near the main sequences of star clusters (all members of which formed around the same time), but typically are more luminous than the turn-off stars and therefore long ago should have evolved off the main sequence to become giants and white dwarfs. They are thought to derive from normal main-sequence stars that have undergone a recent increase in mass. Statistical evidence indicates that in globular star clusters the blue stragglers probably form from binary stars1. The specific formation processes, such as mass transfer, mergers or stellar collisions during dynamical encounters of binary stars, remain unresolved. Here we report that 16 of the 21 blue stragglers (76 per cent) in the old (7-Gyr; ref. 2) open cluster NGC 188 are currently in binary systems, a frequency three times that found among normal solar-type main-sequence stars. These blue straggler binaries have a remarkable period–eccentricity distribution, with all but three h! aving orbital periods of ~1,000 days. Moreover, these stars are rotating faster than normal main-sequence stars of the same surface temperatures. These data show that most, and possibly all, blue stragglers derive from multiple-star systems, and indicate that the several formation processes operate simultaneously. We suggest that rapid rotation of blue stragglers may place upper limits on their ages.
• A strong, highly-tilted interstellar magnetic field near the Solar System
  - Nature 462(7276):1036 (2009)
  Magnetic fields play an important (sometimes dominant) role in the evolution of gas clouds in the Galaxy, but the strength and orientation of the field in the interstellar medium near the heliosphere has been poorly constrained. Previous estimates of the field strength range from 1.8–2.5 μG and the field was thought to be parallel to the Galactic plane1 or inclined by 38–60° (ref. 2) or 60–90° (ref. 3) to this plane. These estimates relied either on indirect observational inferences or modelling in which the interstellar neutral hydrogen was not taken into account. Here we report measurements of the deflection of the solar wind plasma flows in the heliosheath4 to determine the magnetic field strength and orientation in the interstellar medium. We find that the field strength in the local interstellar medium is 3.7–5.5 μG. The field is tilted ~20–30° from the interstellar medium flow direction (resulting from the peculiar motion of the Sun in the Gala! xy) and is at an angle of about 30° from the Galactic plane. We conclude that the interstellar medium field is turbulent or has a distortion in the solar vicinity.
• Observation of molecular orbital gating
  - Nature 462(7276):1039 (2009)
  The control of charge transport in an active electronic device depends intimately on the modulation of the internal charge density by an external node1. For example, a field-effect transistor relies on the gated electrostatic modulation of the channel charge produced by changing the relative position of the conduction and valence bands with respect to the electrodes. In molecular-scale devices2, 3, 4, 5, 6, 7, 8, 9, 10, a longstanding challenge has been to create a true three-terminal device that operates in this manner (that is, by modifying orbital energy). Here we report the observation of such a solid-state molecular device, in which transport current is directly modulated by an external gate voltage. Resonance-enhanced coupling to the nearest molecular orbital is revealed by electron tunnelling spectroscopy, demonstrating direct molecular orbital gating in an electronic device. Our findings demonstrate that true molecular transistors can be created, and so enhance! the prospects for molecularly engineered electronic devices.
• Glaciers as a source of ancient and labile organic matter to the marine environment
  - Nature 462(7276):1044 (2009)
  Riverine organic matter supports of the order of one-fifth of estuarine metabolism1. Coastal ecosystems are therefore sensitive to alteration of both the quantity and lability of terrigenous dissolved organic matter (DOM) delivered by rivers. The lability of DOM is thought to vary with age, with younger, relatively unaltered organic matter being more easily metabolized by aquatic heterotrophs than older, heavily modified material2, 3, 4. This view is developed exclusively from work in watersheds where terrestrial plant and soil sources dominate streamwater DOM. Here we characterize streamwater DOM from 11 coastal watersheds on the Gulf of Alaska that vary widely in glacier coverage (0–64 per cent). In contrast to non-glacial rivers, we find that the bioavailability of DOM to marine microorganisms is significantly correlated with increasing 14C age. Moreover, the most heavily glaciated watersheds are the source of the oldest (~4 kyr 14C age) and most labile (66 per ! cent bioavailable) DOM. These glacial watersheds have extreme runoff rates, in part because they are subject to some of the highest rates of glacier volume loss on Earth5. We estimate the cumulative flux of dissolved organic carbon derived from glaciers contributing runoff to the Gulf of Alaska at 0.13 ± 0.01 Tg yr-1 (1 Tg = 1012 g), of which ~0.10 Tg is highly labile. This indicates that glacial runoff is a quantitatively important source of labile reduced carbon to marine ecosystems. Moreover, because glaciers and ice sheets represent the second largest reservoir of water in the global hydrologic system, our findings indicate that climatically driven changes in glacier volume could alter the age, quantity and reactivity of DOM entering coastal oceans.
• Tremor-tide correlations and near-lithostatic pore pressure on the deep San Andreas fault
  - Nature 462(7276):1048 (2009)
  Since its initial discovery nearly a decade ago1, non-volcanic tremor has provided information about a region of the Earth that was previously thought incapable of generating seismic radiation. A thorough explanation of the geologic process responsible for tremor generation has, however, yet to be determined. Owing to their location at the plate interface, temporal correlation with geodetically measured slow-slip events and dominant shear wave energy, tremor observations in southwest Japan have been interpreted as a superposition of many low-frequency earthquakes that represent slip on a fault surface2, 3. Fluids may also be fundamental to the failure process in subduction zone environments, as teleseismic and tidal modulation of tremor in Cascadia and Japan and high Poisson ratios in both source regions are indicative of pressurized pore fluids3, 4, 5, 6, 7. Here we identify a robust correlation between extremely small, tidally induced shear stress parallel to the San! Andreas fault and non-volcanic tremor activity near Parkfield, California. We suggest that this tremor represents shear failure on a critically stressed fault in the presence of near-lithostatic pore pressure. There are a number of similarities between tremor in subduction zone environments, such as Cascadia and Japan, and tremor on the deep San Andreas transform3, 4, 5, 6, 7, 8, 9, 10, 11, 12, suggesting that the results presented here may also be applicable in other tectonic settings.
• The velocity of climate change
  - Nature 462(7276):1052 (2009)
  The ranges of plants and animals are moving in response to recent changes in climate1. As temperatures rise, ecosystems with 'nowhere to go', such as mountains, are considered to be more threatened2, 3. However, species survival may depend as much on keeping pace with moving climates as the climate's ultimate persistence4, 5. Here we present a new index of the velocity of temperature change (km yr-1), derived from spatial gradients (°C km-1) and multimodel ensemble forecasts of rates of temperature increase (°C yr-1) in the twenty-first century. This index represents the instantaneous local velocity along Earth's surface needed to maintain constant temperatures, and has a global mean of 0.42 km yr-1 (A1B emission scenario). Owing to topographic effects, the velocity of temperature change is lowest in mountainous biomes such as tropical and subtropical coniferous forests (0.08 km yr-1), temperate coniferous forest, and montane grasslands. Velocities ! are highest in flooded grasslands (1.26 km yr-1), mangroves and deserts. High velocities suggest that the climates of only 8% of global protected areas have residence times exceeding 100 years. Small protected areas exacerbate the problem in Mediterranean-type and temperate coniferous forest biomes. Large protected areas may mitigate the problem in desert biomes. These results indicate management strategies for minimizing biodiversity loss from climate change. Montane landscapes may effectively shelter many species into the next century. Elsewhere, reduced emissions, a much expanded network of protected areas6, or efforts to increase species movement may be necessary7.
• A phylogeny-driven genomic encyclopaedia of Bacteria and Archaea
  - Nature 462(7276):1056 (2009)
  Sequencing of bacterial and archaeal genomes has revolutionized our understanding of the many roles played by microorganisms1. There are now nearly 1,000 completed bacterial and archaeal genomes available2, most of which were chosen for sequencing on the basis of their physiology. As a result, the perspective provided by the currently available genomes is limited by a highly biased phylogenetic distribution3, 4, 5. To explore the value added by choosing microbial genomes for sequencing on the basis of their evolutionary relationships, we have sequenced and analysed the genomes of 56 culturable species of Bacteria and Archaea selected to maximize phylogenetic coverage. Analysis of these genomes demonstrated pronounced benefits (compared to an equivalent set of genomes randomly selected from the existing database) in diverse areas including the reconstruction of phylogenetic history, the discovery of new protein families and biological properties, and the prediction of f! unctions for known genes from other organisms. Our results strongly support the need for systematic 'phylogenomic' efforts to compile a phylogeny-driven 'Genomic Encyclopedia of Bacteria and Archaea' in order to derive maximum knowledge from existing microbial genome data as well as from genome sequences to come.
• Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila
  Grandison RC Piper MD Partridge L - Nature 462(7276):1061 (2009)
  Dietary restriction extends healthy lifespan in diverse organisms and reduces fecundity1, 2. It is widely assumed to induce adaptive reallocation of nutrients from reproduction to somatic maintenance, aiding survival of food shortages in nature3, 4, 5, 6. If this were the case, long life under dietary restriction and high fecundity under full feeding would be mutually exclusive, through competition for the same limiting nutrients. Here we report a test of this idea in which we identified the nutrients producing the responses of lifespan and fecundity to dietary restriction in Drosophila. Adding essential amino acids to the dietary restriction condition increased fecundity and decreased lifespan, similar to the effects of full feeding, with other nutrients having little or no effect. However, methionine alone was necessary and sufficient to increase fecundity as much as did full feeding, but without reducing lifespan. Reallocation of nutrients therefore does not explain! the responses to dietary restriction. Lifespan was decreased by the addition of amino acids, with an interaction between methionine and other essential amino acids having a key role. Hence, an imbalance in dietary amino acids away from the ratio optimal for reproduction shortens lifespan during full feeding and limits fecundity during dietary restriction. Reduced activity of the insulin/insulin-like growth factor signalling pathway extends lifespan in diverse organisms7, and we find that it also protects against the shortening of lifespan with full feeding. In other organisms, including mammals, it may be possible to obtain the benefits to lifespan of dietary restriction without incurring a reduction in fecundity, through a suitable balance of nutrients in the diet.
• Secreted semaphorins control spine distribution and morphogenesis in the postnatal CNS
  Tran TS Rubio ME Clem RL Johnson D Case L Tessier-Lavigne M Huganir RL Ginty DD Kolodkin AL - Nature 462(7276):1065 (2009)
  The majority of excitatory synapses in the mammalian CNS (central nervous system) are formed on dendritic spines1, and spine morphology and distribution are critical for synaptic transmission2, 3, 4, 5, 6, synaptic integration and plasticity7. Here, we show that a secreted semaphorin, Sema3F, is a negative regulator of spine development and synaptic structure. Mice with null mutations in genes encoding Sema3F, and its holoreceptor components neuropilin-2 (Npn-2, also known as Nrp2) and plexin A3 (PlexA3, also known as Plxna3), exhibit increased dentate gyrus (DG) granule cell (GC) and cortical layer V pyramidal neuron spine number and size, and also aberrant spine distribution. Moreover, Sema3F promotes loss of spines and excitatory synapses in dissociated neurons in vitro, and in Npn-2-/- brain slices cortical layer V and DG GCs exhibit increased mEPSC (miniature excitatory postsynaptic current) frequency. In contrast, a distinct Sema3A–Npn-1/PlexA4 signalling casca! de controls basal dendritic arborization in layer V cortical neurons, but does not influence spine morphogenesis or distribution. These disparate effects of secreted semaphorins are reflected in the restricted dendritic localization of Npn-2 to apical dendrites and of Npn-1 (also known as Nrp1) to all dendrites of cortical pyramidal neurons. Therefore, Sema3F signalling controls spine distribution along select dendritic processes, and distinct secreted semaphorin signalling events orchestrate CNS connectivity through the differential control of spine morphogenesis, synapse formation, and the elaboration of dendritic morphology.
• Novel mutant-selective EGFR kinase inhibitors against EGFR T790M
  - Nature 462(7276):1070 (2009)
  The clinical efficacy of epidermal growth factor receptor (EGFR) kinase inhibitors in EGFR-mutant non-small-cell lung cancer (NSCLC) is limited by the development of drug-resistance mutations, including the gatekeeper T790M mutation1, 2, 3. Strategies targeting EGFR T790M with irreversible inhibitors have had limited success and are associated with toxicity due to concurrent inhibition of wild-type EGFR4, 5. All current EGFR inhibitors possess a structurally related quinazoline-based core scaffold and were identified as ATP-competitive inhibitors of wild-type EGFR. Here we identify a covalent pyrimidine EGFR inhibitor by screening an irreversible kinase inhibitor library specifically against EGFR T790M. These agents are 30- to 100-fold more potent against EGFR T790M, and up to 100-fold less potent against wild-type EGFR, than quinazoline-based EGFR inhibitors in vitro. They are also effective in murine models of lung cancer driven by EGFR T790M. Co-crystallization stud! ies reveal a structural basis for the increased potency and mutant selectivity of these agents. These mutant-selective irreversible EGFR kinase inhibitors may be clinically more effective and better tolerated than quinazoline-based inhibitors. Our findings demonstrate that functional pharmacological screens against clinically important mutant kinases represent a powerful strategy to identify new classes of mutant-selective kinase inhibitors.
• DNA nanomechanics allows direct digital detection of complementary DNA and microRNA targets
  Husale S Persson HH Sahin O - Nature 462(7276):1075 (2009)
  Techniques to detect and quantify DNA and RNA molecules in biological samples have had a central role in genomics research1, 2, 3. Over the past decade, several techniques have been developed to improve detection performance and reduce the cost of genetic analysis4, 5, 6, 7, 8, 9, 10. In particular, significant advances in label-free methods have been reported11, 12, 13, 14, 15, 16, 17. Yet detection of DNA molecules at concentrations below the femtomolar level requires amplified detection schemes1, 8. Here we report a unique nanomechanical response of hybridized DNA and RNA molecules that serves as an intrinsic molecular label. Nanomechanical measurements on a microarray surface have sufficient background signal rejection to allow direct detection and counting of hybridized molecules. The digital response of the sensor provides a large dynamic range that is critical for gene expression profiling. We have measured differential expressions of microRNAs in tumour samples! ; such measurements have been shown to help discriminate between the tissue origins of metastatic tumours18. Two hundred picograms of total RNA is found to be sufficient for this analysis. In addition, the limit of detection in pure samples is found to be one attomolar. These results suggest that nanomechanical read-out of microarrays promises attomolar-level sensitivity and large dynamic range for the analysis of gene expression, while eliminating biochemical manipulations, amplification and labelling.
• Rational design of a structural and functional nitric oxide reductase
  Yeung N Lin YW Gao YG Zhao X Russell BS Lei L Miner KD Robinson H Lu Y - Nature 462(7276):1079 (2009)
  Protein design provides a rigorous test of our knowledge about proteins and allows the creation of novel enzymes for biotechnological applications. Whereas progress has been made in designing proteins that mimic native proteins structurally1, 2, 3, it is more difficult to design functional proteins4, 5, 6, 7, 8. In comparison to recent successes in designing non-metalloproteins4, 6, 7, 9, 10, it is even more challenging to rationally design metalloproteins that reproduce both the structure and function of native metalloenzymes5, 8, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20. This is because protein metal-binding sites are much more varied than non-metal-containing sites, in terms of different metal ion oxidation states, preferred geometry and metal ion ligand donor sets. Because of their variability, it has been difficult to predict metal-binding site properties in silico, as many of the parameters, such as force fields, are ill-defined. Therefore, the successful design of! a structural and functional metalloprotein would greatly advance the field of protein design and our understanding of enzymes. Here we report a successful, rational design of a structural and functional model of a metalloprotein, nitric oxide reductase (NOR), by introducing three histidines and one glutamate, predicted as ligands in the active site of NOR, into the distal pocket of myoglobin. A crystal structure of the designed protein confirms that the minimized computer model contains a haem/non-haem FeB centre that is remarkably similar to that in the crystal structure. This designed protein also exhibits NO reduction activity, and so models both the structure and function of NOR, offering insight that the active site glutamate is required for both iron binding and activity. These results show that structural and functional metalloproteins can be rationally designed in silico.
• Divine diseases
  - Nature 462(7276):1088 (2009)
  An act of faith.