News this Week

Science  13 Nov 2009:
Vol. 326, Issue 5955, pp. 920
  1. Diplomacy

    U.S. Takes Steps to Use Science To Improve Ties to Muslim World

    1. Robert Koenig
    Islamic outreach.

    U.S. Secretary of State Hillary Clinton unveiled a new science initiative to the 57 Muslim-majority countries (below) during a trip to Morocco.

    CREDIT: JEAN BLONDIN/REUTERS/LANDOV

    In a surprise announcement, U.S. Secretary of State Hillary Clinton last week named three prominent scientists as special envoys to assess the potential for scientific partnerships with Muslim-majority countries. The move is the first concrete step in a broader U.S. effort to expand the role of science in diplomacy.

    Speaking in Morocco on 3 November, Clinton said the new envoys will help “to fulfill President Obama's mandate to foster scientific and technological collaboration” and to “develop the capacity to meet economic, social, and ecological challenges.” She announced the selection of Egyptian-born Ahmed H. Zewail, a chemistry Nobelist at the California Institute of Technology in Pasadena; Algerian-born Elias Zerhouni, a radiologist who stepped down last fall as director of the National Institutes of Health (NIH); and biochemist Bruce Alberts, former president of the U.S. National Academy of Sciences (NAS) and current editor-in-chief of Science. Clinton said that the State Department is also bolstering its scientific and environmental expertise at embassies around the world.

    Clinton's speech to the Forum for the Future, a group that fosters dialogue between countries in the region and industrialized nations, builds upon Obama's highly publicized 4 June speech at Cairo University that called for a “new beginning” in relations with the Muslim world. Within the scientific realm, the president also promised to establish at least three technology “centers of excellence” in the Middle East, North Africa, and Muslim-majority regions in Asia, an idea now under discussion by an interagency group.

    While these initiatives are aimed at the 57 Muslim-majority countries, officials at both the State Department and the White House told Science that the goal is to bolster the department's science capacity across the board. Assistant Secretary of State Kerri-Ann Jones, who directs the Bureau of Oceans and International Environmental and Scientific Affairs, says the department wants “to better engage science as part of our diplomacy.”

    CREDIT: (SOURCE) ORGANIZATION OF THE ISLAMIC CONFERENCE

    Pradeep Ramamurthy, senior director for global engagement at the National Security Council, says the envoys program and the expansion of science diplomats “reflects a broader, long-term commitment by this Administration to the role of S&T in global engagement.” A bill (S.838) to create such envoys cleared the Senate Foreign Relations Committee this spring, and its sponsor, Senator Richard Lugar (R–IN), praised the initial appointments and said that he “look[s] forward to more envoys that will be announced in the coming months.”

    The trio was selected from a list, drawn up by the White House Office of Science and Technology Policy and the State Department, of “illustrious scientists who have shown global leadership and the ability to build partnerships with excellent research institutes abroad,” Jones said. The National Academies helped winnow down the list, she said, and the final selection was made by Jones, White House science adviser John Holdren, and State Department science adviser Nina Fedoroff.

    Zewail, who earned his initial degrees at Egypt's Alexandria University, plans to travel to the Middle East next month to ask government officials and scientists “to help come up with a visionary road map of how to create new partnerships.” He has called for “scientopolitical” initiatives (Science, 12 September 2008, p. 1417) that focus on education and science to advance political and social goals.

    Zerhouni, a graduate of the University of Algiers Medical School, says, “We want to open doors that others cannot.” A senior adviser to the Johns Hopkins University School of Medicine and a senior fellow at the Bill and Melinda Gates Foundation, Zerhouni notes that “we've made great strides in ‘health diplomacy’ worldwide, and we hope to extend that success to science diplomacy.”

    As NAS president, Alberts helped create and co-chaired the InterAcademy Council in Amsterdam, an international organization of science academies that produces reports on major science, technological, and health issues. A strong advocate for increased international science cooperation, he has also been active in reforming science education in the United States and around the world.

    Arden Bement, director of the National Science Foundation, thinks the envoys initiative is a good concept but suggested adding an engineer to the list to help evaluate potential technology collaborations. “It is critically important to establish closer ties with Muslim-majority countries and to make use of science diplomacy to identify research areas of mutual interest,” says Bement, a nuclear engineer who led the U.S. delegation that attended this fall's opening ceremonies for the King Abdullah University of Science and Technology in Saudi Arabia (Science, 16 October, p. 354). Officials say they expect some future envoys to have backgrounds in engineering and the physical sciences.

    In the meantime, senior officials from the White House, State Department, U.S. Agency for International Development, and NIH are working to implement Obama's centers-of-excellence pledge. Options range from traditional “brick and mortar” institutes to virtual centers of excellence. “We're trying to figure out which models work best, where they should be located, and what their primary focus should be—such as water or energy or climate change,” says Ramamurthy. The new envoys will help to define the best foci for such centers.

    Zerhouni says improving the quality of science officers at embassies “is long overdue. There is a scarcity of S&T–capable diplomats around the world.” Jones says the department plans to increase the number of diplomats who focus primarily on science, the environment, and health. There are 42 full-time science and environmental officers at embassies and a dozen more at the 12 “regional hubs” around the world, including one in Jordan. They supervise other diplomats who devote part of their time to science issues.

    Last month, the White House followed up on yet another promise that Obama made in Cairo. The government's Overseas Private Investment Corp. (OPIC) has issued a call for proposals to manage one or more funds to promote the growth of technology in the Middle East, North Africa, and Asia. Depending on how much private capital is raised, OPIC would provide financing of between $25 million and $150 million.

  2. Philanthropy

    Wellcome Trust to Shift From Projects to People

    1. Jocelyn Kaiser

    Scientists often complain that they spend too much time chasing after their next grant and not enough time doing research. Now the Wellcome Trust, the giant biomedical research charity in the United Kingdom, wants to remove those constraints by giving no-strings-attached funding to nearly all the independent researchers it supports.

    This week, Wellcome officials announced that they are phasing out their biomedical research grants for U.K. scientists, which consists of 3-year to 5-year awards focused on a specific problem. Instead, starting in 2011, the organization will put that money, about 20% of its total budget, or $183 million, into a new program called Investigator Awards. The awards will be bigger, more flexible, and longer—up to 7 years.

    “The idea is to empower the very best scientists to tackle difficult, long-term questions,” says Wellcome Trust Director Mark Walport. Although the trust already provides this kind of support, including salaries, through fellowships, the new awards will expand this model to researchers who receive their salary from their institutions.

    The change puts the $21 billion Wellcome Trust in line with the policies of the smaller Howard Hughes Medical Institute (HHMI) in Chevy Chase, Maryland, to fund “people, not projects.” More than 350 Hughes investigators each receive $1 million a year (including overhead costs) for 5 years under the institute's major program to support research, and that support can be extended indefinitely. The U.S. National Institutes of Health supports nearly 200 researchers with similar programs it began a few years ago.

    Wellcome already offers fellowships that provide salaries and research funds for more than 500 independent researchers for 4 to 7 years. But the foundation also funds about 200 investigators a year with 3-year project grants that range from $250,000 to $500,000 in total. It awards another 45 or so program grants for up to $2 million over 5 years. Wellcome will hold one more competition next summer for these awards before taking applications in the fall for the new program.

    Cutting strings.

    The Wellcome Trust's Mark Walport hopes that phasing out project-based research grants will encourage creativity.

    CREDIT: WELLCOME IMAGES

    Whereas HHMI selects its investigators through paper applications, Walport says that, as with the fellows, Wellcome plans to interview candidates in person to “test their mettle.” Reviewers will focus less on paperwork and more on qualifications and the importance of the research. The trust hopes this interaction will create a “community of scientists,” says Walport. Researchers will remain free to seek grants from other sources as well.

    Walport declined to specify the annual funding level per investigator, noting that researchers will request what they need. But the total number of researchers supported is expected to be lower than the 245 or so now with project or program grants. (Although the grants may be smaller than HHMI's, investigators can also apply for supplemental grants for equipment, travel, and other expenses.) A subset of the new program will be reserved for early-career scientists.

    “I fully support the move,” says Paul Nurse, a British Nobel Prize–winner who is now president of Rockefeller University in New York City. “I think it's the most effective way to fund science.” Molecular biologist Angus Lamond of the University of Dundee in the United Kingdom, a Wellcome fellow and grants review panel chair, predicts that the reaction of U.K. scientists will be mixed. Dundee, who was not part of the decision, says it will be important for the trust to “listen to feedback” and address any problems that crop up.

  3. Pandemic Influenza

    Europe Reconsiders H1N1 Flu Shots for Children

    1. Martin Enserink*

    PARIS—On 27 October, the White House announced that President Barack Obama's daughters, Sasha and Malia, had received their shots against the H1N1 pandemic virus, at the same time that the vaccine became available to other children in Washington, D.C. No European leader has made a similar announcement, for a simple reason: Until recently, no European country had included healthy children in the priority groups targeted for vaccination. But as the outbreak gathers speed and more vaccine becomes available, some countries are now telling families that healthy children—or at least infants—are candidates for vaccination after all. The change of mind did not reassure a jittery public.

    In France, where vaccination has just begun, the government announced a plan this weekend to offer the vaccine to children from preschool through high school starting on 25 November. In the Netherlands, health minister Ab Klink promised on Monday to follow fresh advice from the Health Council to start vaccinating children between ages 6 months and 4 years as soon as possible. The United Kingdom is considering an expansion of its vaccination program as well but is awaiting scientific advice.

    Ouch.

    Irish 7-year-old Aoife Maher, who's in one of the risk groups, gets a swine flu shot. But Ireland is not yet vaccinating healthy children.

    CREDIT: PA PHOTOS/LANDOV

    How many European children will eventually be vaccinated remains to be seen, partly because distrust of the new vaccines is running high. In France, for instance, polls show that fewer than one in five people would take it, and even Jean-François Copé, leader of the ruling party in the National Assembly, has acknowledged having qualms. In Germany, prominent doctors have denounced pandemic hype that benefits big pharma. Amid the confusion, many parents may ignore the new advice to vaccinate children.

    Like the public response, the availability of vaccines varies widely. Some countries such as Norway and the Netherlands have erred on the side of caution by ordering two doses of vaccine for every resident—much more than they now think they will use. Spain, by contrast, has bought 37 million doses for more than 46 million people. Economic stragglers along the European Union's eastern flank have purchased none at all. But even those who had plenty did not at first include healthy children among the priority groups. “They have a very different outlook,” says Lone Simonsen, a Danish-born epidemiologist at George Washington University in Washington, D.C.

    That may seem strange, given the fact that the same epidemiological and clinical trial data prompted U.S. officials to recommend the vaccine for everyone from 6 months through 24 years of age. Their reasoning: The risk of severe disease, hospitalization, and death is the highest in these groups. But European experts tend to point out that the risk is still very small and has to be weighed against the small risk of serious side effects. “With pandemic vaccines, which are being developed in a relatively short amount of time and tested in a limited number of subjects, you've got to be extra-careful,” says André Knottnerus, chair of the Dutch Health Council. Until last week, his panel had recommended against vaccinating small children; the group changed course after experience in Australia and New Zealand suggested that pediatric intensive care units in Holland may be overwhelmed.

    One reason behind Europe's reticence is that, unlike the United States, it is using vaccines containing potency-enhancing compounds called adjuvants. Although one such vaccine for seasonal flu, Novartis's Fluad, has been on the market for over a decade, there's limited data on its safety in children. Experience with GlaxoSmithKline's adjuvanted pandemic vaccine, Pandemrix, is limited to just several tens of thousands of people.

    Experience with seasonal flu also helps explain the different responses, says Simonsen. Since 2002, the United States has vaccinated healthy children under 2 against seasonal flu, and since 2008 it has recommended the seasonal shot for anyone under 18. In Europe, only five countries, with a combined population of 15 million, recommend giving healthy children annual flu shots, and none of them beyond 6 years of age. As a result, protecting children against the pandemic was less obvious in Europe, she says.

    U.S. health officials have cited another benefit of vaccinating children: Studies have suggested that, because they contribute most to the spread of the disease, protecting them may offer some protection to the rest of the population as well (Science, 12 November 2004, p. 1123). But the evidence for this herd immunity effect is not very strong, says epidemiologist Arnold Monto of the University of Michigan School of Public Health in Ann Arbor, who calls it an “added bonus” at best. European countries generally did not find the argument persuasive, says Johannes Löwer, head of the Paul Ehrlich Institute, which is responsible for licensing vaccines in Germany.

    Whatever the reasoning, the jump in H1N1 cases in Europe over the past few weeks—and the deaths of some previously healthy people—has contributed to a changed view in several countries. In Germany, the Association of Pediatricians had strongly opposed vaccination of children under 3 but reversed itself last week in the face of increasing numbers of pediatric cases and growing confidence in the vaccine. “Everybody reads the same literature,” Monto says, “but when you have the disease in your own country, the impact is greater.”

    Another transatlantic contrast has emerged. The U.S. is satisfied with data from clinical trials indicating that one dose of unadjuvanted vaccine suffices for persons 10 years and older, a view endorsed by an expert panel at the World Health Organization. But the European Medicines Agency isn't sure yet, and most European countries are sticking to two doses for all age brackets for now. There's a certain irony in that, because European policymakers pride themselves on buying adjuvanted vaccine, which requires less antigen per shot, allowing for the production of more vaccines and a more equitable global distribution. By recommending two shots, they're hogging more of the precious resource than they had hoped.

    • * With reporting by Gretchen Vogel in Berlin.

  4. Russia

    Restructuring Physics Labs Brings Delight and Despair

    1. Andrey Allakhverdov* and
    2. Vladimir Pokrovsky*
    Old guard.

    Moscow's Kurchatov Institute was key to the Soviet nuclear weapon and energy programs.

    CREDIT: SERGEI RUBLIOV/WIKIMEDIA

    MOSCOW—Four of Russia's most prominent physics labs are to be merged into a new national research center. The institutes, which have languished in the post-Soviet era, have cautiously welcomed the raised profile the merger will bring. But a different reform aimed at separating basic and applied research at one of the institutes—the Kurchatov Institute in Moscow, Russia's premier lab for nuclear energy research—has researchers up in arms.

    The merger, announced in a presidential decree last month, will combine the Institute for High Energy Physics (IHEP) in Protvino, 100 kilometers south of Moscow; the B. P. Konstantinov Petersburg Nuclear Physics Institute (PNPI) in St. Petersburg; and two Moscow labs—the Institute for Theoretical and Experimental Physics (ITEP) and the Kurchatov. The reorganization is aimed at smoothing the path of innovations into industry, says Sergei Kiriyenko, chief of the nuclear energy agency Rosatom and one of the key officials behind the decree.

    ITEP and IHEP are currently managed by Rosatom, a state corporation created out of the Ministry of Atomic Energy. Many researchers felt uncomfortable as part of a body geared toward the energy industry. “For us and for IHEP, it has crucial significance. This is the way for us to get away from Rosatom's aegis,” says ITEP's Boris Ioffe.

    PNPI also sees a positive side to the merger. The institute, which is part of the Russian Academy of Sciences, is desperate to complete a reactor-based neutron source that began construction in 1976. “It was impossible with an academic budget,” says Ioffe, who hopes the prospects will be better in the combined center.

    Although Kurchatov researchers appear content with the merger plans, the ongoing internal restructuring has prompted dissent. The newspaper Troitsky Variant, published in the town of Troitsk near Moscow that is home to many physics institutes, ran a letter last month from 59 researchers in the Kurchatov's Nuclear Fusion Institute (NFI). The letter protested against splitting the institute into three parts, fusion, applied science, and production.

    “At the very least,” says NFI Director Valentin Smirnov, such a division, “would seriously complicate our part of work on the [international ITER fusion] project.” Those who signed the letter argued that the same specialists previously worked on fusion research and applied issues, which made the staff flexible and made it easier to hold onto highly qualified personnel when funding was scarce. Ksenia Razumova, who signed the letter, cites the example of two groups that used to work on plasma-wall interactions in tokamak fusion reactors. “As a result of the division, our group doesn't exist any longer: All the staff left for the national agency in charge of ITER. They now have highly paid managerial positions,” Razumova says.

    Although the merger of the four institutes is already in motion, some think it may flounder through lack of funding. “Financial plans for the coming year are already finalized, and they don't stipulate any merger,” says Nikolay Ponomarev-Stepnoy, honorary vice president of the Kurchatov Institute. “The plans for 2011 are being made at the moment, but even there it's impossible to envisage anything of this kind.”

    • * Allakhverdov and Pokrovsky are reporters in Moscow.

  5. ScienceInsider

    From the Science Policy Blog

    ScienceInsider explored why academic biomedical scientists report that they are receiving less corporate support for their research now than in the 1990s. Possible reasons for the shift include the 5-year doubling of the National Institutes of Health budget and a public debate over whether funding from drug companies can distort research results.

    The Dutch House of Representatives rejected a motion asking the government to sever all ties with virologist Albert Osterhaus of Erasmus Medical Center in Rotterdam, who had been accused of conflicts of interest in his role as a health adviser.

    The U.S. Senate rejected an attempt to strip funding for political science research out of the National Science Foundation's (NSF's) 2010 budget.

    A planned meeting in March of 150 scientists to discuss governance issues related to geoengineering drew praise but also some criticism from scientists who believe that some of the organizers are tainted by ties to companies with an interest in the technology.

    African science academies have released a joint report that suggests a 20% increase in the use of affordable medical interventions such as immunizations could save the lives of about 770,000 children and young mothers each year in nine countries in sub-Saharan Africa.

    U.S. Energy Secretary Steven Chu seems to have stretched the truth when he said that scientists at a DOE lab he once led had been wasting energy by forgetting to unplug equipment that hadn't been used in many years.

    Biofuels experts Tim Searchinger and John Sheehan debated whether biofuels could be carbon friendly in a six-part e-mail conversation.

    For more science policy news, visit blogs.sciencemag.org/scienceinsider.

  6. Climate Change

    No Sign Yet of Himalayan Meltdown, Indian Report Finds

    1. Pallava Bagla

    NEW DELHI—Are Himalayan glaciers beating a rapid retreat in the face of global warming? That would seem to be the case, according to a flurry of recent reports by BBC and other mass media. But the picture is more complex—and poses scientific puzzles, according to a review of satellite and ground measurements released by India's Ministry of Environment and Forests earlier this week.

    The report, by senior glaciologist Vijay Kumar Raina, formerly of the Geological Survey of India, seeks to correct a widely held misimpression based on measurements of a handful of glaciers: that India's 10,000 or so Himalayan glaciers are shrinking rapidly in response to climate change. That's not so, Raina says. Even if it were, other researchers argue that severe loss of ice mass would not entail drastic water shortages in the Indian heartland, as some fear. Both concerns were cited in the Asia chapter of the U.N. Intergovernmental Panel on Climate Change's (IPCC's) 2007 Working Group II report, which asserted that Himalayan glaciers “are receding faster than in any other part of the world and, if the present rate continues, the likelihood of them disappearing by the year 2035 and perhaps sooner is very high if the Earth keeps warming at the current rate.”

    Hanging tough.

    Gangotri glacier, source of the Ganges River, retreated a few dozen meters from 2004 to 2008—“hardly an abnormal retreat” that would have been expected from rising temperatures, states a provocative new report.

    CREDITS (TOP TO BOTTOM): IIT MUMBAI; ISHWAR SINGH (PROVIDED BY V. K. RAINA)

    Some glaciologists hew to IPCC's view, disputing Raina's conclusions. Any suggestion that the retreat of Himalayan glaciers has slowed is “unscientific,” charges Syed Iqbal Hasnain, a senior fellow at the Energy and Resources Institute in New Delhi. He says the Indian government has an “ostrichlike attitude in the face of impending apocalypse.”

    However, India's environment minister, Jairam Ramesh, told Science, “We don't need to write the epitaph for the glaciers, but we need a concentrated scientific and policy focus on the Himalayan ecosystem since the truth is incredibly complex.” India, he says, needs to measure and monitor Himalayan glaciers as a matter of national security.

    With ice and snowfields covering more than 30,000 square kilometers, the Himalayas are often called the “third pole.” Records that began in the 19th century show that most glaciers advanced through that century as the Little Ice Age that gripped the Northern Hemisphere tapered off. Glaciers began to retreat in the early 20th century. Since 1960, almost a fifth of the Indian Himalayas' ice coverage has disappeared, says Anil V. Kulkarni of the Space Applications Centre in Ahmedabad, who has mapped more than 1000 glaciers using satellite data.

    Raina's report, Himalayan Glaciers: A State-of-Art Review of Glacial Studies, Glacial Retreat and Climate Change, concurs with that assessment. But it questions a link to global warming. Findings in the past few years, it states, demonstrate that “many” Himalayan glaciers are stable or have advanced and that the rate of retreat for “many others” has slowed. The report does not enumerate glaciers in either category.

    The Raina report draws on published studies and unpublished findings from half a dozen Indian groups who have analyzed remote-sensing satellite data or conducted arduous surveys at remote sites often higher than 5000 meters. The report revises perceptions of a number of glaciers, including two iconic ones. For example, the 30-kilometer-long Gangotri glacier, source of the Ganges River, retreated an average of 22 meters a year and shed a total of 5% of its length from 1934 to 2003. But in 2004 and 2005, the retreat slowed to about 12 meters a year, and since September 2007 Gangotri has been “practically at a standstill,” according to Raina's report, which cites, among other observations, field measurements by ecologist Kireet Kumar of the G. B. Pant Institute of Himalayan Environment and Development in Almora. Even more stable is Siachin glacier in Kashmir, where Indian and Pakistani forces are stationed eyeball to eyeball at 6000 meters. Claims reported in the popular press that Siachin has shrunk as much as 50% are simply wrong, says Raina, whose report notes that the glacier has “not shown any remarkable retreat in the last 50 years.”

    Several Western experts who have conducted studies in the region agree with Raina's nuanced analysis—even if it clashes with IPCC's take on the Himalayas. The “extremely provocative” findings “are consistent with what I have learned independently,” says Jeffrey S. Kargel, a glaciologist at the University of Arizona, Tucson. Many glaciers in the Karakoram Mountains, which straddle India and Pakistan, have “stabilized or undergone an aggressive advance,” he says, citing new evidence gathered by a team led by Michael Bishop, a mountain geomorphologist at the University of Nebraska, Omaha. Kenneth Hewitt, a glaciologist at Wilfrid Laurier University in Waterloo, Canada, who just returned from an expedition to mountain K2, says he observed five glacier advances and a single retreat in the Karakoram. Such evidence “challenges the view that the upper Indus glaciers are ‘disappearing’ quickly and will be gone in 30 years,” Hewitt says. “There is no evidence to support this view and, indeed, rates of retreat have been less in the past 30 years than the previous 60 years,” he says.

    Why are many Himalayan glaciers bucking the trend of rapid retreat seen in the Alps, for example, or at Mount Kilimanjaro as reported in the Proceedings of the National Academy of Sciences last week? “Glaciers at lower elevations are going to respond faster to a warming climate than those at the highest elevations,” says Richard Armstrong, a glaciologist at the National Snow and Ice Data Center in Boulder, Colorado. Snowfall patterns are more important to Himalayan glacier stability than temperatures, adds Rajinder Kumar Ganjoo, a glaciologist at the University of Jammu in India. “If rising temperatures were the real cause for the retreat, then all ice masses across the Himalayas should be wasting away uniformly,” he says. “At issue in scientific circles,” Kargel notes, “is how lengthy the response time is, and how it varies among glaciers.”

    The bottom line is that IPCC's Himalaya assessment got it “horribly wrong,” asserts John “Jack” Shroder, a Himalayan glacier specialist at the University of Nebraska, Omaha. “They were too quick to jump to conclusions on too little data.” IPCC also erred in its forecast of the impact of glacier melting on water supply, claims Donald Alford, a Montana-based hydrologist who recently completed a water study for the World Bank. “Our data indicate the Ganges results primarily from monsoon rainfall, and until the monsoon fails completely, there will be a Ganges river, very similar to the present river.” Glacier melt contributes 3% to 4% of the Ganges's annual flow, says Kireet Kumar.

    Atmospheric scientist Murari Lal, chair of the Climate, Energy and Sustainable Development Analysis Centre in New Delhi and coordinating lead author of the 2007 IPCC report's Asia chapter, rejects the notion that IPCC was off the mark on Himalayan glaciers. But he acknowledges that the report's 10-author team relied on unpublished work when assessing the status of the glaciers. India's U.N. delegation had objected to the wording, Lal recalls, but in the IPCC plenary session the analysis got wide support.

    Raina's report is by no means the last word. The surprising stability of some glaciers may be a temporary phenomenon, says Hewitt: Melting may have been reduced by a change in summer weather, such as increased cloudiness, and possibly unusually heavy snowfall, he says. “There needs to be a lot of research on [Asia's] mountain glaciers,” adds glaciologist Lonnie G. Thompson of Ohio State University, Columbus. “Truly, we know less about them than any other place on Earth.” Both sides of the debate agree on one point: Forecasts hold little water, so only a robust observation campaign will reveal whether the third pole's resistance to climate change is durable—or ephemeral.

  7. Climate Change

    Could Glacier Research Help Thaw Himalayan Standoff?

    1. Pallava Bagla*

    NEW DELHI—On climate change policy, India and China are on the same page: They oppose mandatory carbon emissions reductions. But they don't see eye to eye on the Himalayas. Both countries claim a swath of the mountains as their own, a dispute that sparked a brief war in 1962. Because of lingering tensions, a diplomatic initiative to get Chinese and Indian scientists working together on glaciers has quietly been put on ice.

    Last August, officials from the Wadia Institute of Himalayan Geology in Dehradun, India, and the Cold and Arid Regions Environmental and Engineering Research Institute in Lanzhou, China, were preparing to ink an agreement in Beijing that would have paved the way for the sharing of glacier data and hosting of research exchanges. But the signing ceremony was nixed at the last minute. An Indian diplomat says the territorial dispute would have “led to limited ground access for the joint teams of researchers in the disputed regions.” A Chinese government official places the blame squarely on India: “Indian scientists can receive permits for research expeditions with Chinese colleagues [in the Tibetan Himalayas], but India refuses to allow Chinese scientists to join fieldwork in its territory,” he says.

    The impasse frustrates scientists. “Unless we combine data sets from both sides of the Himalayas, a holistic understanding of the ‘third pole’ will just not emerge,” says former Wadia Institute Director Baldev Raj Arora. He says both sides are now crafting a legal framework that would allow academic exchanges. Neither side will speculate on when an accord might be reached.

    • * With reporting by Richard Stone in Beijing.

  8. ScienceNOW.org

    From Science's Online Daily News Site

    Experts Criticize Nanoparticle Study The headlines are laced with fear. All of them seem to suggest that a new study has found that nanoscale materials, used in everything from medical imaging to cancer treatments, can damage genetic material in our bodies. But this particular study has little relevance to human exposure risks, experts say, and it is deeply flawed in other ways.

    More Support for Human Role in Chinese Quake When the Wenchuan earthquake killed some 80,000 people in southwest China in May of last year, suspicion immediately fell on the reservoir behind the nearby Zipingpu Dam. Seismologists knew that several hundred million tons of water had filled the reservoir in the preceding few years and that either the water itself or its weight might have weakened a nearby fault and unleashed the quake. A new analysis finds that both scenarios are plausible, but further insight will require the cooperation of the Chinese government.

    CREDIT: ORTHOPEDIC SPECIALTY HOSPITAL

    No Sprinting Advantage With Prosthetic Limbs In 2007, South African double-amputee sprinter Oscar Pistorius became the first disabled athlete to compete against able-bodied runners, placing seventh in the British Grand Prix. But his J-shaped, carbon-fiber prostheses, called the Össur Flex-Foot Cheetah, sparked a debate within the athletic world: Do the devices give him an unfairadvantage over able-bodied competitors? The answer, according to a new study of six amputee sprinters, is no.

    Don't Shush That Baby; It's Learning A newborn's cry is a call to action. “Quick, somebody help me!” But bawling babies are getting something else besides attention: language practice. A new study finds that, in the first few days of life, babies produce cries that mimic the melodies of their native language.

    Read the full postings, comments, and more on sciencenow.sciencemag.org.

  9. Climate Change

    Amid Worrisome Signs of Warming, 'Climate Fatigue' Sets In

    1. Richard A. Kerr

    As scientists debate whether climate is changing faster than anticipated, some worry that a drumbeat of dire warnings may be helping to erode U.S. public concerns about global warming.

    CREDIT: GAZIMAL/GETTY IMAGES

    Climate news seems to have been all bad since the Nobel Prize–winning Intergovernmental Panel on Climate Change (IPCC) came out with its fourth assessment in February 2007. Within months of the sober but disquieting report, Arctic summer sea ice coverage plunged to a dramatic new record low, prompting talk about catastrophic tipping points. Glaciologists watched as record meltwater on the Greenland ice plunged into chasms, slicking the bottoms of glaciers and sending them racing to the sea. Swelled by glacier losses both north and south, the sea had been rising as fast as IPCC's worst-case scenario predicted, researchers reported. Lacking ice to hunt on, gaunt polar bears roamed Arctic lands in search of food. And newly crunched numbers showed that greenhouse gas emissions had shot up in the previous 5 years to exceed IPCC's worst scenarios.

    “We are basically looking now at a future climate that is beyond anything that we've considered seriously,” ecologist and IPCC author Christopher Field of Stanford University in Palo Alto, California, said in February at the annual meeting of the American Association for the Advancement of Science (which publishes Science), according to a media report. In March, a meeting of 2000 climate scientists in Copenhagen prompted the headline “Projections of Climate Change Go From Bad to Worse, Scientists Report” (Science, 20 March, p. 1546).

    This September, the United Nations Environment Programme issued an IPCC-like report that, according to a UNEP press release, showed that “the pace and scale of climate change may now be outstripping even the most sobering predictions of the last report of the … IPCC.” In the foreword of the UNEP report, U.N. Secretary-General Ban Ki-moon delivered the intended takehome message: The report “is a wake-up call. The time for hesitation is over.” In the run-up to next month's climate summit in Copenhagen, some researchers have argued that the worsening prospects for Earth's climate system make the negotiations all the more urgent.

    Others, however, say the picture since the IPCC report is more complicated than that—though no brighter. “Things are looking much worse than was thought in the 1970s and '80s,” says climate scientist Stephen Schneider of Stanford University, who has been deeply involved in global climate issues since the 1970s. “But ‘much worse than IPCC 2007’ is only true for a few things.” And some anticipated climate changes are actually behind schedule, at least for the time being, notes the U.K. Meteorological Off ice's head of climate change advice, Vicky Pope. “It's at least as bad as expected,” she says. “I don't think it's worse.”

    Almost all climate scientists are of one mind about the threat of global warming: It's real, it's dangerous, and the world needs to take action immediately. But they disagree about the best way to convey the urgency of the situation to the public and policymakers. “Where do you go after ‘unequivocal’?” asks Roger Pielke Jr., a science policy scholar at the University of Colorado, Boulder, referring to the measure of certainty IPCC applied to its core findings in 2007. By sounding the alarm too loudly, Pielke and others say, scientific climate campaigners could be driving potentially sympathetic audiences to tune them out or could even provoke a backlash. Recent surveys in the United States show such “climate fatigue” may indeed be on the rise.

    A glass half-empty

    The UNEP report entitled Climate Change Science Compendium 2009 (www.unep.org/compendium2009) presents the latest and perhaps most comprehensive case for heightened climate concerns. It is not the exhaustively peer-reviewed consensus assessment of peer-reviewed literature that IPCC produces every 5 or 6 years, but UNEP did compile its report “in association with scientists around the world” as a review of “some 400 major scientific contributions … released through peer-reviewed literature or from research institutions over the last three years,” according to its press release.

    Burning brighter.

    The red denoting high risk has crept down to smaller warmings since 2001.

    SOURCE: J. B. SMITH ET AL./PNAS

    The UNEP update finds more sobering, even scarier, climate changes under way than IPCC did. The prime driver of global warming, emissions of carbon dioxide from burning fossil fuel, surged between 2000 and 2006, the report notes. The rate of emissions growth nearly tripled compared with the 1990s as economic growth surged, particularly in China and India. According to the report, that spurt has already contributed to a host of sooner-than-expected climate impacts, including “faster sea-level rise, ocean acidification, melting of Arctic sea-ice cover, warming of polar land masses, freshening in ocean currents, and shifts in circulation patterns in the atmosphere and the oceans.”

    The UNEP report also appears to update IPCC 2007 by citing an unofficial but peer-reviewed revision of IPCC 2001's “reasons for concern.” The 2001 assessment used a color-coded diagram to lay out the risk of five climate-change consequences expected for a range of possible future warmings. The risk of having more extreme-weather events, for example, was considered low at small warmings of 1°C or less (coded yellow at the bottom of a column), but it would be high (red at the top of a column) at large warmings of more than 3°C or 4°C (see figure).

    IPCC 2007 didn't update the “burning embers diagram.” But 15 climate scientists, including some of the 2001 IPCC authors, did so in a March 2009 paper in the Proceedings of the National Academy of Sciences (PNAS). Things now look worse in all five risk categories; the red of high risk has inched down to smaller warmings in each column. Several factors caused the reassessments, says PNAS author Gary Yohe of Wesleyan University in Middletown, Connecticut. After Hurricane Katrina struck in 2005, for example, the group realized that developing countries aren't the only ones at considerable risk of intensified coastal storms aggravated by rising sea level.

    Many climate scientists share the heightened sense of urgency. A group of 25 or so researchers has prepared a document “very similar in tone” to the UNEP report. They will deliver it in a press conference to attendees in Copenhagen next month, says long-time climate researcher Richard Somerville, a professor emeritus at Scripps Institution of Oceanography in San Diego, California, and an author of the report. “We're seeing things happen more rapidly” than IPCC 2007 anticipated, he says. “I think IPCC has done a very responsible job, but now we know more, and the trends are all in the wrong direction.” Especially worrying, Somerville says, is that greenhouse-gas emissions have increased faster than in IPCC's most pessimistic scenario, leaving even less time to rein them in before great harm is done. The world's ice also seems to be in particular trouble, threatening to raise sea level by a meter or more by the end of the century instead of the few tens of centimeters that IPCC projected.

    No more, no less concerned

    Amid the calls for action, other climate researchers—equally concerned but less vocal—are advising caution in interpreting recent trends. The departures from IPCC 2007, they say, are not that large, not that unexpected, or not that indicative of future trends. Accelerating emissions growth is a case in point, says economist James Edmonds of the Joint Global Change Research Institute in College Park, Maryland. The speedup of the past 5 to 10 years marked a spurt in the world economy. Soon, Edmonds says, “we're going to see the effects of the recession.” Such near-term fluctuations are a bad basis for forecasting far-future emissions, he says, and the IPCC scenarios were never intended to track them. Over the long term, however, “the trend is really clear: If there's no intervention, emissions are going to rise. Up, up, up is inconsistent with stabilization” of atmospheric greenhouse gases below dangerous levels, which is the stated goal of “every country on the face of the earth.”

    Most of UNEP's other “sooner-than-expected” climate effects—from ocean acidification to shifts in ocean circulation—have likewise failed to heighten concern among more guarded scientists. The lone exception, says glaciologist and IPCC author Richard Alley of Pennsylvania State University, University Park, is dwindling ice. The cryosphere—both floating sea ice and ice sheets on land—is reacting to the warming faster than IPCC projected, Alley says. In the Arctic, the 2007 report noted that some model projections had late-summer sea ice almost entirely disappearing “by the latter part of the 21st century.” Models and sea-ice specialists now point to summer sea ice being gone by about 2030 (Science, 27 March, p. 1655).

    On land, IPCC authors did recognize that losses from both the Greenland and West Antarctic ice sheets had picked up in recent years, owing in part to a surprising acceleration of glacier tongues draining ice to the sea (Science, 9 October, p. 217). But even with the observed accelerations factored in, IPCC projected that sea level would rise by only a few tenths of a meter by the end of the century. Subsequent analysis has suggested that the rise in sea level is running near the extreme high end of IPCC projections and could reach about a meter by century's end (Science, 8 June 2007, p. 1412).

    The UNEP report dwells in detail on such fast ice responses. But some researchers say that the plight of the ice—although serious—is old news and is symptomatic of deeper concerns. Pope, for one, sees Arctic sea ice decline as a combination of a long-term loss due to global warming and bursts of ice loss like 2007's that are due to natural, temporary changes such as wind shifts. The long-term threat was already obvious to IPCC authors, Pope says.

    Likewise, the recent faster rise in sea level fed by wasting ice sheets certainly concerns geoscientist Michael Oppenheimer of Princeton University, but he's long had a greater fear. “We still can't project sea-level rise,” he says. “That worries me.” A major problem is understanding how glaciers would behave in a warmer world—faster or slower than today's—and getting them to act that way in predictive models. Compounding the uncertainty is the slow response of kilometers-thick ice sheets to warming. Humans could put enough greenhouse gases in the atmosphere this century to guarantee that Greenland's ice will melt centuries from now, Oppenheimer says. The UNEP report discussed such irrevocable climate commitments, but they got little public attention.

    Declining concern.

    Gallup polls suggest that more Americans feel that the seriousness of global warming is exaggerated and fewer are worried about it.

    SOURCE: GALLUP INC.

    And finally, the new “burning embers” do indeed tell an ominous story, says Schneider, who was second author on the PNAS paper that presented the updated graph. But it is a story, he says, of which the IPCC 2007 was already largely aware.

    Unintended consequences?

    Why does it matter whether the bad news is old news or new? Climate scientists feel that they are speaking with two voices, one much louder than the other. That worries Arctic climate researcher John Walsh of the University of Alaska, Fairbanks. “We have a delicate task of conveying the seriousness of the situation without overselling it as a done deal. We have a [climate] process that comes in fits and spurts,” he says, referring to the big loss of summer sea ice in 2007 as well as recent losses from Greenland. “We have to be careful not to extrapolate” a short spurt far into the future. With all the attention given Arctic ice after the heavy 2007 loss, “I am a little concerned the imminence of rapid [Arctic] change is being oversold or the uncertainties aren't being conveyed,” he says.

    And Pielke wonders whether the louder, more insistent voice is the best one for the job. “One of the strengths of the IPCC is it can make a pretty solid claim to be a consensus process,” he says. “I'm a little bit leery of the process at [the meeting in] Copenhagen earlier this year and the UNEP effort. They don't have the same institutional legitimacy” as IPCC.

    Whether or not the public is hearing the right tone of voice from the right places, it doesn't seem to be getting the message anymore. Recent polling suggests that U.S. citizens, at least, are if anything less concerned about global warming than they were a few years ago. In polling at the end of September conducted by the Pew Research Center for the People and the Press, the proportion of Americans who “think there is solid evidence that the average temperature on earth has been getting warmer over the past few decades” dropped to 57% from 71% in April 2008, according to Pew pollsters. The proportion of the American public that views global warming as a very serious or somewhat serious problem dropped from 73% to 65%. And in a Gallup poll released in March, the proportion of Americans who believe that the seriousness of global warming is exaggerated hit 41%, a record high in the 12 years Gallup has asked that question.

    Apparently, anxious warnings of imminent climate crises are no longer getting through. Matthew Nisbet thinks he knows why. The political communications researcher at American University in Washington, D.C., says that “it's very difficult for any single [climate] event to break through competing issues and information.” For Americans, those issues now include two wars, a lurching economy, and health care reform.

    “Given the complexity of climate change,” Nisbet says, “any one event will be downplayed [by partisan critics]. I think the real long-term challenge is public education, to prepare people. What does it mean to be an American in an era of climate change?” Climate scientists need to refocus their message, he says, from the broad sweep of global warming to small regions such as New England and the Southwest and to immediate issues such as personal health. At the same time, new conduits to individuals need to be created to replace crumbling traditional media. A tall order.

  10. Cell Biology

    Internal Affairs

    1. Mitch Leslie

    Newly discovered cytoplasmic defenses called inflammasomes sound the alarm when pathogens penetrate our cells.

    Enemies within.

    Our cells' internal defenses keep busy warding off intruding pathogens.

    CREDIT: J. NEWFIELD/SCIENCE

    For many pathogens, the interior of the cell is a prime place to settle down and start a family. Once they sneak into our cells, bacteria can plunder nutrients and duck the immune system. Viral intruders gain access to the molecular machinery they need to replicate. No wonder, then, that myriad microbes, including the germs responsible for the world's biggest infectious killers—AIDS, tuberculosis, and malaria—barge into our cells.

    Our cells fight back against these intrusions, relying on a network of novel internal alarms that can trigger an infected cell to try to save itself, or to at least provoke the body to defend other cells. The ultimate goal is to ensure “the sanctity of the cytoplasm is preserved,” says immunologist Katherine Fitzgerald of the University of Massachusetts Medical School in Worcester. Although researchers have long known that cells attempt to repel invaders—for example, by blocking viral replication—over the past decade or so, scientists have discovered protections that are more elaborate and have a much broader impact than anyone suspected.

    To keep watch for internal intruders, a cell deploys a cytoplasmic surveillance system that parallels the one detecting menaces outside of its membrane. When infiltrating pathogens trip one of these alarms, the cell retaliates with measures that range from instigating inflammation to committing suicide in a way that alerts other cells to the threat. In turn, microbes have evolved a plethora of countermeasures to disrupt, deceive, and dodge these intracellular weapons.

    The medical importance of our cells' internal defenses goes beyond battling pathogens. Errant responses by these alarm systems underlie illnesses such as gout, Crohn's disease, which is a type of intestinal inflammation, and the lung deterioration provoked by asbestos. Some of what scientists have learned about the mechanisms of such diseases has already made it to the clinic: The discovery that faulty microbial receptors inside the cell are behind several rare but debilitating “fever syndromes” inspired a successful new treatment for those conditions. Researchers have been testing the same drug against gout. Furthermore, scientists have just realized that a chemical long used to boost the effectiveness of vaccines might work by activating one of the cell's internal tripwires. This insight could lead to the production of better, safer ingredients for future immunizations. “We lack vaccines for many infections,” says immunologist Russell Vance of the University of California, Berkeley, but understanding our cytoplasmic defenses “might help us trigger the right kind of immune responses to get protection.”

    Looking inward

    Many animal cells, especially immune sentinels such as dendritic cells and macrophages, scrutinize their surroundings with Toll-like receptors (TLRs), more than a dozen of which have been identified. These cell-surface proteins recognize specific conserved features of broad classes of microbes, so-called pathogen-associated molecular patterns (PAMPs). For example, the PAMP for TLR-5 is the protein flagellin, a component of the flagellum that propels many kinds of bacteria. When triggered, TLRs unleash the primary, or innate, immune response and also help guide the subsequent adaptive response from T and B cells, which rely on microbe-specific receptors.

    The study of plant defenses sparked the discovery that the cytoplasm of animal cells contains equivalents of TLRs. Plants detect invaders inside their cells with so-called resistance, or R, proteins (Science, 8 May, p. 744), and nearly a decade ago researchers began searching mammalian genome databases for analogs of these proteins. They found plenty. In animals, “there's an elaborate intracellular detection array, just like there's an elaborate extracellular array,” says immunopathologist Brad Cookson of the University of Washington (UW), Seattle. So far, the intracellular array in humans numbers more than 20 pathogen sensors called nucleotide-binding domain and leucine-rich repeat containing proteins (NLRs) that distinguish bacteria, parasites, and other interlopers. Other pathogen detectors within cells include at least three so-called RIG-I-like receptors, which check mainly for the genetic material—RNA or DNA—of viruses, and proteins called AIM2 and DAI, which scan for the DNA of microbial interlopers. Identifying these cytoplasmic molecules “gave us the tools to examine more rigorously the role of these mechanisms in host defense,” says immunopathologist Gabriel Nuñez of the University of Michigan, Ann Arbor, whose team was one of the first to demonstrate that an NLR could discern a pathogen.

    What the pathogen detectors actually sense is one of the field's biggest questions. Scientists have notched progress in understanding how particular intracellular receptors identify invaders. Like TLRs, some intracellular receptors bind PAMPs. RIG-I, for instance, homes in on viral RNA molecules, allowing it to spot killers such as HIV and the hepatitis C virus.

    A cellular trick expands the range of pathogens that RIG-I can detect, biochemist Zhijian Chen of the University of Texas Southwestern Medical Center at Dallas and colleagues reported in the 7 August issue of Cell. In a cell's nucleus, the enzyme RNA polymerase naturally makes an RNA copy of a gene, the first step in synthesizing the protein the gene encodes. Chen and colleagues found, however, that in the cytoplasm, RNA polymerase copies any stray DNA it encounters—which likely comes not from the cell but from a pathogen—into double-stranded RNA that RIG-I can recognize. This mechanism enables RIG-I to discern not only DNA-carrying viruses such as adenoviruses and the Epstein-Barr virus but also certain bacteria. “Cells have found a way to take advantage of the RIG-I pathway to sense DNA in the cytosol,” says Chen.

    Triggering the alarm.

    When the cytoplasmic sensor NLRP3 recognizes a pathogen (1), it sets off a chain of events that lead to inflammation. The activated sensor draws in more NLRP3 molecules and other kinds of proteins to form an inflammasome (2). After the enzyme caspase-1 (purple) switches on, it activates the cytokines IL-1β and IL-18 (3). The end result is the release of these inflammation-promoting molecules (4).

    CREDIT: J. NEWFIELD/SCIENCE

    Still, researchers remain in the dark about how most of the cytoplasmic receptors spot their microbial targets. A prime example is the intracellular protein NLRP3, which responds not only to bits of bacterial cell wall within the cytoplasm but also to stimuli as diverse as the monosodium urate crystals that torture gout patients and the industrial toxicants asbestos and silica (Science, 2 May 2008, p. 674). “You can't find a binding place on this protein for all these activators,” says biochemist Jürg Tschopp of the University of Lausanne in Switzerland.

    Undiscovered receptors might serve as the actual detectors of each stimulus, with NLRs functioning as their intermediaries, suggests biologist Ed Miao of UW Seattle. If so, a cell might have one internal sensor for monosodium urate, one for bacterial cell walls, and one for asbestos—all of which relay their status to NLRP3.

    Alternatively, says Vance, the triggers that activate NLRs might be internal cell changes that result from attack or from injury by toxicants such as asbestos. “Instead of sensing microbes or microbial products directly, it [the receptor] would sense some kind of damage that the microbe causes,” he suggests. An example of these “danger signals,” Tschopp says, is monosodium urate, which forms when dying cells discharge the metabolic waste product uric acid. If the danger signal mechanism is valid, researchers still need to explain how NLRs are able to respond to such diffuse activators. Tschopp suspects that the common trigger for NLRP3 is the reactive oxygen species that cells produce in their cytoplasm when under stress, such as when they attempt to swallow asbestos fibers or encounter monosodium urate.

    Gotcha—now what?

    Once a cell perceives an internal invasion, it has several options. The cell might attempt to destroy the interloper. For example, an assortment of bacteria and viruses can provoke autophagy, a “self-eating” mechanism in which cells envelop and digest part of their cytoplasm—and any microbes it contains. Infected cells can also call for help that may prevent other cells from succumbing to their fate. As Tschopp and colleagues discovered in 2002, activated NLRs can convene several kinds of cytoplasmic proteins to form what the scientists dubbed an inflammasome. Joining the NLRP3 inflammasome, for instance, are multiple copies of NLRP3, an adaptor protein called ASC, and an inactive form of the enzyme caspase-1. Non-NLR receptors such as AIM2 can also induce inflammasomes. These protein clusters appear to be crucial for immune defenses. Without them, mice die from what are normally nonlethal doses of influenza virus, researchers reported earlier this year.

    An inflammasome furnishes an editing platform where caspase-1 activates itself and then prunes and switches on the cytokines interleukin-1β (IL-1β) and IL-18, which the cell then releases. Both cytokines, but particularly IL-1β, are formidable pathogen-fighters, triggering inflammation and attracting other immune cells to battle. They can even draw in T and B lymphocytes, potentially unleashing the adaptive immune system on the invader. Although these responses may not save the infected cell, they can prevent other cells from falling victim.

    The multistep system for activating cytokines might seem baroque, but it makes sense from a safety perspective, says systems biologist Alan Aderem of UW Seattle. “The innate immune system is very dangerous,” he says. Inflammation helps stanch infection, but it also promotes many of our most deadly illnesses, including heart disease, Alzheimer's disease, cancer, and diabetes. Triggering cytokines through the inflammasome, rather than directly from an NLR, adds another safeguard against inappropriate inflammation, says Aderem.

    Hot and cold.

    In people with a rare condition called familial cold autoinflammatory syndrome, chilly temperatures trigger a rash, fever, and joint pain. A faulty inflammasome protein is the culprit.

    CREDITS (LEFT TO RIGHT): WIKIPEDIA; LESTER V. BERGMAN/CORBIS; WIKIPEDIA

    Stimulation of NLRs can even prompt cells to sacrifice themselves by committing suicide. “If they can't clear the pathogen and remain viable, they clear it by dying,” says microbiologist Craig Roy of Yale University. The most familiar kind of cell suicide—apoptosis—doesn't result in the release of cytokines or the immune system being alerted. But when certain NLRs detect intracellular invaders, they switch on caspase-1 in a manner that instigates the cell death program and the production of IL-1β and IL-18. Cookson and his then–grad student Molly Bergman dubbed this process pyroptosis: essentially, a fiery death. Not only does a pyroptotic cell pour out cytokines that spur inflammation and fever, but it also spills its insides, which also rouse the immune system. The combination sends out a stronger warning signal than cytokines alone. A further benefit is the elimination of “a ‘Trojan horse’ loaded with pathogenic invaders,” Cookson says.

    Cheaters do prosper

    Our survival depends on cytoplasmic defenses, and microbes' survival depends on evading them. Researchers have already compiled several examples of bacterial and viral chicanery. For example, Chen and colleagues have discovered that when RIG-I senses a viral invader, it transmits the alarm through MAVS, a protein they named in honor of their local pro basketball team, the Dallas Mavericks. Just as the Mavericks have the Los Angeles Lakers, MAVS also has its nemesis—an enzyme carried by the hepatitis C virus that snips the protein off at the base. This ability to cut the receptor's line of communication helps make the virus a killer, says Chen.

    Other microbes attempt to stymie intracellular defenses by defusing the inflammatory cytokine IL-1β or blocking activation of caspase-1. The tuberculosis bacterium prevents the inflammasome from switching on, researchers discovered last year, although they don't know how. To avoid being digested, the bacterium that causes Legionnaire's disease hinders autophagy, as microbiologist Michele Swanson of the University of Michigan, Ann Arbor, and colleagues have found.

    So far, the most important medical insight to emerge from research on NLRs involves the little-known fever syndromes, which affect about 500 people worldwide. Patients with familial cold autoinflammatory syndrome, for example, can develop a fever, skin rash, and joint pain after only a few minutes outside on a chilly day. The more severe Muckle-Wells syndrome often brings on kidney damage and deafness. About 10 years ago, researchers discovered that this disease family stems from different mutations in the NLRP3 gene. When Tschopp and colleagues discovered that NLRP3 spurs IL-1 production through the inflammasome, other researchers decided to treat patients with what was then a new drug, known as anakinra. This substance blocks the IL-1 receptor and was originally developed to soothe rheumatoid arthritis. It worked against the fever syndromes, and in 2007 the U.S. Food and Drug Administration approved it for that purpose. Nuñez describes this case as “a beautiful example” of how a basic science discovery can lead to a new treatment.

    But patients with these rare illnesses aren't the only ones who could benefit. Nearly half of people with Crohn's disease carry mutations in an NLR called NOD2. Scientists have yet to discover how faulty NOD2 foments the condition's intestinal agony; it may undermine intestinal protections against bacteria or provoke excess inflammation. Faulty internal defenses might even contribute to chronic diseases such as heart disease and diabetes that involve inflammation. “There's some evidence but no definitive studies,” Nuñez says. Nonetheless, researchers have reported that anakinra benefits patients with type 2 diabetes.

    Better vaccines will be another payoff from this field, several researchers predict. Vaccines contain additives called adjuvants that amplify the immune response. In the United States, the only approved adjuvant is aluminum hydroxide, or alum. Although alum can boost immunity, it can also trigger fever and other side effects. One obstacle blocking vaccine improvements is that researchers didn't know how alum tweaks the immune system. But some recent studies suggest that alum provokes the inflammasome. If so, researchers might be able to fine-tune adjuvants to induce a strong inflammasome response while provoking fewer side effects.

    Whether we will be able to manipulate cytoplasmic defenses for our benefit is unresolved. However, natural selection will keep tinkering with our internal defenses to ensure that our cells aren't hopelessly defeated for long. But in this evolutionary arms race, the microbes that want to settle inside our cells have the advantage, Roy says. “Because the bugs evolve faster, they are always going to stay a few steps ahead.”

  11. Fusion

    ITER Blueprints Near Completion, But Financial Hurdles Lie Ahead

    1. Daniel Clery

    As staff put finishing touches to the fusion project's final design, member governments mull over the latest cost estimates and prepare to raid piggybanks.

    Ready to roll.

    Ground is prepared at the ITER site in France. Cement mixers are due next spring.

    CREDIT: ITER ORGANIZATION

    CADARACHE, FRANCE—When diplomat Kaname Ikeda took the job of director-general of the ITER fusion reactor project in 2006, he quickly realized that he was building something literally from the ground up. “There was just a forest here when I started and six or seven people working,” he says. Now a large, if temporary, office building houses more than 400 staff members and another one is taking shape next door. Meters away, beyond a fence and up a bank, stretches a vast flat expanse of gravel, 1 kilometer long and 500 meters wide, made by slicing off the top of a hill. Next spring, this area—which ITER staff members jokingly liken to a huge terrain for pétanque, the game of bowls played in towns and villages across France—will be a bustling construction site as the world's largest scientific experiment takes shape. But for now, quiet expectation reigns.

    But this quiet is not a sign of inactivity. Inside headquarters, researchers are working feverishly toward one of the project's early milestones: completion of the Project Baseline, a complete description of the machine's scope, design, construction schedule, and cost. This set of documents, which runs to thousands of pages, will be presented for approval on 18 November to the ITER Council, representing the project's seven international partners: China, the European Union, India, Japan, South Korea, Russia, and the United States. The meeting will be a turning point for the project. “It's a bit like a starting pistol. It [the baseline] is a big framework on which to hang the work of the next 10 years,” says David Campbell, deputy head of ITER's fusion science and technology department. From the point of view of the project's paymasters, one part of the baseline will be subject to special scrutiny: the cost.

    ITER, or the International Thermonuclear Experimental Reactor, seeks to demonstrate that nuclear fusion—the power source of the sun and stars—can be tamed on Earth to generate electricity. In the 3 years since the partners formally agreed to work together on the project, its estimated cost has ballooned. Earlier underestimates, rising construction costs, and design and schedule changes aimed at reducing risks have landed the partners with bills substantially higher than they were expecting. Although all appear committed to the project, tough discussion is likely at this month's council meeting. “Everyone's concerned about cost containment,” says Campbell. “There's a tension between cost and time to completion, but if you move too fast you can get technical difficulties. You have to strike the right balance.”

    First milestone.

    Staff from ITER and French and European agencies celebrate the end of site preparation.

    CREDIT: ITER ORGANIZATION

    Plasma physicists have been working on the design of ITER since the mid-1980s. When the agreement was signed to set the ball rolling in 2006, the estimated cost was roughly €5 billion to build the reactor and another €5 billion to operate it for 20 years. Those figures, however, were based on a 5-year-old design drawn up before the site was decided (Cadarache was chosen in 2005) and when only three partners (the European Union, Japan, and Russia) were on board. In addition, fusion science had moved on since 2001, and researchers were itching to make changes to ensure that the project was a success.

    So even as the ink was drying on the ITER agreement, the seven partners called for a design review. “We asked the whole international community to say what their worries were” by filling out “issue cards,” says Campbell. By early 2007, researchers had registered about 500 issues. ITER staff and external experts were assembled into eight panels that worked through all the issues. Some problems required only minor tweaks and some could be discounted, Campbell says. By the end of 2007, the panels had whittled the number down to 13 major issues that needed more effort. “We spent another 6 to 12 months working on them. Some significant changes in design were needed,” Campbell says.

    One of the most significant changes was a new system to help control the plasma, a maelstrom of ionized hydrogen gas heated to 150 million degrees so that nuclei will have enough energy to smash together and fuse. But instabilities in the plasma called edge-localized modes (ELMs) act like quakes at the plasma boundary. They can make it bulge out unpredictably, damaging the wall of the doughnut-shaped reactor, known as a tokamak, or the divertor, a structure around the bottom of the reactor that extracts helium, the spent fuel of fusion. “ELMs have a devastating effect. A reliable mitigation technique would have tremendous value,” says Norbert Holtkamp, ITER's second in command and construction leader.

    ITER already had one system for combating ELMs: firing small pellets of frozen deuterium into the plasma at regular intervals to provoke small quakes, which do less damage and seem to suppress the larger ones. But researchers working with the U.S. tokamak DIII-D in San Diego, California, discovered that they could suppress ELMs with an extra magnetic field. So the review team modified the design to include magnetic coils for quelling ELMs behind the blanket tiles that line the inside of the reactor vessel.

    The blanket also came under scrutiny in the design review. It absorbs the heat and fast-moving neutrons flying out of the plasma once fusion is taking place, protecting components, and people, outside. It is made up of 440 tiles, most of them 4.6-tonne slabs of copper and steel measuring 1 meter by 1.5 meters. The plasma-facing side of the tiles is key. It must be tough enough to withstand the touch of plasma at 150 million degrees but also made of a material that won't pollute the plasma if it does get burned off. This “first wall” will be made of beryllium, but other materials may be tested later. The first wall of the divertor, which faces a higher heat load, will be carbon composite and tungsten. “We needed to review the heat loads and make corrections to the design,” says Gary Johnson, head of ITER's tokamak department.

    Heart of the matter.

    A cross section through the ITER tokamak (left) showing the vacuum vessel, blanket tiles, and the divertor at the bottom. A coil of prototype superconducting cable (above) is tested by engineers in Japan.

    CREDITS: ITER ORGANIZATION

    Another key change to come out of the design review was a requirement to test all of ITER's magnets at cryogenic temperatures. ITER uses 48 huge magnet coils to control the plasma. Each of the 18 toroidal field magnets, which loop through the center of the tokamak, weighs more than 360 tonnes, as much as a fully laden Boeing 747. The magnets are made of superconducting cable that works at about 4 kelvin. Thorough testing “can reduce the risk of installing a flawed device,” says Johnson, so new facilities will be built on site and elsewhere in Europe to test each magnet at low temperature.

    These and other changes resulting from the design review “have a major impact scientifically,” says Holtkamp, but they increase the project's cost by less than 15%. As work progressed, however, it emerged that the 2001 design had seriously underestimated the cost. And as staff continued refining the design and drawing up the project baseline, it soon became obvious that the planned construction and schedule was “too risky,” Holtkamp says. “Certain things needed to be added or adjusted to ensure the scientific goals were achieved.” But such changes would bring higher costs, delays, or both.

    The issue came to a head at the council meeting in June 2008 when the partners told ITER staff members that they had to get a better handle on costs and not let the start date slip. “We received clear guidance,” Holtkamp says. “Make a schedule to reach first plasma by 2018, quantify the risk, and report back.” At the same time, the council formed two independent panels to assess the work of the ITER organization: one looking at how costs are estimated and managed, the other at systems engineering and management.

    One reason for the uncertainty in ITER's cost is the way in which the reactor is constructed and paid for. The ITER organization does not have a large sum of money to buy all the parts. Instead, partner countries carve up the design and then each pays its own industries to make their share of the components and ship them to Cadarache. Hence ITER staff members control only 10% of the machine's cost; the rest comes as these in-kind contributions. As a result, ITER's true cost is very hard to pin down. The 2001 design had put a value on each component so they could be shared out fairly and then calculated an overall cost from those values. But “different countries [cost things] in different ways,” Campbell says, and the 2001 estimates have proved inaccurate. Because of the different systems in different parts of the world, “a simple addition of the cost in each country is an unfair representation of the cost of ITER,” Holtkamp says.

    Another factor pushing up the cost is the ITER collaboration's principle that all partners get an equal share in the knowledge of how to build the reactor. “Each member wants to learn how to make everything,” says Ikeda. So large items, such as the magnets and the vacuum vessel, are not built in one place but are divided between the partners. That approach seemed reasonable for three partners in 2001, but with seven partners economies of scale are lost. ITER staff members have negotiated some cost-saving rationalizations with relevant agencies in the seven partner countries, although Holtkamp emphasizes that the council has yet to approve them.

    Over the past year, as staff members continued to analyze the construction schedule, “it became clear we had to change something in the sequence of assembly. We had to take an approach that reduces risk for the project,” says Holtkamp. To reduce pressure on the schedule, ITER planners proposed firing up a stripped-down version of the reactor in 2018 without many components needed for later power-producing plasmas. “If something is wrong, it will be easier to repair,” says Holtkamp. “Once we know this is okay, we can install the rest.” Some 15% to 20% of components would be installed later, and the scheduled start date of 2026 for power production is little changed.

    In June, the council approved the new schedule, contingent on its approving the full baseline this month. The issue of cost still hangs heavy in the air. E.U. documents suggest it may need to fork out twice what was originally forecast. (The European Union, as host, must pay a 45% share of ITER's construction costs; the others pay 9% each.) A few months ago, “the E.U. had asked for a number of remedial measures for cost containment and improved management to be put in place. This is work in progress,” says E.U. research spokesperson Catherine Ray. “We need a realistic timetable, we need to be sure that we are basing our decisions on credible cost estimates, and we need to be sure that responsible organizations will be able to deliver on it.”

    “The fact that it will cost more is more or less accepted. Parties are carefully addressing how to handle the increase, such as through cost optimization,” says Ikeda, though he concedes that “some partners may be struggling.” “The partners want to understand the risk,” says Holtkamp. “All countries want to find a comfort level. Has [all our work] provided comfort? I hope so. We'll find out soon.”

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