News this Week

Science  03 Dec 2004:
Vol. 306, Issue 5702, pp. 1662
  1. U.S. SCIENCE BUDGET

    Science Agencies Caught in Postelection Spending Squeeze

    1. Andrew Lawler,
    2. Jeffrey Mervis*
    1. With reporting by Charles Seife, Jocelyn Kaiser, Constance Holden, and Yudhijit Bhattacharjee.

    An Administration determined to hold down spending in all but a handful of priority areas imposed its will on a lame-duck Congress shortly before the Thanksgiving holiday (Science, 26 November, p. 1453). The result was a turkey of a 2005 science budget for the majority of researchers—and the odds are that next year's menu will feature more of the same.

    Homeland security and defense research came away the big winners in the budget for the 2005 fiscal year, which began on 1 October, with NASA getting a last-minute boost and the Department of Energy's (DOE's) science programs doing surprisingly well. The National Science Foundation (NSF), on the other hand, took a cut despite promises of lofty growth, while the formerly high-flying National Institutes of Health (NIH) eked out a small increase for the second year in a row. Those spending decisions by Congress, wrapped into a massive omnibus appropriations bill (H.R. 4818), met the Bush Administration's goal of holding discretionary spending not related to defense and homeland security to a mere 1% rise over 2004. That squeezed most domestic programs, including nearly all basic research (see table; more details at aaas.org/spp/rd/approp05.htm). And it left individual legislators feeling powerless.

    “While I understand the need to make hard choices in the face of fiscal constraint, I do not see the wisdom in putting science funding far behind other priorities,” complained Representative Vernon Ehlers (R-MI), a former physicist and senior member of the House Science Committee, shortly before the House acted on 20 November. “Under protest I will vote for the bill. But my vote does not in any way represent my approval for the funding cuts to the NSF.”

    The Administration's support for national security was never in doubt. But its commitment to the moon-Mars exploration vision that the president outlined last winter (Science, 23 January, p. 444)—and ignored during the campaign—was a surprising twist to the budget finale. The White House pushed strongly for a significant budget boost for such exploration, according to congressional and Administration aides, and persuaded legislators to impose a 0.8% tax on all agencies to raise the extra money for NASA and a few other priorities. “We are really excited about it,” said Alphonso Diaz, the agency's new science chief, promising that the appropriation will lead to a “very robust science program.”

    View this table:

    That optimism glosses over the hidden costs NASA has accumulated since the beginning of the year, leaving the agency $1.4 billion in the hole for the current fiscal year. Congress directed NASA to spend $291 million of its $16.1 billion budget on servicing the Hubble Space Telescope, a cost not anticipated by the Administration. The cost of returning the space shuttle to orbit has risen by $762 million. Lawmakers also added more than $200 million for projects not requested by the president that benefit specific districts and states. “Somebody isn't going to get what they need,” says Lennard Fisk, an astrophysicist at the University of Michigan, Ann Arbor, who chairs the National Academies' Space Studies Board.

    The spending bill gives NASA Administrator Sean O'Keefe unprecedented power to move money between the agency's science and aeronautics accounts and the exploration portfolio, although Congress must approve his operating plan early next year. Many researchers fear that NASA's science program will bear the brunt of the inevitable cuts. That view is shared by the American Physical Society (APS), which released a report on 22 November warning that NASA's exploration plan could eat science's lunch. Congress is also worried and has asked NASA to have the National Academies conduct a thorough study of the plan's implications for science.

    Sitting at the other end of this year's spending seesaw is NSF, facing the biggest cut in its research budget in 35 years as part of a record $106 million reduction. The new budget is probably the death knell for a 2001 law that authorizes a 5-year doubling of NSF's budget, and it's already triggering some serious soul-searching at the agency. “This budget won't give us what we need, so we will have to figure out a way to live within our means,” says newly confirmed NSF Director Arden Bement, whose 9-month stint as acting director was converted into a full 6-year term by the Senate just before it left town on 21 November. Warren Washington, chair of NSF's oversight body the National Science Board, worries that “we may be reaching the point where some very good scientists are discouraged from even applying.”

    The legislators left Bement with some hard choices. One is whether to fund a new, $30 million round of science and technology centers now undergoing final review. Bement says he's inclined to support as many of the six planned centers as he can afford. At the same time, Bement says a $20 million workforce initiative that Congress has rejected 2 years running will be reworked to make its goals clearer, and a $10 million innovation fund that legislators nixed will be scrapped because NSF has other ways to support high-risk research.

    Two proposed starts—a high-energy physics experiment at Brookhaven National Laboratory in Upton, New York, and a renovated ocean drilling vessel—survived the budget squeeze, although at 50% and 40% of their requested amounts. “It's a dream come true,” says Michael Marx of Columbia University about Brookhaven's Rare Symmetry Violating Processes project. But a proposed ecological network received only planning and design money. The slowdown promises to clog NSF's pipeline of planned major construction. At the same time, legislators told the agency to spend $5 million to begin designing a $700 million, 30-meter segmented telescope that is still undergoing NSF review.

    CREDIT: PHOTOS.COM

    At NIH, the success rate for individual investigators is expected to dip in 2005 because the agency received only a 2% hike and needs more money to sustain existing research projects. Institute officials “had already expressed it would be a very difficult year, and [the final number] certainly doesn't help,” says David Moore, head of governmental relations for the Association of American Medical Colleges.

    The boost to DOE's Office of Science budget comes courtesy of the people heading the agency's two spending panels, Representative David Hobson (R-OH) and Senator Pete Domenici (R-NM). “They are very strong proponents of science, and there was a meeting of the minds on this bill,” says APS's Michael Lubell. Highlights include $10 million to start designing a facility for characterizing proteins and molecular tags at a site not yet chosen and $30 million more for the office of Advanced Scientific Computing Research. Legislators also encouraged DOE to proceed with a dark energy mission, a joint DOE-NASA project that could fall victim to impending cuts at NASA.

    Work on inertial confinement fusion—inducing a small pellet of heavy hydrogen to fuse by slamming it with lasers—received a $50 million boost, but lawmakers cut $25 million from the $4 billion National Ignition Facility at Lawrence Livermore National Laboratory in California, the prime U.S. inertial confinement lab, and asked for an outside study to determine whether the project is on the right track.

    The president's budget request for 2006, which he will submit to Congress in early February, is expected to continue this year's emphasis on science aimed at strengthening national security. The Administration is also expected to support continued planning for a Hubble rescue mission, which Congress said “should be one of NASA's highest priorities.” Conversely, NSF and NIH officials are bracing for tiny increases, at best. That won't be a new experience for Bement. For the past 3 years he's also been director of the National Institute of Standards and Technology (NIST), whose in-house research budget took a sharp hit in 2004 before rebounding this year. So he's diplomatic when asked about prospects for 2006. “We had hoped for better [in 2005]. And so did most people. But we'll keep trying.”

  2. The Omnibus Bill Isn't Only About Dollars

    1. Yudhijit Bhattacharjee,
    2. Constance Holden,
    3. Charles Seife,
    4. Jocelyn Kaiser

    The massive spending bill that each house of Congress adopted last month wasn't just a budget bill. It addressed many controversial issues, including the following science-related items:

    • H-1B visas: The omnibus bill allows the State Department to grant 20,000 additional H-1B visas every year to foreign nationals with a master's or a Ph.D. from a U.S. university. Business and academic organizations lobbied for the legislation after this year's quota of 65,000 H-1B visas—open to skilled foreign workers regardless of educational qualification—was reached on 1 October, the first day of the fiscal year. A previous cap of 195,000 expired in 2003. -Y.B.

    • Census: The American Community Survey, a streamlined form designed to provide continuously updated, neighborhood-level census data, has finally gotten the green light for the 2010 census. The survey is getting its 2005 request of $146 million, reversing a Senate vote to allocate only $65 million. “This was a do-or-die year,” says Census Bureau spokesperson Jefferson Taylor. “Without the money we would have had to begin preparations to go back to the long form.” -C.H.

    • Nuclear weapons: For the Department of Energy and the National Nuclear Security Agency, the big news is that there is no money for the so-called bunker buster warhead. Congress rejected the Administration's request for $27.6 million to design a weapon that could burrow meters into the ground—and told the White House that a $9 million bid for research on other new weapons should be used to make existing designs safer and more reliable. -C.S.

    • NIH management: The omnibus bill drops provisions added by the House of Representatives that would have barred funds for two psychology research grants opposed by conservatives and imposed a 50-person limit on NIH attendance at foreign meetings. The bill also tells NIH officials to consider all the comments on its proposal to increase public access to NIH-funded research papers and to provide Congress with a cost estimate. -J.K.

  3. TOXICOLOGY: Factory Study Shows Low Levels of Benzene Reduce Blood Cell Counts

    1. Erik Stokstad

    There's no doubt that benzene, a widely used industrial chemical, can be harmful. Workers highly exposed to benzene fumes, for example, run an increased risk of leukemia and bone-marrow toxicity. But the risk from smaller exposures is unclear. Now a tightly controlled study in Chinese factories, reported on page 1774, provides reason for concern: Workers who inhaled less than 1 part per million (ppm) of benzene—an exposure considered safe under U.S. occupational guidelines—had fewer white blood cells than did unexposed workers.

    Although the workers weren't sick, the results hint that low doses of benzene may alter the bone marrow and could lead to health problems, some experts say. The study also provides the first direct evidence in humans that benzene harms the progenitor cells that give rise to blood cells. “It really breaks new ground on the potential effects of low levels,” says toxicologist Bernard Goldstein of the University of Pittsburgh's School of Public Health.

    Hazard?

    A study of shoe workers in China suggests that even low doses of benzene affect blood cells.

    CREDIT: MICHAEL S. YAMASHITA/CORBIS

    Benzene is ubiquitous. People are commonly exposed to it from secondhand cigarette smoke, gasoline vapors, and air pollution, although typically only on the order of parts per billion. Studies of the chemical's health effects in industrial settings, where benzene is used as a solvent and in chemical manufacturing, led the United States in 1987 to regulate the maximum allowable workplace exposure at 1 ppm of benzene averaged over 8 hours.

    To determine whether blood cells are affected at even smaller exposures, a group of researchers from the U.S. National Cancer Institute (NCI) in Bethesda, Maryland, the Chinese Center for Disease Control and Prevention in Beijing, the University of California, Berkeley, and other institutions compared 250 workers exposed to benzene-laden glues in two shoe factories in China to 140 unexposed workers who sew clothes in other Chinese factories. The researchers carefully gauged benzene exposure by taking urine samples and testing air in the factories, as well as at each worker's home. After 16 months, they took blood samples from the workers.

    As expected, workers exposed to benzene at levels of 1 ppm and higher had fewer white blood cells, such as granulocytes and B cells, than did unexposed workers. But this also held true for the 109 workers exposed to less than 1 ppm benzene, even after controlling for smoking and other potential confounding factors. These workers had on average 15% to 18% fewer granulocytes and B cells than did unexposed workers—raising concerns about bone-marrow health, says Qing Lan of NCI.

    Luoping Zhang of the University of California, Berkeley, and others in the research team also studied the effect of benzene on the progenitor cells that give rise to blood cells. They found that the ability of progenitor cells to grow and multiply declined with higher exposures. “The key point is that high levels of benzene had a more toxic effect on the progenitor cells than on mature cells,” says study co-author Nathaniel Rothman of NCI. “That may suggest we're underestimating the effects of benzene by just studying mature cells.”

    But Richard Irons of the University of Colorado Health Sciences Center in Denver and Fudan University in Shanghai suggests that counting progenitor cells from blood samples probably does not accurately reflect what's happening to such cells in bone marrow. Irons, who leads a $20 million industry-funded study of benzene effects in Shanghai, also says it's possible that the low-dose changes seen in the Science paper stem from exposure to other chemicals or factors such as nutrition. “Because the magnitude of the changes are so small, it becomes difficult to discriminate between transient effects and benzene toxicity,” he says.

    Still, the findings may lead to demands for lowering the benzene exposure standard, says geneticist Gilbert Omenn of the University of Michigan Medical School in Ann Arbor: “This paper should cause a stir in occupational and environmental health circles.”

  4. LUNAR EXPLORATION

    India, China Vie for Best Look at the Moon

    1. Pallava Bagla

    UDAIPUR, INDIA—The new kids on the space block are having their own race to the moon. Last week, at an international meeting here* on lunar exploration, Chinese scientists presented details of the country's planned lunar orbiter mission, named Chang'e, to be launched sometime in 2007. Not to be outdone, Indian space officials revealed at the same time that they have added an impactor probe to the suite of instruments aboard Chandrayaan-1, which is headed to the moon the same year. The increased attention to Earth's closest neighbor is not lost on space scientists from other countries.

    Moonstruck.

    Wu Ji leads China's team that is building a 2007 lunar orbiter.

    CREDIT: PALLAVA BAGLA

    “It has all the makings of a new race,” says German high-energy physicist Horst Uwe Keller of the Max Planck Institute for Solar System Research in Katlenburg- Lindau, which hopes to build a payload for the Indian spacecraft. “And that's good. Healthy competition has never killed anybody.”

    The Chinese mission, the country's first outside Earth's orbit, hopes to put a 2-ton satellite into a 200-kilometer circular polar orbit for a year's worth of exploration. Its 150-kg scientific payload will include a stereo camera to map the terrain of the moon and a gamma and x-ray spectrometer to study its elemental and mineral composition, as well as instruments to measure solar winds and spot high-energy particles from deep space. The Chang'e mission will also carry a microwave radiometer to analyze the density, depth, and composition of the lunar soil, the first time such an instrument has been trained on the moon.

    There are no international partners on the Chang'e mission, which the Chinese government approved last year on an accelerated timetable. “We are in a real hurry and don't have time to get any foreign payloads,” says Wu Ji, executive director of the Center for Space Science and Applied Research in Beijing. China hopes to send a lander and a rover to the moon in 2012, adds Wu, who emphasized that there are no plans to place humans there. “It is out of the question,” he says.

    India has no plans for a human mission either, Madhavan Nair, chair of the Indian Space Research Organization in Bangalore, told Science. But it is expanding its robotic observations. Nair announced that Chandrayaan-1 will now include a 30-kg probe to penetrate the lunar surface. He called the probe a necessary step in preparing for a proposed soft landing and lunar rover mission by 2015. “We do not want to lag behind,” he says.

    • *International Conference on Exploration and Utilization of the Moon, Udaipur, Rajastan, 22–26 November.

  5. CELL BIOLOGY

    Long-Term Stress May Chip Away at the Ends of Chromosomes

    1. Constance Holden

    We all know stress makes you haggard and causes you to lose your hair. Now comes even more depressing news: Stress may also rob you of DNA. In a report published online this week in the Proceedings of the National Academy of Sciences, investigators conclude that the harried mothers of chronically ill children show more cellular aging, as evidenced by shortened chromosomal tips, than do mothers of healthy children.

    There is already abundant evidence that long-term stress leads to poor health and reduced immune activity. To delve further into this connection, researchers led by Elissa Epel of the University of California, San Francisco, compared the stress levels and telomeres of 39 mothers of chronically ill children with those of 19 mothers with healthy children. Telomeres, complexes of DNA and protein that cap the ends of chromosomes like the tips of shoelaces, typically shorten with every cell replication and thus can serve as markers of the biological age of most cells.

    The scientists gave each mother a questionnaire to assess her level of psychological stress over the preceding month and examined blood samples to determine telomere lengths and measure the activity of telomerase, the enzyme that maintains the telomeres. To assess oxidative stress, a process destructive to cells that is caused by unstable free-radical molecules, the researchers also took urine samples from each mom and measured levels of compounds associated with oxidation.

    When divided into groups based on their questionnaire answers, the women with the highest perceived stress, which included some with healthy children, had shorter telomeres than less-stressed women. And within the caregiving group, the older the ill child—and therefore the longer the period of high-stress mothering—the lower the telomerase activity, the greater the oxidative stress, and the shorter the mothers' telomeres. This result persisted independent of age and body mass index. In the highest-stress group, this meant a loss of about 550 base pairs from the mothers' telomeres. Based on the telomere clock, the researchers estimate that the white blood cells of the high-stress mothers had aged 9 to 17 years more than the cells of the low-stress group of the same chronological age.

    The scientists say oxidative stress is the most likely mechanism for translating a harried life into shortened telomeres. It has already been demonstrated that chronic activation of stress hormones generates oxidative stress, and that such stress can shorten telomeres in vitro.

    Stress researcher Janice Kiecolt-Glaser of Ohio State University in Columbus notes that the study shows that stress, which has already been shown to prematurely weaken the immune response, contributes to “cellular aging more broadly … [and] suggests that major deleterious effects of stress may in fact be far worse for younger adults than previously thought.” Cell biologist Jerry Shay of the University of Texas Southwestern Medical Center in Dallas adds that it would be interesting to see if telomere lengths “bounce back” when the stressful situation ends.

  6. GENETIC DIVERSITY

    Consortium Hopes to Map Human History in Asia

    1. Dennis Normile

    TOKYO—Researchers from 11 Asian countries and regions have forged a landmark agreement to study genetic diversity throughout Asia. Describing their goal as a “genetic map of human history in Asia,” they intend to collect blood samples from their populations and analyze them for single nucleotide polymorphisms (SNPs)—sites where a single nucleotide in the genome sequence varies from one individual to another. In addition to hinting at the patterns of migration and settlement throughout the continent, the map could be a step toward identifying genetic characteristics associated with certain diseases.

    “We are aware that scientifically, the impact of this work may be considered by some as incremental. But we are convinced that this heralds the rise of Asian biosciences,” says Edison Liu, executive director of the Genome Institute of Singapore and one of the key organizers of the effort.

    On track.

    Singapore's Edison Liu hopes that SNPs will explain Asian migration patterns.

    CREDIT: GENOME INSTITUTE OF SINGAPORE

    The Pacific Pan-Asian SNP Initiative was formally adopted on 18 November by scientists from institutions based in China, India, Indonesia, Japan, Korea, Malaysia, Nepal, Philippines, Singapore, Thailand, and Taiwan. “This is very much a grassroots effort,” says Yoshiyuki Sakaki, director of the RIKEN Genomic Sciences Center in Yokohama, Japan, and president of the Pacific branch of the Human Genome Organization, which sponsored the meeting in Singapore. Organizers estimate the project could take more than 2 years and cost up to $3 million.

    Scientists in the consortium hope to collect a total of 2600 samples, including between 20 and 100 samples from each ethnic group. Liu says one challenge will be defining “ethnic group.” China has 50 recognized minorities, and Indonesia and India claim to have hundreds. Sakaki says the total should be enough to outline the extent of genetic diversity and similarity throughout Asia, data that should clarify relationships among ethnic groups and suggest how and when successive waves of human ancestors populated the region. Future genomic medicine studies, he says, could answer questions about why some populations seem predisposed to certain diseases or react differently to certain drugs.

    All data will be put in an open database, and Liu says the group is amenable to cooperating with other efforts such as the International HapMap Project, which is developing a database of genes associated with diseases and drug responses, although there have been no official contacts as yet. Affymetrix Inc. in Santa Clara, California, will be providing at reduced cost new microarrays that allow researchers to probe 50,000 SNPs in each sample. The initiative will rely on a set of previously defined SNPs whose frequencies are already known to be highly divergent among populations.

    Institutions in Japan, Singapore, China, and Korea are likely to provide technical and scientific training for scientists in less-developed countries if sufficient funding can be found. “For us in Indonesia, the benefit is that we can access state-of-the-art technology which is currently out of reach,” says Sangkot Marzuki, head of the Eijkman Institute for Molecular Biology in Jakarta. Liu says the group is still looking for collaborators from Laos, Burma, Cambodia, and Mongolia.

    Researchers at institutes without the capacity to prepare and analyze the microarrays may have to reconcile their work with local regulations prohibiting the export of DNA materials. One possibility may be to prepare the DNA for chip hybridization while rendering the sample unusable for further research before shipping. Another is that participating scientists may be able to hand deliver samples to one of the technology centers, collaborate in the typing, and then bring the remaining materials back home. Liu says they are still investigating whether these approaches will be accepted by authorities.

    Despite these obstacles, and a modest budget, Liu hopes the SNPs consortium is a forerunner of larger collaborations. “It's a good time for us in Asia to take the first steps toward working together as colleagues,” he says.

  7. ITER

    Cadarache: More Than Just a Candidate Site

    1. Daniel Clery*
    1. With reporting from Dennis Normile in Tokyo.

    CAMBRIDGE, U.K.—Government ministers from the 25 European Union (E.U.) countries declared last week that they want to keep negotiating with the other five partners in the international effort to build a $6 billion fusion reactor. But the one thing that is not up for negotiation, they say, is the site.

    That message was contained in the new instructions they gave to the European Commission, the E.U.'s executive arm: It declared that the southern French town of Cadarache is no longer Europe's candidate site for the International Thermonuclear Experimental Reactor (ITER), but instead it is the site. The six ITER partners have been arguing for a year over whether to locate the reactor in Japan or France. All that remains to be decided, E.U. leaders say, is how many of the six partners will remain on board.

    Here we stand.

    E.U. ministers expect ITER to be built at this site in Cadarache, France.

    CREDIT: CEA CADARACHE

    Scientists hope ITER will show that fusing deuterium and tritium in a sustained reaction can produce more power than the reactor consumes and so form a viable new source of energy. An international consortium spent nearly 15 years designing ITER, but the current partners—China, the E.U., Japan, Korea, Russia, and the United States—are divided on whether to build at Cadarache or at the Japanese site at Rokkasho.

    The statement that came out of last week's council of ministers seemed less confrontational than other recent comments. After a council meeting in September, observers hinted that the E.U. was ready to press ahead without an agreement (Science, 1 October, p. 26). And when E.U. officials suggested that Japan was ready to concede before a meeting of ITER partners last month, Japanese negotiators were furious (Science, 19 November, p. 1271). E.U. officials “misread the signs coming from Japan,” says a senior European fusion researcher. As a result, last week's statement did not mention ultimatums or deadlines but instead called for a project involving “all six parties currently negotiating.”

    This more diplomatic stance won praise from the Japanese. “We appreciate that [the E.U.] now reaffirmed the importance of the six-party framework. There is no mention of unilateral action; that is quite good,” says Satoru Ohtake, head of the Office of Fusion Energy at Japan's Ministry of Education, Culture, Sports, Science, and Technology.

    The ministers showed no flexibility, however, on the site. In return for Cadarache, they offered Japan the role of “privileged partner,” meaning that Japan would receive more than its share of industrial contracts for ITER components and could choose the ITER director general and have its pick of the extra facilities that have been bolted onto the project to speed the transition to commercial power generation. This could include a materials testing center, a supercomputer lab for fusion simulations, or a beefing up of Japan's own JT-60 fusion reactor.

    Members of the European fusion community argue that Cadarache has a clear advantage on scientific grounds. They note that Europe is home to the world's largest fusion reactor, the Joint European Torus near Oxford, U.K., and that it has the largest fusion research program in the world, equal to that of the United States and Japan put together. The decision may be overdue, but for the sake of decorum, the E.U. ministers seem prepared to wait a little while longer.

  8. SCIENCE POLICY

    Europe Advances a Plan for Merit-Based Funding

    1. Martin Enserink

    PARIS—The European Research Council (ERC)—a new funding agency that would support basic research based solely on quality—inched closer to reality at a meeting of the European Union's (E.U.'s) science, education, and industry ministers in Brussels last week. All but two of the E.U.'s 25 member countries support the idea and have asked the European Commission to work out a proposal.

    The ERC, a brainchild of Europe's scientific organizations, has quickly gained popularity over the past 2 years among researchers and politicians alike. It would be created as part of Framework Programme 7, the E.U.'s science funding round for the period 2007–10. In early November, it got a new high-level nod of approval from an expert group led by former Dutch prime minister Wim Kok; his panel backed the ERC in a report about the lack of progress on the Lisbon strategy, Europe's plan to reinvigorate its economy.

    The Dutch government, which currently holds the rotating presidency of the E.U., had hoped that last week's meeting of the council of ministers would result in a formal invitation to the European Commission to come up with a plan. But Italy and Poland refused to go along. The Italian government objected to the ERC, as it explained in an earlier statement, in part because the agency's merit reviews might lead to some grants being awarded to groups from just one country, which Italy says violates E.U. principles. Poland, for its part, is worried that it may lose out in the competition for ERC funds. The lack of unanimity was “quite disappointing,” says Peter Nijkamp, head of the Netherlands Organisation for Scientific Research, who, along with the Dutch government, had invested a lot of time trying to win over the Italian government.

    But Jose Mariano Gago, who chairs the Initiative for Science in Europe, a lobby group created to promote the ERC, says unanimity at this point would be too much to expect; he says he's very pleased with the outcome. The meeting's conclusions, although not shared by all, send a “strong positive message,” he says, adding that European Commissioner Janez Potoc?nik now knows he has the backing of the vast majority of countries to come up with a plan.

    Meanwhile, the Italian government has come under attack from its own scientists for opposing the ERC. The Italian Academy of Sciences issued a position paper supporting the ERC last month, pointing out that it had not been consulted on the matter and calling the government's position “dangerous for the prestige of the Italian scientists in Europe.” In addition, more than 2200 scientists have signed an online petition in favor of the ERC launched by an association of young researchers.

  9. Revisiting the Bhopal Tragedy

    1. Charlene Crabb*
    1. Charlene Crabb is a science writer in Paris. With reporting by Pallava Bagla.

    Twenty years after the event, researchers are returning to the site of the world's worst chemical spill to pick up health studies that some believe were set aside too soon

    BHOPAL, INDIA—Ashraf lies on a corner bed in the ophthalmology ward of the Bhopal Memorial Hospital and Research Centre (BMHRC), a thick, white bandage covering his left eye. For the second time in 3 years, the 38-year-old is recuperating from cataract surgery. His sight has not been the same since the night 20 years ago when water entered a storage tank filled with methyl isocyanate (MIC) at a pesticide factory here, triggering a runaway reaction that sent a lethal cloud of chemicals wafting through his neighborhood. The vapors attacked his eyes, which led to a severe infection that gave way to chronic tearing and gradually, cataract-clouded vision. The gases also ravaged Ashraf's lungs, and today he suffers from chronic breathlessness and fatigue.

    CREDIT: PALLAVA BAGLA

    Like thousands of survivors, Ashraf has turned to the BMHRC medical staff for help with the injuries he received in the world's worst chemical accident. More than half a million people claim to have been exposed to the MIC-derived cloud on the night of 2 to 3 December 1984. At least 3000 men, women, and children died from breathing the lethal gases. And now at least 5000 survivors line up every day outside clinics and hospitals here to be treated for gas-related illnesses.

    Despite a flurry of studies in the 1980s documenting the initial effects of MIC exposure, scientific follow-up has waned. An ambitious long-term monitoring effort led by the New Delhi-based Indian Council of Medical Research (ICMR) ended in 1994 when the council abruptly pulled the plug. ICMR handed oversight of its cohort of 80,021 gas victims and 15,931 nonaffected Bhopal residents to the Madhya Pradesh state government, which still keeps tabs on the original ICMR cohort, now numbering about 50,000 people, through the Centre for Rehabilitation Studies (CRS).

    Aftermath.

    Protests mark the 20th anniversary of a gas leak that has been blamed for chronic ailments such as lung disease.

    CREDIT: PALLAVA BAGLA

    ICMR has never fully discussed why it removed itself from the gas tragedy. But some scientists speculate that the government, eager to modernize India's economy, was concerned that tallying up the health consequences too aggressively would scare away foreign investment. Many still bemoan ICMR's decision. It was “ridiculous,” says Nalok Banerjee, research officer at CRS. “The state government has no specific expertise in designing studies.”

    Confounding matters, the Indian government in 1985 filed a civil suit against the Union Carbide Corp. in the United States—parent of the firm that owned and ran the plant—and imposed restrictions on publishing data on the Bhopal incident, deeming some details too sensitive to be released. The legal wrangling dragged on for 6 years, and subsequent disaster-related lawsuits are still in the courts. “Unfortunately, a lot of research never got published because the scientists retired, or moved on, or lost interest,” says Indraneel Mittra, director general of BMHRC.

    In May, ICMR published the first of three promised technical reports on the investigations it carried out through 1994. Checking the data was slow and difficult work, says immunologist Nirmal Kumar Ganguly, director general of ICMR, who adds, “It took a long time for the government to give clearance for publication.”

    The 117-page document describes the findings of some 20 epidemiological studies, noting that death, miscarriage, and general morbidity rates were higher in exposed areas in the decade following the gas leak. Most long-term complications involved the eyes and lungs, but the report gives few specifics. “After 20 years they should have come out with some complete results,” says Bhopal oncologist Shyam Agrawal, a member of a new Indian Supreme Court-appointed advisory panel for the gas victims. More details may be elucidated in the next several months when the technical reports on ICMR's toxicological and clinical studies are published.

    Researchers in India and North America are poised to conduct a handful of studies that could shed new light on the Bhopal tragedy and its health consequences. Although not lavishly funded, they cover topics from the biology of lung surfactants to the MIC gas cloud.

    Picking up the pieces

    BMHRC in a perverse way owes its very existence to the gas leak. The medical complex opened 4 years ago and is operated with interest accrued from about $20 million from the sale of Union Carbide's 50.9% stake in the Indian subsidiary that ran the infamous pesticide plant. Recently, the hospital trust's board members earmarked $1 million to develop research facilities, and in August, they okayed the start-up next year of an epidemiology and biostatistics department. The department will study the 270,000 gas victims registered at the hospital and its eight outreach clinics. Because each patient is issued a memory chip-equipped “smart card,” the potential new cohort is fully enumerated, identified, and easy to track—a situation found nowhere else in India or any other developing country, says Mittra: “It gives us a unique opportunity to do first-class epidemiological studies, whether gas-related or not.”

    Other BMHRC research teams set up shop earlier this year. One group plans to delve into the anomalies in lung surfactants of gas victims. Pulmonary surfactant is a lubricant packed with proteins and phospholipids that fights off respiratory pathogens and aids breathing by keeping a low surface tension in the lungs' tiny air sacs, or alveoli. The researchers will compare the levels of various phospholipids and proteins in exposed and nonexposed patients suffering from chronic obstructive pulmonary disease, pulmonary fibrosis, bronchial asthma, and pulmonary tuberculosis. Once an internal board approves the $45,000 project, BMHRC will provide start-up funds.

    Heavy toll.

    Researchers are planning health studies of those living near the ruins of the pesticide plant.

    CREDIT: PALLAVA BAGLA

    Another BMHRC research group aims to use new molecular technology to look for genetic mutations that MIC, a suspected mutagen, or other chemicals in the gas cloud may have triggered in gas victims and their children. Studies conducted in the 1980s detected alterations in the chromosomes of some gas victims. More recently, cytogeneticist Narayanan Ganesh of the Jawaharlal Nehru Cancer Hospital and Research Centre, has noted birth defects such as syndactyly—fused or webbed fingers or toes—and pigeon chest among the offspring of people who were exposed to the lethal cloud. The new research team is awaiting approval to revisit these findings.

    The health of young adults who were exposed in utero to the gas is the focus of a $75,000 study getting under way at the comparatively cramped offices of the Sambhavna Trust Clinic, just west of the derelict pesticide factory. Community health workers are tracking down almost 400 children born to women who were pregnant at the time of the gas leak and participated in a 1985 study led by Daya Varma of McGill University in Montreal, Canada. That study, published 2 years later in Environmental Health Perspectives, found that 43.8% of 865 pregnancies in 3270 families ended in miscarriages. The current project, which Varma is also heading and which is being funded by the Canadian Institutes of Health Research, will analyze the health problems of the young people and measure various physical parameters. It builds on work, reported by the team last October in the Journal of the American Medical Association, which found growth retardation in young boys, but not young girls, who were exposed to the gas in the womb or as toddlers.

    Ramana Dhara, a specialist in occupational and environmental medicine at Emory University in Atlanta, Georgia, hopes to determine what toxins were unleashed that night by recreating the runaway reaction at the U.S. Department of Energy's (DOE's) hazardous materials test site in Nevada. If that study gets funded—it's couched in terms of emergency preparedness for a terrorist attack—scientists at DOE's Frenchman Flats facility will add water to a tank of MIC and monitor the resultant gas cloud. Early autopsy studies as well as analyses of the gooey residue left in the Bhopal storage tank found about two dozen chemical constituents. “But we still don't know exactly what compounds were in the cloud itself,” Dhara says.

    By determining the cloud's contents, Dhara and his colleagues could answer one of the more acrimonious debates that raged for months after the tragedy: whether victims should have been treated with sodium thiosulfate, an antidote for cyanide poisoning. In the days immediately after the leak, there was no information about the toxicity of MIC nor what chemicals could result from its pyrolysis and their toxicities. Doctors suspected that the color of the lungs—“cherry red”—was due to hydrogen cyanide, which binds to hemoglobin and blocks its ability to transport oxygen. A study of 20 gas victims given the antidote found a reduction in symptoms and an increased excretion of thiocyanate in urine, evidence to some that cyanide was present and that the treatment was helping people. But the medical community soon split over the efficacy of administering sodium thiosulfate, saying there was not enough evidence to back up its use, and abandoned it as an antidote for the majority of gas victims when the issue was moot.

    The potential findings of the experiment in the Nevada desert will have no direct impact on the treatment of gas survivors today because “the chemicals have long since left the bodies of the victims,” Dhara says. “But at least the information should be out there, if only to say to the victims that we've finally got some answers.”

    Although the recent ICMR report notes that it would be “desirable” to extend the long-term observation of the Bhopal cohort to monitor for “cancer and long-term involvement of other organs,” that hasn't happened. Banerjee says CRS has little money to do comprehensive epidemiological studies on the cohort of gas victims. “How can you cook food,” he says, “without fire.” ICMR did set up an outpost of its population-based registries in Bhopal in 1986 to monitor for various cancers that experts thought would ensue after the chemical exposure. Surprisingly, the expected rise in cancers of the blood, bone marrow, and lung never materialized. “There are slight differences between the exposed and nonexposed population, but they are not significant,” says Biswajit Sanyal, director of the Jawaharlal Nehru Cancer Hospital and Research Centre.

    Sanyal and other Bhopal doctors nonetheless are bracing for cancers to begin popping up in the gas-affected population in the next 5 years. “A person can get lung cancer 30 years after smoking,” says BMHRC's Mittra. “In the same way, it is still possible that the rise in cancer incidence is yet to be.”

    Another source of cancer risk is pollution from the derelict pesticide plant, which looms as a general threat to Bhopal's future. Abandoned shortly after the gas leak, the site was never properly cleaned up. Its remediation is the subject of an ongoing civil suit in U.S. courts by gas victims who claim that chemicals, including some carcinogens, are leaching into the drinking water of some of the city's poorest neighborhoods, where more than 20,000 people live. In May, the Indian Supreme Court directed the state government to supply clean drinking water to the residents. Plans for a pipeline to bring potable water to the affected communities have yet to be drawn up.

    In the meantime, gas victims are marking the 20th anniversary of the tragedy with demonstrations in Bhopal and New Delhi. “They are thought of as second-class citizens,” says Agrawal. “But the gas victims are a scientific treasure. The opportunity to study them should not be wasted.”

  10. AGRICULTURE

    Plant Pathologists Gear Up for Battle With Dread Fungus

    1. Erik Stokstad

    No soybean can resist a rust that has finally arrived in the United States, spurring a search for new varieties, predictive models, and monitoring techniques

    On 6 November, plant pathologist Ray Schneider of Louisiana State University AgCenter gave a routine tour of the research fields near Baton Rouge to a visiting soybean farmer. “I offered to show him diseases he probably didn't have in Illinois,” Schneider recalls saying. Both got a shock. In the course of the tour, Schneider came across signs of a disease never seen before in North American fields: the devastating fungal disease called soybean rust.

    Schneider alerted the U.S. Department of Agriculture's Animal and Plant Health Inspection Service (APHIS) and FedEx'ed samples to a USDA lab in Beltsville, Maryland. When DNA tests came back positive on 9 November, APHIS sent in its soybean rust SWAT team the next day. Four groups of plant pathologists then fanned out across the state, surveying fields in 14 counties. Samples from four came back positive. Within days, APHIS had detected soybean rust in Arkansas, Mississippi, Alabama, and Florida.

    Trouble spots.

    Leaf lesions helped Ray Schneider discover soybean rust in Louisiana. Early diagnosis is crucial, so pathologists are teaching farmers to identify signs of the pathogen.

    CREDITS: RAYMOND W. SCHNEIDER/LOUISIANA STATE UNIVERSITY AGCENTER

    The arrival of this fungus, although expected, could be very bad news for U.S. soybean growers, who raised more than $18 billion worth last year. Soybean rust spreads rapidly and hits plants hard, defoliating fields in less than 2 weeks. “It's an aggressive, hungry beast,” says Martin Draper, a plant pathologist at South Dakota State University in Brookings. All commercially planted soybeans are susceptible to the fungus. If applied quickly, fungicides help, but USDA has estimated that losses could still range from $240 million to $2 billion a year, depending on the severity of outbreaks.

    Unfortunately, the invader is the most aggressive kind of soybean rust, Phakopsora pachyrhizi. The spores are thought to have blown in with September hurricanes from South America, where farmers have incurred huge costs from fighting the disease. “In my country, we have two eras,” says Alvaro Almeida, a plant pathologist at the Brazilian Ministry of Agriculture, EMBRAPA Soja, in Londrina, “before the arrival of soybean rust and after.” The good news for the United States is that almost all soybeans had already been harvested this year, and researchers have a few months to refine their plans. This week, top experts are gathering at a USDA conference in Baltimore, Maryland.

    Work is already under way, as infection has long been seen as inevitable: Every major soybean-producing area of the world except North America has the fungus. Over the past few years, plant epidemiologists have created computer models to predict its arrival and spread. Others have been working out ways to track the disease from airplanes and satellites. USDA researchers have been testing the efficacy of various fungicides in countries already infested and screening germ plasm for signs of resistance that could be bred or genetically engineered into commercial varieties. “We're throwing everything we can at this,” says molecular biologist Reid Frederick of USDA's Agricultural Research Service (ARS) in Fort Detrick, Maryland.

    Searching for resistance

    Soybean rust is a formidable foe. Unlike most rusts, P. pachyrhizi has a broad range of hosts—more than 95 species including other crops and common weeds such as kudzu—so it's impossible to eradicate. It releases massive numbers of wind-blown spores that have been reported to hang like haze over infected fields. “There's just no way to contain it,” Schneider says. First reported in Japan in 1902, soybean rust was later found in China and other Asian countries, where it sometimes slashes yields by as much as 80%. The fungus jumped to Africa in 1996, with alarming effects. Worries among USDA scientists heightened when the fungus arrived in South America in 2001, spreading north from Paraguay. In Brazil last year it cost farmers $2 billion. The United States is likely to be spared such huge losses; the rust cannot survive freezes, so it will live year-round only in the southern states. From there it could spread north each spring.

    About 2 years ago, USDA researchers set up field experiments in Zimbabwe and Paraguay to test the efficacy of 15 kinds of fungicides. All seem to work well, including the two that are currently approved for use in the United States. Concerned that supplies might be inadequate, 25 states have applied to the Environmental Protection Agency for emergency exemptions that would allow farmers to spray other fungicides. Researchers also want a variety of fungicides at farmers' disposal to lessen the chances of the fungus evolving resistance. “It's a recipe for disaster if you use the same thing over and over,” says Kent Smith of USDA's Office of Pest Management Policy in Washington, D.C.

    The best defense, however, would be a soybean variety that resists rust. That has been a challenge to researchers. For starters, the pathogen can't be cultured. A sequencing effort launched in 2002 hit snags when the genome turned out to contain at least 700 million base pairs—14 times larger and much more difficult to assemble than expected. And because APHIS considers soybean rust a bioterrorism “select agent,” it must be studied at biosafety level-3 greenhouses, located only at Fort Detrick, Maryland.

    Frederick and others there have been evaluating the most commonly planted varieties and their ancestral stock. All of the roughly 1000 lines tested so far have proved highly susceptible to soybean rust. But there is reason to hope. In the 1970s, researchers found four varieties that each exhibited resistance to a single strain of P. pachyrhizi. These varieties didn't succeed in the field, however, succumbing to other strains of the pathogen. Plant breeders are now trying to broaden crop resistance by combining the genes from these varieties.

    Researchers are also racing to find other sources of resistance. In the last 18 months, Frederick and Glen Hartman of the ARS in Urbana, Illinois, have tested all 17,000 types of soybean in the USDA germ plasm collection. Nothing has shown exceptional resistance, but the team is now examining 500 candidates that suffered lesser symptoms, such as fewer lesions or delayed onset of spores. To get a better feel for how these traits might fare in the field, USDA researchers have sent 180 varieties to collaborators in South Africa, Zimbabwe, China, Thailand, Brazil, and Paraguay. Progress has been bumpy so far, with comparisons hindered by differences in experimental conditions.

    Resistance traits could also come from other plants. This year Frederick and Marcial Pastor-Corrales of ARS tested 16 varieties of common beans (Phaseolus vulgaris), such as pinto and black beans, and found that five were much more resistant to the pathogens than were soybeans. If those resistance genes can be cloned, they could potentially be genetically engineered into soybean.

    Rust belt.

    A model predicted the path of soybean rust spores (inset) and will forecast their spread.

    CREDITS: Z. PAN AND X. B. YANG; (INSET) REID D. FREDERICK/USDA

    In another approach, plant physiologist Bret Cooper of the ARS in Beltsville is using mass spectrometry to search through thousands of plant proteins for those that play a role in disease resistance. They've also begun working on dry bean rust, which can be studied outside the biosecure greenhouse, and plan to expand the search to P. pachyrhizi. In collaboration with James English of the University of Missouri, Columbia, Cooper will be looking for peptides that would interfere with infection or block spore germination. Such peptides might eventually be turned into sprays or engineered into soybean.

    Early warning?

    In the meantime, plant pathologists and extension agents are gearing up to educate farmers. Rust is easily confused with other diseases, and early identification is crucial. Researchers are also setting up a system of sentinel plots, planted early with prime conditions for infestation, to monitor for the disease. Work is under way on a hand-held sensor, based on an immunological assay, to detect the pathogen in the field.

    Remote sensing could provide early detection, too. Forrest Nutter, a plant disease epidemiologist at Iowa State University (ISU) in Ames, has been working in Brazil and elsewhere on satellite detection of soybean rust. The spectral signature of leaf loss, although not unique to rust, can pinpoint outbreaks on the scale of meters. The same approach may work from airplanes, a cheaper and faster way of getting images, he says. Nutter plans to try tracking the disease this way next spring. “There's no doubt that rust is going to be established in the United States. The question is how it's going to spread,” he says.

    Farmers may also eventually get even earlier warning from a model developed by plant pathologist X. B. Yang of ISU and atmospheric modeler Zaitao Pan of St. Louis University in Missouri. They use a short-term climate model to project likely trajectories of spores over the next 120 days. In August, they predicted that spores would be more likely to enter because of the hurricane season and highlighted Louisiana as a probable beachhead.

    Now the model can be adapted to predict the spread of spores from southern states north each spring. If it works, Pan says, a 3-month prediction could help farmers decide whether to stock up on fungicides, reserve spraying equipment—or even whether to plant soybeans at all.

  11. CLINICAL TRIALS

    Nail-Biting Time for Trials of COX-2 Drugs

    1. Jennifer Couzin

    Preliminary studies suggest that the COX-2 inhibitor Celebrex may stem cancer and Alzheimer's disease, but testing these possibilities has just gotten tougher

    Psychiatrist John Breitner was in a hotel room in Sun City, Arizona, when he heard the news on television. It was 30 September, and CNBC was reporting that the COX-2 inhibitor Vioxx would be yanked off the market by its maker, Merck, after experts saw a frightening increase in cardiovascular side effects. Breitner's own heart skipped a beat. In an instant, he realized that his effort to stop Alzheimer's disease using Celebrex, a Vioxx competitor, had just gotten trickier.

    Similar but different.

    The withdrawal of Vioxx has put Celebrex in the spotlight.

    CREDIT: MARY ALTAFFER/ASSOCIATED PRESS Breitner, an expert on aging based at the University of Washington, Seattle, is one of dozens of researchers exploring whether COX-2 inhibitors can do more than they were designed to do—ease the painful inflammation of arthritis. Over the years, animal studies have suggested that these medications, along with more traditional nonsteroidal anti-inflammatory drugs (NSAIDs), may be able to lower the risk of cancer and reduce inflammation suspected in Alzheimer's.

    In the past few years, scientists have launched one study after another to put these hopeful ideas to the test. The pace picked up after the U.S. Food and Drug Administration (FDA) confirmed data in 1999 showing that Celebrex reduces intestinal polyps in patients with familial adenomatous polyposis, a hereditary condition that leads to colon cancer. Excitement has focused on COX-2 inhibitors because they are believed to be less likely than NSAIDs to cause stomach problems, a big drawback in long-term prevention trials.

    Few Vioxx prevention studies have been conducted or were planned, researchers say, partly because Merck was less willing than Pfizer, the maker of Celebrex, to donate a COX-2 inhibitor to such trials. The result is that about 10,000 volunteers are participating in or being recruited for Celebrex studies, but scientists can't say for certain whether the drug shares Vioxx's hazards. Now trial managers are debating the risks, reassuring study participants, and keeping a hand on the emergency brake just in case.

    The last 2 months have been nail-biters for these researchers and their funders. The concern is heightened because in most of these trials, volunteers are healthy, and although many are at risk, not all will develop disease. “This is not fun for anybody,” says Curtis Meinert, chair of the steering committee for the Alzheimer's Celebrex trial and a clinical trials expert at Johns Hopkins University in Baltimore.

    “Obviously, I was concerned” about the Vioxx announcement, says Jenny Mao, a pulmonologist at the University of California, Los Angeles, who's enrolling 180 former smokers in a lung cancer prevention trial that's testing Celebrex. Her biggest fear, she says, is that Celebrex, too, will be pulled, and that “all this work over all these years would go down the drain.”

    Like most researchers, Mao believes that Celebrex doesn't induce the heart attacks and strokes seen with Vioxx. Although both drugs are COX-2 inhibitors, Vioxx is a more potent blocker of the COX-2 enzyme—a potential source of its problems—and also has a longer half-life. In addition, some cardiologists had warned for years of Vioxx's cardiovascular risks.

    But a heightened level of scrutiny brought down Vioxx: The trial that persuaded Merck to withdraw its drug lasted 18 months and included 2600 people—longer than any single large, published Celebrex study. The purpose was to test whether Vioxx could prevent colon polyps—a precursor of cancer—in those at risk for developing them. Among volunteers on Vioxx, 3.5% suffered heart attacks or strokes, compared to 1.9% on placebo.

    So far, “the data that are available … don't show the same” risks for Celebrex, says Meinert. “That,” he hastens to add, “isn't proof they don't exist.”

    If there are cardiac problems, they might be hard to detect; researchers are straining to catch warning signs. The largest and longest running Celebrex prevention trial, a 2000-person study looking at the reappearance of colon polyps in patients with a history of them, has added a cardiovascular expert to its data safety and monitoring board (DSMB). In a meeting after Vioxx was withdrawn, DSMB members pored over trial data and agreed that the trial should continue, says Ernest Hawk, a chemoprevention expert at the U.S. National Cancer Institute who is program manager for the NCI-funded trial. NCI has also created a “cardiovascular adjudication process,” essentially asking a group of cardiologists to review and classify every potential cardiovascular event. Although DSMBs overseeing Celebrex prevention trials have been on heightened alert, and many have added a cardiac expert to their ranks, they “have not halted the trials or demanded changes to them based on cardiovascular risk,” says Hawk. (A Pfizer spokesperson confirmed that the company is not running any prevention trials with Bextra, its other COX-2 inhibitor.)

    Alzheimer's prevention trials face challenges, too. Breitner's 2500-person study, the Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT), funded by the U.S. National Institute on Aging (NIA), uses Celebrex. All subjects must be at least 70 years old, putting them at a high risk of heart disease to begin with. Susan Molchan, NIA's program director for Alzheimer's disease clinical trials, contacted FDA after Vioxx was pulled off the market “to see if they had information” about Celebrex “that they could share,” she says. “They confirmed we weren't missing any information.”

    NCI is trying to improve monitoring of Celebrex studies, according to Hawk. Meinert has urged agency officials to meld safety data from all the trials, making small signals easier to detect. “Trials are fairly weak instruments at finding adverse events,” he says, especially if they occur infrequently. “We need to have a better model, in my opinion, with regard to the harvest of safety data” among different trials studying the same drug. NCI's Hawk confirmed that the institute is speaking to Celebrex investigators about better ways to evaluate cardiac safety.

    As scientists probe the Vioxx-Celebrex relation, they find that study participants are often primed with questions. “I've conducted town hall meetings for patients,” says Peter Lance, a gastroenterologist at the University of Arizona in Tucson, who's heading a 1600-person colorectal adenoma prevention trial involving Celebrex and the mineral selenium. Several dozen attended recent meetings in Tucson and Phoenix, where Lance explained that, thus far, there has not been an “imbalance” in cardiac problems among those taking Celebrex. “We're taking otherwise healthy people and asking them to take a medication or an intervention for which we don't have scientific evidence” of a clinical benefit, he says. “Our thoughts about safety are very intense.”

    In the ADAPT trial, says Breitner, “we have people who are being advised to drop out by their physicians” and patients “who say they were going to enroll but aren't. We're definitely taking a hit from this.” Between 20 and 50 participants have refused to continue taking study medications (Celebrex, naproxen, or placebo), Breitner adds. To keep enrollment steady, ADAPT's coordinators have sent information about Celebrex, in lay language, to field sites. Although Breitner agrees that more information about Celebrex's long-term cardiac effects are needed, he doesn't think it poses anything like the risk of Vioxx: “I don't think that I'm running a trial where we're poisoning people.”

    Many other trials haven't suffered much. UCLA's Mao says her staff was far more concerned with how the Vioxx withdrawal might influence their study than were participants. Other trials, moreover, include patients with such a high chance of cancer that cardiac risks pale in significance. For example, the 360 patients to be enrolled in the oral cancer prevention study headed by Scott Lippman of M. D. Anderson Cancer Center in Houston, Texas, will have a 60% chance of developing cancer in the next 3 years.

    Celebrex researchers are hopeful that regardless of whether these trials show any effect on cancer or Alzheimer's risks, they will answer once and for all the question that's lingered since boxes of Vioxx were shipped back to Merck: whether Celebrex shares Vioxx's downside, and to what degree. Says Mao: “We'll keep our fingers crossed.”

  12. DIVISION FOR PLANETARY SCIENCES MEETING

    Did Jupiter and Saturn Team Up to Pummel the Inner Solar System?

    1. Richard A. Kerr

    LOUISVILLE, KENTUCKY—With time off to catch a couple of races at nearby Churchill Downs, about 700 solar system researchers met here 8 to 12 November at the annual meeting of the Division for Planetary Sciences.

    The solar system may have passed through a violent youth before it came of age. More than a half-billion years after the inner solar system's molten beginnings, a barrage of impacters slammed into Earth and the moon, according to some dating studies of the impact craters left behind on the moon (Science, 1 December 2000, p. 1677). That bombardment would have formed the huge, lava-filled basins that shape “the man in the moon.” It would also have snuffed out any but the most deeply buried life struggling to get a start on Earth.

    Battered.

    An outer planet pairing may have led to the late cratering of the moon.

    CREDIT: NASA

    But where could those impacting bodies have been lurking all that time, and what could have prompted the delayed onslaught? At the meeting, planetary dynamicists showed how Jupiter and Saturn could have joined forces to fling debris toward Earth from a reservoir in the outer reaches of the solar system.

    The key to creating a late heavy bombardment is the orbital migration of Jupiter and Saturn, according to an international team of planetary dynamicists including Rodney Gomes of the National Observatory in Rio de Janeiro and Kleomenis Tsiganis of the Observatory of the Côte d'Azur in Nice, France. When chunks of planet-building debris wander too close to one of the growing giant planets, the big guys can catch them in a net of gravity and fling them away.

    But hurling planetesimals one way inevitably sends the hurler the other. Although Jupiter was too massive to move much by tossing planetesimals, the far less hefty Saturn would have spiraled outward as it cleared its neighborhood of planetesimals. Gomes and his colleagues used a computer model to study this migration process. Their innovation was to start all four of the outer planets in the simulations bunched together and well inward of their present orbital distances.

    That planetary placement means that as Saturn migrated outward, it would eventually be orbiting the sun once each time Jupiter orbited twice. At that point, the two planets would be in their so-called 1:2 resonance—in which every second jovian orbit, they would be closest together at the same point in their orbits. Whenever that occurred, the larger planet could give Saturn repeated gravitational nudges whose effects could accumulate, the way repeatedly pushing a swing at the same point in its arc sends it higher.

    The resonant interactions of the two largest planets would have stirred the outer solar system into a chaotic frenzy. In the group's simulations, Jupiter pumps up the orbital energy of Saturn, which in turn destabilizes the orbits of the far smaller and more distant Uranus and Neptune. That scatters the two smaller planets outward, where they encounter an undisturbed disk of planetesimals. Then, as many as a billion years after planet formation, enough of the planetesimals rain toward the inner solar system to produce more than 1015 hits on the moon in a bombardment lasting less than 100 million years. Thus, the modeled late heavy bombardment triggered by a resonance passage matches the one often inferred from dating of craters, Tsiganis noted. It's as late, as intense, and as brief.

    Once the model's planetesimals are cleared out, migration ceases, and the restless outer planets lock into slightly elongated, tilted orbits, much like the planets' actual orbits. This is the first time, said Tsiganis, that an orbital simulation has gotten anything but circular, flat orbits for the four outer planets. Likewise, the Trojans, minor planets that share Jupiter's orbital space, have hard-to-explain large orbital inclinations in the present-day solar system that also show up in simulations as Jupiter and Saturn pass out of their 1:2 resonance.

    Planetary dynamicists find passage through a resonance promising as a trigger for a late heavy bombardment. “It does tie together several things,” says Martin Duncan of Queen's University in Kingston, Ontario. “It definitely deserves attention.” It should also prompt the crater daters to prove once and for all that there was indeed a late heavy bombardment.

  13. DIVISION FOR PLANETARY SCIENCES MEETING

    Hydrocarbon Seas of Titan Gone Missing

    1. Richard A. Kerr

    LOUISVILLE, KENTUCKY—With time off to catch a couple of races at nearby Churchill Downs, about 700 solar system researchers met here 8 to 12 November at the annual meeting of the Division for Planetary Sciences.

    Like the dog that didn't bark in the night, the sunlight that didn't glint off the surface of Saturn's big moon Titan spoke volumes. When the Cassini spacecraft flew by for a close look late last month, scientists expected to see sunlight reflected from liquid surfaces, but none of Cassini's cameras picked up the anticipated telltale glint (Science, 5 November, p. 952). That was a surprise because Titan's thick haze was thought to hide a network of “rain”-fed hydrocarbon seas—perhaps the dark areas spied telescopically in recent years at haze-piercing infrared wavelengths. At the meeting, Cassini scientists reported that these dark areas appear to be as dry as the “seas” that Galileo spotted on Earth's moon. Liquids on Titan seem to be confined to scattered lakes or even underground, if they exist at all.

    Mystery shadings.

    From Earth, Titan's dark regions looked like seas, and even more so from Cassini (above), but the details of how light reflects from them are wrong for liquid.

    CREDIT: NASA/JPL/SPACE SCIENCE INSTITUTE

    The way light reflects off a surface can provide a wealth of information. If sunlight glints off, the surface must be very smooth, almost mirror smooth. The only natural surface that approaches mirror smoothness is that of a liquid. But variations in the composition, texture, and topography of a nonliquid surface can produce subtle but revealing variations in the intensity of reflected sunlight. Cassini scientist Robert M. Nelson of NASA's Jet Propulsion Laboratory (JPL) in Pasadena, California, and other members of the Visible and Infrared Mapping Spectrometer team reported their analyses of light reflected at various angles from two dark, circular features that looked like possible impact craters 1000 kilometers across and from a similarly sized but irregularly shaped dark feature.

    The three dark regions seemed likely places for hypothesized methane rains to collect, but Nelson's analysis found nothing that indicated pools of liquid. Brightness variations across the three features were too large to be coming from liquid surfaces or even varying topography. They only made sense as variations in surface reflectivity. Apparently, the two circular features are not depressions but perhaps ancient impact scars that are now filled in. There's “no evidence whatsoever to suggest there are accumulations of liquid of any form,” says Nelson.

    The search for liquids on Titan is not over, however. Their nondetection has “certainly been a surprise,” said Cassini project scientist Dennis Matson of JPL, but “we've only seen a part of Titan to this stage.” Nelson allows that small lakes might yet be found. The liquid methane might even be hiding beneath the surface like groundwater. If so, the Huygens probe scheduled to parachute to the Titan surface on 15 January would arrive with a thudding jolt rather than a splash.

  14. DIVISION FOR PLANETARY SCIENCES MEETING

    Amazing Shrinking Kuiper Belt Objects

    1. Richard A. Kerr

    LOUISVILLE, KENTUCKY—With time off to catch a couple of races at nearby Churchill Downs, about 700 solar system researchers met here 8 to 12 November at the annual meeting of the Division for Planetary Sciences.

    They aren't actually shrinking, of course, but the icy leftovers from the solar system's formation that orbit out beyond Neptune are getting smaller in the eyes of astronomers. Thanks to two independent means of determining the true reflectivity of subplanetary-size bodies, the so-called Kuiper belt objects (KBOs) now look to be 40% smaller than had been assumed. That's good news for Pluto supporters. They've been holding their breath as new discoveries drove up the apparent size of the largest known KBO, threatening to knock Pluto from its status as a bona fide planet. Now a usurper seems much less likely.

    No longer coal black.

    Kuiper belt objects are brighter and therefore larger than thought.

    CREDIT: NASA/JPL

    KBOs are “shrinking” because until recently astronomers could only guess what fraction of sunlight they reflect. When a solar system object is so small and far away that even the largest telescope shows only a point of light, the only way astronomers can calculate the object's size is from its brightness. To do that, they must assume a reflectivity. KBOs were discovered in 1992 after planetary dynamicists suggested they had to be there to supply icy comet nuclei to the inner solar system. Because comets are pitch black—they reflect just 4% of the sunlight hitting them—planetary scientists reasoned that KBOs were in all likelihood inky black, too, and therefore large.

    Now that picture is changing. At the meeting, astronomers reported how improving technology is allowing them to determine KBOs' reflectivities. The more reflective the objects actually are, the smaller they must be for a given brightness. Astronomer John Stansberry of the University of Arizona, Tucson, and his colleagues reported results from infrared observations of eight KBOs using the Spitzer Space Telescope, which has been in Earth orbit since August 2003. By measuring the brightness of a KBO at both a short wavelength, at which the light is entirely reflected, and a long wavelength, where it is emitted, they could calculate a reflectivity because both reflected and emitted brightness depend on the size of the object. The reflectivity of the eight KBOs ranged from 7.5% to 18% and averaged 12%, three times the assumed KBO reflectivity.

    In an entirely different approach, two groups, respectively led by Jean-Luc Margot of Cornell University and by Keith Noll of the Space Telescope Science Institute in Baltimore, Maryland, watched KBOs orbit about each other in binary pairs, in essence a system of a miniplanet and its minimoon. From a binary's orbital dynamics, they could calculate a total mass for the pair. Assuming a density of 1 (a reasonable assumption), they could calculate a reflectivity. Of the dozen binary KBOs known, Margot found estimated reflectivities for four of them ranging from 8% to 41%, averaging 22%. Noll has observed eight binaries that average 12% reflectivity.

    KBOs averaging 12% reflectivity would be 60% of the size estimated on the basis of low cometary reflectivities and just 20% of the mass. Presumably, astronomers were misled by comet nuclei that start out as relatively reflective KBOs—“dirty snowballs”—but darken as the sun's heat drives off their bright ices. KBO hunters are far less likely to turn up a rival the size of Pluto anytime soon, notes Noll. Long live planet Pluto.

  15. DIVISION FOR PLANETARY SCIENCES MEETING

    Snapshots From the Meeting

    1. Richard A. Kerr

    LOUISVILLE, KENTUCKY—With time off to catch a couple of races at nearby Churchill Downs, about 700 solar system researchers met here 8 to 12 November at the annual meeting of the Division for Planetary Sciences.

    Ring hits. Planetary scientists knew that any solar system body continually sweeps up bits and pieces of debris, but they never expected to hear the impacts. So space physicist Donald Gurnett of the University of Iowa, Iowa City, drew applause for “the music of the rings,” a plasma-wave signal from Saturn's rings, stepped down to audible frequencies. Gurnett's plasma-wave instrument onboard the Cassini spacecraft recorded the signal as it flew over the rings last July. The music resembled the sound of crickets: short, 1- to 2-second tones every second or so, each with a narrow frequency range. Gurnett decided that marble-size, 200,000-kilometer-per-hour ring impacters were producing the tones. Ring specialists will want to use his recorded impact tempo in their studies of how impacts age and erode the rings.

    A dark mystery. Saturn's two-faced moon Iapetus is not giving up its secrets easily. Spectroscopist Bonnie Buratti of the Jet Propulsion Laboratory in Pasadena, California, reported that the Visible and Infrared Mapping Spectrometer on the Cassini spacecraft managed to get the first clean spectrum of the side of this moon that always points forward as it orbits Saturn. It is dark, while the trailing side is icy bright. In the infrared, the spectral signature of the dark side resembles that of Saturn's distant moon Phoebe and smaller moons beyond it. The similarity supports the “It Came From Outer Space” theory of Iapetus's dark side, said Buratti. According to that scenario, small meteorite impacts knock dark material off the outer satellites, and Iapetus sweeps it up on its leading side. But the new spectrum also shows that at visible wavelengths Phoebe and the Iapetus dark stuff look quite different. That prompted hallway chatter about the alternative: dark goo oozing from the interior. A much closer look by Cassini scheduled for New Year's Day may help.

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