News this Week

Science  21 Mar 2003:
Vol. 299, Issue 5614, pp. 1661

You are currently viewing the .

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution


    Scientists Chase Fast-Moving and Deadly Global Illness

    1. Martin Enserink*
    1. With reporting by Gretchen Vogel in Berlin.

    A mysterious disease that causes flulike symptoms and pneumonia moved quickly around the world last week after sickening dozens in Asia. More than 160 people in seven countries have fallen ill in the past few weeks, according to the World Health Organization (WHO), and at least four have died. Those numbers raise fears about a new pandemic.

    As Science went to press, researchers in many labs were frantically trying to determine the cause of severe acute respiratory syndrome (SARS), as WHO has dubbed the disease. German researchers reported finding particles resembling paramyxoviruses—a group that has caused several deadly outbreaks in Australia and Southeast Asia in recent years—in respiratory samples from one patient. But they warned that the findings needed to be confirmed, and even then the paramyxovirus might not be the causative agent.

    Researchers have tried “a phenomenally large range” of diagnostic tests on available samples, says Klaus Stöhr, an influenza expert at WHO in Geneva, but they have all been negative. “We really have to start from scratch and put all our assumptions aside” in the search for a culprit, he says. It's also unclear how the disease spreads, or how it can be prevented and treated. Hospital workers appear to be most at risk, suggesting that close contact with a patient is required for an infection—unlike highly contagious diseases such as influenza.

    The unknowns are troubling, as is the disease's global reach, says C. J. Peters, director of the Center for Biodefense at the University of Texas Medical Branch in Galveston. Having studied deadly outbreaks in many corners of the world, Peters says, “I don't know one that has left me with such a feeling of danger.”

    Early symptoms of the disease include high fever, muscle aches, sore throat, and headache, sometimes followed by pneumonia and acute respiratory distress. The first known patient in the current outbreak was a U.S. businessman living in Hong Kong, who fell ill in Hanoi and was hospitalized in late February. The patient was evacuated to Hong Kong, where he died; since then, at least 20 hospital workers in Hanoi have been diagnosed with the disease, and dozens more medical personnel in Hong Kong have become sick. And by Monday, international travelers appeared to have carried the disease to Thailand, Singapore, Canada, Switzerland, and Germany, with serveral more countries reporting suspected cases.

    Flight risk.

    Passengers at Hong Kong's international airport wear masks to help ward off infection from a mysterious agent.


    WHO says the outbreak is probably related to an equally puzzling one with similar symptoms that sickened 305 people and killed five between November 2002 and February 2003 in the southern Chinese province of Guangdong. A bacterium called Chlamydia pneumoniae was found in two of the patients who died, but it's unclear whether that microbe was the culprit. On Monday, WHO said it would send an expert team to the province to assist Chinese officials. The outbreak there seems to be on the decline, although it is unclear why.

    Flulike symptoms and pneumonia can be caused by a variety of agents. As of last weekend, no single culprit had been ruled out, says Julie Gerberding, head of the U.S. Centers for Disease Control and Prevention in Atlanta, leaving experts to speculate about potential causes. “It sort of screams ‘flu,’” says Brian Hjelle, a virologist at the University of New Mexico in Albuquerque. Indeed, some initially thought the epidemic might be linked to a small outbreak of a virulent bird flu strain, called H5N1, which killed a man from Hong Kong last month and sickened his 9-year-old son (Science, 7 March, p. 1504). But no such link has been found, and most scientists say that if the disease were influenza, doctors would have known it by now. Hong Kong public health authorities have ample experience with that disease, which is relatively easy to diagnose.

    Paramyxoviruses gained notoriety after a vicious outbreak 4 years ago in Malaysia and Singapore killed more than 100 people and ravaged the Malaysian pig industry (Science, 16 April 1999, p. 407). A few years earlier, a member of the same family, named Hendra, had killed two people in Australia. Fruit bats turned out to be the natural reservoir for both viruses. Other potential culprits in the SARS outbreak, says Peters, include a human parvovirus or a hantavirus. Although most hantaviruses aren't transmissible from person to person, there is one, notes Hjelle, that is: the Andes virus, discovered in 1995 in southern Argentina.

    Meanwhile, this new outbreak puts public fears of bioterrorism and ballooning biodefense budgets into perspective by reasserting the impact of naturally occurring diseases, says Marjorie Pollack, who is monitoring the outbreak for ProMED, a worldwide electronic reporting system. Says Pollack: “Mother Nature is by far the worst bioterrorist out there.”


    Can Outsiders Do Better in Managing NIH Grants?

    1. Jocelyn Kaiser*
    1. With reporting by Jeffrey Mervis and Evelyn Strauss.

    A White House push to contract out federal jobs is stirring fears that any shakeup could touch a sacred cow: the system used by the National Institutes of Health (NIH) for reviewing grant proposals. At stake, say NIH scientists, is the continuity and expertise they bring to their jobs. “It's got everybody neurotic,” says one NIH program director who asked not to be named.

    The source of their neurosis is an effort by the White House Office of Management and Budget (OMB) to put up for competition the work now done by up to 50% of the federal work force. This plan, known as “A-76,” is based on a 1998 law and an updated OMB circular on downsizing. Agencies must decide whether certain jobs are “inherently government” or “commercial,” NIH management explained in a staff memo last September. By the end of 2004, NIH expects to review 13% of its 18,000 positions—including those in grants programs. NIH can compete for contracts, and NIH and the Department of Health and Human Services (HHS), its parent agency, have said that those who lose out will be given other jobs.

    Although many jobs on the list are clerical or technical, NIH scientists say they are worried about two types of Ph.D. positions —scientific review administrators (SRAs) and other health scientist administrators (HSAs)—totaling more than 1300 positions across NIH's 27 institutes and centers. The SRAs organize over 150 study sections, and HSA program staff make final award decisions and monitor grants. Program staff members also organize workshops and plan new research programs.

    NIH believes that these functions are “inherently governmental,” says Charles Leasure Jr., NIH deputy director for management. But he adds that OMB or HHS “could decide they could be done by the private sector.” The Department of Defense (DOD), for example, uses contractors to organize peer review of $350 million worth of independent research proposals per year, mainly for research on breast and other cancers.

    Outside scientists say that the job entails much more than pushing paper. NIH staff members also solicit proposals or entertain requests initiated by independent investigators, skills that require them to stay abreast of cutting-edge research. Some observers doubt that this expertise can be hired on contract. “The SRAs are the spinal cord of the NIH system,” says University of Pittsburgh psychologist Karen Matthews, who chairs the advisory council of the Center for Scientific Review, which reviews 70% of the 40,000 grant proposals that NIH receives each year. “It would be nearly impossible” to have contractors do the same job, Matthews says.

    Council member Susan Berget, a molecular biologist at Baylor College of Medicine in Houston, Texas, says it is “very revealing” that DOD turned to retired NIH scientific staff to help review its breast cancer proposals. “These professionals are deeply valued by the American scientific community,” she says.

    The other main funder of nondefense science, the National Science Foundation (NSF), has stayed out of the contracting fray so far. Last year, it hired management consulting giant Booz Allen Hamilton for a 3-year, $12.8 million study of its 1290- person work force. Some 200 or more are “rotators” who come from academia for a few years. The use of rotators, combined with the thousands of hours contributed by volunteer reviewers, “fits the spirit of competitive sourcing,” says Joseph Burt, NSF's human resources chief.

    Concerned that NIH grant managers might be replaced by contractors, some scientific groups say they would be ready to lobby their representatives in Congress. “They can't take a shotgun approach in choosing how they cut down the government,” says George Martin, president of the Gerontological Society of America and an Alzheimer's researcher at the University of Washington, Seattle.

    The battle may be joined within the next few months once NIH submits its latest inventory of positions to the White House. That's when staffers will learn whether their fears are justified.


    New Cuts Slam Most Research Agencies

    1. Barbara Casassus*
    1. Barbara Casassus is a writer in Paris.

    PARIS—Thousands of French scientists, still reeling from budget cuts last autumn, are being asked to tighten their belts again as part of government austerity measures to revive the sagging economy. The exact scale of the cuts, however, is mired in confusing statistics.

    The unions say that most institutes have had between 25% and 40% of their operating budget frozen for this year in addition to an immediate cut of about $125 million. The research ministry dismisses these allegations. It admits that 30% of operating and investment credits have been frozen but insists that “a simple procedure for regulating the consumption of credits must not be confused with a loss of resources.”

    Yet confusion remains the order of the day. “This is the first time I have been lost in budget figures, and I have been following them for 20 years,” laments chemist Henri-Edouard Audier, a board member of SNCS, the main research union. The union has urged scientists to take to the streets to protest what SNCS secretary-general Jacques Fossey calls the state's failure “to face up to its responsibilities.”

    The unions say the fresh cuts will hit almost all major public research institutes. The situation is looking particularly bleak at CNRS, the main basic research agency. It “is on the verge of financial collapse,” says biologist Gérard Chaouat, a member of the CNRS scientific council. The ministry says the operating budget for CNRS has been cut by 9.3%.

    Chaouat says that CNRS director-general Geneviève Berger has warned staff that she may have to recall some funds already distributed to make up a $42 million shortfall in this year's $1.6 billion salary budget. Berger declined to be interviewed by Science, but she told Paris's Le Monde newspaper that the cuts will “make it extremely difficult to maintain the quality of our research.”


    Blood Banks in a 'Race Against the Mosquitoes'

    1. Jennifer Couzin

    Public health agencies and companies are racing against the clock to protect the North American blood supply from West Nile virus, which is expected to reappear soon after a winter hiatus. The mosquito-borne disease is dormant in cold months, but a score of infections linked to blood transfusions last fall prompted a rush effort to design a rapid and sensitive blood test. Last week, experts at a blood-products advisory committee meeting held by the U.S. Food and Drug Administration (FDA) in Gaithersburg, Maryland, said they were cautiously optimistic that a new test would be ready by 1 July.

    Last year was the worst season ever for West Nile infections in the United States, with over 4000 documented cases. At least 21 of them came from blood transfusions. Twelve of those patients developed meningoencephalitis and six died, although some may have succumbed to underlying conditions. Another 21 cases may stem from transfusions, but the source couldn't be determined, says Lyle Petersen of the Centers for Disease Control and Prevention (CDC) in Atlanta. Additional transfusion recipients may have been infected but remained asymptomatic.

    In October, FDA urgently asked companies to develop a West Nile blood test for 2003, condensing into months a process that normally takes years. Two industry groups—Roche, and an alliance of Gen-Probe and Chiron—have been working furiously on separate tests, and both presented updates at the FDA meeting. “It's a race against the mosquitoes,” and researchers are working 7 days a week to stay ahead, says James Gallarda, director for blood screening development at Roche Molecular Diagnostics in Pleasanton, California. “We'll be ready.”

    As they prepare, researchers warn that uncertainties about the virus raise questions about how a test should be designed and used. For example, it's not clear whether people who get the virus from a blood transfusion are more likely to suffer life-threatening infections than are those who get it from mosquito bites. Nor is it known how long a potential donor continues to pose a health threat after becoming infected.

    Safety check.

    After transfusion recipients were infected with West Nile virus last year, FDA sought a new test to protect the blood supply.


    Both industry groups, with FDA's encouragement, are proposing a major shift in how blood is screened for pathogens. Blood banks chiefly rely on antibody tests to determine whether a potential donor has been infected and generated an immune response. But antibodies aren't always detectable early in an infection. Researchers discovered after the fact that all the known West Nile transfusion cases received blood from individuals who were antibody negative; the donors had presumably been infected too recently for antibodies to be identified. This prompted FDA to call for a more sensitive nucleic acid test, which tallies levels of genetic material and can pick up an infection earlier.

    The companies designing such a test have also produced nucleic acid tests to screen blood for hepatitis C virus and HIV. But that effort took years. Concerns about blood safety are prompting this summer's West Nile tests to reach the market prior to full-scale clinical testing. Screening for West Nile may be tough in any case: Infection appears to produce only low levels of virus—a few thousand copies per milliliter of blood, compared with tens of thousands or millions of copies for other pathogens. Because blood samples are pooled for testing, FDA is asking for detection at a scant 100 copies per milliliter. But even some negative results could be problematic: It's not known whether donors with extremely low virus levels can be infectious.

    Blood bank managers agree that potential donors infected with West Nile virus should be excluded from the system, but only temporarily. The question is, for how long. The American Red Cross, which supplies about half the nation's blood, plans to defer donations from anyone who tests positive for West Nile virus for 28 days—a number agreed upon by FDA and CDC—on the grounds that the virus will disappear from donors' blood by then. But that figure is based on slim evidence from a 1950s study in which cancer patients were infected with West Nile. It's still unknown how long it takes healthy people to clear the virus and whether a more sensitive test might pick up traces of the virus after a month. Blood banks are gearing up for pilot studies next month to answer such questions.

    FDA is also crafting contingency plans in case the companies fail, including the possible suspension of blood collections in hard-hit regions. That proposal triggered a harsh response at the meeting, however. Suspending donations would “play havoc with the donor system,” said committee member James Allen of the American Social Health Association in Research Triangle Park, North Carolina. The lack of appealing alternatives only raises the stakes for test developers.


    Congress Lets States Share the Wealth

    1. Jeffrey Mervis

    When Congress finally completed work last month on the 2003 federal budget, it contained an item championed by Representative Vernon Ehlers (R-MI): $101 million tucked into the Department of Education (DOE) budget for a state-by-state program to train science and math teachers. Ehlers says it took weekly phone calls to the chair of the House spending panel that controls the department's budget, and personal visits to every legislator on the 15-member panel, to win support for the program, which will bring together university researchers and local school districts to improve math and science instruction.

    The National Science Foundation (NSF) runs a similar program, funded to the tune of $127 million this year (Science, 11 January 2002, p. 265). But there's one big difference: NSF disburses its funds through a national competition, with a handful of big winners and large chunks of the country unserved. The DOE program, in contrast, will spread the wealth according to a student-based formula, with every state guaranteed at least $500,000. “We're very pleased that it will go to each state,” says Jodi Peterson, legislative director for the National Science Teachers Association. “Every child deserves to have a properly trained science teacher.”

    The Bush Administration, which proposed the NSF program, argued that competitive awards are likely to result in higher-quality programs than block grants. But members of Congress, hewing to the dictum that all politics is local, wanted to ensure that its constituents weren't shut out. “There are good arguments on both sides,” Susan Sclafani, counselor to Education Secretary Rodney Paige, says diplomatically. “Either way, we will focus our efforts on improving math and science teaching.”

    In any case, Ehlers's persistence will be needed again this year. DOE requested only $12.5 million for the program in 2004—the same amount it received in 2002 when the program debuted as a national competition like NSF's. “I'll do whatever it takes,” Ehlers promises.


    Foundation Goes to Bat for African Farmers

    1. Erik Stokstad

    Kenyan scientists are in the final stages of testing a virus-resistant sweet potato developed through a collaboration with Monsanto. It took 13 years to get to this point—a glacial pace for subsistence farmers. Eugene Terry wants to grease the skids for such partnerships.

    Last week, Terry, a plant pathologist and native of Sierra Leone, began setting up the headquarters of the African Agricultural Technology Foundation (AATF), an organization that will act as a clearing-house and technology broker for African agriculture. Based in Nairobi, the foundation's $1.5-million-a-year budget comes from the Rockefeller Foundation and the U.S. Agency for International Development (USAID). “We see it as a focal point where Africans can access new materials and information on which technologies can be built,” says Rockefeller president Gordon Conway.

    Along with depleted soils, numerous pests, and pathogens, African agricultural scientists face restrictions on their access to the right scientific tools. “Intellectual property rights are a barrier to us,” says Peter Hartmann, director of the International Institute of Tropical Agriculture in Ibadan, Nigeria. Even though many companies are willing to waive intellectual property (IP) rights, he says, getting the technology is a slow, daunting process. “Just trying to string the ‘ownership’ rights together requires investigations and a plethora of negotiations,” he says. That's where AATF comes in.

    Sweet deal.

    Monsanto technology has helped African scientists develop disease-resistant sweet potatoes.


    The foundation, which will officially open in September, hopes to help match companies with African researchers, negotiate IP agreements, and provide advice on regulation. Terry says he's scouting around for the right projects, based on consultations with regional agricultural organizations. “We'll be learning by doing,” he says.

    The sweet potato project could have used such help. Its roots go back to 1990, when scientists at the Kenyan Agricultural Research Institute (KARI) in Nairobi hooked up with Monsanto, which controlled key technology for adding a resistance gene. Monsanto granted KARI a royalty-free license and taught its scientists to create new varieties. As the first genetically modified (GM) crop in Kenya, however, it was hardly an overnight success. “The project has not moved rapidly, because KARI doesn't have the expertise to manage transgenic crop development,” explains USAID's Josette Lewis.

    The new foundation intends to provide that expertise, with help from major biotech companies. And industry, in the long run, hopes to recoup more than just good will. “As for the shareholder benefits,” says Sam Dryden of Emergent Genetics in Boulder, Colorado, “the foundation is developing commercial markets.”

    Before AATF can make a dent in poverty rates, however, it must overcome issues ranging from legal wrangling to public skepticism about GM crops. “Companies are very aware that they could have liability slapped on them,” Terry says. A mistrust of multinational companies may stigmatize AATF, warns Pat Mooney of the ETC Group in Winnipeg, Canada. “They could become [seen as] a kind of a Trojan trade rep for companies.”

    Monsanto's Gerard Barry, a member of the foundation's initial advisory committee, believes that AATF's African leadership and management will neutralize such criticism. “It gives it incredible credibility,” he says. The foundation's real success, however, will be measured not by who sits in its boardroom, but rather by what it can deliver to the tables of millions of impoverished Africans.


    Rising Deficits Could Doom Science Programs

    1. Jeffrey Mervis

    Two years ago, as head of the New Jersey Commission on Science and Technology, John Tesoriero handed out $25 million a year in research funding to universities and high-tech companies, fertilizer for the state's growing economy. Now the former cell biologist has received new marching orders from the state's governor: Shut down your office by 27 June, lay off an eight-person scientific staff, and pull the plug on 20 projects in a 5-year pipeline of funded grants.

    Rocked by the current economic downturn, governors across the United States are pruning science and technology programs aimed at fostering economic development. New Jersey's $5 billion budget deficit, which triggered Governor James McGreevey's proposed cut last month, is dwarfed by a $40 billion hole in California, where Governor Gray Davis wants to shut down all state-funded technology programs. Michigan's Life Sciences Corridor, once a $45- million-a-year initiative backed by the state's billion-dollar slice of a nationwide settlement with the tobacco industry, is in the midst of two rounds of cuts that would shrink it to $20 million —while adding homeland and energy security to the mix of eligible projects. The recession may even swallow up the innovative Alaska Science and Technology Foundation, set up in 1988 with a $100 million endowment that is unique among states. This month Governor Frank Murkowski proposed shifting the entire fund, which has shrunk to $87 million because of the slumping stock market, into the general treasury and killing off the foundation.

    Severe damage.

    The demise of the Alaska Science and Technology Foundation would cut off funding for earthquake motion sensing and other high-tech projects.


    The irony in cutting programs designed to bolster economic growth during a recession isn't lost on scientists. “It's not a good idea to eat your seed corn,” says George Happ, a biologist at the University of Alaska, Fairbanks, and director of Alaska EPSCoR, a federal program to raise the quality of the state's academic research. “Once that money disappears into operating funds, it's not likely to be used again for science.”

    Most chief executives say that they are swinging the budget ax reluctantly but that plummeting state revenues and constitutional requirements to avoid running a deficit leave them no alternatives. This month, for example, newly elected Michigan Governor Jennifer Granholm listed a proposed $12.5 million cut in the Life Sciences Corridor for 2004—after lopping off $12.5 million for this year's competitive grants program—under “other tough choices.” In January, California's Davis touted the state's Regional Technology Alliances, one of several programs in an $18-million-a-year effort to promote research, barely a week before his proposed 2003–04 budget zeroed them out. Tellingly, Davis also promised in his 3 January speech to be “more aggressive in partnering with the federal government,” announcing his hope that Uncle Sam might bail out the state's beleaguered research activities.

    The New Jersey commission, formed in 1985, had recently earned high marks from two outside panels that studied its efforts to build the state's research capacity in strategic areas and to “incubate” start-up companies. “One said that if the state didn't have a commission, the governor would have to create one,” says Tesoriero. He's hoping that supportive state legislators might salvage at least bits of his program, which had already shrunk to $14 million this year.

    Hans Roeterink, who just became head of the Alaska foundation on 15 January, says that he was prepared for the challenge of carving out a high-tech sector within what Happ describes as “a resource-driven economy.” His goal was to focus on talented entrepreneurs and give them the tools to succeed. But he admits that “creating the right soil for high-tech companies to grow” will be next to impossible if the entire organization disappears. “The governor's budget message talks about cutting redundant programs,” says Roeterink. “But there's nobody else doing what we are doing.”


    Gravity Mission Faces Make-or-Break Review

    1. Andrew Lawler

    A controversial space mission to test Einstein's General Theory of Relativity has been on the brink of extinction several times in its 4-decade-long development. But just as the $600 million mission is finally poised for launch, it faces perhaps its toughest challenge yet. NASA officials have ordered another review of the mission, called Gravity Probe B (GP-B), in the wake of a failed engineering test and continuing cost overruns. A negative review, they say, would doom the project. Mission supporters say the space agency is exaggerating what are only minor technical troubles.

    The probe, the brainchild of Stanford University physicist Francis Everitt, consists of four exquisitely sensitive gyroscopes that will search for evidence that time and space are dragged along by Earth's rotation, as relativity predicts. Such measurements of frame dragging, taken by a 700-kilometer-high spacecraft, require a degree of precision that the Stanford- industry team building the instruments has struggled to achieve. As they have labored, scientists have proposed other ways—some far cheaper—to measure the same effect, although their efficacy is hotly debated. NASA space science chief Ed Weiler says he wants to know “if the time has come to put an end to GP-B.”

    GP-B has endured a bumpy ride on its long journey to the launch pad. The latest difficulties surfaced late last year, when the probe failed an important engineering test in a sealed, airless chamber that simulates the extreme thermal conditions of space. After the test, engineers found several blown fuses on the spacecraft.

    It's not clear what caused the problem. One outside researcher familiar with the test results says that leaks in ground-support equipment likely led to short circuits of the fuses before the test and do not indicate a problem with the spacecraft itself. “This project is not broken by any measure,” says Charles Pellerin, an astrophysicist and former NASA manager who has served on GP-B advisory panels and calls the latest event “an ordinary technical problem.” But NASA officials have demanded another round of tests, and Weiler says he won't sign off on a launch without “a completely successful thermal vac[uum] test.”

    Under stress.

    Gravity Probe B, shown here before undergoing a critical thermal vacuum test that simulates conditions in space, faces new scrutiny from NASA.


    Everitt says that the test likely will be done again. But he insists that the probe is sound and that NASA's response is “an extreme overreaction.” Other mission supporters worry that too much thermal testing could damage the delicate spacecraft.

    Everitt estimates that the additional tests will require pushing back the launch from June to September, adding $26 million to the cost. But NASA's more conservative estimates suggest a November launch and a new tab of at least $36 million. “And that's on top of $130 million [in overruns] since 1999,” complains Weiler. Another NASA official estimates that GP-B's launch date has slipped by nearly 3 years since 1999. Although NASA has already spent more than $600 million on the mission, Everitt says that GP-B's overall costs are higher because it never received the usual boost in funding at critical times during its development.

    Last week, Weiler set up two independent teams to review the scientific and technical worthiness of the mission and report back in mid-April. The scientific team, to be led by University of Chicago astrophysicist Michael Turner, will pit GP-B against a range of potential alternatives and examine whether GP-B's merits outweigh delays to other space science efforts. A technical panel will study why the vacuum test failed and whether there are other outstanding engineering issues.

    A 1995 National Research Council report gave GP-B a yellow light, calling it “an extraordinarily well-designed experiment” but warning that technical hurdles remain. The panel did not compare GP-B with other space science missions. Weiler warns that another bailout will force him to defer work on the Laser Interferometer Space Antenna, newly proposed in the 2004 budget request and slated for a 2011 launch. Grounding GP-B would also save $60 million in launch costs, he adds.

    There is no love lost between Weiler, a blunt-talking manager who has long expressed skepticism about the mission's cost and scientific value, and Everitt, a soft- spoken and articulate lobbyist with friends in Congress who have thwarted past attempts to kill the program. Weiler already faces a budget crisis without GP-B, thanks to rising cost estimates for the James Webb Space Telescope. But Everitt is determined to save his project: “I never relax.”


    Academy to Mediate Debate Over Rocket-Fuel Contaminants

    1. Rebecca Renner*
    1. Rebecca Renner is a writer in Williamsport, Pennsylvania.

    Should tens of millions of U.S. residents worry that their children's drinking water is contaminated with tiny amounts of a rocket-fuel ingredient? The Environmental Protection Agency (EPA) says yes; the Department of Defense (DOD) and the defense and aerospace companies that manufacture or use the chemical, perchlorate, say no. Now, hard on the heels of a senator's call for rapid regulatory action, EPA, DOD, and several other agencies have agreed to let the National Academy of Sciences (NAS) settle the issue. But some scientists are worried that the new study may be more of a way to delay new standards than a quest for truth.

    Both sides agree that perchlorate can decrease thyroid hormone levels, and thyroid hormone levels affect brain development. But EPA relies primarily on lab animal data that show effects at low levels of exposure, whereas the defense groups emphasize human data that show no such effects. A January 2002 EPA draft report recommended a drinking water concentration of 1 part per billion (ppb) as safe for human health, whereas DOD says the number is likely to be much higher.

    The academy study will push back the final version of the EPA toxicological review, which had been expected early this year, says William Farland, EPA's acting deputy administrative director for science: “I feel strongly confident in the scientific analysis that we have put forward, but there are also genuine differences of opinion.” Jeff Cornell, adviser to the deputy assistant secretary of the Air Force, agrees: “We have a difference in interpretation that we can't solve, so the best thing to do is take it to the NAS—the Supreme Court of science.”

    The latest development caught most EPA scientists involved with perchlorate by surprise. Some suspect that DOD called for the review with the goal of delaying costly cleanup operations. The military was “involved with study design and paid for much of the work,” says Kevin Mayer, EPA's regional perchlorate coordinator in San Francisco. “But when they saw how the data was interpreted, they didn't like it,” he says.

    Not so, says Cornell. “The overriding concern of the Air Force and the Department of Defense is public health. What we know about the human health, environmental, financial, and operational impacts of perchlorate contamination is that it is a very large, important issue, and we have to get it right.”

    The Administration request came 1 week after Senator Barbara Boxer (D-CA) introduced a bill that would require EPA to set a regulatory standard for perchlorate in drinking water by 1 July 2004. Three days later, military officials told the Senate Armed Services readiness and management support subcommittee that things are moving too fast. “We've excited the American people with little science to back it up,” said H. T. Johnson, acting secretary of the Navy. DOD officials argue that EPA cannot order testing and cleanup of perchlorate until it sets a drinking water standard.

    Point source.

    Perchlorate seeps via ground water into the Colorado River from this Kerr-McGee facility near Las Vegas.


    Military and defense industry sites are the principal sources of perchlorate contamination. Perchlorate salts are used as oxidizers in solid rocket fuel, which has a limited shelf life and must be replaced regularly. From the 1950s until recently, large volumes were washed out of missiles and rocket boosters onto the ground or into holding lagoons, according to a report by the American Water Works Association Research Foundation. To date, 75 perchlorate release sites have been located in 22 states. Cleanup costs are likely to be enormous, say environmental engineers familiar with the problem.

    EPA's draft recommendation draws upon studies suggesting that mothers who drink perchlorate-contaminated water could give birth to children with lower-than-average IQ, according to EPA toxicologist Annie Jarabek of Research Triangle Park, North Carolina, the EPA draft's principal author. In a 1999 study, the IQs of 48 children of hypothyroid women were 7 points lower at age 7 to 9 than were those of children of mothers without the condition. Rat experiments conducted for the EPA review indicate that low levels of perchlorate disrupt thyroid hormones and interfere with brain development in pups.

    Studies involving adult volunteers suggest that low levels of perchlorate are not a cause for concern, however, at least in people with sufficient levels of iodine. Monte Greer and colleagues at Oregon Health and Science University in Portland and other teams used radioactive iodine isotopes to find out the relation between perchlorate and iodine uptake by the thyroid. Greer has reported that 180 to 220 ppb should be safe. But such studies aren't relevant, insists Grant Anderson, who studies thyroid hormones and brain development at the University of Minnesota, Twin Cities. Thyroid hormones exert their greatest effect on brain development just before and shortly after a baby is born, he says.

    The now-delayed EPA review is the first step toward setting a regulatory standard for drinking water. The process usually takes 6 years after the review is finalized. The NAS request will slow this process; such reviews usually take about 2 years.


    Stem Cells Lose Market Luster

    1. Gretchen Vogel

    Companies racing to turn human embryonic stem cells into disease treatments are reducing their staffs—and, in some cases, their expectations

    When John Gearhart first asked the U.S. National Institutes of Health (NIH) whether it might fund his efforts to extract stem cells from aborted human fetuses, he got the cold shoulder. “Phone calls just went unanswered,” says Gearhart, a developmental geneticist at Johns Hopkins University in Baltimore. “When I'd see [NIH managers] at meetings, they'd run away.” The proposed work, although legal and within NIH's guidelines, was apparently too hot to handle.

    But just as he was about to shelve the idea, Gearhart met Michael West, the CEO of a small biotech company called Geron, who had heard him pitch his plans at scientific meetings. West bankrolled the work, and in November 1997, Gearhart's team and a rival group led by James Thomson of the University of Wisconsin, Madison, reported that each had isolated human pluripotent stem cells. Without Geron's backing, Gearhart says, his team might never have been in the running to make that important discovery.

    Biomedical researchers aren't likely to receive that kind of corporate manna these days. The stock market slump and subsequent evaporation of venture capital is being felt keenly across the biotech landscape. Hit particularly hard is one of the hottest areas of all: human embryonic stem (ES) cells and therapeutic cloning, the creation of stem cell lines that are identical genetically to a prospective patient's. According to the biotech analysts BioCentury, the amount of venture capital invested in cell therapy companies has fallen 50% in 3 years, to $50.2 million in 2002, mirroring the plunge in stock prices in the sector. The depth of suffering among stem cell companies reflects how far off profits may lie. “The days when [venture capitalists] invested in such speculative research are over,” pronounces Robert Lanza of Advanced Cell Technology (ACT) in Worcester, Massachusetts, a privately held firm. “The time frame to reach the clinic is too long for them.” Analyst Steven Dickman of Techno Venture Management in Boston agrees. “The science remains very interesting, but from a [venture capitalist's] perspective, the bloom is off the rose.” The outlook for publicly traded companies such as Geron isn't much better, Dickman says. “They have to spin their results so that shareholders see the excitement. But it's not the same level of excitement people saw a few years ago, and so far investors haven't gotten any money back.”

    Indeed, the companies that funded much of the early work on human ES cells—prized for their potential to develop into any tissue in the body—are trimming their sails or fighting for survival. West's current company, ACT, has lost three of the four high-profile scientists it recruited with much fanfare in early 2001: Tony Perry and Teruhiko Wakayama, the first researchers to have cloned mice, and Tanja Dominko, a top expert on efforts to clone primates. Well-endowed new labs at Japan's RIKEN Center for Developmental Biology lured Perry and Wakayama, and Dominko is attempting to get a new company called CellThera off the ground. PPL Therapeutics in Edinburgh, U.K., and Blacksburg, Virginia, announced last spring that it would get out of the stem cell business and focus on projects that could make money sooner. In January, Geron, based in Menlo Park, California, laid off 40 of its 90 staff members, including two dozen who were involved primarily in stem cell research. And at BresaGen, a company that has derived several human ES cell lines, the stem cell division has lost nearly a third of its staff in the last 6 months.

    Arrested development.

    Work with human embryonic stem cells (here in undifferentiated colonies) has slowed with the slump in the biotech market.


    This retrenchment means that in the United States, at least, the vast majority of stem cell scientists will have to rely for funding on the source that initially gave Gearhart the brush-off: the federal government. And that means they will be hemmed in by restrictions on their research, the most cumbersome of which limits federally funded work on ES cells to cell lines derived before 9 August 2001 (Science, 17 August 2001, p. 1242). Only nine such lines are now available. “It's like doing experiments with one hand tied behind your back,” says Doug Melton of Harvard University. Access to the approved lines is often slow, and any research on how human ES cell lines change over time is crimped, as the NIH lines have all been kept in culture for months or years. “No early-passage ES cells are available, period,” Melton says. Moreover, the drying up of private funds could achieve something the U.S. Congress has so far been unable to bring about: a block on research involving human therapeutic cloning. Without access to deep private pockets, says Lanza, such research is unlikely to make big gains in the United States any time soon.

    After the fall

    The breakthroughs from Thomson's and Gearhart's labs in 1997 occurred when private money was relatively easy to come by: Investors were pouring cash from the booming stock market into biotech firms, which were riding a wave of excitement generated by the race to sequence the human genome. Other potential funding sources could afford to sit back and watch. “At the start, there weren't a lot of academic or government grants going to the area,” says Robert Klupacs, CEO of ES Cell International (ESI), a company based in Australia and Singapore. “Most of the money came from private sources.”

    And flush the companies were. In March 2000, Geron's share price peaked at more than $69, valuing the company at more than $1 billion. As Science went to press, Geron shares were selling for $1.70, and the company, on paper, was worth $42.6 million. PPL Therapeutics, which was involved mainly in animal cloning but also ran stem cell projects, traded as high as $320 in early 2000. Last week: $11.

    The response at Geron has been to lay off more than half of its work force, among them 62 scientific staff members. In a round of layoffs last June, the company let go 33 researchers, most of whom were searching for inhibitors of telomerase, an enzyme that the company hopes to exploit in cancer treatments. A second round of layoffs in January included 29 researchers, many of whom worked on stem cells. CEO Tom Okarma explains that the company's work had matured to the point that it could be handed over to Geron's collaborators in academia, as the cell lines it studies are all eligible for NIH funding. The company is continuing to fund human ES cell work in a dozen academic labs and at the Roslin Institute near Edinburgh. Both rounds of layoffs, Okarma explains, have helped Geron keep 2 years' worth of cash in the bank.

    Okarma was upbeat about Geron's prospects at a biotech conference in New York last month. He told investors and fellow CEOs that Geron researchers have managed to coax their human ES cell lines to become liver, heart muscle, and blood cells as well as neurons. He predicts that the first clinical trials will take place within 5 years.

    Lanza is not so optimistic about ACT's path to the clinic. Although he says the company is nearing a deal that will put it on stable financial footing, recent belt-tightening has crimped research. “We've had a number of experiments that had to come to an abrupt halt while we struggled to stay alive,” he says. Lanza claims that ACT has a series of promising animal results with its line of monkey stem cells. But the expensive experiments have been put on hold, he says, while the company shores up its finances.

    BresaGen, too, has curtailed its research, as its stock price fell from more than 90 cents a share in late 2000 to 15 cents last week. With only a year's cash left, says CEO John Smeaton, “the next year or two is going to be pretty challenging.” The company, based in Athens, Georgia, and Adelaide, Australia, is continuing its efforts to coax its human ES cell lines—which are also eligible for NIH funding—into nerve cells that could treat spinal cord injuries. But the pace has slowed as layoffs and attrition have reduced its stem cell division from 35 to 25 people.

    Still optimistic.

    In spite of a stock price slide (see graph), Geron CEO Tom Okarma is bullish on his company's outlook.


    PPL Therapeutics has taken an even more drastic step: It is getting out of the stem cell business altogether. In February 2001, the company grabbed headlines when it claimed it could reprogram skin cells from cattle into stem cells that could turn into a range of tissues, including heart muscle. Exploiting that approach in humans would be far less controversial than using cells from fetuses or embryos, but it is years away from treating patients, says David Ayares, PPL's vice president of research. In an effort to reorganize and conserve its dwindling cash, the company announced in March 2002 that it would shed its “regenerative medicine” assets: its stem cell work and its patented techniques for creating transgenic animals to harvest for organs. After an unsuccessful search for a buyer, Ayares says, PPL has cobbled together enough private capital to underwrite a spinoff called Regenecom, which will be announced officially in the next few weeks. Attracting investors was not easy, Ayares says. Without the nearer-term prospect of xenotransplantation products, he says, it would have been impossible to launch a company exclusively on stem cells.

    Growth potential

    One island of stability in the uncertain stem cell world is Australia. Instead of layoffs, ESI plans to add staff in 2003, says Klupacs. The company initially received $17 million from the Singapore government and private backers, and both sources of funding “are prepared to continue to invest in these tough times,” Klupacs says. While other firms downsize, ESI, which owns five of the NIH-approved stem cell lines, has grown from seven employees to 20 in the past year and plans to double that number in the coming year or two. At the same time, he says, the firm has narrowed its focus to the development of pancreatic islet stem cells for treating diabetes. Klupacs aims to have the cells in clinical trials by October 2005. As part of that thrust, ESI last December bought the rights to diabetes-related stem cell research at Curis, a biotech firm based in Boston. The deal allows Curis's six stem cell staff members to remain in Boston but work for ESI.

    That kind of arrangement may become more prevalent if global financial conditions continue to worsen, says BresaGen's Smeaton. “We've been offered the chance to buy most of the cell-therapy companies in Europe in recent months,” he says. “There's a lot of intellectual property out there at very low prices.” At the moment, though, potential buyers, whether venture capitalists or drug companies, are wary. “Big pharma has been burned by new technologies,” Smeaton says. “They put lots of money into xenotransplantation and gene therapy, with little to show for their investment.” Klupacs adds, “The companies don't do deals anymore until you have real clinical data.”

    Although stem cell companies have suffered serious setbacks, the technology is by no means moribund. “We've seen patterns like this before in biotech,” says Smeaton. “Commercial interest in fields like gene therapy or monoclonal antibodies went into hibernation for awhile. Research activity went back to the academic sector for several years and then came back.” Enthusiasts can only hope that stem cells will be able to work their powers of rejuvenation in the marketplace as well as on the bench.


    New Asian Schools Look West for High-Quality Instruction

    1. Dennis Normile

    South Korea, Japan, and Taiwan are all launching graduate universities that hope to attract English-speaking faculty members, students—and international respect

    TOKYO—The job market for academic scientists has gone global. Job seekers routinely mail or e-mail applications across borders. Search committees are multinational, the better to ferret out candidates from around the world. And a scientist who has earned a Ph.D. in one country, done a postdoc in a second, and held an academic position in a third would scarcely raise an eyebrow among personnel managers.

    Most of this mobility involves Europe and North America, however. Exchanges with Asia remain largely one-way, as Asian scientists fill academic positions in the West but few Westerners make the move East. Now, a new breed of Asian graduate schools and institutes—the first one opened this month in South Korea—hopes to redirect the flow by offering English-language instruction and attracting faculty members and students from outside their home countries.

    The new schools (see chart) are seen as the next stage in the steady improvement of graduate education throughout the region. “It's an evolutionary step toward being part of the world of science and scholarship at the highest levels,” says Philip Altbach, director of the Boston College Center for International Higher Education. Observers warn, however, that success is likely to take a long time and require sustained support, both financial and political.

    View this table:

    In January, Seoul National University (SNU) announced plans for the Korea Bio MAX Center, a biotechnology institute that will concentrate on research but whose faculty members will have some teaching duties. Seoul Information Technology University (SIT) debuted on 3 March with an initial class of 100 students. This month, officials in Japan are expected to select a site for a new graduate science university in Okinawa, an experiment in using graduate education and research to help revitalize an impoverished region. This spring, Taiwan's Academia Sinica hopes to receive legislative authorization to grant doctoral degrees.

    Japan's effort is the most ambitious. The new graduate university is intended to be a multidepartment, world-class research university, stocked with Nobel Prize-level talent—all built from scratch in a remote area. The school could eventually host 200 faculty members, recruited without regard to nationality. A second goal is to boost the economy of Okinawa, Japan's poorest region.

    Organizers say that Okinawa's isolation is actually an asset because the school is trying to avoid a long-running battle between the Ministries of Health and Education that has thwarted attempts to more closely integrate experimental molecular biology and patient care. “There is nothing there now,” says Ken-ichi Arai, dean of the University of Tokyo's Institute of Medical Science and a member of the international advisory committee, adding that “Okinawa's status as a special economic zone” makes it easier to tear down bureaucratic walls.

    But going it alone comes at a price. Japan's academic community is unhappy about being left out of the planning. “This proposal grew out of political considerations without thought of how it should fit into Japan's overall higher education policy,” says Toru Umakoshi, a professor of education at Nagoya University, who has just returned from a sabbatical year at SNU. He says that preparation for the Okinawa grad school has largely sidestepped Japan's education ministry and academic community. In contrast, he says, the planning for Bio MAX involved representatives from all relevant university departments. “There is a question as to whether Okinawa can ever be a center of learning,” he says.

    SNU molecular biologist Yim Jeongbin, who will direct Bio MAX, says the rigid separation among the school's academic departments has limited the multidisciplinary approach that has fertilized biotechnology elsewhere. Bio MAX, he says, will offer a common home for molecular biologists, agricultural and medical researchers, informatics specialists, and device engineers. Officially launched in January, Bio MAX will start recruiting staff members shortly and hopes to fill at least a third of its 60 new professor positions with non-Koreans. While it doesn't intend to enroll its own students, Bio MAX faculty will be expected to offer some classes through existing departments. SNU hopes that non-Korean faculty members will help spread the use of English through its graduate programs and boost the school's appeal to foreign students.

    In contrast, the Taiwan International Graduate Program at Academia Sinica is all about students. The new graduate program is intended to expose students to cutting-edge experimental work using techniques and equipment not available at existing universities, says program director Ovid Tzeng. Academia Sinica is currently offering Ph.D. programs in cooperation with local universities, but it wants to take full responsibility for the programs. Adding a graduate program won't trigger a hiring boom, however, because the courses will be taught by existing Academia Sinica staff members. That staff is still dominated by ethnic Chinese, although it is recruited internationally.

    SIT's distinguishing characteristic will be “very strong interaction with the IT industry,” says Chung KunMo, president of Hoseo University in Seoul and chair of SIT's advisory committee. Located in the heart of Teheran Valley, South Korea's answer to Silicon Valley and the home of the country's booming IT sector, SIT is offering internships and work-study programs and hopes to link future entrepreneurs with venture capitalists to better prepare students for the real world. For the first semester, only one member of the faculty is a foreigner, and he's a part-timer borrowed from an international management consulting firm. But the school anticipates hiring several top-level U.S. academics as it expands.

    New kid on the block.

    SIT is wedged into Seoul's version of Silicon Valley.


    One challenge facing all the new schools is attracting sufficient numbers of foreign faculty members and students to provide an international flavor. “The success of this project really depends on recruiting qualified non-Korean researchers,” says SNU's Yim. Academia Sinica, sensitive to charges that it is out to steal the best students from local universities, hopes that three-fourths of its Ph.D. candidates will be non-Taiwanese.

    One existing institute suggests that it is at least possible to attract good foreign faculty members to Asia: Singapore's Institute of Molecular and Cellular Biology (IMCB), at which 13 of 35 principal investigators hail from North America or Europe. “When we were starting, no one believed we could attract qualified researchers from the advanced countries, but we did,” says Chris Tan, who became IMCB's founding director in 1987 after working overseas for many years. Tan stepped down as director last year and serves on the board of advisers to the Okinawa graduate university. But even IMCB has yet to attract more than a handful of graduate students from the West.

    Adequate funding is critical, says Tan. Yim says that South Korea's Ministries of Education and Trade and Industry have jointly promised at least $200 million over 5 years to get Bio MAX up and running. But government support is still a dream for the private SIT, bankrolled by Kang Chul-Koo, an entrepreneur with interests in architecture, construction, and real estate. George Strawn, executive officer for the computing sciences directorate at the U.S. National Science Foundation and an adviser to the program, says that SIT really needs “a broader financial base.” Organizers hope South Korean IT companies will lead the way.

    Japan's new school also faces formidable financial hurdles. As Japan's poorest region, Okinawa receives approximately $3 billion a year in economic subsidies from the central government, mostly for public-works projects. The university's supporters hope to tap into those road-building funds to cover the operating costs of the school. But that idea may not sit well with local and national construction officials, contractors, and site workers. The outcome of that tug of war may become clear this fall when the budget for the next fiscal year takes shape.

    Backers of all these schemes admit that their ventures are hardly risk free. But they believe that the consequences of standing pat—and failing to train their students to world-class standards—leave them no choice but to try.


    Robotic Telescopes Catch Up With Gamma Ray Bursts

    1. Robert Irion

    Optical flashes spotted just minutes after two bursts portend a bright future for understanding the universe's most violent explosions

    Robots still can't master the mundane—like mowing the lawn or washing your socks—but they can pull off some spectacular feats. Astronomers have trained robotic telescopes to sweep the skies in one of the field's most glamorous pursuits: the hunt for gamma ray bursts (GRBs), brief but enormously powerful blasts of high-energy radiation from deep space. Now, after years of unrealized hopes, the automatons have come through—with surprising results.

    Reports this week describe two GRBs spotted late last year by an x-ray satellite, which beamed the locations of the bursts to an Internet-based alert network on the ground. Within minutes, rapidly pivoting optical telescopes photographed fiery “afterglows” of lower energy visible light, created as shock waves from the bursts reverberated through space. The events—just the second and third ever seen so quickly—have thrilled experts by revealing one unusually persistent fireball and illuminating the brief life of another that otherwise would have passed unnoticed.

    “These are about as different as you could possibly imagine two bursts being,” says astrophysicist George Ricker of the Massachusetts Institute of Technology (MIT) in Cambridge. “People now realize how much can be done in the first few minutes” to explore those differences, he says.

    Theorists believe that so-called long GRBs—those lasting a few seconds to a few minutes—arise within ferocious beams of particles and energy spawned when a massive spinning star collapses to form a new black hole, which swallows most of the star. Models predict that such a “collapsar” spits out narrow jets that explode into space along the star's axis. Gamma rays stream from turbulence within the jet itself, the theory holds. “These should be the fastest bulk motions in the universe,” says astrophysicist Bing Zhang of Pennsylvania State University (PSU), University Park. Only the small fraction of explosions with jets aimed directly at Earth would appear as GRBs; the rest might look like ordinary supernovas.

    According to the currently reigning model, GRB afterglows arise when a jet hits gas or dust in space near the burst. A violent “reverse shock” cascades back into the jet itself and sparks a flash of optical light that quickly expires, says astrophysicist Peter Meszaros of PSU. The leading edge of the jet then keeps plowing forward, spewing x-rays and optical light as it gradually slows down during the next hours and days.

    In a flash.

    The 0.76-meter KAIT, a robotic telescope at Lick Observatory in California, nabbed the glow of a December gamma ray burst less than 2 minutes after a satellite spotted it.


    “This fireball model is a nice description, but we have needed more detail about its initial evolution,” says astrophysicist Andrew MacFadyen of the California Institute of Technology (Caltech) in Pasadena, a creator of the collapsar scenario. That's because the jet moves fastest during the earliest phases of the afterglow, opening the clearest window onto the central engine that powers it.

    Not long ago, such early detections seemed set to become routine. Several groups of astronomers built small robotic telescopes to monitor wide swaths of the sky, often several times a night, in a quest for rapidly varying or moving objects. Programmers designed the systems to interrupt their scans if they received an Internet alert from NASA's Compton Gamma-Ray Observatory (CGRO) or the Dutch-Italian BeppoSAX satellite. Most systems weren't cheap—typically $250,000 in hardware costs and perhaps four times that for the complex software needed to control them. Still, astronomers knew there was no other way to ensure a rapid GRB follow-up on the ground, because big telescopes can't whip to a random spot on the sky that quickly.

    The first sighting was spectacular. On 23 January 1999, the Robotic Optical Transient Search Experiment (ROTSE), telephoto lenses on a swiveling platform near Los Alamos National Laboratory in New Mexico, caught the fantastically bright optical emission from the most powerful burst yet seen, GRB 990123 (Science, 26 March 1999, p. 2003). That image, snapped just 22 seconds after the explosion began, remains the only optical record of a burst in progress.

    But the robots wouldn't strike again for nearly 4 years. Burst alerts dwindled as CGRO and BeppoSAX expired in 2000 and early 2002, respectively. Meanwhile, on Earth, astronomers realized that their robot scopes needed bigger lenses or mirrors to catch typical GRB optical glows, which are less than 1% as bright as GRB 990123's flash. Consequently, most GRB images on the ground were taken hours or days later by astronomers at larger telescopes, long after the crucial initial flash was gone.

    The current GRB sentinel in orbit is the High-Energy Transient Explorer-2 (HETE-2), launched in October 2000. HETE-2 spent its first year beset by a degraded optical filter and funding woes (Science, 30 November 2001, p. 1817). But now, says mission leader Ricker of MIT, it's all systems go as HETE-2 beams down sky positions for about 20 bursts per year. Even so, it takes a chain of good fortune—quick and accurate positions, accessible spots on the sky, clear observing conditions—for robots to spot the glows within a minute or two.

    Two of HETE-2's latest detections have set the field abuzz. On 4 October 2002, the satellite spotted a bright GRB about 10.7 billion light-years away. Although it was too low in the sky for U.S.-based robotic telescopes to see, an automated system in Wako, Japan, captured an image just 193 seconds after the explosion. The burst alert also jangled the cell phone of Caltech astronomer Derek Fox, who leapt out of bed to send a command to the upgraded 1.2-meter Oschin Telescope at Caltech's Palomar Observatory, which ordinarily scans for near-Earth asteroids. That telescope took several images starting 9 minutes after the burst.

    As Fox and his colleagues report this week in Nature, these and myriad other observations of GRB 021004 paint a fascinating portrait of a stubbornly bright afterglow. Its light subsided at a leisurely rate, in stark contrast to that of GRB 990123 and the other recent burst spotted by HETE-2 (see figure, p. 1833). “Our story is that something continuously refreshes the reverse shock,” says Caltech astrophysicist Shrinivas Kulkarni, who was scheduled to appear with Fox this week at a NASA press briefing in Washington, D.C. “The only way to do that is to keep adding energy.”

    Not fadeaway.

    An October burst (red curve) dimmed far more gradually than two other rapidly detected afterglows.


    Fox and Kulkarni see two plausible explanations. First, the central explosive engine powering the jets could remain active for much longer than expected. If so, the collapsar would be a sort of inferno rather than a single detonation, perhaps driven by material falling back onto a raging accretion disk around the newborn black hole. Second, the jets themselves might drag slower material along their edges, forming an extended spray of matter to feed the reverse shock.

    No such behavior was evident in a much shorter burst seen by HETE-2 on 11 December 2002, for which robots played the critical role. First on the scene in 65 seconds was RAPTOR, an advanced telephoto-lens system based at Los Alamos. At that early phase, the afterglow was the second-brightest yet seen, says astronomer W. Thomas Vestrand, leader of the RAPTOR team. Vestrand's group has fixed a software bug that prevented an even faster image, so he expects RAPTOR to take data as early as 10 seconds after future explosions.

    The best records of GRB 021211 came from the Katzman Automatic Imaging Telescope (KAIT) at Lick Observatory near San Jose, California. KAIT, a 0.76-meter telescope designed to discover scores of supernovas per year, swung to the GRB less than 2 minutes after the blast. In the next 10 minutes, KAIT took 18 exposures, producing by far the most detailed tracing of a GRB's early output.

    GRB 021211 dimmed so fast that its afterglow might have escaped notice without the robots, says KAIT director Alex Filippenko of the University of California (UC), Berkeley. In earlier years, astronomers might have classified the event as a mysterious “dark” GRB with no visible afterglow. “Now, it seems that dark bursts may just fade very quickly and be faint to begin with,” says astronomer Weidong Li of UC Berkeley, lead author of a report on GRB 021211 in the 20 March Astrophysical Journal Letters.

    It's too soon to draw conclusions about early GRB behaviors with just three good samples in hand, Filippenko notes. That will soon change. A NASA satellite called Swift, set for launch in December, should spot and study about 100 bursts per year. A growing fleet of perhaps two dozen telescopic robots worldwide will respond obediently to Swift's notices. Leading systems include Super-LOTIS at Kitt Peak National Observatory in Arizona and a Spanish collaboration called BOOTES. ROTSE, now an international program led by the University of Michigan, Ann Arbor, is installing four identical telescopes in Australia, Namibia, Texas, and Turkey. An Italian team has erected a new 0.6-meter Rapid Eye Mount automated telescope for GRB studies in Chile, and an older 1.5-meter telescope at Palomar Observatory will be fully roboticized later this year.

    Even veterans of cosmic mayhem are bracing themselves for more surprises about GRBs from Swift and this robot army. “Ten years ago, I would have said that we understand how massive stars die,” says Kulkarni. “Now, I think there is a huge variety of ways, and gamma ray bursts are the tip of the iceberg.”


    Unwelcome Bison May Face a DNA Test

    1. Anne Minard*
    1. Anne Minard is a science writer in Flagstaff, Arizona.

    The tools of modern genetics could help biologists determine whether a troublesome bison herd has a historical right to roam the Grand Canyon

    GRAND CANYON, ARIZONA—Biologists may hold in their hands the fate of a wandering bison herd at Grand Canyon National Park. The animals, which rumbled into the park recently, are remnants of a cow-bison hybrid experiment nearly a century ago. No one is certain whether the beasts are descendants of pure bison used in crosses or the crosses themselves. But park managers do know one thing: They want the destructive bison to leave. And evidence of cattle genes in the animals' DNA could be the ticket.

    The trouble started last year when the herd, typically culled by the Arizona Game and Fish Department to about 100 individuals, doubled in number and began to roam. Hunters haven't been as lethal as usual. And a years-long drought has scorched forage in the “House Rock Valley” area of the Kaibab National Forest, sending the animals in search of greener pastures to the south. Park biologists say the massive creatures—males can weigh a ton or more—are making pests of themselves by creating mud and dust wallows on the park's North Rim, crushing native grasses, and trampling archaeological sites. Park officials say their mission is to preserve and protect the native wildlife, not coddle exotic species.

    At first, the state and federal agencies debated how to keep bison out of the park. A fence seemed an unlikely solution. Anything designed to keep out bison would likely preclude the migration of other, undisputedly native species such as mule deer. And any fence capable of stopping bison would have to be a real bear: The behemoths can clear obstacles nearly 2 meters high.

    But the argument has gone deeper now. It centers on two issues: whether bison have a historical claim as native species in this region, and, second, whether the animals in the herd are pure bison.

    For state biologists, history isn't a problem: “The department maintains buffalo herds for the people of Arizona and has not needed to resolve the question of whether buffalo were historically present,” says John Goodwin, a Game and Fish biologist based in Flagstaff. The agency brought in about $40,000 last year from buffalo hunting permit sales.

    But for park biologists, history is the key. Nobody disputes that the large, shaggy beasts were here during the Pleistocene, more than 10,000 years ago. But there's no record of them between the Pleistocene and the early 20th century, ruling them out as a native species. “We don't have a consensus” even among park staff, says Jeffrey Cross, Grand Canyon's chief of natural resources. “If you draw the line at 10,000 years, yeah, bison were native. So were a lot of other things. We're not talking about bringing everything back.”

    James Mead, a paleontologist at Northern Arizona University in Flagstaff, says bison did roam the Four Corners area after the last ice age, albeit in smaller herds than those roaming across the plains. But their remains have not been found around House Rock Valley. Mead says that could be because no one has really looked in areas where habitat was suitable: caves and lush forests frequented by the existing herd.

    “If the park really wants to say there's no historic record, we need to go out and look in obvious places,” he says. The park may enlist Mead for that work.

    Buffalo Jones's legacy?

    Park officials want to evict a bison herd of suspect lineage that has trampled archaeological sites.


    Park scientists are also considering another tactic. They want to conduct genetic tests to see if the bison are harboring cattle genes. It's a gamble. If they turn out to be part cow, the park will have a strong case for their removal. If they're pure bison—and native—they're likely to be guaranteed the right to stay.

    The ancestors of the House Rock Valley bison were herded into Arizona in the early 1900s by an infamous character named Charles Jesse “Buffalo” Jones. He had the idea of breeding cattle-bison hybrids, which he dubbed “cattalo.” It didn't go smoothly. Male calves from the first crosses, owing to their characteristic humped back, often aborted or caused their mothers' death. The hybrid heifer calves could breed with bison bulls, but their male offspring were usually sterile. Jones's investors got impatient and bailed out, and the bison were eventually sold to the state of Arizona.

    James Derr, a molecular geneticist at Texas A&M University in College Station, is eager to tell the rest of the cattalo story. Derr and his colleagues have found evidence of cow mitochondrial DNA, which is passed down from mothers, in about 40% of modern bison herds across the country. “We know what Charles ‘Buffalo’ Jones mitochondrial DNA looks like,” he says, adding that Jones used a limited number of cattle breeds in his crosses. Mitochondrial DNA is a good first test for hybridization, he says, but it's not the last word. If hybrid bulls are crossed back to bison heifers, those offspring will have pure bison mitochondrial DNA but will retain cattle genes in their nuclear DNA. Within several generations, Derr says, a herd could look like bison and show pure bison mitochondrial DNA but conceal cattle genes in the nuclear genome.

    For that scenario, Derr has identified 54 microsatellite markers —repetitive, highly specific DNA sequences—which he uses to distinguish the nuclear DNA of cattle from that of pure bison. “No other wildlife species has been attacked with so much technological horsepower,” Derr says. He has tested bison at Badlands, Yellowstone, Grand Teton, Wind Cave, and Theodore Roosevelt national parks, and he now has his eye on the Grand Canyon's problem herd. If its members are pure, he says, “there is potential it could be a genetically and historically valuable bison herd.”

    Such a finding could force Grand Canyon to accommodate—and even protect—the “intruders” that have wandered into the park. And Mead sees wider implications. Don't just limit the bison to the Kaibab Plateau and the Grand Canyon, he says: “Make darn sure they're real bison—not tofu-eating half-breeds”—and then let them roam all over the West.


    How Much Are Human Lives and Health Worth?

    1. Jocelyn Kaiser

    By using new assumptions on the dollar value of a human life, among other things, John Graham hopes to determine which regulations deliver the biggest bang for the buck

    The Bush Administration's Clear Skies plan for cutting the emission of air pollutants from power plants looks like a great deal for public health. Cleaning up the air will, by 2020, prevent some 12,000 premature deaths each year and thousands of cases of bronchitis. Economists at the Environmental Protection Agency (EPA) say the value of these and other health benefits totals $93 billion—14 times the $6.5 billion cost of reducing emissions. But the agency adds a caveat: An “alternative analysis” states that the benefits add up to just $11 billion, for a much slimmer benefit-to-cost ratio of 2:1—barely worth the effort, some might say.

    The lower figure comes compliments of White House budget officials, who urged EPA to plug different numbers into its formulas for calculating benefits—for example, by assuming that old people's lives are worth less than those of younger folks. It is part of a push from the Office of Information and Regulatory Affairs (OIRA) within the Office of Management and Budget (OMB) to get agencies across government to change the way they do cost-benefit analyses for major rules. The goal is both “quality” and uniformity: “OMB has a strong interest in cross-agency comparisons,” says OIRA director John Graham, who says they can help “allocate scarce resources.”

    Activists and some government economists, however, assert that these techniques are an excuse for inaction, as the new analyses invariably eat away at the benefit side of the equation. Although the new math is too recent to have swayed a regulatory decision, Wesley Warren, a former OMB official now at the Natural Resources Defense Council (NRDC) in Washington, D.C., predicts it soon will: “Once [OIRA has] got the framework in place, they can consistently justify a weaker level of protection.”

    Apples and apples?

    Recent OIRA calculations suggest that vehicle safety regulations save lives more cheaply than a smog (NOx) rule and one protecting workers from methylene chloride.


    Although economists generally support the call for more rigorous cost-benefit analyses, some question whether OIRA's techniques are ready for prime time. Especially controversial is Graham's proposal that agencies incorporate into environmental regulations some measures used in health care. “People are both apprehensive and expectant about the effects” on regulation, says environmental economist Alan Krupnick of Resources for the Future (RFF), a think tank in Washington, D.C.

    Graham came to Washington 2 years ago hoping to bring more rigor to the setting of regulatory priorities (Science, 14 December 2001, p. 2277). A former Harvard professor, Graham has long championed the idea that the billions of dollars spent on cutting environmental pollution might actually improve health more if they funded less costly health and safety interventions, such as preventing accidents. But the inconsistency in how various agencies add up costs and benefits posed an obstacle. On 3 February, in draft guidelines updating OMB's guidance on risk analysis, Graham laid out new procedures that make it easier to compare alternatives.

    Some of the specific approaches OIRA is encouraging can drastically lower economic benefits. A key variable in calculating benefits of health regulations is the dollar figure put on a human life. EPA's original Clear Skies analysis values a human life at $6 million, an average derived mostly from studies of wages for high-risk jobs and surveys asking people what they think a life is worth. OIRA considers the wage studies unreliable because they reflect the preferences of workers, not the general population. At the office's urging, EPA redid the analysis using a figure of $3.7 million per life, based on surveys alone. OIRA also asked EPA economists to assume that the lives of people over 70 are worth just 63% of this amount, based on a 20-year-old British survey that found that older people valued their lives less than younger people.

    When EPA factored in these and other changes, the benefits from the Clear Skies initiative shrank by one-seventh. To Warren, this means that a tougher (and more expensive) proposal in Congress probably won't go anywhere.

    Similarly, EPA originally calculated that a proposed rule cutting emissions from snowmobiles and other off-road vehicles would yield benefits by 2030 of $77 billion; when the agency redid the analysis using OIRA's instructions, the benefits shrank to $9 billion. Another controversial Graham recommendation—assigning less value to an avoided cancer death—will also likely push down the benefits for water and pesticide regulations, say activist groups.

    Al McGartland, director of EPA's National Center for Environmental Economics, acknowledges that there are legitimate arguments about what specific numbers should be used. Krupnick and colleagues at RFF, for instance, take issue with the practice of valuing the lives of the elderly at 63% of those of the young. In their recent surveys in Canada and the United States, they say, the elderly put nearly the same value on their lives. Others have disputed OIRA's push to use a higher “discount rate”—a technique to account for what money spent on regulations would earn if it were instead invested—of 7% rather than the 3% EPA normally uses. (OIRA's new draft concedes somewhat on this point.)

    Also problematic, say a number of economists, is OIRA's proposed requirement that, in addition to calculating costs and benefits, environmental economists assess regulations based on health tradeoffs—an example of a process known as cost-effectiveness analysis. This approach doesn't put dollar figures on the benefits of different health outcomes; it converts them to health units, such as reduced illness or lives saved.

    For example, health economists use surveys to rank outcomes on a 0 to 1 scale, with 1 being a year of perfect health and 0 death. They then multiply this value by the years of illness—so 4 years of avoided heart disease might be 0.6 × 4 = 2.4 years of health, known as Quality of Life Years (QALYs). If the same number of QALYs can be gained with, say, a $1000-per-year new heart drug as with a $10,000 surgery, then a doctor might recommend the cheaper drug.

    Many economists agree that such health-outcome measures could be useful for comparing environmental alternatives—for example, reducing radon in water versus air. But Graham wants to use them to compare regulations across agencies to determine the “biggest bang for the buck.” Harvard risk analyst James Hammitt cautions, however, that health-outcome measures, which place a premium on years of perfect health, are biased against the elderly and infirm. Critics say that means environmental regulations, which often protect the weakest, tend to look less effective compared to, say, use of child car seats.

    The QALY approach for air pollution, EPA economist Bryan Hubbell has found, makes the value of saving elderly lives dwindle compared to that of avoiding bronchitis cases in younger people. He concludes that QALYs “may not be appropriate” if the goal is the best outcome for the entire population. Nor does cost-effectiveness analysis take into account subjective factors such as people's greater fear of involuntary risks and nonhealth benefits. But OIRA's guidelines say that agencies can't use these nonquantifiable effects as “trump cards” to overturn the hard numbers.

    Objections aside, Graham has asked agencies to supply raw data on cost effectiveness so OIRA can do its own comparisons of regulations across agencies (see table). Ultimately, he says, OMB will use these comparisons to help set agency budgets.

    View this table:

    Graham acknowledges that the analyses he recommends have limitations and says OIRA will revise the draft guidance in response to comments. But critics doubt that tweaking the details will mean much to the public and policy-makers, who pay attention only to the final numbers. Says NRDC's Warren: “These numbers take on a hyperreality of their own.”


    Wielding the Data-Quality Cudgel

    1. Jocelyn Kaiser*
    1. With reporting by Erik Stokstad.

    John Graham, the White House's enforcer of regulatory policy, has a new instrument that his predecessors didn't have—a so-called data-quality act that took effect last October. It allows anyone to challenge the accuracy of agency reports and rules in the name of improving government decisions.

    Although its goals may be laudable, many scientists, legal experts, and environmentalists fear that this law could block agencies from using new, emerging science and bog down regulations. In a broad swipe at global warming research, for example, one business-oriented group last month asked the White House to withdraw the 2000 National Assessment of Climate Change, saying that the report by a federal advisory committee was based not on solid facts but on “meaningless” computer models. “I am completely freaked out about the data-quality act,” says Wendy Wagner, an environmental law expert at the University of Texas, Austin. “The potential [for harm] is tremendous.”

    The law, slipped into a 2001 spending bill in response to lobbying by an industry group, says that government-issued information has to meet standards for “quality, objectivity, utility, and integrity.” Studies used in “influential” documents have to meet a higher standard than publication in a peer-reviewed journal; agencies must provide enough details to “facilitate the reproducibility [of a study] … by qualified third parties.”

    Ellen Paul of the Ornithological Council in Washington, D.C., worries that the law will trigger complaints that “will burden staff and discourage scientists from working for the government.” And the law “will be exploited to slow regulations,” asserts Virginia Sharpe of the Center for Science in the Public Interest in Washington, D.C. It could even “choke” discussion of preliminary findings, so that “none of us will really ever know what the agency has excluded,” says Wagner.

    Test case.

    Industry groups are using a new “data-quality” law to challenge the government's use of studies finding that the herbicide atrazine is harming frogs.


    Of the handful of petitions filed so far, one criticizing the Environmental Protection Agency's (EPA's) review of the herbicide atrazine could be an important test case. The petition, filed by corn growers and others, concerns studies published last year suggesting that low levels of atrazine in the environment are deforming the reproductive organs of frogs (Science, 1 November 2002, p. 938).

    The petitioners argue that the agency cannot use these studies to regulate until it has developed valid test methods for such hormonelike pollutants, or endocrine disrupters. Otherwise, the frog studies are “unreliable” and do not satisfy the data-quality act, the petition says. “We feel you cannot use EPA's weight-of-the-evidence test,” which says that all relevant studies should be considered, says Jim Tozzi of the industry-supported Center for Regulatory Effectiveness in Washington, D.C., a co-petitioner.

    EPA has sidestepped this argument for now in a January response to comments on its atrazine risk assessment. The agency noted that it was already planning to soon have a scientific advisory panel review the frog studies. Jon Devine of the Natural Resources Defense Council in Washington, D.C., is encouraged that EPA “didn't exclude data simply because there wasn't a protocol.” And EPA risk assessment chief William Farland insists that the agency can use studies that don't follow standardized test methods. “Reproducible,” he says, means that the methods have been explained and that “scientific principles were followed.”

    Industry groups say they're preparing more petitions and are ready to go to court against EPA with the right case. Legal opinion is mixed on whether courts will deem the data-quality act subject to judicial review, Wagner says. But if they do, “it could create an entire new avenue of challenging regulations.”