News this Week

Science  18 Feb 2005:
Vol. 307, Issue 5712, pp. 1022
  1. HIGH-ENERGY PHYSICS

    NSF Stunned by Higher Costs of Proposed DOE Facility

    1. Charles Seife

    The National Science Foundation (NSF) has apparently lost a bet that it could do high-energy physics on the cheap. The bet involves the Rare Symmetry Violating Processes (RSVP) project, which turns out to be far more costly than envisioned a year ago. The fallout has cast doubt on the future of the long-delayed experiment and triggered a reshuffling at its host lab, the Department of Energy's (DOE's) Brookhaven National Laboratory in Upton, New York.

    RSVP is designed to give scientists new ways to measure the properties of the “weak force” that is responsible for nuclear decay. It may also produce evidence for an as-yet-undetected class of particles that could account for most of the matter in the universe. Although DOE rejected the proposal in the mid-1990s as part of a decision to concentrate on nuclear physics at Brookhaven, NSF officials viewed RSVP as an exciting piece of frontier research. They also liked the fact that it would use an existing accelerator, the Alternating Gradient Synchrotron (AGS), as the source of its proton beams, an arrangement that promised to hold down costs. So NSF decided to pick up the tab.

    One of the experiments, MECO, hopes to spot the decay of a muon into an electron, an event that, if it happens, would point to a flaw in the Standard Model of matter. The second experiment, dubbed KOPIO, looks at the decay of the K-long meson. Its results would measure one of the fundamental parameters of the weak force.

    Last fall, after a long wait in NSF's queue of proposed facilities, RSVP received $15 million to start building what was projected to be a $158 million facility. “It was finally put in the [construction] budget,” and things looked great, recalls Joseph Dehmer, head of NSF's physics division.

    Anticipating a green light for construction, NSF last spring appointed physicist William Willis of Columbia University as project manager. Willis promptly commissioned a top-to-bottom review of RSVP, including updated cost estimates for construction and operations. That's when things got ugly.

    In November, project scientists revealed that preparing AGS to handle the high-intensity, long- duration demands of RSVP would cost a good deal more than anticipated and bump up the price of the experiment. “Right before our eyes, huge numbers started to emerge,” says one knowledgeable lab official. “It ballooned up to $300 million or above.”

    Cursed ring?

    The Alternating Gradient Synchrotron, which feeds the RHIC accelerator, isn't currently able to support RSVP. The fiscal implications of that problem have apparently cost Brookhaven's Thomas Kirk (left) his position.

    CREDITS: (LEFT) COURTESY OF BROOKHAVEN NATIONAL LABORATORY (BNL); GRAPHIC ADAPTED FROM BNL

    Willis says that figure, which includes a much larger contingency fund than originally planned, is the outer limit of what RSVP will cost. “The feeling now is that the [final] number will be considerably lower than the upper bound,” he says.

    Nevertheless, the news turned heads at NSF, which promptly informed the National Science Board, its oversight body, as well as the legislators who set NSF's budget. “We thought it was a clever idea for doing science at a small, incremental cost,” says Michael Turner, head of mathematics and physical sciences at NSF. “But the assumption of parasitic operations just didn't work out because circumstances have changed. … I've had a number of unpleasant weeks going around Washington, explaining that we've had a significant increase in costs.”

    To understand why RSVP's price tag soared, Turner says, think of AGS as an expensive racing car that is used only to commute to work. The commuter is Brookhaven's Relativistic Heavy Ion Collider (RHIC), the centerpiece of the lab's nuclear physics program. AGS was the premier U.S. proton accelerator of its day during the 1960s and was intended to feed ISABELLE before that proposed accelerator was canceled in 1983. “The stewards of the AGS used to be high-energy physics,” Turner explains. “The stewards are now nuclear physics. This means that the mentality of running that complex has changed.”

    Instead of running AGS as an independent, high-energy physics machine and maintaining it accordingly, Turner says, Brookhaven used it as a mere injector—which was all that was needed for RHIC operations. The problem, notes Turner, is that NSF hadn't anticipated the need to get AGS back into shape to do high-energy physics.

    Those changing circumstances appear to have toppled Thomas Kirk, Brookhaven's associate laboratory director for high-energy and nuclear physics. “I didn't jump; I was pushed,” says Kirk, who in early February was given the new position as special assistant to Praveen Chaudhari, Brookhaven's director. His successor is Sam Aronson, who has been chair of the physics department at Brookhaven. Chaudhari declined comment on the reshuffling.

    This week Turner asked DOE's High Energy Physics Advisory Panel to examine the significance of the science RSVP will perform under different funding scenarios. That information will be combined with RSVP's internal review of costs, due to be completed this spring, into a report that could determine RSVP's fate. “We will reevaluate [RSVP's] scientific value, its cost, and then make a decision,” says Turner.

  2. NIH FUNDING

    Success Rates Squeezed as Budget Growth Slows

    1. Jocelyn Kaiser

    The president's 2006 budget request last week contained dismal news for biomedical researchers—a mere 0.7% raise, to $28.8 billion, for the National Institutes of Health (NIH). And the fine print was just as bad: Success rates for grant applications are projected to be 22% this year, down from 30% in 2003. That slump, along with an 8% drop in the number of new grants (see table, below), confirms predictions of tough times following the recent 5-year doubling of NIH's budget if NIH received annual increases of less than 6% (Science, 24 May 2002, p. 1401).

    In the last years of the doubling, NIH held the success rate (the portion of applications funded) at around 30% to avoid creating an unsustainable number of new grants. Instead, administrators increased average grant size and put more money into infrastructure. A year ago, NIH hoped it could pull off a “soft landing” after the doubling ended in 2003: It predicted only a slight dip in new and competing grants in 2004 and recovery in 2005, with a still-healthy 27% success rate. (“New and competing” refers to newly funded projects and grants coming up for renewal, which make up about one-fourth of all grants in the NIH portfolio. The rest are continuations of multiyear grants.)

    CREDIT: NIH

    But NIH received less money in 2005 for research grants than even the 2.7% increase it had expected, explains NIH Associate Director for Budget Richard Turman. NIH has also received far more applications than predicted since 2003, as some investigators increased the number of proposals they submitted. On the bright side, says NIH Deputy Director for Extramural Research Norka Ruiz Bravo, the number of new investigators supported each year continues to rise.

    At NIH council meetings last month, some institutes announced a lowered pay line in 2005, the peer-review ranking that is the cutoff for funding. That news is raising the specter of a return to the early 1990s, when tight budgets forced reviewers to make “dysfunctional” decisions about equally good applications, says Howard Garrison, public affairs director for the Federation of American Societies for Experimental Biology.

    He and others are worried that some investigators may be forced to trim staff or even leave research. “It's very hard, after downsizing your lab, to build back up again,” says Susan Gerbi, who until recently was chair of molecular biology at Brown University. She hopes Congress will heed that message as it considers NIH's 2006 budget. “We are holding our breath” in current competitions, says Gerbi.

  3. U.S. IMMIGRATION POLICY

    New Rules Ease Scientific Exchanges

    1. Yudhijit Bhattacharjee

    The United States last week changed its visa rules to make it easier for foreign students and scientists working on sensitive technologies to reenter the country after overseas trips. The new policy, announced last week by the State Department, extends the validity of security clearances, now 1 year, to 4 years for international students and 2 years for foreign scientists.

    Until now, foreign scholars working in certain fields had to undergo an extensive interagency security review—known as a Visas Mantis check—every time they wanted to reenter the United States. Only those who had received a clearance within the preceding 12 months were exempt. In the tightened security environment after the 2001 terrorists attacks, that procedure resulted in major delays for thousands of international graduate students and researchers returning to the United States after visiting their home countries or attending conferences overseas. After complaints from scientific and educational associations, federal officials promised to extend the validity of Mantis clearances (Science, 27 August 2004, p. 1222).

    “We now have better information sharing between federal agencies and systems to track whether students and researchers have changed their fields of study,” says C. Stewart Verdery, outgoing assistant secretary for Border/Transportation Security Policy at the Department of Homeland Security and one of the officials who worked on the extension. “Given those factors, it seems like a redundancy to do repeat security checks for the same individual.”

    The new policy “eliminates a lot of uncertainty for foreign students in the United States,” says Nils Hasselmo, president of the Association of American Universities. More broadly, he says, “it sends a message that international students and scholars are welcome here.”

    Scientists in other countries who visit the United States often will also benefit from another change that extends the validity of a Mantis clearance for such visits from the duration of a single visit to a year. Verdery says the change ensures that “security constraints don't make the United States less attractive as a venue for scientific conferences.”

  4. PLANETARY SCIENCE

    And Now, the Younger, Dry Side of Mars Is Coming Out

    1. Richard A. Kerr

    The news from Mars lately has been all wet: a shallow, salty sea where the rover Opportunity landed, and rock-rotting groundwater, at least, where Spirit is roaming in Gusev Crater's Columbia Hills (Science, 17 December 2004, p. 2010). Although the planet was indeed drenched in potentially life-giving water, it didn't stay that way long, according to papers published online this week by Science (http://www.scienceexpress.org/). In the papers, 39 researchers led by Jean-Pierre Bibring of the University of Paris, Orsay, report their first results from the mineralogical mapper OMEGA (Observatoire pour la Minéralogie, l'Eau, la Glace, et l'Activité) orbiting Mars on board the European Mars Express spacecraft.

    Among other things, notes planetary scientist James Head of Brown University, OMEGA has spotted water-altered minerals well beyond the two rover landing sites—but none that appear to have formed during the past several billion years. The researchers conclude that for most of its history, Mars resembled the Dry Valleys of Antarctica at their driest rather than a landscape of shallow seas. OMEGA's global perspective “is ushering in an entirely new era of geoscience analysis on Mars,” Head says.

    Scientists say the new, dry-eyed view of martian history came about largely because OMEGA's spectrometer, unlike those on earlier missions, sees well in near-infrared light. In that range, the mineral products of water alteration absorb solar radiation at distinctive wavelengths. Thanks to its spectral edge, OMEGA is handily identifying sulfate salts of the sort the Opportunity rover found at two sites in Meridiani Planum. Sulfuric acid from volcanic eruptions apparently combined with water to corrode martian rock and produce sulfates around the planet. The several hundred meters of light-toned, sulfate-rich sediments beneath Opportunity also appear hundreds of kilometers to the north and east of the rover's landing site, OMEGA found. The intermittently puddled salt flats and salt dunes making up the layered deposit seen by Opportunity were no fluke.

    Whole lot of weathering.

    In Juventae Chasma, a 2.5-kilometer-high pile of sulfate-rich layered sediments (top, in 3D; bottom, from overhead) attests to sulfuric acid alteration.

    SOURCE: J.-P. BIBRING ET AL., SCIENCE, FROM HRSC/MEX (TOP) AND NASA/JPL/MSSS (BOTTOM)

    In fact, OMEGA's partial coverage of the planet has also found light-toned, sulfate-rich layered formations in parts of the great canyon system of Valles Marineris and in the chaotic terrain of Margaritifer Terra. It also found a 60-by-200-kilometer patch of terrain rich in gypsum, a calcium sulfate salt, hard against the northern ice cap. Even the Spirit rover kicked in its own sulfate find this week with the discovery in Gusev Crater's Columbia Hills of finely layered, sulfate-rich sandstone bedrock, says rover science team leader Steven Squyres of Cornell University.

    All the sulfate finds are, as Squyres says of the Spirit discovery, “profound evidence for [rock] interaction with liquid water.” It's just that Mars seems to have been wet so long ago. The rover sulfates almost certainly date from 3 billion or 4 billion years ago, says Squyres, in the planet's first billion years. The canyon and chaos formations appear to be equally ancient, says Bibring, and need not have been formed by surface waters; he and his teammates emphasize instead the possible role of groundwaters and acidic snow and frost. And the gypsum deposit could well be the evaporative residue of a one-time outburst of groundwater at least a couple of billion years ago, says Head.

    Beyond ancient sulfate salts, OMEGA isn't finding much water alteration. “We don't see hydrated minerals like clays” to any great extent, says Bibring. Researchers have debated whether the northern lowland plains, which account for a third of the planet, are covered by silica-rich lavas or water-altered weathering products. OMEGA sees no clear signs of either. Instead, the plains may be masked by the same spectrally enigmatic coating Spirit found on rocks on the floor of Gusev. That gunk may have required no more than a molecular layer of water to form. Hydrated minerals, including clays, do show up in a few scattered spots, most notably in and around craters of Syrtis Major Planitia. But once again, the alteration seems to have been ancient, perhaps due to groundwater altering crustal rock.

    All in all, Mars since ancient times is looking awfully cold and dry. “There should be clays everywhere if Mars truly was warm and wet,” says planetary scientist Philip Christensen of Arizona State University in Tempe. “In isolated places and times, lots of water made evaporites,” he says, but for billions of years, Mars seems to have been “incredibly dry and unweathered.” Perhaps the most dynamic force shaping the martian surface during those eons, Bibring and his colleagues suggest, has been the snow, ice, and glaciers that move between polar and lower latitudes as the planet tilts back and forth on its axis (Science, 11 April 2003, p. 234).

    Next up in martian spectroscopy is the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) that will be launched on board the Mars Reconnaissance Orbiter this August. Even more capable in the near-infrared than OMEGA, CRISM will be checking out likely places for the Mars Science Laboratory rover to look in 2010 for signs of water and life.

  5. INFLUENZA

    Study Questions the Benefits of Vaccinating the Elderly

    1. Jon Cohen

    Because elderly people are most likely to be hospitalized or die from influenza, U.S. policy puts them at the front of the line for flu shots. But a provocative new analysis of influenza-related mortality in the United States over the past 3 decades suggests that the vaccine has had far less success than presumed at preventing death in those over 65.

    The study, led by epidemiologist Lone Simonsen of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, focuses on the riddling fact that U.S. influenza mortality rates in the over-65 population have increased despite a concurrent jump in vaccination rates in that group, from 15% to 20% in 1980 to 65% in 2001. “There's a huge disconnect here,” says Simonsen, whose group published its findings in the 14 February Archives of Internal Medicine.

    Researchers have previously explained this disconnect by pointing to two main factors. One is the aging of the elderly population: Death from influenza increases in the so-called elder elderly. The second is that several particularly nasty flu strains circulated in the 1990s, causing higher mortality rates among those infected. Simonsen and colleagues, whose “ecological” study relied on a mathematical model that crunched data from various databases, attempted to control for these two confounding variables. They concluded that “the mortality benefits of influenza vaccination may be substantially less than previously thought,” that the shortage of vaccine for the elderly this year “will have little impact” on flu-related mortality, and that the mortality benefit found in several “observational” studies—which compare cohorts of vaccinated and unvaccinated people—reflects “systematic bias.”

    Simonsen says the vaccine may benefit some elderly, and she acknowledges that it may reduce hospitalizations, a parameter her study does not analyze. But several studies show that the vaccine is not as effective in the elderly, she stresses, because their immune systems “senesce.” Simonsen and colleagues also say their findings “strongly suggest” that the cohort studies may have wrongly credited the vaccine with preventing deaths because the unvaccinated groups had a disproportionate number of very ill people. People in fragile health right before flu season, they reason, are more likely to die and less likely to receive the vaccine.

    Discordant harmony.

    Why have U.S. influenza rates in the elderly risen in synchrony with vaccination rates?

    CREDIT: WALTER ORENSTEIN/EMORY UNIVERSITY

    The study has provoked starkly different reactions. “This is a very important, troubling study,” says Walter Orenstein, the associate director of the vaccine center at Emory University in Atlanta, Georgia, and the former head of the National Immunization Program at the Centers for Disease Control and Prevention (CDC). “It is a paradigm shift.” But CDC influenza expert William Thompson sharply disagrees: “I think it's extremely weak and overstates the results,” says Thompson, who studies influenza-related disease and death in the United States. Thompson insists that his studies and others have accounted for the bias Simonsen points to in the selection of control groups.

    The polar reactions in part speak to the difficulty of gauging the true impact of influenza. Both the observational studies and this new ecological study “raise interesting questions,” says Kristen Nichol, an epidemiologist at the Veterans Administration in Minneapolis, Minnesota, who has published several observational studies that find a benefit from vaccinating the elderly, “but neither of us really knows what the baseline of mortality is in the absence of influenza.” Specifically, Nichol notes that Simonsen's group measures influenza deaths by looking at “excess mortality” that occurs during the influenza season. But other respiratory illnesses that circulate during the same season can cause death. Cohort studies also have a shortcoming, she says: They rarely analyze blood to assess whether ailing people had influenza.

    Whoever is correct, the Simonsen paper raises policy questions that promise to catalyze a hot debate. The current U.S. flu vaccine policy targets the elderly and the very young—but not school-age children. Yet several studies suggest that vaccinating school-age children, the main spreaders of flu, could provide a substantial indirect benefit to the elderly (Science, 12 November 2004, p. 1123).

    In the United States, about 36,000 people, mostly elderly, die each year from influenza-related disease. “In a way, this study is good news: It says there's room for improvement,” says Simonsen. “There's really a need to get to the bottom of this.”

  6. AVIAN FLU

    First Human Case in Cambodia Highlights Surveillance Shortcomings

    1. Dennis Normile

    The confirmation last week that the H5N1 strain of avian influenza had claimed its first human victim in Cambodia has raised concerns about surveillance capabilities there and in nearby countries. The diagnosis was made not in Cambodia but in neighboring Vietnam, where the 25-year-old woman had sought treatment and died on 30 January. The Cambodian Ministry of Health and the World Health Organization (WHO) confirmed the case on 5 February. Cambodian health authorities subsequently learned that the woman's 14-year-old brother had died earlier of an apparent respiratory disease now suspected to be H5N1, but his remains were cremated before any samples were taken.

    Health authorities believe the two were most likely infected by exposure to sick poultry. WHO and Cambodian health officials heard reports that the disease had wiped out small flocks of chickens in the vicinity of the woman's village in Kampot Province at the southern tip of Cambodia but were unable to confirm H5N1. Cambodia's Ministry of Agriculture later confirmed an outbreak of H5N1 among poultry in Kandal Province, about 100 kilometers away.

    These incidents underscore the need to increase surveillance for H5N1 infections in both animals and humans in Cambodia, Laos, and Myanmar, says Klaus Stöhr, coordinator of WHO's Global Influenza Program. Because they have relatively small poultry populations, there is probably less H5N1 virus in circulation in these countries. But their underdeveloped surveillance capabilities also offer less chance of early detection of an outbreak. Especially if the virus becomes easily transmissible among humans, “the lead time we have to prepare vaccines or distribute antivirals to try to quell the outbreak at its source will depend on the sensitivity of surveillance,” Stöhr says.

    Cambodia and Laos reported minor outbreaks of H5N1 in poultry last year. Many international health experts assumed that additional outbreaks were dying out undetected and without intervention, given low poultry densities and the absence of large-scale commercial poultry operations, unlike Vietnam and Thailand, which have large and highly concentrated poultry farms.

    False security?

    While Vietnam has reported widespread outbreaks of avian flu, Cambodia has confirmed just one human case and one infected farm.

    CREDIT: ADAPTED FROM FAO TECHNICAL TASK FORCE ON AVIAN INFLUENZA

    Because viruses thrive in cooler weather, virologists had expected another wave of H5N1 outbreaks this winter. And since December, both Vietnam and Thailand have reported dozens of outbreaks among poultry. Vietnam has also reported 10 human cases and 9 deaths. International health experts suspected that the H5N1 virus must also be present in Cambodia and Laos, because they are sandwiched between countries with major outbreaks. Both the U.N. Food and Agriculture Organization (FAO) and WHO have been assisting Laos and Cambodia in building surveillance capabilities since last year. But Megge Miller, a WHO epidemiologist in Cambodia, says that country still relies on an informal disease reporting system.

    Monitoring animal health seems equally sporadic. With FAO support, the Cambodian Ministry of Agriculture has been surveying chickens brought to markets. But WHO's Miller says this largely misses chickens families raise for their own consumption. Typically, she adds, these families eat diseased birds; preparing and cooking birds that have died of H5N1 is a suspected route of human infection. After the recent human case, Cambodian officials launched an advertising blitz, with leaflets and radio broadcasts warning of the dangers of contact with sick poultry. Similar efforts seem to have paid off in Thailand, says Supamit Chunsuttiwat, senior expert on communicable diseases at Thailand's Ministry of Public Health, where no human cases of H5N1 have been reported since last fall.

    Meanwhile, FAO is planning to dispatch additional technical consultants to both Cambodia and Laos. Regional bird flu cooperation is likely to get a boost from a joint meeting on avian influenza control to be held by FAO and the World Organization for Animal Health 23 to 25 February in Ho Chi Minh City, Vietnam.

  7. BIOMEDICAL RESEARCH

    Despite Protests, MRC to Move Its Largest Institute Into London

    1. Eliot Marshall

    CAMBRIDGE, U.K.—Researchers at one of Britain's top biomedical centers learned last week that their months-long campaign to prevent the sale of the center's 19-hectare campus has failed. The National Institute for Medical Research (NIMR)—which has a staff of more than 700—will be relocated from the London suburb of Mill Hill to the city-center campus of University College London (UCL). The university intends to appoint an undetermined number of NIMR's 66 research leaders to its faculty.

    The move represents a “unanimous decision” of the Medical Research Council, the government funding agency that runs the center, according to an MRC statement on 11 February. MRC chiefs had long argued that the suburban institute should sit alongside a medical school and hospital to advance “translational research” (Science, 4 February, p. 652). UCL beat out its rival King's College London to become NIMR's home because it has more depth in physics and chemistry, as well as greater “maturity” in clinical research, the MRC statement said.

    Scientists at NIMR had mounted strong resistance to the planned move, with some even threatening to resign. Malcolm Grant, provost of UCL, immediately set out to reassure them. He hopes they will stay with NIMR because the partnership “will bring huge benefits on both sides,” he says. The university already has strong collaborations with NIMR scientists, he notes, particularly in research on children's diseases. He proposes that the main part of NIMR's campus be set alongside the university's new medical complex on Gower Street. Grant planned to meet with NIMR researchers in person on 15 February.

    New home.

    University College London has been chosen to host the U.K.'s National Institute for Medical Research.

    CREDIT: UNIVERSITY COLLEGE LONDON

    There are still “a number of hurdles to be cleared” before the relocation can occur, Grant concedes. Among others, the project must win a large chunk of government funding. It must also receive approval for extensive renovation of buildings in the city and must find a home for NIMR's extensive animal lab—a tricky proposition in Britain, where animal-rights extremists have fought construction of animal facilities. And Grant fears UCL may not be able to duplicate one of the advantages the institute now enjoys: a category 4 biosafety research lab. “We will explore this,” he says.

    Some NIMR research leaders who had opposed the move from Mill Hill were not available for comment last week, but others were looking on the bright side. NIMR immunologist Dimitris Kioussis says, “This could be a very good thing for the institute,” although he acknowledges that “we haven't heard about any detailed plans of what they are offering.” Guy Dodson, head of structural biology at NIMR, also stressed that “there are a lot of positives” in MRC's decision, because “UCL is a very strong university.”

    An inquiry into the controversy by the House of Commons' science and technology committee, meanwhile, brushed aside allegations that MRC chief Colin Blakemore had improperly pressured NIMR staff to go along with the relocation. Released on 8 February, the report faulted some aspects of MRC's review of the move but concluded that Blakemore handled his part with “professionalism, objectivity, and competence.”

  8. GENE THERAPY

    As Gelsinger Case Ends, Gene Therapy Suffers Another Blow

    1. Jennifer Couzin,
    2. Jocelyn Kaiser

    Five years after 18-year-old Jesse Gelsinger died in a gene therapy experiment, the U.S. Department of Justice has reached a settlement with the researchers and with their institutions. The department announced last week that the University of Pennsylvania (U. Penn) will pay fines of $517,496, and Children's National Medical Center in Washington, D.C., will pay $514,622. The settlement also restricts the clinical research of the three investigators.

    The Department of Justice alleged that toxic reactions in humans should have halted the trial earlier and that the lead investigators misrepresented clinical findings to the study's overseers, such as the National Institutes of Health (NIH) and the Food and Drug Administration (FDA). James Wilson of U. Penn, who had a financial interest in a company that stood to profit if the trial was successful, has agreed not to lead any FDA-regulated clinical trials for 5 years and be monitored for 3 years. Steven Raper of U. Penn and Mark Batshaw of Children's face less severe restrictions. Under the agreement, the scientists do not admit responsibility for Gelsinger's death. “Outrageous,” responds Gelsinger family attorney Alan Milstein, who said the family had hoped for a formal apology and the release of the clinical trial documents.

    While the Gelsinger case drew to a close, the field of gene therapy suffered another setback last month: A third child in a French trial for X-linked severe combined immunodeficiency (X-SCID) developed leukemia, French authorities reported on 24 January. Seventeen children have been successfully treated for SCID using gene therapy, making it the field's bright spot. But two patients in the French trial developed leukemia in late 2002 after a vector inserted near an oncogene; one child died last October. In response to the third leukemia case, the French trial has been halted again and FDA has suspended three U.S. SCID trials, but a trial in Britain continues.

    The two previous leukemia cases in France occurred in infants treated at 3 months of age or less, which led to speculation that cells with the oncogene insertion proliferate more readily in very young children. But the third child was treated at 9 months, suggesting that older children may also be at risk, says Harry Malech of NIH, who heads one of the U.S. trials. Experts expect to discuss the case when FDA's gene therapy advisory committee and NIH's Recombinant DNA Advisory Committee meet in March.

  9. GERMAN SCIENCE

    Board Protest Stops a Shake-Up of the Dahlem Conferences

    1. Gretchen Vogel

    BERLIN—A crisis over the future of the prestigious Dahlem Conferences in Berlin that was brewing into a major furor has been calmed—at least for now. On 14 February, president Dieter Lenzen of the Free University in Berlin, which administers the conferences, agreed to reinstate a staff member whom the administration had dismissed and to protect the meetings from outside meddling with the scientific agenda.

    Lenzen took these steps after he received a letter from members of Dahlem's scientific advisory board charging that the university was damaging the scientific reputation of the meetings and announcing their decision to resign. Several had said they would try to reestablish the conferences outside the university. But Lenzen's last-minute change of heart appears to have mollified at least some of the critics, who say they will give the university another chance.

    The Dahlem conferences, named for the West Berlin neighborhood of villas and leafy boulevards where the conferences are held, were founded in 1974 as a way to boost the divided city's scientific reputation. Two or three conferences are held per year on broad topics such as “Genetic and Cultural Evolution of Cooperation” and “The Dynamics of Fault Zones.” During the weeklong, invitation-only sessions, roughly 40 participants break into working groups to discuss position papers—often drafted to be as provocative as possible—and prepare a synthesis statement to be presented on the final day. The proceedings are published in book format.

    More than 4000 scientists from around the world have taken part in 95 conferences over the past 3 decades. Fans of Dahlem say it offers a unique approach to tackling problems and making interdisciplinary connections. “The Dahlem format is such a great alternative” to the standard conference design, says Gerd Gigerenzer of the Max Planck Institute for Human Development in Berlin, who has led two Dahlem workshops.

    Back from the brink.

    A feud over Dahlem's leadership has calmed.

    CREDIT: THE MIT PRESS

    In recent months scientists involved with the conferences charged that the university was undermining their scientific integrity. Specifically, they claimed that members of an International Advisory Board, established in 2003 to raise funds for the meetings, were attending scientific planning meetings uninvited and that the administration had pressured organizers to highlight Free University researchers instead of international experts in the lineup of participants. In early November, administration officials removed the longtime coordinator of the conferences, Julia Lupp, from her position and forbade her from speaking to anyone connected to the conferences. They said she was on sick leave.

    Members of the scientific advisory board protested that the administration should have consulted them about such an important staffing change and that Lupp had done nothing to deserve firing. In January, an inquiry by a board member and the university found no fault in Lupp's job performance, but the administration refused to reconsider its decision.

    By mid-February, nearly half of the advisory board had decided to resign, and organizers of three planned conferences had withdrawn their proposals and were looking for new venues. The international outcry apparently had an effect. Lenzen agreed on 14 February to reinstate Lupp and to draw up new guidelines to protect the science from fundraising or other pressures.

    Observers say they are cautiously optimistic about Dahlem's future. Eörs Szathmáry of the Institute for Advanced Study in Budapest, who has been coordinating a conference scheduled for May, says he would reconsider his decision to withdraw the workshop if he received “an official, written” letter from the university confirming Lupp's reinstatement and “guaranteeing protection from nonacademic influences.” Gigerenzer says he hoped the university would follow through on its promises. “The first Dahlem conference was one of the best I've ever organized,” Gigerenzer says. “If the conflict is solved, that is good news.”

  10. BIOCHEMISTRY

    Irresistible Lure for Cockroaches Determined

    1. Elizabeth Pennisi

    In search of mates, frogs croak, birds sing, and cockroaches wear their own special perfume. For almost 10 years, researchers have tried to decipher the chemical formula of the male-luring scent emitted by female German cockroaches. Now that formula is finally in hand. As a result, city dwellers may one day be less squeamish about turning on the light at night: The chemical may result in a “very powerful system” for pest control, says Walter Leal, a chemical ecologist at the University of California, Davis.

    On page 1104, Satoshi Nojima, a chemist now at the Shin-Etsu Chemical Co. in Tokyo, Japan, and his colleagues describe the arduous path they took to characterize this chemical, one of several pheromones produced by cockroaches. They also show that a synthetic version of it is a potent attractant for the insects. “It was very difficult to do, very time-consuming,” says Robert Kopanic Jr., an entomologist at S. C. Johnson and Son Inc. in Racine, Wisconsin.

    German cockroaches are the bane of urban residents. As many as 100,000 can live in a single apartment or house; baits and sticky traps are only moderately effective, and insecticides are not environmental friendly.

    So it was exciting news when Coby Schal, an urban entomologist at North Carolina State University in Raleigh, and Dangsheng Laing, now at Atex Bait Co. in Santa Clara, California, reported in 1993 that female cockroaches gave off a volatile compound, or pheromone, that attracts males from meters away. But taking the next step, identifying the pheromone, proved almost impossible. “Every time [we] tried to isolate it, it fell apart,” recalls Wendell Roelofs, a biochemist at the New York State Agricultural Experiment Station in Geneva.

    Love is blind.

    A synthetic version of the female scent that attracts males (on female's back) may help with cockroach control.

    CREDIT: NOJIMA ET AL., SCIENCE

    Adding to the challenge, females produce so little pheromone that researchers needed to dissect 15,000 of them, removing the pheromone-producing gland from each, to extract enough material for analysis. And Nojima—who was working with Roelofs at the time—had to come up with new ways to pin down the attractant among the many compounds in the extracts.

    Nojima joined a single detached cockroach antenna to electrodes and exposed it to the chemicals exiting a gas chromatograph, which had separated the roach extract into discrete components. If the antenna sent a signal to the electrodes, he knew he had a good candidate pheromone. The night before he flew back to Japan—his postdoc was ending—Nojima struck cockroach gold when his system recorded a hit. “After 10 years of work, it came down to one night,” says Schal.

    Fran Webster of Syracuse University in New York found that the newly isolated compound, called blattellaquinone after the cockroach's Latin name Blattella, has a novel structure. But it is similar enough to a commercial product that it is relatively inexpensive to synthesize. The compound clearly attracts male roaches: They prefer the dissolved synthetic pheromone over a control solvent about 93% of the time, on par with their preferences for the natural pheromone. Moreover, field tests at a cockroach-infested pig farm indicate that many males can't resist the synthetic version.

    If the compound proves to be effective over long periods, it could be quite useful for pest control, says Kopanic. Even though blattellaquinone only attracts males, they are the wanderers among the two sexes. The new pheromone should lure males into traps or to poison laced with the compound. In the latter case, they would then transfer the poison, through their feces, to females and their young, suggests Schal. If so, for male roaches, the female scent may one day lead to poison, not procreation.

  11. AGRICULTURAL RESEARCH

    Ag Schools Say They Can't Afford Budget Boost

    1. Amitabh Avasthi,
    2. Erik Stokstad

    Agricultural researchers have long been green with envy at the budgets of U.S. research agencies that fund their colleagues in other disciplines. So President George W. Bush's request last week for a 39% increase in the U.S. Department of Agriculture's (USDA's) signature competitive grants program would seem to be cause for celebration. Instead, university lobbyists have declared war on the proposal because it siphons money from a different program that assured some schools steady funding for infrastructure, salaries, and research on local problems.

    At issue is the Administration's 2006 budget request for $250 million for the National Research Initiative (NRI). USDA officials say it will improve accountability and yield big dividends for agriculture. “We know that competitive grants usually bring out the better science,” says Joseph Jen, USDA's undersecretary for research, education, and economics. USDA also wants to remove a mandated cap on the amount of overhead that institutions can receive for the cost of supporting federally funded research.

    A larger NRI, Jen says, would include more research on obesity prevention and agricultural biosecurity, such as applying genomics to develop better diagnostic tests for animal and crop disease. That's an appealing vision, especially to officials at larger schools. “It's a good move,” comments Peter Barry, director of the Center for Farm and Rural Business Finance at the University of Illinois, Urbana-Champaign. “Increased funding will take the program to a new level and significantly extend its capacity to address major societal problems.”

    Universities don't object to the boost for NRI, which has never come close to being the half-billion-dollar-a-year program recommended in a 1994 report from the National Academy of Sciences. But the 2006 request, they complain, takes a knife to a $550-million-a-year pot that funds agricultural experiment stations at so-called Land-Grant Colleges—mostly state universities—using a formula based on the number of small farmers in the state. The $104 million reduction “would be devastating,” says Thomas Fretz, who heads the Northeastern Regional Association of State Agricultural Experiment Station Directors.

    Plucked?

    Researchers worry that poultry flocks, livestock herds, and other research infrastructure, such as greenhouses, might be cut.

    CREDIT: UNIVERSITY OF MARYLAND COLLEGE OF AGRICULTURE AND NATURAL RESOURCES

    Deans at land-grant colleges worry about activities that don't typically get supported by grants, such as local applications of research. For example, researchers at Colorado State University support the state's $200 million potato industry by working with growers to breed resistance to particular diseases during growth or storage. “We are not likely to get national competitive grants” for such applied research, says Marc Johnson, dean of the College of Agricultural Sciences at Colorado State. Without another source of funding, Johnson and other deans say they will be forced to end applied research and shrink graduate programs.

    Another concern is that the cut in formula funds will hurt infrastructure, such as greenhouses and herds of research animals. “Grant agencies in the past have not liked funding facilities,” says Fretz. But these expenses are no less real, he notes: “You can't have breaks in funding and maintain a dairy herd.”

    To soften the blow, USDA has proposed fencing off $75 million for a competition among land-grant colleges. But department officials are still working out the details, leading to concern that these competitive grants won't be awarded in time to replace the cut in formula funding. “That will leave a pretty big hole for the year,” says Johnson.

    The next step is up to Congress, and lobbyists are already gearing up. “Our number one priority is to reinstate the formula funds,” says Fred Cholick, dean of the College of Agriculture at Kansas State University and chair of the agriculture budget and advocacy committee for the National Association of State Universities and Land-Grant Colleges. Even advocates for NRI doubt that the president will get all that he wants. “I can't see [legislators] giving up their earmarks,” says Karl Glasener, who tracks federal agricultural policy for three scientific societies.

  12. ENVIRONMENTAL RESTORATION

    To Save a Vanishing Sea

    1. Christopher Pala*
    1. Christopher Pala is a writer based in Almaty, Kazakhstan.

    A project backed by the World Bank aims to reverse the Aral Sea's rapid decline, but it could also increase traffic to an abandoned bioweapons testing site

    AKESPE, KAZAKHSTAN—Amid a parched landscape, Denis Zhakupov draws his hand across his chest, recalling how shoreside reeds grew “up to here” in his childhood. The air was full of birds, and the sea was full of fish. “We had everything,” the 60-year-old medic recalls. But his community, like many other towns near the coast of the Aral Sea, has lost its shoreline and its easy fishing. They are victims of an avoidable environmental catastrophe that has devastated this region and given Akespe a problem all its own.

    As the sea withdrew several kilometers to the south, it bared a bottom of fine, alluvial sand. The winds picked it up and blanketed the village, piling up dunes higher than houses that now make the place look like a Saharan oasis—without the palms. Some houses have collapsed under the pressure of drifts. “We have to dig ourselves out every day when the wind blows,” Zhakupov complains.

    Beached.

    A Soviet decision to divert river water to cotton farming hastened the Aral Sea's retreat.

    CREDITS: C. PALA

    Desiccation has been eating at the Aral Sea for 30 years, turning a bountiful source of fish into a salty, inhospitable body of water. The sea shrank by 75% and split into two parts joined by an isthmus: the Small Aral in the north, which includes Akespe, and the Big Aral in the south.

    A regional governor in the north decided to do something about the crisis a dozen years ago and built a primitive dike to prevent the Small Aral from completely draining away. But the dike quickly breached. Workers rebuilt it again and again—seven times in all—finally giving up in 1999.

    After years of monitoring the local efforts, the World Bank agreed to finance a properly engineered dike that includes a sluice to release excess water. The bank also committed to major works aimed at doubling the flow of the Syr Darya, the main river that feeds into the Small Aral. The $85 million project, now under way, “is the biggest attempt to repair a damaged lake that we've seen so far,” says Philip Micklin, an Aral Sea specialist at Western Michigan University in Kalamazoo.

    The new dike and sluice are to be completed this summer. Within 3 years, the Small Aral is expected to rise at least 3 meters and cover about 1000 square kilometers of now-dry former seabed, extending its surface by 25%.

    The water's rise is also expected to increase rainfall, improve pastureland, and cut down on dust storms. The sea's salinity, now at 15 grams per liter, is predicted to fall to 10 grams, a third of the concentration of the ocean and roughly that of the Aral Sea before desiccation began. Fish and other freshwater aquatic life forms that retreated into the Syr Darya delta when the sea became too salty are expected to return, perhaps including the commercially valuable caviar-yielding ship sturgeon. If it succeeds, the restoration will partly undo the damage wrought by 3 decades of Soviet policy. But the dike may also decrease water flow to the south and expose land in the Big Aral that was partially submerged. This in turn is likely to increase traffic across a land link to Vozrozhdeniye (Renaissance) Island, a remote site where the Soviet military once did field tests of plague and other bacteria whose lethality had been artificially increased. Thus the paradox: Reviving the Small Aral could worsen problems around the Big Aral.

    Sacrificed to cotton

    The recent disruption of the Aral Sea began in the 1940s with Josef Stalin's decision that the Soviet Union needed to become self-sufficient in cotton production. This could be done, he declared, by massively increasing the amount of water diverted for irrigation from Central Asia's two big rivers, Uzbekistan's Amu Darya in the south and Kazakhstan's smaller Syr Darya in the north. The sea, which got most of its water from these, would shrink, and a 50,000-ton-a-year fishery would be lost, but the Kremlin calculated there was plenty of seafood coming in from its Pacific and Atlantic fisheries. Today, the skeleton of a huge fish cannery towers over the town of Aralsk, Kazakhstan, once the main port on the northern part of the sea, now 80 kilometers away.

    Since the heavy irrigation began in 1961, the Aral Sea has dropped 22 meters and lost 90% of its volume (Science, 2 April 1999, p. 30). Dust storms have picked up millions of tons of salt and scattered it over neighboring areas, spurring desertification. Pesticides, herbicides, and chemical fertilizers used with abandon during the Soviet period were also picked up by winds, resulting in steep increases in respiratory diseases and cancers—one consequence the Soviets hadn't expected.

    As the sea level dropped, the sea's only nature preserve, located on an island called Barsa Kelmes, became accessible by car in 2000. It had been a primary research center for Soviet-era university studies of desert botany and zoology. Hundreds of saiga antelopes once grazed there; poachers have decimated all but a few, and the park administration no longer bothers keeping wardens there. A summer visitor, after driving for hours on the caked mud of the former seabed, found the scientific station deserted and partly in ruins. Because the water table had dropped, even the sturdy saxaul trees that form the region's biggest vegetation were dying.

    This wasn't the first time irrigation had damaged the Aral Sea region. The Zoroastrian civilization built a vast agricultural network that collapsed in the 3rd century. In the 16th century, the British traveler Anthony Jenkinson noted that abuse of irrigation by Islamic settlers had caused “the great destruction” of the Amu Darya. Both civilizations discovered a simple fact of nature: The region is steeped in plant-stunting calcium sulfate, which is why very little grows, even near rivers. This salt leaches to the surface when land is excessively irrigated and requires increasing amounts of water to wash it away. The modern ecosystem collapse differs from earlier ones in two ways: It happened faster and was accompanied by chemical contamination from fertilizers, herbicides, and pesticides.

    As the crisis deepened, Soviet scientists and policymakers drew up grandiose plans for digging huge canals to divert and bring southward the waters of two of Siberia's northward-flowing great rivers. But when Mikhail Gorbachev came to power in 1985 with a mandate for change, he tossed out the plan as environmentally dangerous and ordered a reduction in the use of river water for irrigation. Uzbekistan, for whom cotton is the main export, ignored him.

    The Amu Darya was still pouring some water into the Big Aral when Uzbekistan gained independence in 1991. To rescue the wetlands around its delta, Uzbek authorities, with international support, built a half-dozen more dikes. As a result, the Big Aral dropped another 7 meters and became so salty that today only brine shrimp survive in it.

    Grim legacy.

    Abandoned buildings on Vozrozhdeniye Island, a former bioweapons testing facility.

    CREDIT: C. PALA

    The economic collapse brought one positive change, however: The use of agricultural chemicals plummeted. Residues seem to have settled or dissipated; the remaining fish in the Small Aral have fewer poisons in their fatty tissues than those in Europe, says Sergei Sokolov, a hydrochemist monitoring the project for the World Bank.

    But the risk isn't gone, Sokolov says. As Kazakhstan's economy improves, the use of fertilizers has been rising. They flow into the river in the fall, after the harvests of rice and cotton, when farmers rinse the ground to wash out salt. “There needs to be a system under which, for 1 month a year, this water is not sent into the river but into special lakes,” Sokolov argues. If not, he warns, “the Small Aral will become polluted.” But Masood Ahmad, the World Bank official in charge of the project, disagrees: He says pollutants will be diluted to a safe level by the river's increased flow.

    New prospects

    Standing atop the smooth, new, 13-kilometer dike financed by the World Bank, most of which is already completed, Aitbai Kusherbayev, the dam's chief engineer and a former governor of the Aralsk region, says he's confident the barrier will work this time. It stands 6 meters high, 3 meters above the planned new sea level, and slopes gradually for about 120 meters toward the water. The seaside will be covered with gravel to resist the waves and the winter ice that dislodged the previous dike in 1999.

    The structure will indisputably benefit the Small Aral. But the three-times-larger Big Aral will suffer as water from the Syr Darya is retained in the north for several years to raise the Small Aral by 3 meters.

    Already, desiccation around the Big Aral has caused Vozrozhdeniye to grow from a 33-kilometer-long island into a 145-kilometer peninsula attached to the coast of Uzbekistan. Until last year, this southern end was too wet even in summer for any vehicle to pass. But access may soon be possible.

    Because of its remoteness, Vozrozhdeniye was used as the main Soviet center for testing bioweapons, antidotes, and vaccines in complete secrecy. In the 1970s and 1980s, the only town, Kantubek, had a population of 2000 in the summer when experimenters were busy. Researchers exposed monkeys, horses, and other animals to weaponized anthrax, tularemia, brucellosis, plague, typhus, Q fever, smallpox, botulinum toxin, and Venezuelan equine encephalitis.

    Biowarrior.

    Former lab supervisor Gennady Lepyoshkin worries that lethal plague bacteria may have survived among the island's rodents.

    CREDIT: C. PALA

    In 1992, Uzbekistan acquired the southern part of the deserted island; Kazakhstan, the northern part. But neither country bothered posting guards, so Kazakh scavengers were able to travel there episodically in small boats to take away pipes, wires, and other materials and sell them on the mainland.

    To a visitor 2 years ago, Kantubek presented a rare glimpse of the world's biggest bioweapons program in ruins. Cages and lab equipment were piled haphazardly, and unused germ suits still could be found in boxes. Most of the equipment in the “hot zone” had been evacuated.

    Russian and Kazakh scientists agree that one potential hazard remains: Military-grade, antibiotic-resistant plague bacteria—very different from the strain endemic in Central Asia—may have survived among the rodents in the testing range, 16 kilometers from Kantubek, despite attempts to minimize risk. Gennady Lepyoshkin, who spent 18 summers supervising a laboratory testing weaponized bacteria such as plague and brucellosis, recalls: “Before we tested, we would spray a poison over the area to kill all wildlife. Then we would bring in our testing animals and release the aerosol with the germs. But there's a good chance that some rodents had stayed in their burrows when the poison gas was released and came out when the germs were passing around them.” Rodents and camels are natural carriers of plague; they don't die of it but spread it through fleas.

    Lepyoshkin says Uzbeks will eventually cross the land bridge to Vozrozhdeniye, and the weapons-grade plague, if it has indeed survived, will spread when island and mainland populations of rodents begin to mingle. “An environmental catastrophe is inevitable,” he claims.

    There is a solution, according to Nikolai Aladin, a professor at the Zoological Institute of the Russian Academy of Sciences in St. Petersburg. Aladin, 51, has been studying the Aral Sea for 27 years, perhaps longer than any other scientist (see sidebar on p. 1033). He proposes building a dike from the northern part of Vozrozhdeniye to the Kazakh mainland that would cause the shallow water on the eastern side to rise and return the foot of the peninsula to marsh, making it impassible for vehicles.

    “There has been talk about it,” says the World Bank's Ahmad, “but so far no work has been done to investigate its feasibility or find financing for it.”

    Micklin, while acknowledging the bioweapons threat, calls the dike project backed by the World Bank “a reasonable approach” for now. He says, “You can't restore the whole sea, given the amount of water you have available now, so restoring the Small Sea and bringing back the fishery is a wise idea, even though it may speed up the decline of the Big Aral.” It boils down to a tradeoff between the clear benefits of restoring part of a devastated ecosystem and the uncertain risks of resurrecting an old threat.

  13. ENVIRONMENTAL RESTORATION

    From Samizdat to Celebrity--and Back

    1. Christopher Pala

    Portly, pony-tailed, and richly opinionated, Russian zoologist Nikolai Aladin has been infatuated with the Aral Sea for nearly 3 decades. The affair began in 1978 when he decided to take a break after defending his thesis at the St. Petersburg Zoological Institute, a part of the Russian Academy of Sciences. Aladin's adviser suggested that he go diving in the Aral's exceptionally clear and pleasant water. But when the 25-year-old reached the port of Aralsk, the sea was nowhere in sight: It had receded more than 30 kilometers—something the adviser had failed to mention.

    Aladin did eventually reach the water, though, and observed that its salinity had increased from 10 grams per liter to nearly 20 in just 18 years—possibly the fastest such rise on record. Yet the sea was alive. He set out to study how salinity impacts aquatic ecosystems.

    But back in St. Petersburg, his proposals were met with evasive refusals. Soviet leaders had decided in the 1950s to sacrifice the fish-rich, closed sea by diverting its source waters to cotton irrigation; they did not wish to publicize the toll on the environment.

    Aladin found a way around them. “My father was relatively well-off as a naval doctor,” Aladin recalled in an interview. “He offered to pay for my field trips.” But it wasn't easy to share his findings. “To publish my first paper in the Soviet Journal of Hydrobiology, which was the first paper on the subject ever, I had to wait for 4 years and agree that all precise geographical coordinates be deleted,” Aladin recalled. He went on to read papers at scientific meetings but had to print and circulate them himself. “It was a soft form of samizdat,” he said, referring to the underground literature of the Soviet days. During official hours, he studied how variations in salinity affect crustaceans in other seas.

    Crusader.

    Zoologist Nikolai Aladin points to where the first dike was built.

    CREDIT: C. PALA

    Aladin's Aral research did not go unnoticed. “Not only is his scientific work impressive, but he has done more than anyone to make people aware of the problems in the region,” says Dietmar Keyser, an Aral Sea specialist at the University of Hamburg in Germany. “He is something of a crusader.”

    Western scientists knew from satellite photographs that the sea was shrinking, but they were unable to gain access to it. “In 1987, I flew over the Aral Sea with a map on my knees,” recalled Rene Letolle, then a professor of geochemistry at Pierre and Marie Curie University in Paris. “I asked my Russian colleagues when I got to Tashkent if it was possible to visit the sea. But they said no, it was a military zone.” He didn't get there until 1995.

    Things began to change in 1986 when Mikhail Gorbachev initiated a policy of glasnost (openness) to expose and improve the sort of policies that had led to the Aral Sea catastrophe. Outrage followed. “It was the Russians who made it a huge public issue, and that's what got the Western attention,” recalled Philip Micklin, an Aral Sea specialist at Western Michigan University in Kalamazoo.

    Aladin, his work now recognized, was handed his own lab, the Laboratory of Brackish Water Hydrobiology in St. Petersburg, which he still heads. He led or participated in many expeditions to the Aral, including one in 1988 involving 100 scientists and intellectuals and a major scientific trip in 1990. “I had lots of funding, and I thought I was making a difference,” he says. He takes credit for impressing upon the Aralsk governor in 1992 the need for a dike to save the Small Aral and for bringing in World Bank officials to see it, which helped prompt the bank's current investment in the area (see main text).

    But when the Soviet Union broke apart, the Russian Academy of Sciences stopped funding Aral Sea research on grounds that it might appear materialistic. International scientific and educational institutions, according to Micklin, also began to “feel that the Aral Sea is not in Russia, so why should we give money to Russians?” Aladin says he was “lucky” to get good support during the early 1990s, but donors since then have favored citizens of Kazakhstan and Uzbekistan.

    For Aladin, there's a sense of déjà vu: “I feel in the same situation as I was in the '80s, except that my father passed away, and I now pay for my field trips from the salary I earn from research of other seas.”

  14. WILDLIFE BIOLOGY

    A Devil of a Disease

    1. Adam Bostanci*
    1. Adam Bostanci is a science writer in Exeter, U.K.

    Tasmanian devils are being wiped out by a deadly facial cancer that may spread when the animals fight each other

    Geoff King, a farmer in Northwest Tasmania, sees a lot of fights at dinner. That's because he also runs a “devil restaurant,” a tour in which customers watch the island's most famous animal, the Tasmanian devil, devour carcasses left out for it. Known as Taz in the cartoon incarnation of the marsupial, the Tasmanian devil is in reality a relatively shy scavenger. But at suppertime, and during the mating season, devils engage in the fighting and biting that have made them legendary. That violence may now be the death of the devils—but in a most unusual way.

    A disfiguring and deadly facial cancer has slashed Tasmanian devil numbers by up to one-half in the past decade. “It's an aggressive cancer that is spreading rapidly and killing animals within 6 months,” says Menna Jones, a zoologist at the University of Tasmania in Hobart. Although several hypotheses are still in the running, clues are emerging that the devils may be transferring tumor cells directly from animal to animal during fights. While research into the unusual cancer, known as devil facial tumor disease (DFTD), continues, biologists this month outlined a management strategy aimed at safeguarding the survival of the species.

    In DFTD, tumors grow on an animal's face and muzzle so that the devil eventually cannot feed. Although the facial tumors were first recorded by a wildlife photographer in 1996, the true threat only became apparent in 2000 when the same tumors were found in statewide surveys. Research picked up momentum in November 2003, when the Tasmanian government dealt out a $1.8 million funding package to tackle DFTD.

    Field research indicates that between one-half and one-third of the 150,000 devils that lived in Tasmania 10 years ago have been lost. According to a report released in January, the disease is now present across at least 65% of the island. And that may be a low estimate; with no diagnostic tests, scientists can only record the disease in obviously sick animals. Instead of breeding four to five times in their life, devils have been reduced to breeding only once before they succumb to the disease, says Jones.

    Although there is no immediate threat of extinction, biologists fear that devils may become “functionally extinct” and no longer perform their role as a bush janitor. Already farmers are noting that dead stock is not cleaned up from their farms, says wildlife biologist Nick Mooney of the Department for Primary Industries, Water, and Environment (DPIWE). His biggest worry is that illegally introduced foxes, which were discovered on the island in 2001, may take over the devils' ecological niche.

    Cancer concern.

    The facial tumors killing Tasmanian devils have a characteristic abnormal karyotype.

    CREDITS (LEFT TO RIGHT): CHRISTO BAARS; DEPARTMENT OF PRIMARY INDUSTRIES, WATER, AND ENVIRONMENT

    The disease management strategy focuses on isolating devils that are already living in captivity—approximately 70 in zoos on the Australian continent and 100 in parks in Tasmania—from wild populations afflicted with the disease. So far there is no indication that devils in captivity are catching DFTD. Wildlife managers will also capture young, apparently healthy devils to establish further insurance populations. Should these devils develop tumors in quarantine, this would provide further opportunities to study the disease. Finally, scientists will experiment with strategies to suppress the disease's spread in the wild, such as removing affected animals in order to protect nearby healthy populations.

    “It's an excellent example of a sensible response to a new wildlife disease about which we know very little,” says Andrew Dobson, a population ecologist at Princeton University who studies wildlife diseases.

    At first, researchers assumed that a virus was behind the spread of DFTD, as similar viral conditions are known in cats and other animals. But efforts over the past year to detect virus particles in tumors have come up empty, prompting research into whether cancer cells themselves spread the disease. “Field observations are consistent with direct biting transmission, and we are waiting for the lab work,” says Jones.

    The lab work so far is provocative but not conclusive. The tumors have been characterized as a neuroendocrine cancer, and tumors studied so far have identical chromosomal rearrangements. That suggests that all the animals with DFTD are being affected by the same cancer cell line. “That's the hypothesis that I would put my money on,” says Jonathan Stoye, a virologist at the National Institute for Medical Research in London, who is impressed by the chromosomal evidence.

    Only one known cancer is spread in a similar fashion. Canine transmissible venereal tumor is passed among dogs during sex, sniffing, and licking. The similar karotypes of these canine tumors had led to the suggestion that the cancer cells themselves are infectious. Indeed, viral oncologist Robin Weiss and his student Claudio Murgia at University College London have recently carried out experiments—soon to be submitted for publication—that demonstrate that these tumors are caused by a single transmissible cancerous cell line. Weiss suggests that profiling the nuclear and mitochondrial genomes of DFTD tumor cells could confirm whether they, too, are a transmissible cell line.

    If direct contact is required for transmission of DFTD, then removal of sick devils would be a very effective way of controlling the disease. But if a virus does turn out to be the culprit, other animals could be asymptomatic reservoirs for the disease. Researchers are continuing to investigate possible causes, from a virus to environmental and humanmade toxins, says Stephen Pyecroft, a veterinary pathologist with DPIWE.

    Tasmania's government and opposition parties have been quibbling over whether to list the devil as a threatened species, but with the data in hand, it is now expected that nomination to threatened species status will go ahead later this year. Worried Tasmanians have donated an additional $50,000 to study DFTD and to make sure the devil does not go the same way as the island's other iconic animal: the now-extinct Tasmanian tiger.

  15. TAXONOMY

    Will DNA Bar Codes Breathe Life Into Classification?

    1. Eliot Marshall

    Biologists hope that a simple tag on all forms of life, and even a hand-held reader, will make classification a 21st century science

    LONDON—The sometimes-dusty world of taxonomy and biological collections held a revival meeting here last week. In the imposing surroundings of the Natural History Museum, on Charles Darwin's birthday, more than 220 experts from 46 countries gathered to discuss a new technology that could change their profession and—some predict—energize the museums in which they work. It makes use of short but specific DNA tags, or “bar codes”—parts of genes present in all living things—to distinguish one species from another. Enthusiasts aim to create a portable device that will identify an anonymous specimen by species and link to a database crammed with biological information. Proponents say they're going to “bar code the planet.”

    The Consortium for the Barcode of Life (CBOL), which convened the meeting,* wants to tag every organism on Earth, starting with the 1.7 million species that have been named and moving on to the estimated 10 million to 20 million that have not. CBOL's leaders foresee many applications, from fundamental research on biodiversity to enforcement of food laws, protection of wildlife, and even biodefense (Science, 13 June 2003, p. 1692).

    It's a grand vision, but the London museum's science chief Richard Lane says it's feasible. He told reporters that a “proof of principle” for DNA tagging has been demonstrated in a study of North American birds, recently published by a group led by Mark Stoeckle of the Rockefeller University in New York City and Paul Hebert of the University of Guelph in Canada. Hebert meanwhile leads a group that's tagging fish in the northern Atlantic Ocean. During the meeting, researchers announced a third major project—one that uses a novel bar code for plants—which will test the method on 8000 plant species in Costa Rica. Partners in this project include scientists from Costa Rica, the Royal Botanic Gardens at Kew, U.K., the University of Pennsylvania in Philadelphia, and the Smithsonian Institution in Washington, D.C. (where botanist John Kress is developing a new plant bar code).

    Hebert, dubbed the “father of bar coding” by Lane and others, explained one reason for the current optimism among those in the field: The price for reading bar codes is dropping. Hebert developed what has become a standard method for DNA-tagging animals. It uses a small part of the mitochondrial genome, 650 to 750 bases of the cytochrome c oxidase I gene (COI), to provide a unique fingerprint. For most eukaryotes, COI variation appears to be lower among individuals within a species than among those from different species; in the study of North American birds, it is about 18 times lower. Hebert said the cost of testing a specimen for COI variation is now about $2, not counting labor, or about 10% of what it was 2 years ago. This prompted Lane to predict that bar coding all of life would be “relatively cheap in terms of other big science projects”: less than $1 billion.

    Muddled over your moths?

    Just check the bar code.

    CREDIT: CHIP CLARK/SMITHSONIAN INSTITUTION

    CBOL's executive secretary, David Schindel of the Smithsonian, said that the push has already begun. The big genome databases—GenBank in the United States and its partners in Europe and Japan—“quietly” set up a bar codes section this month that includes the precise location the specimen came from, he says. About 1000 entries have been made so far, according to Scott Federhen of the National Center for Biological Information in Bethesda, Maryland. Guelph's Hebert and Bob Ward of Australia's Commonwealth Scientific and Industrial Research Organisation aim to supply tags for 15,000 marine and 8000 freshwater fish by 2010. During this time Stoeckle and a group of collaborators plan to bar-code 10,000 bird species. In an independent project, Ann Bucklin of the University of New Hampshire, Durham, and colleagues are gathering bar codes on ocean plankton.

    Some big obstacles remain. One is technical: Experts are not sure that simple bar codes will work for all species. Plants, for example, cannot be tracked with the COI gene. Kress proposes to use a combination that includes a bit of highly variable DNA between two genes on the chloroplast genome. It worked well in a test on Plummer's Island near Washington, D.C., he says, and is now being tried in Costa Rica. Amphibians also pose a challenge because for many, the COI gene varies so much from one individual to the next that it cannot be used reliably to mark species, said Miguel Vences of the Institute for Biodiversity and Ecosystem Dynamics in Amsterdam, the Netherlands. Herpetologist James Hanken, director of Harvard University's Museum of Comparative Zoology, suggested that for certain species such as the amphibians he studies, COI variation may need to be supplemented by extra tests. And very young species—including orangutans—may not be easily distinguished by COI bar coding.

    Another challenge is to find money. Jesse Ausubel of the Alfred P. Sloan Foundation in New York City has steered support to this area and helped launch CBOL, he said, ever since hearing Hebert describe the idea in 2002. Others have joined in, but so far foundations have helped pay for start-up work. To scale up, research groups will need to tap into government budgets, and it remains to be seen how much policymakers want to spend.

    Ausubel said the field is gathering momentum and that funding will follow. He pointed out that several companies sent delegates to the meeting and have invested in the field, including the bioprospecting firm Diversa Corp. of San Diego, California, gene chip maker Affymetrix of Santa Clara, California, and enzyme supplier New England Biolabs of Beverly, Massachusetts. Government agencies, including the U.S. Food and Drug Administration and the U.S. Department of Homeland Security, are also jumping in. “Environmental genomics is going to be huge,” says Ausubel. But the prediction—like many at this meeting—comes from a true believer.

  16. TAXONOMY

    Linnaeus's Legacy Carries On

    1. Greg Miller

    Following the tradition of its most famous taxonomist, Sweden aims to be the first country to complete an inventory and pictorial guide to its biodiversity

    UPPSALA, SWEDEN—Nestled in the heart of this historic university city is a quiet garden with tidy rows of raised beds. It has been restored to the way it looked 260 years ago, when Carl Linnaeus occupied the adjacent house and paced the garden paths, formulating his influential Systema Naturae—a scheme for grouping and naming organisms according to their shared characteristics.

    Linnaeus is a source of national pride for Swedes, many of whom share his appreciation of nature, says Ulf Gärdenfors, deputy director of the Swedish Species Information Center (SSIC), which compiles “red lists” of threatened flora and fauna that are used to guide national and international conservation policy. An entomologist, Gärdenfors is spearheading an effort that would continue the legacy of Linnaeus by making Sweden the first country to create a complete inventory of all of the multicellular species living within its borders. Known as Svenska Artprojektet, or the Swedish Taxonomy Initiative (STI), the project has just entered its fourth year and, Gärdenfors says, is on track to meet its goal of completing the inventory by 2021.

    This is not the first attempt to create an all-taxa biodiversity inventory, as such catalogs are known. But although many biodiversity inventories, including the better-known INBio project in Costa Rica, have struggled to find secure funding (see sidebar), the Swedish project, headquartered at SSIC's woodsy campus just outside of Uppsala, seems to be picking up steam. Last fall, the Swedish government nearly doubled STI's budget to $9.3 million for 2005. If the money keeps coming, supporters say, it will not only fund the inventory but also help revitalize Sweden's natural history museums, train a new generation of taxonomists, and produce a lavishly illustrated set of encyclopedias-cum-field guides written for laypeople.

    Rich heritage.

    In this house 260 years ago, Linnaeus formulated his system for classifying organisms.

    CREDIT: G. MILLER

    The project's two audiences, scientific and popular, are equally important, says STI co-founder Fredrik Ronquist, who's now on sabbatical from Uppsala University at Florida State University in Tallahassee. “There's a lot of emphasis in Sweden on the broader impact of scientific research,” Ronquist says. “[We recognize] the importance of spreading scientific knowledge to the public and making sure it's used by policymakers.”

    No rainforests

    It's fair to say that Sweden is not a biodiversity hot spot. Its 450,000 square kilometers contain an estimated 60,000 species. The same number might be found in a few hundred square kilometers of tropical rainforest, says Daniel Janzen, an ecologist at the University of Pennsylvania in Philadelphia and INBio co-founder. Still, Janzen and others applaud the taxonomy effort. All-taxa inventories “are building blocks that can get us closer to understanding biodiversity,” says Peter Raven, director of the Missouri Botanical Garden in St. Louis. “Whatever someone has the resources and funding to do is great.”

    A complete inventory of all the flora and fauna in any particular area would be a huge boon for ecologists, says Ronquist. Without the full cast of characters, it's impossible to determine how all the players in an ecosystem work together, he says.

    Such inventories are also key for conservation and management. In Sweden, Ronquist says, only about 20,000 species have been considered for inclusion in the red lists: “There is a large number of species for which there's not enough information to even say whether they're threatened or not.”

    Even so, most of Sweden's flora and fauna have already been discovered, which gives STI a big head start. In 2003, SSIC published a list of 50,741 known species. But about two-thirds of these are described in obsolete scientific literature, using outdated criteria, says Gärdenfors.

    Perfect specimen.

    An artist's rendition of the Eastern Puss Moth, based on a blemished museum specimen (right).

    CREDITS: TORBJÖR ÖSTMAN

    Revising the descriptions to bring them up to date with modern naming conventions and species delimitations is a large part of STI's task and will ultimately occupy about 100 taxonomists. Another 40 or so researchers are working on filling in the gaps. Sweden has never had a good inventory of its marine species, Gärdenfors notes: “We had one in the 1920s, but it wasn't systematically done.” Last summer, STI led a team of scientists and divers on a pilot survey of 80 locations off Sweden's west coast, and they are gearing up for a larger and more systematic survey of the west coast in 2006.

    To survey terrestrial organisms, STI scientists are enlisting the help of Sweden's amateur naturalists. Many Swedes, especially among the older generations, pride themselves on being able to identify all of the plants and animals near their homes, says SSIC director Torleif Ingelög, and more than 1000 amateur naturalists contribute data used to compile the Swedish red lists.

    The largest survey at the moment is of two relatively understudied groups: Diptera (flies) and Hymenoptera (ants, bees, and wasps). Amateur naturalists monitor a network of insect traps located at select points throughout the country, periodically emptying the trapped insects into an alcohol solution and mailing them off to a natural history museum, where professional taxonomists identify and catalog them. The estimated 100 million insect specimens collected in 2003 and 2004 may contain hundreds of species previously unknown to science, Gärdenfors says. He adds that 20 new species already have been identified in a single fly genus, Megalesia. As the major gaps in the inventory are filled in, additional surveys will be planned to address the remaining holes.

    But even in the country that gave birth to taxonomy, there aren't always enough taxonomists to go around. A major goal of STI is to bolster this taxonomic infrastructure. STI's current funding supports four or five new taxonomy Ph.D. students each year, a rate that would more than double the number of Ph.D.s in the field in Sweden over the project's 20-year lifetime. And nearly $3 million a year will go to refurbishing another neglected but important part of Sweden's taxonomy infrastructure, its natural history museums, some of which house important collections that date back to Linnaeus's time.

    Pretty as a picture

    While the scientists are busy collecting and cataloging, a team of illustrators is working hard to make the species look their best. Torbjörn Östman is one of nine Swedish artists STI has commissioned to work on the encyclopedias. In a 100-year-old schoolhouse near Lake Malvern that he's converted into his home and studio, Östman shows off a piece of recent work, a fantastically detailed rendering of the Eastern Puss Moth, Cerura erminea.

    To illustrate the moth, Östman worked from two museum specimens, both of which were in bad shape. Using a digital camera attached to a microscope, he captured a set of images of each specimen at different focal planes. He then merged those images and doctored the composite on a computer to create an archetypical example of the hairy black-and-white moth.

    The illustrators working on the encyclopedias use a variety of techniques, but the images all end up looking more or less like watercolor paintings. That's partly because watercolor is a traditional medium for natural history illustrations, Gärdenfors says, and partly because it allows the artists to include all of the key markings and other characteristics for identification—a convergence that's rare in real-life specimens.

    Back to nature.

    Ulf Gärdenfors oversees hundreds of scientists and amateur naturalists working on the all-taxa inventory.

    CREDIT: G. MILLER

    The first volume of the encyclopedia, on Lepidoptera, the order of insects that includes moths and butterflies, is scheduled for release in April, followed later this year by others on myriapods (centipedes and millipedes) and bryophytes (mosses and their relatives). In all, 120 volumes are planned and will include the roughly 30,000 species that can be identified easily by nonspecialists. The books will also contain distribution maps and identification keys.

    Christer Engström, editor in chief of the series, envisions families passing the encyclopedias down through the generations, keeping the Swedish naturalist tradition alive. Indeed, there are signs that the naturalist spirit isn't lost on the younger generation. Sweden's popular Princess Victoria, 27, has given the project her blessing. Visiting the STI team last year, Victoria confided that biology was her favorite subject in school. “It's the best patronage we could have,” says Engström.

  17. TAXONOMY

    Taxonomy's Elusive Grail

    1. Greg Miller

    A complete catalog of life on Earth ranks near the top of biologists' all-time wish list. To date, fewer than 2 million species have been described—perhaps a fifth of the planet's total.

    In 2001 an ambitious group of Silicon Valley-types teamed up with several prominent researchers, including Harvard's E. O. Wilson and Peter Raven of the Missouri Botanical Garden in St. Louis, to launch the All Species Foundation, with the goal of cataloging every species on Earth in 25 years (Science, 26 October 2001, p. 769). Unfortunately, says Raven, the dream died when the dot-com bubble burst and donations dried up. A recent visit to the All Species Foundation Web site brought up a page simply titled: Gone.

    Several other efforts are under way to inventory all of the species in a restricted area within some limited time frame—what's known as an all-taxa biodiversity inventory (ATBI). Three major projects are up and running, says Daniel Janzen, an ecologist at the University of Pennsylvania in Philadelphia.

    The most recently launched ATBI, based in Uppsala, Sweden, aims to inventory that country's estimated 60,000 species within 20 years (see main text). Janzen helped set up the first in Costa Rica in 1989. The mandate of Costa Rica's Instituto Nacional de Biodiversidad (INBio), based outside San José, was to inventory all of that country's estimated 500,000 species. Janzen initially hoped to jump-start INBio with a 7-year project to inventory the species-rich Area de Conservación Guanacaste. But those plans fell apart amid political wrangling in 1997 (Science, 9 May 1997, p. 893).

    The national survey continues today, Janzen says, but efforts are dispersed across the country with no definite time frame for completion. Part of the problem is inconsistent funding. INBio is not supported by the Costa Rican government; instead, it patches together money from a variety of sources, including contributions from foreign governments and ticket sales from its conservation theme park, INBioparque. In 2003, INBio raised $6.1 million.

    The first project in the United States, the Great Smoky Mountains National Park All Taxa Biodiversity Inventory, started in 1999 (Science, 11 June 1999, p. 1747). It is run jointly by the National Park Service and a nonprofit organization called Discover Life in America. Work on the inventory reaches a fever pitch each summer when scores of scientists and thousands of volunteers converge on the park. Keith Langdon, the National Park Service's coordinator for the project, says it's hard to say how many species have been cataloged because each taxa goes into a separate database, but others say it's in the neighborhood of 12,000 to 15,000 of the 100,000 species estimated to live there. And the project may spark imitations: Langdon says several other parks and conservation areas in the United States have approached him for advice on setting up their own inventories.

    But they may face an uphill battle for funding. The Great Smokies project has relied almost entirely on donations, which have totaled about $150,000 per year. This year, however, Langdon is optimistic that the project will get some money—perhaps as much as $200,000—from Congress. In the meantime, he says, “we're doing the best we can with the limited funding we have.”

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