News this Week

Science  07 Jun 2002:
Vol. 296, Issue 5574, pp. 1778

    Germany Gets in Step With Scientific Misconduct Rules

    1. Adam Bostanci

    BERLIN— Five years after a major fraud scandal rocked the scientific establishment, Germany's universities are about to get their first binding standards of ethical research. Universities must implement the new rules by the end of this month or risk being ruled ineligible for grants from the country's main research funding body, the Deutsche Forschungsgemeinschaft (DFG).

    The rules follow international norms in defining scientific misconduct as “deliberate or grossly negligent falsification or fabrication of data.” Other serious transgressions listed are deceit, plagiarism, and damage to the research of others. Possible sanctions include the loss of research contracts and the revocation of academic titles. Moreover, says DFG president Ernst-Ludwig Winnacker, “failure to cooperate with investigations will be considered an admission of guilt.”

    The regulations are a welcome tonic for a community embarrassed by misconduct inquiries that have dragged on for months or years and in some cases held little consequence for implicated individuals. The rules also try to ease the publish-or-perish pressures that, some argue, tempt young researchers to commit fraud. According to the new code, promotion decisions should no longer be based on quantitative measures—such as publication volume—but on quality and originality. “This is a crucial point, especially in clinical research,” says Ulf Rapp, a cell biologist at the University of Würzburg.

    The misconduct rules are the fruits of much soul-searching after a DFG-funded task force found falsification in dozens of papers authored by a pair of cancer researchers, Friedhelm Herrmann and Marion Brach (Science, 23 June 2000, p. 2106). A special DFG commission developed the regulations in consultation with international fraud experts. Any institution that receives DFG funding—meaning the vast majority of Germany's research centers and universities—has until 30 June to implement the rules. The threat of falling into DFG's disfavor has so far motivated 70% of Germany's research institutions to adopt the guidelines. Most others expect to have them in place by the deadline.

    Laying down the law.

    Stonewalling misconduct investigations is tantamount to guilt, says DFG president Ernst-Ludwig Winnacker.


    It's unclear, however, whether the rules will apply uniformly to all scientists. For those holding permanent jobs as public servants, it is up to ministerial employers —rather than DFG—to punish misconduct, and proving deliberate or gross negligence in data fabrication is notoriously difficult. However, talks are currently under way over possible changes to the employment law.

    Under the new rules, institutions must appoint an independent ombudsperson who will initiate probes of misconduct allegations while protecting whistleblowers. In addition, to speed up future investigations, the new rules state that—wherever possible—primary research data must be stored for 10 years. This “is probably the one area in which researchers are most careless,” says Johannes Dichgans, a neurologist and ombudsperson at the University of Tübingen. Failure to archive research records, or their deliberate destruction, could be judged as gross negligence and hence be punishable.

    Some experts are less impressed with the new regulations. Hans-Jürg Kuhn, an anatomist at the University of Göttingen, says that the rules often “state the obvious” while being hard to follow in practice. He is currently leading an investigation into alleged fraud in a cancer vaccine trial. The inquiry has been going for 16 months and is under mounting pressure from the media and from scientific leaders to deliver a verdict. Kuhn says he is not convinced that the rules, if they had been in place earlier, would have speeded up his investigation, which he says has been thwarted by slow access to patient information. “Privacy protection laws make it virtually impossible to store patient information in a manner that is easily accessible to later investigations,” he says—and the new rules don't change that.

    View this table:

    After 30 June, DFG will assess how institutions have implemented the rules. Peter Hans Hofschneider, a professor emeritus at the Max Planck Institute for Biochemistry in Martinsried who raised the alarm in the Herrmann-Brach case, says that DFG should come down hard on any institution that fails to adopt the rules. “If our efforts to put the guidelines into place are to be taken seriously, the DFG should act decisively,” he says.


    High Court Reins In Patent Pirates

    1. David Malakoff

    The U.S. Supreme Court has scaled back a controversial lower court ruling that some feared would open the door to wholesale copying of patented inventions. Research universities and some technology firms are applauding last week's unanimous decision,* saying it will help protect valuable discoveries. But others say it will do little to reduce the growing number of costly patent fights.

    “The decision is a slam dunk for universities,” says attorney Susan Braden of Baker & McKenzie in Washington, D.C., who represented 20 research institutions and academic groups that saw the earlier ruling as a threat to the more than 16,000 patents that universities have won over the past 2 decades. Opponents are also claiming victory, however, saying that the ruling will make it harder for inventors to file frivolous infringement claims. And attorney Dan Bagatell of Brown & Bain in Phoenix, Arizona, who represented technology firms asking the court to uphold the ruling, thinks that the picture is still cloudy. “The patent system as a whole may not be any better off,” he says, because the decision still leaves “a lot of uncertainty about what constitutes infringement.”

    The legal battle—dubbed “the patent case of the decade” by court watchers— focused on a 150-year-old legal concept called the “doctrine of equivalents.” The doctrine bars inventors from making minor changes to a patented technology and then claiming it as their own. Companies that have patented proteins, for instance, have invoked the doctrine to prevent competitors from marketing molecules with slightly different amino acid sequences that perform the same biological function.

    Legal roller coaster.

    This amusement-park ride at Disneyland uses a technology that is at the center of a high-stakes patent fight.


    The decision came in a decade-old case involving a mechanical cylinder made by Festo Corp. of Hauppauge, New York, that has been used in everything from sewing machines to amusement park rides. Festo claimed that SMC Co. of Japan had infringed on its patent by producing a cylinder that, although not an exact copy, was equivalent to Festo's. Two years ago, a federal appeals court stunned many experts by ruling that the doctrine of equivalents doesn't apply to patent claims that were narrowed during their review by the government. It's a process that most patents go through.

    Festo appealed the decision to the Supreme Court, which was swamped by briefs from dozens of biotechnology, computer, and other firms on both sides of the issue (Science, 21 December 2001, p. 2460). In general, individual inventors and small companies said the lower court ruling left them with few options for battling infringement, whereas companies with vast patent estates backed the decision because it clarified their vulnerability.

    In a 17-page opinion, Justice Anthony Kennedy handed Festo and its allies a partial victory by declaring that the earlier ruling went too far. Because “language remains an imperfect fit for [describing an] invention,” Kennedy wrote, the holders of narrowed patents should still be able to employ the doctrine of equivalents to fight infringement. But the justices also put more of a burden on inventors to prove that a competing invention infringes on their discovery. In sending the case back to the lower court, the justices also hinted that Festo might lose to SMC under the tougher standards.

    Overall, the decision “enhances the economic value of patents” and restores to judges the leeway to decide infringement claims on a case-by-case basis, says attorney Edward W. Gray of Fitch, Even, Tabin, & Flannery in Washington, D.C. That is good news for critics of the earlier ruling, who warned that it could undermine 1.2 million existing patents—including university patents that have generated more than $4 billion in income.

    But Bagatell says the high court gave little comfort to corporate executives who would like to know if a new technology might be covered by someone else's patent before they invest in it. Uncertainty about the outcome of a doctrine-of-equivalents claim, he adds, might cause companies to pay up on even weak legal challenges to avoid further litigation. The justices were willing to accept such costly uncertainty “because they believe that the [patent] system works and promotes innovation,” says Braden. Applying the doctrine of equivalents “is an art, not a science,” she adds, a warning to scientist-inventors that going from discovery to commercialization might include a roller-coaster ride.


    Australia Pushes Stem Cell Advantage

    1. Leigh Dayton*
    1. Leigh Dayton writes from Sydney.

    SYDNEY— Australia's new policy on embryonic stem (ES) cells has already started to pay big dividends for researchers. Last week the government announced that it will invest $25 million in a new Center for Stem Cells and Tissue Repair at Monash University in Melbourne that will work to develop therapies for blood and tissue diseases based on new and existing ES cell lines. “We want to take stem cells all the way through to the patient,” says cell biologist Alan Trounson, head of the Monash Institute of Reproduction and Development and director of the new center.

    The center, a consortium involving some 300 scientists at a dozen institutions, won a stiff competition to become the country's first National Biotechnology Center of Excellence. (Last month the government also selected a center of excellence in information and communications technology.) The biotechnology center is a direct outgrowth of an agreement struck 2 months ago in Canberra between federal, state, and territory leaders to allow scientists to work with established ES cell lines and derive new cell lines from surplus in vitro fertilization embryos created before 5 April (Science, 12 April, p. 238).

    All smiles.

    Prime Minister John Howard (left) and Monash's Alan Trounson welcome new center.


    Those rules are much less restrictive than the ones federally funded U.S. researchers have to follow: They can use ES cells only from cell lines created before 9 August 2001 (Science, 17 August 2001, p. 1242). Curt Civin, a cancer expert and stem cell researcher with the new Institute for Cell Engineering (ICE) at Johns Hopkins University School of Medicine in Baltimore, says more research and new cell lines will be “great” for getting better treatments to patients faster. “Hopefully,” he says with a touch of envy, “the U.S. would someday approve our use of them.”

    The center's first task will be to produce ES cells in bulk quantities from the 10 to 12 lines that researchers will bring to the consortium. It also hopes to generate 20 new ES and adult stem cell lines. Its most difficult challenge, however, will be to coax stem cells to develop into specific tissue types that could be used for therapies. Trounson says he hopes that the center can develop treatments for blood conditions such as leukemia that could go into clinical trial within 5 years and be available commercially a few years later, with help for solid-tissue disorders like Parkinson's to follow. Reagents for identifying stem cells will be ready “straight away,” he adds.

    Researchers also anticipate a collaboration with a primate research center, Maccine, at the Bogor Agricultural Institute in Indonesia. Trounson says he hopes to use animals at the primate center to test potential therapies involving blood, skin, cardiac muscle, lung, liver, and brain cells.

    The government is preparing legislation to codify the April agreement, which appears to have resolved a heated public debate on the use of ES cells in research. Speaking 30 May at a press conference in Canberra, Prime Minister John Howard called the potential benefits from stem cell research “quite literally unlimited” but said that the work would be “guided by the community's ethical considerations.” A raft of committees will be set up to oversee research in the field, and Trounson emphasized that “any procedures banned under these agreements will not be undertaken by the center.”

    The new center will also receive money from state governments and two companies, ES Cell International and BresaGen, created to commercialize work conducted at Monash and Adelaide universities, respectively. Trounson anticipates that a staff of 150 scientists will eventually work at the center, which will occupy its own building on campus. “Some very well-known U.S. scientists,” he adds, have already expressed interest in coming aboard.

    Stem cell researcher Ronald McKay of the U.S. National Institute of Neurological Disorders and Stroke doesn't think the new center will cause U.S. researchers to migrate to Australia. Nonetheless, he says that it, combined with the work done in Singapore to derive the Monash cell lines, gives the South Pacific a substantial presence in stem cell research.


    Report Aims to Rescue Science From Doldrums

    1. Giselle Weiss*
    1. Giselle Weiss is a writer in Allschwil, Switzerland.

    BERN— A decade of stagnation has sent Swiss science into a downward spiral that only broad reforms and a massive infusion of funds can reverse. That, at least, is the diagnosis offered last week by the Swiss government's science advisory body. However, it's unclear whether leaders of the Swiss Federal Council, the government's executive branch, are prepared to prescribe strong medicine.

    At a press conference here, officials of the Swiss Science and Technology Council (SSTC) followed up a warning shot they fired last fall by offering a laundry list of actions for remedying the country's most urgent woes. The proposals include unifying Switzerland's fragmented higher education system, installing a modern tenure-track system, shoring up support for long-term basic research, and increasing the science and technology budget by 10% a year from 2004 to 2007. The recommendations “make a lot of sense,” says Patrick Aebischer, president of the Swiss Federal Institute of Technology in Lausanne.


    Gottfried Schatz is pressing for action.


    The latest symptom of a research community in crisis, scientists say, is the Swiss drug giant Novartis's announcement last month that it would set up a $250 million research facility in Cambridge, Massachusetts (Science, 17 May, p. 1216). “You have to give something back to industry to keep industry here,” says Silvia Arber, a neurobiologist at the University of Basel's Biozentrum.

    Part of the problem is money. Federal R&D budgets have remained essentially unchanged over the past decade: The $1.7 billion in 2000, adjusted for inflation, is roughly the same amount spent in 1992. But there are deeper structural issues as well. For instance, most universities have few stable positions below the level of full professor. “It's an old-fashioned system,” says Jürg Stöcklin, a population biologist at the University of Basel who has what he calls one of the “rare permanent positions in the Mittelbau”: the limbo that researchers occupy while waiting for professorial slots to open. “For junior people, it's lousy,” says Peter Chen, a physical-organic chemist at the Swiss Federal Institute of Technology in Zürich, which like its sister institute in Lausanne is one of the few with a tenure-track system. Bright young Swiss researchers can save 10 years and become independent earlier, Chen says, by starting their careers in the United States.

    The seven-member Federal Council views the recommendations as grist for an action plan on R&D and education funding for the 2004–07 period that it will present to parliament in November. Two council members have publicly avowed support for a 6.5% increase in the R&D budget—a figure that's short of what SSTC is pressing for but far more robust than recent budgets. They have also warned against sacrificing long-term research for the sake of the more politically expedient targeted research programs. SSTC president Gottfried Schatz and his colleagues will be making appearances before the relevant parliamentary commissions to build on this support. Says Schatz, “I do nothing else these days.”


    Lighting Initiative Flickers to Life

    1. David Malakoff

    An alliance of industry, academic, and U.S. government scientists is getting closer to flipping the switch on a 10-year, $500 million initiative to revolutionize lighting. Researchers met in New Mexico last week to map out priorities for the proposed Next Generation Lighting Initiative (NGLI) embedded in a broader energy bill moving through Congress. The project is designed to help the United States stay ahead of competitors in Japan, Europe, and Korea for global leadership in the $40 billion lighting industry. “We've lost [the lead in] other technologies to other countries; hopefully, we can keep this one,” says Arpad Bergh, head of the Optoelectronics Industry Development Association in Washington, D.C., which helped draft the initiative.

    Over the past decade, researchers have developed new light-emitting diodes and organic thin films that could form the basis of solid-state lights that would be more versatile and efficient than current vacuum-tube bulbs. Analysts say the new lights, if adopted widely, could cut global electricity consumption by 10% or more, reducing environmental problems and spurring economic growth. But technical obstacles, including problems with making brighter and more rugged materials at lower costs, have slowed progress.

    To clear those hurdles, researchers at the Department of Energy's (DOE's) Sandia National Laboratories in Albuquerque, New Mexico, and Hewlett-Packard Co. in Palo Alto, California, proposed 2 years ago that DOE, leading lighting companies, and academia pool their skills. A research road map hammered out last year (lighting. caught the eye of Senator Jeff Bingaman (D-NM), who helped insert language creating NGLI into energy bills that have passed the House and the Senate.

    Lighting up.

    New public-private effort aims to give U.S. companies the edge in developing new lighting devices, such as these light-emitting diodes.


    Although differences over nuclear power and other issues might block a final agreement on the energy bill, NGLI is a good bet to survive. Dozens of lawmakers have already asked Senate and House appropriators to provide $30 million for the fiscal year that begins 1 October, with a boost to $50 million annually in subsequent years. Bush Administration officials have been quietly supportive. “It's looking increasingly likely that something is going to happen,” says Jerry Simmons, who runs a lighting research program at Sandia.

    The initiative's backers project that industry-led consortia would receive about two-thirds of any government funding through a competition, with the remainder going directly to universities and government laboratories. Companies that want to participate would have to match the government's contribution to applied studies, whereas federal funds would finance the riskier basic research. That arrangement gives industry “an incentive to support additional research,” says Bergh.

    Academic researchers are also upbeat about the initiative, saying it will connect their work to important practical applications. “A concentrated effort to reach superhigh-efficiency lighting … is good for consumers and the environment,” says materials scientist Steven DenBaars of the University of California, Santa Barbara.

    Some DOE-funded scientists have already begun to prepare for the initiative. Sandia, for instance, plans to invest nearly $6 million by the end of 2003 in solid-state lighting studies. The work includes modeling potential materials on a supercomputer—precisely the sort of research that's beyond the reach of most companies.


    Dark-Matter 'Sighting' Returns to Shadows

    1. Charles Seife

    MUNICH, GERMANY— Dark matter is, officially, still dark. Results presented at a meeting here last week* have convinced most physicists who have seen them that a controversial “discovery” of dark matter is in error.

    The original claims stemmed from an experiment performed in 1998 deep underneath the Italian Alps. A sensitive detector at the heart of the DAMA (for Dark Matter) experiment at Gran Sasso National Laboratory showed a yearly increase and decrease in the number of particles it encountered. Although each individual “detection” had a high probability of being background noise in the instrument, the DAMA team concluded that the yearly cycle might be the signature of dark matter, the mysterious material that vastly outweighs the ordinary matter that makes up the visible universe. As Earth orbits the sun, the scientists proposed, it zooms toward and away from a “wind” of dark matter that blows through the solar system, and the shifts in orientation cause the number of dark-matter particles striking the detector to wax and wane (Science, 1 January 1999, p. 13; 3 March 2000, p. 1570). From this conclusion, the team calculated some properties of the dark-matter candidates, such as their energy. Although the claim was met with skepticism, the scientific community took it seriously—until now.

    Blown away.

    Seasonal ups and downs in particle detections were not due to a dark-matter “wind,” a new study shows.


    The challenge comes from a French experiment called EDELWEISS (for Expérience pour Detecter les Wimps en Site Souterrain). Like DAMA, EDELWEISS centers on a particle detector buried under tons of alpine rock to shield it from cosmic rays. For 3 months, EDELWEISS tried to sense DAMA's dark matter candidates. It failed.

    “There is no event” that could correspond to DAMA-type dark matter, says Gilles Gerbier of the French Center for Atomic Energy (CEA) in Saclay, a member of the EDELWEISS team. During its run, EDELWEISS saw only one possible dark matter candidate—much too energetic to be DAMA-type dark matter and probably just experimental noise.

    Rita Bernabei of the University of Rome, a physicist with the DAMA collaboration, says differences in the two detectors make a direct comparison between the results misleading. But other researchers say EDELWEISS has all but put the matter to rest. “For the first time, you exclude this DAMA positive evidence for dark matter,” says Michel Spiro, also at CEA Saclay. “I'd prefer that it was confirmed than excluded, but this is important physics.”

    Yorck Ramachers of Oxford University suspects that DAMA's seasonal variation is a systematic error. The cumulative effects of annual cycles of temperature, humidity, and other factors might explain the “detection,” he says. In any case, he says, several other dark-matter searches are likely to release data this year, so those who were rooting for the DAMA result might soon have fresh puzzles to console them.

    • *20th International Conference on Neutrino Physics and Astrophysics, 25–30 May.


    Cholera Strengthened by Trip Through Gut

    1. Elizabeth Pennisi

    Poor sanitation promotes the spread of cholera, but that's not the only way humans foster the deadly diarrheal disease. Microbiologists have discovered that the human gut seems to prime the bacteria responsible. Before Vibrio cholerae exit the body in watery stools, something about the intestinal environment causes them to rev up the activity of certain genes. These genes, in turn, seem to prepare them for ever more effective colonization of their next victims, possibly fueling epidemics, says Andrew Camilli, a microbiologist at Tufts University School of Medicine in Boston.

    “The hypothesis that passage through the host enhances infectivity is quite provocative,” comments Matthew Waldor, a microbiologist at Tufts-New England Medical Center in Boston. Adds Vic DiRita, a microbiologist at the University of Michigan, Ann Arbor: “It's really amazing. It may explain the rapid and explosive nature of these epidemics.”

    A thwarted experiment put Camilli and his colleagues on the trail of this so-called hyperinfectivity. He and others had long wondered why cholera epidemics become rampant as quickly as they do. Camilli thought the microbes residing in the human gut might develop defenses against the gut's acid environment. As a result, more of the excreted, acid-tolerant bacteria would survive in subsequent hosts. But when the researchers went to Dhaka, Bangladesh, to get fresh Vibrio to test this idea, technical difficulties foiled the experiment.

    Pathogenic squatters.

    In this mouse small intestine, Vibrio cholerae bacteria (inset) have latched onto cells lining the gut.


    Instead, graduate students Susan Butler and D. Scott Merrell, who is now at Stanford University School of Medicine, made a peculiar observation. While in Bangladesh, they injected mice with a mixture of bacteria grown in the lab and isolated from human stools. The stool-derived bacteria greatly outcompeted the lab-derived bacteria, the researchers found, calculating that the former were up to 700 times more infectious than the latter.

    This increased infectivity lasted at least 5 hours in bacteria living in pond water—long enough for someone to drink the infected water, says Camilli. However, the hyperinfectivity disappeared when the microbes were grown more than 18 hours in the lab, the team reports in the 6 June issue of Nature.

    To understand what made excreted Vibrio different from their laboratory counterparts, Camilli and Stanford microbiologist Gary Schoolnik looked for changes in gene expression. They exposed a microarray made with pieces of Vibrio's genes to VibrioRNA isolated from fresh stools or lab strains. Some 3120 of the 3357 genes studied were equally active. But in the stool-derived sample, 44 genes were more active and 193 were less active.

    When the researchers looked at the most logical suspects for increased infectivity, they came up empty-handed. Neither virulence genes nor acid-tolerance genes were up-regulated. But unexpectedly, several genes involved in helping the microbes head toward or away from chemical targets were silenced. As a result, “they don't have directional motility,” Camilli predicts.

    Camilli suspects that this lack might help the bacteria invade the gut. Those that can sense where to go are guided by chemical signals to the lower part of the small intestine, where for unknown reasons they like to settle. But he has shown that mutant strains that are not directional “colonize everywhere in the intestinal tract,” and the same might be true of stool-derived Vibrio. This widespread colonization might mean that more bacteria find space to start multiplying, thereby speeding the development of symptoms.

    The finding could influence the current way that vaccines are developed. For one, “it may change the way we think about trials,” says DiRita; perhaps tests must be done in which people are exposed to Vibrio prevalent during epidemics, rather than the current practice of exposing healthy volunteers to hobbled lab strains. And the proteins up-regulated by exposure to the human gut “might be good vaccine targets,” Camilli speculates. But Harvard microbiologist John Mekalanos cautions that even though the data look convincing, the experiments need to be replicated. And well-controlled tests demonstrating that stool-derived Vibrio is more infectious in humans as well as mice will be difficult if not impossible to do for ethical reasons.


    New-Model Reactions Skip the Drip

    1. Robert F. Service

    If you think organic chemistry is a dry subject now, just wait. Researchers at the Department of Energy's Ames Laboratory in Iowa are trying to make it literally as dry as dust. In the latest issue of the Journal of the American Chemical Society, a team led by Vitalij Pecharsky—a materials scientist with a joint appointment at the Ames lab and Iowa State University, Ames—reports that it has carried out a battery of common organic chemistry reactions using solid compounds, without first dissolving them in the usual liquid solvents. If this new “dry chemistry” approach works for other reactions, it could light a fire under attempts to make everyday compounds without using toxic organic solvents.

    “It's an encouraging result,” says Lawrence Scott, a synthetic organic chemist at Boston College in Massachusetts. The vast majority of organic reactions today require organic solvents, many of which are environmentally hazardous and costly to dispose of. “This new method gets around that completely, because there isn't any solvent present,” Scott says. Dry chemistry, says Kim Janda, a chemist at the Scripps Research Institute in La Jolla, California, “could be a new branch of green chemistry and open up new avenues to simplify a variety of chemical reactions.”

    Dry chemistry.

    Milling machine (top) triggers reactions by shaking organic powders in vials with steel balls.


    Until now, few researchers suspected that scrapping solvents altogether was even possible. For most reactions to occur, precursor compounds must be free to come into contact with one another. That's easy in liquids, where ions and molecules move about freely. “But in solids, things are pretty much frozen,” Scott says. As a result, solids normally make poor reactants for synthesizing new compounds.

    To get around that problem, Pecharsky and his colleagues—organic chemist Viktor Balema and nuclear magnetic resonance (NMR) spectroscopists Jerzy Wiench and Marek Pruski—used a mechanical mill to break up organic crystalline solids, hoping to bring molecules into contact with one another long enough to form new compounds. According to Pecharsky, other groups in Japan and Russia had previously carried out related attempts at such solvent-free chemistry. But in those cases the groups had either melted the materials with heat or added small amounts of solvent, making it impossible to be certain that the reactions were taking place among the solids themselves. This work, Pecharsky says, is the first example that conclusively proves that all the reactions take place in the solid state.

    For their experiment, the Ames researchers started with powdery organic compounds such as phosphonium salts, solid aldehydes or ketones, and anhydrous potassium carbonate. They placed them into 10- centimeter-long hardened steel vials loaded with steel balls the size of marbles and BBs. Then they flipped the switch on the mill, which shook each vial for between 3 and 20 hours. “The balls fly all around the vial and [crush] the powder as they hit one another and the walls,” Pecharsky says. The mechanical energy broke down the crystalline solids and churned the starting compounds together, allowing the reactions to take place. When the Ames scientists examined the resulting products with solid state NMR imaging and other tools, they found that between 70% and 99% of the starting compounds had transformed into the final products.

    Pecharsky says the novel method won't work for all reactions, and it would still require solvents to separate reaction products from unwanted byproducts. “It's no magic wand that will cover the entire field of organic chemistry,” he says. But it might be enough to stir things up a bit.


    Signs of Stress Seen in Snowmobile Season

    1. Jay Withgott*
    1. Jay Withgott is a science writer based in San Francisco.

    As biologists, recreationists, and policy-makers debate whether snowmobiles should be allowed in U.S. national parks, a new study of animal feces suggests that the noisy machines raise the stress hormone levels of elk and wolves.

    In April 2000 the National Park Service announced plans to ban snowmobiles in national parks, but it later reversed itself following a lawsuit by the snowmobile industry. A ban is now being debated again—and the machines' impact on wildlife is at the heart of the issue.

    Earlier studies demonstrated that mammals and birds move to avoid areas of snowmobile use and that their heart rates increase in the presence of the machines. To look for more direct signs of stress, Scott Creel of Montana State University, Bozeman, and colleagues measured levels of glucocorticoid stress hormones in the feces of elk and gray wolves—a reliable indicator of levels in the bloodstream. In the June issue of Conservation Biology, Creel's group reveals that elk in Yellowstone National Park show higher levels of stress hormones during the snowmobile season and that levels rise and fall with the amount of daily snowmobile traffic. Wolves in Voyageurs National Park in Minnesota, where snowmobile use is heavy, show higher hormone levels than those of wolves in nearby Isle Royale National Park in Michigan, which is closed to snowmobiles. During the 2-year study, wolf glucocorticoid levels at Voyageurs dropped 37%, paralleling a 37% drop in snowmobile activity.

    Peace and quiet?

    Elk might be stressed by the drone of snowmobiles.


    Creel says the findings provide an “early warning” that the populations, which have been stable so far, could suffer in the future. Chronically elevated stress hormone levels in vertebrates suppress the immune system, inhibit reproduction, and cause other maladies. But in the absence of population declines, Creel says his team is not out to push recreation from the parks. “We're being careful not to recommend policy to managers; that's their job,” he says.

    Wildlife ecologist Joshua Millspaugh of the University of Missouri, Columbia, says that it's not clear whether the glucocorticoid levels measured are detrimental to the animals, but that the researchers' noninvasive techniques are informative and might indeed suggest incipient population effects. Samuel Wasser, a conservation biologist at the University of Washington, Seattle, adds that policy-makers should err on the side of caution: “If we wait to show a fitness effect, it may already be too late to turn things around.”

  10. CANADA

    Social Scientists Go for a Political Dip

    1. Wayne Kondro*
    1. Wayne Kondro writes from Ottawa.

    TORONTO— For more than 3 decades, sociologist Ralph Matthews of the University of British Columbia in Vancouver had quietly gone about his academic business, producing five books and over 80 journal articles on such issues as how energy megaprojects affect communities. Negotiating a new contract was as close as he ever came to political activism. But last week, within hours of arriving here for the 71st Congress of the Social Sciences and Humanities, Matthews experienced two “unprecedented” events that have turned him—and thousands of his colleagues—into lobbyists for their profession.

    Canada's social scientists have complained for years about getting the short end of the funding stick. They are particularly fond of noting that only 11% of the government's allocation to the country's three funding councils goes to the social sciences, although they represent 54% of all academic researchers. Last week the head of the social sciences council, Marc Renaud, sharpened the rhetoric. He announced that he would be forced to end the council's bread-and-butter awards to individual investigators unless the government came through with substantial funding increases. The threat was designed to get legislators to notice his proposal for more than tripling the council's $92-million-a-year budget. It certainly got Matthews's attention. “It would be close to a tragedy if Standard Research Grants were cut,” he says. “They are the intellectual base for curiosity-driven fundamental research.”

    Campaign headquarters.

    Lobbying instructions came with the registration packet at this year's annual Canadian social sciences conference in Toronto.


    Renaud's threat helped convince Matthews to participate in a novel exercise. His registration packet, assembled by the Humanities and Social Sciences Federation of Canada (HSSFC), which organizes the congress and serves as the national lobbying arm for 90 organizations and their 24,000 members, contained a postcard to be filled in and mailed to Industry Minister Allan Rock and other members of Parliament. Such a campaign might not seem like a big deal in the United States, but it represents a major step for most Canadian scientists. “One of the sad facts about the Canadian scholarly community is that we have tended to let our national representatives do the job for us,” says philosopher Andrew Brook of Carleton University in Ottawa. “But this has served as a real wake-up call. I haven't heard of anybody who hesitated a second about signing the postcards.”

    The $21-million-a-year individual grants program is the largest component of the base budget for the Social Sciences and Humanities Research Council (SSHRC). It provides researchers $15,000 in seed money for studies that ultimately gestate into books or larger research initiatives. Renaud says an inadequate budget is now forcing him to choose between eliminating those grants or dismantling programs aimed at helping society, such as the 37 science shops established over the past 3 years that enlist university researchers in fighting various community ills (Science, 13 November 1998, p. 1237). The latter programs “are changing the nature of research in this country,” Renaud notes, as well as helping SSHRC make allies in the private sector.

    HSSFC president Patricia Clements calls Renaud's threat to suspend basic operating grants “the most serious and chilling thing that I have ever heard in my lengthy career.” And although Renaud says he's invigorated by the community's initial response to his call for political action, he's also aware of the government's propensity to respond to critics by tightening the purse strings. It's a risk he's willing to take. “I'm not directing this against the government,” he says. “But if they don't like it, they can fire me.”


    Syngenta Agrees to Wider Release

    1. Dennis Normile

    TOKYO— In a step anticipated by rice genome researchers, the company that published a draft sequence of the rice genome earlier this year has agreed to a fuller release of its data. On 23 May Syngenta, a Swiss-based agricultural biotechnology giant, announced that it would transfer the assembled sequence together with the underlying data to the publicly funded International Rice Genome Sequencing Project (IRGSP), which is working on its own draft of the rice genome sequence. The Syngenta data will be incorporated into the IRGSP sequence, which will be deposited in public databases.

    On 5 April Science published a draft of the genome sequence of the japonica subspecies of rice that was produced by Syngenta's Torrey Mesa Research Institute in San Diego, California (p. 92). Instead of following the traditional practice of depositing the data in a public database, such as GenBank, the Syngenta group made the sequence available on its own Web site and on a CD-ROM. Researchers could use the raw sequence data in their labs but were limited in how much of the Syngenta data they could publish at one time. Scientists doing commercial work were required to negotiate access to the data. Syngenta says that more than 700 researchers have accessed the data since it became available.

    Rich yield.

    Rice sequencing data will be more accessible under new agreement.


    The most important potential user, however, is the international consortium of publicly funded labs led by Japan's National Institute of Agrobiological Sciences in Tsukuba. The consortium wanted wholesale access to the data, which the new agreement provides. Although IRGSP member laboratories initially must keep the Syngenta data confidential, they can use the information in their sequencing efforts. The consortium has a similar agreement with Monsanto, which has also completed a draft sequence of japonica.

    Consortium members say that it's too early to know how the new agreement will affect their work. Takuji Sasaki, who heads Japan's rice genome sequencing efforts, says researchers need to start working with the information before they can judge its value but that some of the consortium's mapping and sequencing gaps “might be filled by the [Syngenta] data.” Ben Burr, a plant geneticist at Brookhaven National Laboratory in Upton, New York, who advises IRGSP, says that “this [agreement] is not going to have an impact on the overall schedule.” But sequencer Dick McCombie of Cold Spring Harbor Laboratory in New York, a participant, predicts that the additional data will have “a positive impact” on either the speed or the accuracy of the final product.

    Meanwhile, the debate continues over the propriety of allowing private companies to publish sequence data without depositing them in a public database. A committee of the U.S. National Academy of Sciences is preparing a report on these issues. This week in Nature, Ari Patrinos and Dan Drell of the U.S. Department of Energy's Office of Biological and Environmental Research in Germantown, Maryland, propose an approach that might encourage companies to publish more of their data. They suggest that the data remain sequestered—entrusted to a reliable gatekeeper such as the journal —for a specified time period after publication. That delay would protect a company's intellectual property rights, they argue, without excluding the public sector.


    Rain Might Be Leading Carbon Sink Factor

    1. Richard A. Lovett*
    1. Richard A. Lovett is a science writer based in Portland, Oregon.

    “Where's all the carbon going?” Atmospheric scientists have been wondering about that for years. The United States spews out more than 5 billion tons of carbon dioxide emissions each year, but mainland U.S. ecosystems are absorbing an unexpectedly large amount of the gas—somewhere between 10% and 30% of the total—and the amount is steadily increasing. Scientists aren't complaining, mind you, because this absorption or sequestration offsets global warming. But they've been at a loss to explain it.

    Most of the carbon is being sucked up by plants, which use it to manufacture roots, stems, leaves, and wood. Indeed, over the past several decades, researchers have recorded increased vegetation growth across the country. But why all this vegetation is growing so quickly has remained unclear. Theories abound, but the principal ones involve regrowth of forests on previously logged lands and accelerated forest growth spurred by global warming.

    Now, a team is proposing another explanation: rain. A study published online by Geophysical Research Letters on 28 May suggests that the increased rainfall and humidity documented in the continental United States might be the single most important factor spurring increased plant growth; this, in turn, is slowing the accumulation of carbon dioxide in the atmosphere.


    Scientists had overlooked the link between precipitation and carbon sequestration.


    The answer might seem obvious, but carbon sink modelers had overlooked it. They have focused instead on the regrowth of forests, temperature changes, and the encroachment of woodlands on abandoned farmlands. Some have extended these studies to calculations of how many trees must be planted to offset new emissions.

    Then researchers at the University of Montana's School of Forestry in Missoula began pondering the role of rainfall changes in the growth of the North American carbon sink. Working under a grant from NASA, Ramakrishna Nemani and co-workers used a computer model to simulate, region by region, the impact of this previously overlooked factor, focusing primarily on climate data from 1950 to 1993. Even after adjusting for other determinants of plant growth, including temperature changes, Nemani's team found that rainfall increases account for two-thirds of the additional growth.

    Increased moisture helps plants in a number of ways, says the University of Montana's Steven Running, one of the study's co-authors. Not only does it provide more water to the plants' roots, but extra humidity also allows plants to open wider the pores that allow carbon dioxide into their leaves, allowing photosynthesis to proceed more rapidly.

    All told, the researchers calculated that increased moisture in the United States during the study interval produced a 14% spurt in plant growth, with the greatest change occurring in the parts of the country that received the biggest increase in rainfall. And the increased plant growth affects not only replanted forests but vegetation of all types, including shrubs, grasses, and long-standing woodlands.

    Even proponents of other theories admit, in retrospect, that the Montana researchers have a point. Boston University botanist Ranga B. Myneni, for one, recently co-authored a paper that linked increased forest growth to a different factor, temperature change (Science, 31 May, p. 1687). Yet he readily accepts rainfall as an important new variable that must be considered. After all, he says, whatever effect increasing temperatures per se might have on the growing season, plants can benefit only if there's water to support their growth.

    In addition to encouraging other researchers to restructure their carbon sink models, the new findings might mean that proposals to counteract global warming by planting forests are overly naïve. Planting trees is well and good, Running says, but the trees' effectiveness as carbon sinks will depend on rainfall—which could suddenly reverse its trend and decrease. Perhaps rainfall will continue increasing with global warming, but if that doesn't happen, Running cautions, “we could lose a lot of carbon sink strength very quickly.”


    Science Emerges From Shadows of China's Space Program

    1. Dennis Normile,
    2. Ding Yimin*
    1. Ding Yimin writes for China Features in Beijing. Additional reporting by Andrew Lawler.

    China's ambitious program to develop its own astronaut corps is giving basic scientists a chance to push back the frontiers of science—and collaborate globally

    BEIJING— Sometime in the next year or two China will attempt to launch a person into space. If it succeeds, it would become only the third nation to accomplish such a feat, and the achievement would be a powerful symbol of China's increasing technological sophistication.

    But the media coverage of the buildup to the expected launch has so far taken little note of a less flashy development: The rocket and satellite capabilities that underpin the nation's piloted space effort (called the Shenzhou, or divine vessel, program) are being coupled with a growing budget for space science. Over the next 5 years, China is planning to double its launch rate of scientific satellites, with at least seven now on the drawing board (see table). The program, moreover, is moving beyond its traditional emphasis on telecommunications and meteorology toward more basic research, including international collaborations such as a joint project with European scientists to study Earth's magnetosphere (see sidebar, p. 1790). “China's space efforts are entering a new era,” says Wu Ji, deputy director of the Chinese Academy of Sciences' Center for Space Science and Applied Research (CSSAR) in Beijing. Philippe Escoubet, a space physicist with the European Space Agency (ESA), predicts that China “will very quickly become an important power in space science.”

    View this table:

    Such a role would further transform a program that, thanks to military oversight, has long been a black box for Western scientists. That's beginning to change, however, as a civilian agency is now actively seeking international partnerships for science-related missions. But although Science reporters were given unusual access this spring to several of China's leading space science labs, old habits evidently die hard. The scientist reportedly in charge of Shenzhou's scientific program declined requests for an interview, for example, and a researcher involved in Shenzhou life science experiments initially granted but then abruptly canceled an interview on orders from superiors.

    Now that the space science program is gaining resources and independence, China hopes that better ties with the U.S. program will follow. U.S. concerns over human rights and weapons sales are limiting space cooperation between the two countries and preventing Chinese scientists from access to some leading-edge technologies. “The United States not only does not cooperate with us, but it imposes many restrictions,” says Guo Baozhu, deputy director of the China National Space Administration (CNSA), the country's civilian space agency. “It's really a pity.”

    Piggyback science

    China joined the elite club of spacefaring nations with the launch of its first satellite in 1970. Since then, the country has successfully lofted more than 75 spacecraft—roughly two-thirds of them produced at home—and its Long March rockets now compete with U.S., Russian, and European rockets for commercial satellite launches.

    Those launches provided opportunities for a small group of scientists nimble enough to find slots on existing missions. CSSAR, for example, built a series of five scientific satellites in the 1990s to study the effects of high-energy particles on satellite components and the behavior of fluids in microgravity, among other things. “We called them scientific missions, but they were more to test satellite [technologies],” says Wu about the Shijian (Practice) program. Shijian-5, for example, went up in 1999 alongside a meteorological satellite.

    Looking for partners.

    Guo Baozhu's civilian space agency is building ties with basic science programs in other countries.


    Liu Luxiang, a plant breeder at the Institute for the Application of Atomic Energy in Beijing, took advantage of China's efforts to develop recoverable spacecraft to hitch round-trip rides into space for plant seeds. Liu speculated that combining radiation and microgravity might produce more mutations than radiation alone. The effort has led to commercial production of new higher yielding, tastier varieties of rice, tomato, and green pepper. “This allowed us to breed new varieties in just 4 to 5 years, compared with 8 to 10 years for conventional breeding,” Liu says.

    Few outside China know the details of this research, however. This spring Bruce Bugbee, a crop physiologist at Utah State University in Logan who studies the possibility of future space farming for NASA, removed some of the mystery after a visit to Liu's lab. Bugbee, who was impressed with Liu's work, says that it's hard to replicate on Earth some types of radiation found in space. In addition, he says that long-distance space missions could require astronauts to grow their own food, which presupposes a knowledge of how plants grow in space. However, Bugbee says that similar U.S. and Russian experiments failed to produce mutated seeds and that better controlled experiments are needed. Liu defends his work but admits that he is now planning further experiments to address Bugbee's concerns.

    Lifting the veil

    Unfortunately, few of China's space research programs have benefited from such discussions. “There were restrictions on the openness of space projects in the past,” notes Liu Zhen-Xing, a space physicist at CSSAR. The first three Shijian missions were not publicized outside China, he says. Liu, the space plant breeder (who is not related to CSSAR's Liu), says that interactions with foreign scientists have also been hindered by geographical isolation and the language barrier.

    The beginning of the new era dates to the late 1990s, when planners started work on China's 10th 5-year plan for space activities. The plan, which covers 2001–05, reflects a shift in the focus of space efforts. “Over the past several decades, China concentrated on developing rockets and satellites,” says CNSA's Guo. “But people became aware that space activities can be put to use to develop science and technology and the national economy.”

    CNSA was set up in 1998 explicitly to foster closer ties with the international space community. In late 2000, CNSA translated and posted on the Internet a white paper “to explain China's purposes and goals for space science and technology,” Guo says. It was the first time such a document, which doesn't cover the piloted program, had been made public.

    China's space community responded to the new opportunity with what Guo calls “a long list of demands.” One of the winners was Earth remote sensing. Although China has agreements with the United States and ESA for access to remote-sensing data from their satellites, officials felt the need to produce their own. Guo Jianning, director of the China Center for Resources Satellite Data and Application, says the foreign remote-sensing satellites don't provide sufficient coverage of the sprawling country.

    China has at least partly filled this gap with the joint China-Brazil Earth Resources Satellite (CBERS) program. The first of the series was launched in October 1999, the second is scheduled for August, and future CBERS launches are being planned. The data are used to forecast agricultural production, improve land planning, and monitor desertification and environmental pollution in China and Brazil. “And we can provide this data at less than half the cost of the data provided by foreign satellites,” Guo boasts.


    Space experts say it won't be long before live astronauts replace dummies in China's Shenzhou program.


    Last month China's fledgling space science program took another step forward with the launch of the Haiyang satellite. Its primary mission is to monitor China's coastal oceans for fisheries management and to track pollution and coastal development. But the satellite's data on ocean temperatures, for example, “will help our research on global change,” says Ni Yuefeng, vice administrator of the State Oceanic Administration. And space research doesn't get more basic than the Double Star mission, a cooperative effort with ESA to study Earth's magnetosphere. CNSA's Guo says that expenditures on science missions over the next 5 years will more than double, although he says that the multiplicity of sources makes it impossible to provide a specific amount.

    The human element

    The piloted program, which is run separately by a military organization called the General Armament Department, will also have a science component. “If we just send taikonauts [after taikong, the Chinese word for universe] into space, it would be a repeat of what the U.S. and Russia did 40 years ago,” says Wu. China began its crewed program in 1992 and made its first unpiloted test of the Shenzhou spacecraft in November 1999, with some life science experiments and instruments to monitor the cabin environment. The second launch, in January 2001, was less successful, as the capsule apparently lost cabin pressure during flight and the onboard experiments were lost. This past March Shenzhou 3 completed more than 100 orbits before landing safely in the desert.

    A dozen fighter pilots are currently training for future missions, including what appears to be the ultimate goal: a landing on the moon. But officials aren't saying when they will get the green light. Although CNSA's Guo predicts “within 2 years,” foreign observers think such official statements mask more optimistic plans. Phillip Clark, a space consultant based in Heston, U.K., believes the first group could go up in the next 12 months aboard Shenzhou 5. “The real question is whether they will launch two or three people,” he says.

    More importantly for researchers, the Shenzhou spacecraft has a forward module that remains in space, operating for 6 months or more after the crew capsule returns to Earth. The taikonauts are likely to return with some of the experiments, says Wu, while leaving others running on the orbiting module.

    Liu, the space breeder, has sent seeds aloft on previous Shenzhou missions, and Shenzhou 3 reportedly carried chick eggs that later hatched normally. Liu says such experiments also provide a way to check the craft's radiation shielding, and the absence of mutated seeds suggests that the shielding works well. Some researchers have made references to experiments involving protein crystallization and materials science. But details are hard to substantiate.

    CNSA's Guo emphasizes that his program is separate from the military and operates under its own rules. Far from being secretive, CNSA has been actively forging international ties. Those efforts get rave reviews from CNSA's partners. José Raimundo Coelho, manager of the CBERS project for Brazil's National Institute for Space Research, says the CBERS program gave Brazil an opportunity to design a remote-sensing satellite “to our own needs.” He points to the Wide Field Imager, which gives a one-shot picture of much larger areas of Brazil than are available from U.S. or European satellites. The bigger picture is very useful to land planners and mappers, he says, adding that “it would be very difficult for a country like Brazil to get involved in a cooperation like this with a developed country.”

    Karl Bergquist, an ESA official who oversees relations with China, says that European scientists studying Earth's magnetosphere “were extremely happy” with the agreement to make Double Star a Sino-European cooperative mission because it complements a European magnetosphere mission. Guo adds that various neighboring countries are interested in participating in a constellation of small remote-sensing satellites planned for launch in 2005 and later.

    There are even signs that the United States might be rethinking its hard-line position. Current restrictions limit export of sensitive technologies to China because of U.S. concerns over China's sales of missile systems to developing countries and its human rights record. And exports of U.S. satellites for launch on Chinese rockets—a lucrative business for China—have been more tightly controlled since the late 1990s, when a U.S. company was accused of sharing technological secrets with Chinese technicians.

    Double duty.

    Last month's launch of the Haiyang satellite will contribute data to China's global change program as well as monitor coastal conditions and marine pollution.


    But NASA's new administrator, Sean O'Keefe, said in March that he has discussed the idea of Chinese cooperation on the international space station with Richard Armitage, the deputy secretary of state. Any move would require White House approval, and NASA officials say they don't think anything will happen soon. China has not formally asked to be part of the station effort, but its human space program is widely viewed as a way to prove its technological competence. “It's always seemed to me that China's piloted program is predicated on being a station partner,” says John Pike, director of in Alexandria, Virginia.

    Regardless of whether taikonauts ever visit the station, they seem certain to find their way into space. “Peaceful development and mutual benefit should be the basic principle for Sino-American cooperation in space,” says Guo. But China is also prepared to go its own way, he says. Either way, the result should be new opportunities for space scientists.


    China Teams With Europe on Exploration of Magnetosphere

    1. Dennis Normile*
    1. With reporting by Ding Yimin.

    BEIJING— China's space science efforts are dominated by applied studies of Earth resources, meteorology, and oceanography. But the country is also planning one mission that is purely basic research: Double Star, a two-satellite collaborative project of the China National Space Administration (CNSA) and the European Space Agency (ESA).

    “It's an exciting [opportunity] to measure many of the dynamic processes of the magnetosphere,” says Wu Ji, deputy director of the Chinese Academy of Sciences' Center for Space Science and Applied Research (CSSAR) in Beijing, which sponsors the mission. “Double Star brings another set of data to studies of magnetospheric systems,” says Philippe Escoubet, ESA project scientist for Double Star.

    Double Star grows out of theoretical work by Liu Zhen-Xing, a CSSAR space physicist who has long studied magnetospheric substorms: sudden, violent releases of magnetic energy known to occur 10 to 20 times a day. Liu says his theoretical studies were held back “because there have been little data.” In the late 1980s, European scientists won ESA backing for a constellation of four satellites, called Cluster, that would observe the interaction between the charged particles of the solar wind and Earth's atmosphere. When the Cluster group called for proposals to use its data, Liu offered his theories on what triggers substorms. “We weren't expecting to get a proposal from China,” Escoubet says.

    Data reward.

    Liu Zhen-Xing (left) and Wu Ji hope the mission will confirm Liu's theoretical work on magnetospheric substorms.


    Liu's impressive theoretical work earned him a slot as co-investigator, and in 1993 CSSAR set up a ground observation station to supplement the satellite measurements and a center to distribute Cluster data. A failure of Europe's Ariane 5 rocket in June 1996 wiped out the first payload, but in 2000 two Russian rockets successfully launched the replacement mission, Cluster 2. Meanwhile, CSSAR was using its participation in Cluster as a magnet for younger researchers, several of whom were sent to Europe to study and train under senior Cluster scientists.

    By the late 1990s, the space physics group was itching for its own mission, and its scientists spotted a gap in observational coverage. The Cluster satellites—which fly in an elliptical polar orbit ranging from 19,000 to 119,000 kilometers from Earth—focus on the outer edge of the magnetosphere, leaving the core relatively unexplored. Although researchers had once thought the center was not very interesting, more recent findings suggested otherwise. So in the late 1990s, when CNSA solicited proposals for basic science missions, Liu seized the opportunity.

    The result became Double Star: two satellites, one in a near-equatorial orbit passing within 550 kilometers from Earth, the other in a polar orbit 700 kilometers at its perigee. After an extensive review, the proposal was selected for the country's 10th 5-year plan. In addition to its scientific merits, Double Star meshes with China's current launch and satellite capabilities, Wu notes. That allows it to leapfrog other proposed science missions, particularly a well-publicized Space Solar Telescope proposal, that require a new generation of more powerful rockets.

    Seeing double.

    Double Star is a joint Chinese-European mission to monitor the magnetosphere.


    Double Star became an international mission after Cluster scientists knocked on CNSA's door. About half of Double Star's instruments will be identical to those on the Cluster satellites, allowing scientists to combine observations from all six satellites to build a better three-dimensional model of the processes affecting the magnetosphere. “We are very happy with this opportunity,” says ESA's Escoubet. The two satellites, with eight Chinese and eight European instruments, will be launched by Long March 2 rockets starting in June 2003. “Double Star will be the first Chinese space science program for this new national space agency,” says Wu.

    It's not likely to be the last. Although Double Star will be the only basic science mission through 2005, Guo Baozhu, CNSA's deputy director, says he personally believes more basic research missions will be part of future 5-year plans because “science is a very important part of our space activities.” Wu says other groups at his academy are working up proposals for astronomy missions and experiments in microgravity.

    The results of Cluster and Double Star are likely to raise new questions about the magnetosphere. There is also talk of a moon probe, aimed at questions not addressed by the U.S. Apollo missions. “It is more important for us to do something unique,” says Wu.


    Report of Oldest Boat Hints at Early Trade Routes

    1. Andrew Lawler

    A Kuwaiti site yields 7000-year-old bitumen slabs thought to be from a seafaring vessel; a second team reconstructs a younger ship found in Oman

    LONDON— As-Sabiyah, an isolated piece of Kuwaiti desert surrounded by mud flats, seems an unlikely place to store boats, much less sail them. But a team of British and Kuwaiti archaeologists working there believes that more than 7000 years ago, when the Persian Gulf lapped nearby, workers in a small village took apart a seagoing craft made of reeds and tar, its underside still coated with barnacles, and stored it carefully in a stone building. Last year they uncovered those undisturbed remains, which they say represent the world's oldest known boat.

    If their interpretation of the material is correct, the discovery pushes back physical evidence of boats by more than 2000 years and sheds light on what later became trading routes linking two ancient civilizations: those of the Indus River valley and Mesopotamia. In particular, it offers concrete evidence to explain how pottery made in the first cities of ancient Mesopotamia ended up at sites hundreds of kilometers to the south on the Persian Gulf's western shores.

    Next month Italian and French archaeologists hope to add another piece to the emerging picture of how sailing developed when they finish a controversial reconstruction of a similar vessel, found in Oman and dating from 2400 B.C. They intend to build another version in Oman next year and sail it to Pakistan and India. But the puzzle is complex, warns Harvard University archaeologist Carl Lamberg-Karlovsky. The Omani boat provides little data on how ancient mariners mastered the Indian Ocean, he says, and the Kuwaiti boat was built before true sea-trading networks emerged.

    The highlight of the As-Sabiyah find consists of 22 slabs of bitumen, a tarry substance used for a variety of purposes in that region. “I got quite excited and started jumping up and down,” says Robert Carter, an archaeologist at University College London and field director for the expedition. “The barnacles on the bitumen give us confidence it's a seagoing craft.” Rope, string, and reed-bundle impressions left on the bitumen are thought to be materials used to build the boat.

    The age of the site is not in dispute. It was abandoned after the Ubaid period, and calibrated carbon-14 tests put the date at 5511 B.C. to 5324 B.C. Archaeologists working along the Euphrates River in Syria have found similar bitumen slabs dating to 3800 B.C., along with impressions of long-decayed reed bundles, but the slabs lack the barnacles unique to boats used in seas and oceans.

    Preliminary analyses show surprisingly advanced planning in the gathering of the materials needed to build the Kuwaiti boat. The bitumen came from a site nearly 100 kilometers distant. And the tarry substance is not pure but mixed with a variety of ingredients—such as fish oil and crushed coral—that match those used in the Oman bitumen 3000 years later. “It's a very sophisticated mixture,” says Serge Cleuziou, an archaeologist at the University of Nanterre who has closely studied the Omani amalgam.

    Gulf stream.

    Boat evidence from Kuwait and Oman suggests how ancient pottery and, later, trade spread throughout the region and to the Indus River valley.


    Few researchers have looked closely at the As-Sabiyah finds, now at the National Museum in Kuwait City. Joan Oates, an archaeologist at Cambridge University, U.K., who has not seen the materials, says that the prevalence of Ubaid pottery at shore sites makes it clear “there were boats at this time.” Textual evidence is absent in this prehistoric era, but boat models from the fifth millennium B.C. have been found at Eridu, a site near the mouth of the Tigris and Euphrates rivers. Even so, some scholars believe that they might have been bowls used for spinning.

    Sean McGrail, a maritime archaeologist at Southampton University, U.K., who has seen pictures of the Kuwaiti material, notes that the bitumen “is very fragmentary” and that “it's not necessarily a boat.” Then he adds, “but if it is, it will be the earliest around.” The earliest undisputed boat is from an Egyptian tomb dated around 3000 B.C., although log canoes built around 8000 B.C.—considered to be more rafts than boats—have been found in the Netherlands and France.

    Aside from pushing back the start of modern boatmaking, the Kuwaiti find would help explain how Mesopotamian pottery reached so far south at such an early date. The painted shards date from the Ubaid period—6000 B.C. to 3800 B.C.—that immediately preceded the urban explosion at Sumerian sites such as Ur and Eridu. Researchers have assumed that the pottery came via seagoing craft owned by early Mesopotamian merchants eager to exploit marine resources.

    Carter speculates that As-Sabiyah was a peninsula in ancient times and an obvious first port of call for boats from the Tigris-Euphrates river system. The site likely began as a campsite and grew into a small village of stone houses whose residents might have built or repaired boats. Stone tools, coupled with the Ubaid pottery and Mesopotamian-made jewelry, hint at a mixed population of Mesopotamians and Arab Neolithic peoples, says Carter. The Arab peoples might have been nomads—similar to the Bedouin in the region today—whereas the Mesopotamians were farmers and town dwellers.

    Oates maintains that Mesopotamian visitors to the Gulf region traded pottery for fish and perhaps pearls on their way south as far as Qatar and Bahrain. By the middle of the third millennium B.C., their ancestors were exchanging copper from Oman and goods from the distant Indus River valley.

    Old times.

    Bitumen remains from older Kuwaiti boat show rope impressions.


    The Omani find offers clues about the transport of goods back and forth across the Arabian Sea, trade that began some 3000 years after the Kuwaiti boat was built. The work, by a French-Italian team, is based on hundreds of pieces of bitumen slabs uncovered from 1985 to 1994. Led by University of Bologna archaeologist Maurizio Tosi, the team is also putting the finishing touches on a 14-meter-long vessel built of bitumen and reeds that could carry nearly 8 tons of cargo. Tosi says the boat will be ready next month, but it won't be tested in water.

    The reconstruction venture earns the ire of scholars such as McGrail. McGrail says that there is not nearly enough evidence to justify such an effort. He notes that a recent reconstruction of a Viking vessel required 75% to 80% of its remains and decades of research before a realistic replica could be made. He scoffs at the Omani attempt, noting that it is not even certain the remains are from a boat. “It's crazy,” he says. “It's almost wishful thinking.” The boat remains provide little data on the mast, keel, rudder, and sails, adds Lamberg-Karlovsky, and the site shows no evidence of warehousing or other obvious signs of international trade. “It's a teaser,” he says.

    Cleuziou, who hopes to collect enough funding for a second boat to be built next year in Oman that would sail across the Arabian Sea to an area near the mouth of the Indus River in Pakistan, acknowledges that critics such as McGrail “are right to some extent.” But he says that ethnographic and textual material is available to supplement the sparse archaeological evidence. For example, Sumerian writings refer to ships capable of hauling 18 tons of cargo to and from Oman. And other texts from around 2100 B.C. list specific amounts of reed bundles, rope, mats, fish oil, and bitumen to build Oman-bound ships. “Of course, this is not a proper reconstructed boat,” he says, “since there are many hypotheticals.”

    In the absence of textual evidence for sails, for instance, the team has chosen to use reed mats instead of wool or cloth. It's also not known what types of bitumen the Sumerians used for boatbuilding. To fill the gaps, Franco D'Agostino, an archaeologist at the University of Rome, earlier this year visited a small village near Basra in southern Iraq, where bitumen is still used in boatbuilding. These methods—dying out with the draining of the marshes by the Iraqi government—have not been extensively studied.

    Carter says he is also interested in trying to recreate the boat found by the British and Kuwaiti team, and he hopes to do further work next spring at As-Sabiyah. In the meantime, researchers are grateful for what appears to be the first solid evidence that boats plied the Persian Gulf as the great cities of Mesopotamia took shape, setting the stage for an international trading network. “It's damn good to have the archaeological data,” says Lamberg-Karlovsky.


    Comparative Biology Joins the Molecular Age

    1. Elizabeth Pennisi

    Researchers are reaching ever farther down the tree of life to probe basic questions of developmental and evolutionary biology

    “Too narrow,” griped many biologists when in the late 1980s advocates of the Human Genome Project decided to focus sequencing efforts on just a few species. No doubt the sequences of the targeted “model” organisms—the nematode, fruit fly, mouse, human, and, later, zebrafish—would help uncover the genetic underpinnings of human disease, these researchers argued, but limiting research to this slice of the animal kingdom would leave many, more fundamental questions unanswered.

    Those genome sequences couldn't explain many mysteries of development: why flies are different from sea urchins, for example, or eagles nothing like sturgeons. They would also provide few clues about evolution or the complement of genes necessary for each class of organisms. To answer such questions, “we need to sample many [places] on the tree of life,” says Nipam Patel, an evo-devo researcher at the University of Chicago. Now, researchers are beginning to do just that.

    Workers in dozens of labs around the world are sending new species into the sequencing pipeline. And these are not just the next six candidates—the chicken, chimp, honey bee, sea urchin, Tetrahymena, and fungi—the National Human Genome Research Institute (NHGRI) selected 2 weeks ago (Science, 31 May, p. 1589) but also species as diverse as squid, sea squirts, bats, and stickleback fish. “People are accepting the challenge of going out and [working] on organisms that are not the standard models,” says Patel. As a result, the century-old science of comparative biology is making a comeback, this time with a molecular spin.

    This trend was evident last month at an evo-devo meeting.* Some two dozen talks dealt with the fruit fly Drosophila, but dozens more tapped everything from jellyfish and the flatworm planaria to coelacanths, a living fossil fish. For researchers studying the genome sequences of humans and the original model organisms, finding shared regions has been a key goal. That's not necessarily the case with these newcomers. “We feel the [genome sequences of] new species are interesting not only for their conserved features but also for their numerous and unexplored differences,” explains Daniel Chourrout, an evo-devo researcher at the Sars International Centre for Marine Molecular Biology in Bergen, Norway.

    These projects are still in their infancy, with much of the effort aimed at developing the resources needed for sequencing and for interpreting newly generated sequence data. But draft versions of a few species are either done or close to being done, and researchers are already scouring these data for new insights into how life works.

    Biology's rising star

    The once-understudied tunicates—simple marine organisms that live by filtering plankton—are moving toward the limelight. Their place in the history of life has made them a potential poster child for comparative molecular biology—one that might reveal how vertebrates came to be. Many researchers view tunicates as stand-ins for the evolutionary predecessor of vertebrates.

    In their adult stages, most tunicates appear to have little in common with vertebrates. Sea squirts, for instance, have neither head nor tail and live attached to the sea floor. But the free-swimming sea-squirt larvae look a lot like tadpoles, with both heads and tails plus certain key features characteristic of chordates, the phylum to which both tunicates and vertebrates belong. Those features are a hollow nerve cord along the upper back, a notochord—a flexible rod of cells that functions like a backbone—and gill slits.

    Only in the past decade have molecular and developmental biologists begun looking more closely at sea squirts—in particular, the species Ciona intestinalis.Noriyuki Satoh, a developmental biologist at Kyoto University in Japan, opted for Ciona, he recalls, because the body plan of its tadpole is quite sophisticated, making it useful for comparisons with the body plans of more complex vertebrates. Seven years ago he began isolating Ciona genes and has pulled out dozens so far, ensuring Ciona a place in molecular-based laboratories and making it easy for others to take on this organism.

    At about the same time that Satoh began looking at the genetics of Ciona development, Michael Levine of the University of California (UC), Berkeley, and, independently, William Smith of UC Santa Barbara also decided to work on this species. “We believe that Ciona is the best model for future studies” of how development is affected by the regulation of genes, says Levine. Changes in that regulation can explain how organisms evolve to look and behave differently.

    Vertebrates' distant kin.

    Although adult sea squirts look nothing like humans or fish, their embryos (bottom) have key chordate features in common with these vertebrates, including a head, tail, dorsal nerve cord, and gill slits.


    To promote Ciona's utility, researchers at the Department of Energy's Joint Genome Institute in Walnut Creek, California, recently assembled a draft sequence of the 160-million-base Ciona genome. In April, 50 or so tunicate and bioinformatics experts joined forces to analyze the sequence, in the process discovering some 16,000 genes. Levine and Smith have also helped devise methods for introducing DNA into Ciona—a development that should help in determining the functions of those genes.

    The researchers subject Ciona embryos to weak electric pulses that cause them to absorb DNA from the surrounding water. “This permits the simultaneous transformation of hundreds, even thousands of embryos,” says Levine. Because the embryos have just 2600 cells, researchers can then track the effect of the inserted DNA on each cell, watching as it proliferates and specializes over time.

    Using this technique, Levine and his colleagues have begun to piece together the network of genes and regulatory DNA that interact to build the Ciona tadpole. By surveying 200 pieces of DNA, the researchers determined the general locations of the regulatory sequences—so-called cis-elements—that control a gene's activity in different tissues. The elements show up about every 15,000 bases and often turn out to be very close—within 500 bases—to the gene. This proximity means that finding cis-elements in Ciona is “extraordinarily easy” compared to finding them in vertebrate genome sequences, where they are often much more distant from the genes they regulate, says Satoh. It should also make the job of determining the role cis-elements play in Ciona development easier and might even help with the identification of cis-elements in other organisms.

    At the evo-devo meeting, Levine described his group's progress in identifying specific regulatory DNA sequences as opposed to simply determining where they reside. As a pilot test of screening the entire Ciona genome sequence for these elements, he and his colleagues have homed in on a 300,000-base piece of DNA that contains six so-called Hox genes, members of a highly conserved gene family that helps set up the body plans of organisms ranging from hydra to humans.

    The researchers broke that DNA into random 3000-base pieces, added a marker gene to each one, and then inserted the hybrid DNAs one at a time into tunicate embryos. Using this approach, they found 20 regulatory elements, eight of which direct Hox activity. Broadening this work to the whole genome sequence, Levine plans to create “a regulatory atlas of the Ciona genome that could serve as a blueprint for vertebrate genomes.”

    Satoh is looking for genes found in mice, humans, and tunicates, but not in fruit flies or nematodes, he reported at the meeting. His survey of 10 million bases of Ciona DNA turned up about 30 genes that met this criterion. This result suggests that the new genome sequence can help define the genetic code for chordates. In addition, Satoh expects that many vertebrate genes will not be found among Ciona's 16,000. “These [vertebrate-only] genes may help us understand what vertebrates are,” he says.

    Eric Lander of the Whitehead Institute Center for Genome Research in Cambridge, Massachusetts, Arend Sidow of Stanford University, and their colleagues have been sequencing C. savignyi,a close cousin to C. intestinalis.Comparisons of these two genome sequences should help pinpoint regions that underlie the speciation of these animals.

    Smaller, different, better?

    Chourrout is touting the benefits of one of Ciona's more distant relatives, Oikopleura dioica, a so-called larvacean, for evo-devo research. In some ways the two species are quite different. Instead of being sessile, Oikopleuradrifts along in the ocean and retains a head and tail its whole life. Thus, comparing their genome sequences should be useful. Also, because Oikopleura still looks like a chordate as an adult, it's relatively easy to make comparisons between it and other chordates, Chourrout notes.

    Oikopleura has other advantages: It is transparent and has a small genome—only about 72 million bases compared to Ciona's 160 million. It is also small and lives only 4 days, compared with Ciona's 3 months. Consistent with its short life cycle, Oikopleura speeds through development. Its embryo takes just about 4 hours to form the notochord and less than 11 hours to develop the brain, gut, and sensory system. “It's a really nice system to work with,” says Chicago's Patel.

    Chourrout has teamed with Hans Lehrach of the Max Planck Institute for Molecular Genetics in Berlin to sequence Oikopleura's genome. Although progress has been slow, key features have already emerged. For one, the overall organization of the Oikopleura genome resembles that of the nematode Caenorhabditis elegans, suggesting similarities in their life histories.

    Both organisms have compact genomes. Chourrout reported at the meeting that Oikopleura's 15,000 genes are densely packed, as are those of C. elegans. Oikopleura has one gene about every 4500 bases—compared with one gene for every 50,000 to 200,000 bases in the human genome—with far smaller noncoding DNA segments (introns) interspersed between each gene's coding regions. “The small genome may go with a short life cycle since if you have a short life cycle, you need to save a lot of time,” he notes. With this genome, little time is wasted replicating noncoding DNA.

    In another sign of this genomic economy, Chourrout and colleagues Hee-Chan Seo and Anne Maeland found that some of the Hoxgenes in both C. elegans and Oikopleura have lost their integrity. Ordinarily, Hoxgenes are arranged linearly in clusters, but Oikopleura's Hoxclusters “are weird,” says Patel. In some places the arrangement seems skewed, and also several genes usually found in the middle are missing. He suspects that, because of its small size, Oikopleura might not require the organizational powers of Hoxgenes in early development the way larger, more complicated organisms do. In this regard, “Oikopleura is like C. elegans,” which is also relatively small and has a simple body plan, says Chourrout.

    Other aspects of genome organization in Oikopleura might help protect it from genetic instability. Rolf Edvardsen, Chorrout's student at the Sars center, is studying the evolution of gene organization, focusing on how introns are arranged relative to exons, the protein-coding regions.

    Edvardsen first tracked down in Oikopleura 11 copies of the gene coding for α-tubulin, a protein found throughout the animal kingdom that is essential for maintaining cell structure. Generally an organism's α-tubulin genes vary little, and most copies have the same introns in the same places, supposedly because this protein is so key to survival. But that's not what Edvardsen found for Oikopleura. Although two pairs of genes had the same intron structures, the rest had different combinations of introns embedded in different noncoding places in the gene sequence.

    Different but alike.

    Larvaceans build large “cages” for filtering food from the sea, and although these tunicates are chordatelike even as adults (bottom), their genome structure is reminiscent of a nematode's.


    At the meeting Edvardsen reported “a striking difference [in intron arrangements] between Oikopleura and other species.” In most organisms, the nature and arrangement of introns doesn't vary. Aside from other Oikopleura species, C. elegans is the only other species known to have such variability in its introns.

    When introns are arranged the same way in related genes, the genes can readily swap pieces during reproduction; this swapping increases the risk that genes will become ever more similar to each other. The large difference in the intron arrangements of Oikopleura genes could reduce this swapping, Chourrout says.

    Brave new world

    Tunicates are but a few of the dozens of organisms being mined in evo-devo and genomic studies. For example, for a peek into brain evolution, Kiyokazu Agata of the RIKEN Center for Developmental Biology in Kobe, Japan, has tapped the ability of planaria to regenerate their heads. By following the formation of the new brain and characterizing the genes involved, he has early evidence that the brain organization seen in vertebrates had its beginnings in flatworms. Both vertebrate and flatworm brains have discrete regions along the anterior-posterior axis that look and function differently, and planaria's brain regions are organized like those of the embryonic vertebrate brain, he reported.

    At the other end of the species spectrum, Chris Cretekos of the University of Texas M. D. Anderson Cancer Center in Houston is looking into how bats evolved wings. He has found what he thinks is a key piece of regulatory DNA that helped alter the timing and pattern of bat limb development. He hopes to demonstrate this by putting that DNA into mice and observing changes in limb development.

    Other researchers have tapped amphipods—tiny, flat crustaceans—and annelids such as leeches, earthworms, and their relatives to make sense of the development of body segments. Still others are looking at body plan development in squid and hydra.

    And new draft sequences are appearing monthly. The researchers who churned out the 100 million bases of the C. elegans genome are almost done with that of its cousin, C. briggsae. A second fish genome sequence, from Fugu rubripes—the vertebrate with the smallest genome—has been drafted and partially analyzed, as has that of a second insect, a mosquito. Sequencing of the genomes of the chimp, a sea urchin, pig, and honey bee are or are about to be under way, with more species in the wings.

    To boost the comparative approach, the National Science Foundation and the National Institutes of Health have increased funding for the development of so-called BAC libraries. These sets of bacterial artificial chromosomes, which include bits of a species' entire genome sequence, make gene studies and genome sequencing easier.

    The species whose genomes are now being sequenced are unlikely to achieve the status of C. elegans or Drosophilaas model organisms. Nevertheless, Patel says, they are likely to contribute almost as much as these better studied counterparts toward understanding of the biological world.

    • *“Evolution of Developmental Diversity,” held from 17 to 22 April at Cold Spring Harbor Laboratory, New York.

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