News this Week

Science  26 Nov 1999:
Vol. 286, Issue 5445, pp. 1654

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    NIH Gets $17.9 Billion in Another Record Year

    1. David Malakoff

    In an encore performance that is drawing rave reviews from biomedical researchers, Congress handed the National Institutes of Health (NIH) another record budget increase. The $17.9 billion budget passed by the House on 18 November and the next day in the Senate represents a $2.3 billion boost that matches last year's precedent-setting 14.7% raise.

    The 2000 NIH budget is part of a last-minute agreement to wrap $385 billion in government spending into one appropriations bill so that Congress can recess for the year. And the only sour note in that package, which covers nine departments, is a 0.38% cut in total government spending, which White House officials must now spread across many programs, including NIH's parent body, the Department of Health and Human Services.

    The increase for NIH marks another success for a high-profile campaign aimed at doubling NIH's budget by 2004. But lobbyists worry that the big win may add to concerns that the agency is growing too fast and make lawmakers tighten the fiscal spigot next year. For the moment, however, research groups are savoring a year that began with a White House request for just a 3% increase. “There is a tremendous amount of good news in this budget—it lifts all boats,” said Mike Stephens, lead lobbyist for the Federation of American Societies for Experimental Biology (FASEB), which represents more than 66,000 researchers.

    NIH director Harold Varmus said he was “thrilled” with the budget, which provides NIH's 16 institutes with increases ranging from 13.4% to 15.1%. The National Cancer Institute—NIH's biggest research funder—will get a 14.8% boost to $3.3 billion, while spending at the second-ranked National Heart, Lung, and Blood Institute will grow 14.5%, to $2 billion. Several smaller programs were also big winners, with human genome research getting a 25.4% lift, to $337 million, and the controversial center for alternative medicine winning a 37.5% increase, to $69 million. Officials expect a rise in the number of grants to individual investigators and a jump-start for several initiatives, including gene sequencing and biocomputing projects (Science, 11 June, p. 1742). “We plan to do a lot of things that we've been holding in our back pocket,” Varmus told Science.

    In what one House aide called “a last-minute minor miracle,” lawmakers also shrank a plan that would have required NIH to push $7.5 billion in spending into the next fiscal year. Several research groups and White House officials earlier this month had denounced the budget gimmick—designed to protect Social Security accounts—saying it would disrupt research by delaying funding of new and renewed grants. But Varmus, worried about jeopardizing the agency's overall increase, had signaled that NIH could live with as much as $4 billion in delayed spending, and budget negotiators seemed ready to move ahead with that number. As weary House budgeteers prepared the final package, however, NIH backers—including Representatives John Porter (R-IL) and David Obey (D-WI)—convinced colleagues to reduce the deferred spending to just $3 billion. “We agreed [that the delayed spending] had to come down to reduce potential disruptions,” Porter told Science.

    Exactly how NIH officials will spend the new funds remains to be seen. And it could be another month or more before NIH knows whether it will be affected by the across-the-board cut—estimated to save just $1.5 billion from the entire federal budget—that Republican leaders insisted upon in the final round of negotiations. Clinton Administration officials will be able to pick where to make the cuts but can't slash particular programs by more than 15%. Although NIH will probably lose some money, Varmus said cuts were “unlikely to create any particular difficulties. No one is feeling unhappy about this.”

    Another decision that NIH officials face is how much of the new money to commit to multiyear grants. Tying up too much money in long-term awards could reduce the funds available for new grants if Congress holds down increases in future years, observers note.

    NIH allies, however, are already discussing how to keep the agency on the doubling path. Whereas some see this year's outcome as adding momentum to the doubling train, others wonder if this year's bruising political battle—which included lawmakers such as Senator Pete Domenici (R-NM) expressing concern that the agency won't be able to spend its growing budget properly—may have torn up the tracks. “Some toes got stepped on this year in pushing the increase,” says one congressional aide, noting that several Republican leaders were unhappy that some biomedical groups joined the White House in attacking the delayed budgeting concept.

    But Porter, who is retiring next year after 22 years in Congress, says that he and other “supporters of biomedical research have long realized that [doubling] is a very difficult goal.” Next year, he notes, NIH will need another huge increase—$2.7 billion—to keep up the pace. A continued strong economy would help, he says, and might dampen complaints. “There is so much good science out there,” he adds, that any new funds can be “extremely well spent.”


    Genentech, UC Settle Suit for $200 Million

    1. Marcia Barinaga

    San Francisco–A bitter episode in biotech history was finally put to rest last week when South San Francisco biotech pioneer Genentech agreed to pay the University of California (UC) $200 million to settle a long-running patent suit. UC and Genentech were locked in a court battle over UC's claim that the company's $2 billion drug, Protropin, had infringed its patent on engineered human growth hormone. The deal, which includes a $50 million donation toward a research building at UC San Francisco—the campus that holds the disputed patent—will result in payments of $17 million each to five former UCSF scientists.

    UC's claim was the subject of an 8-week trial last spring that ended with the jury deadlocked 8 to 1 in favor of the university. Because Genentech survived that first round so narrowly, many viewed the retrial, scheduled to begin on 3 January, as a “slam dunk” for UC, says San Francisco patent attorney Richard Osman, who followed the case closely. If UC had won, damages could have topped $1 billion. But the outcome was far from assured, says Zach Hall, vice chancellor of research at UCSF, and “whoever had won, the other side would have felt aggrieved.” The settlement, he adds, “provides a basis for future cooperation and allows us to put behind us whatever bad feeling may have been engendered by this dispute.”

    Genentech is not admitting that it infringed UC's patent, says the company's chair and chief executive, Arthur Levinson. “I can't tell you that I know for a fact that we were not [infringing the patent], and I think if you were to ask the UC folks, they probably couldn't say with 100% assurance that we were. The way we approached this was largely as a risk mitigation exercise. We could have ended up paying more than $200 million, and we could have ended up paying nothing.” Investors apparently liked the deal; after news of the settlement began to leak out on 15 November, shares of Genentech stock began a 4-day climb from $71.75 to close Friday at $87.06.

    In addition to the $50 million toward the new research building—which will be on UCSF's new Mission Bay campus and which Genentech will name—the company is paying UC $150 million in cash. Based on a UC formula for distributing royalties that was in place when the patent was issued, UC's general fund will get $30 million, UCSF will receive an additional $35 million, and the remaining $85 million will be split equally among five scientists who first cloned the gene for human growth hormone. They are the three inventors named on the patent—former UCSF professor Howard Goodman, who is now at Harvard; his former postdocs Peter Seeburg, now director of the Max Planck Institute for Medical Research in Heidelberg, Germany; and John Shine, now executive director of the Garvan Institute of Medical Research in Sydney, Australia—and two collaborators, John Baxter of UCSF and his former postdoc Joseph Martial, now of the University of Liege in Belgium. The university's legal fees, which Hall estimates at $20 million to $24 million, have already been paid by UCSF and the five scientists from other patent income, including more than $41 million from the human growth hormone patent.

    The settlement ends a case that burst into public view last April when Seeburg took the stand for UC during the trial and offered explosive testimony. He said that when he was working as a scientist at Genentech in 1979, he had used growth hormone DNA that he had cloned while a postdoc at UC, and subsequently removed from his former lab, to make the DNA vectors from which Genentech produces Protropin. What's more, he testified that he and former Genentech scientist David Goeddel, now chief executive officer of the South San Francisco biotech company Tularik Inc., had agreed to misrepresent the source of the DNA in a 1979 paper in Nature. Goeddel has vigorously denied that they used the UC material or struck any such agreement. Legal experts have questioned whether Seeburg's testimony was relevant to the underlying patent case, and some have argued that it shouldn't even have been admitted in the trial (Science, 11 June, p. 1752).

    Regardless of the relevance of his testimony, Seeburg's court appearance has had personal repercussions for the prominent German scientist. Following his testimony last spring, the Max Planck Institute opened an investigation of whether he had committed scientific misconduct 20 years ago. The results of that investigation, which have not yet been made public, were delivered to Max Planck president Hubert Markl last week.

    The settlement will avoid a replay of the spectacle of two well-respected scientists challenging each other's veracity under oath about the origins of the growth hormone DNA. UC and Genentech have agreed that despite the wealth of evidence that has been presented, it will never be known for sure where the DNA in the Genentech clone came from. In the end, says Levinson, “there is no way you could conclude one thing or the other that would satisfy 100% of the people.” And maybe with a new UCSF research building that carries Genentech's name, and the legal case finally closed, most people eventually will cease to care.


    NSF Proposes Marriage of Rocks and Waves

    1. Richard A. Kerr

    Despite their common subject—the planet Earth—practitioners of geology and geophysics generally keep their distance. The lone field geologist stomps over “her” mountain or favorite outcrop, hauls back some rocks, and tells her fellow geologists about them at a meeting of the Geological Society of America. The geophysicist pores over the squiggles of seismic waves, increasingly gathered by consortia of his colleagues, and reports his results at a meeting of the American Geophysical Union. But that may be changing: The National Science Foundation (NSF) has proposed a $75 million project for its next budget in which the twain would meet.

    The project, dubbed EarthScope, would create a downward-looking geophysical “telescope” to probe the continent from the surface to its very roots and beyond. NSF would like to make a $19 million downpayment in fiscal 2001 on a 4-year, two-part effort that would create a network of scientific instruments to analyze the continent over a range of spatial and temporal scales. Geophysicists seeing the subsurface in unprecedented detail would presumably join geologists dissecting surface rocks to answer questions that neither group can answer alone, such as how and why classic geologic provinces came to be juxtaposed.

    “Times are changing, and I think people are changing,” says Karl Karlstrom of the University of New Mexico, Albuquerque, who describes himself as a dyed-in-the-wool field geologist. “I think 10 years from now we'll look back on this as a time of major change in the way [earth] science gets done.” Still, many scientists are worried that operating costs could take a big bite out of the money available for traditional “small” science. “I would hate to see that suffer,” says Clark Burchfiel of the Massachusetts Institute of Technology, who works on the geology of the Tibetan Plateau.

    NSF's 2001 budget proposal, now under review, would fund two elements of the project. USArray would be the “Bigfoot” of seismic networks, 400 mobile seismometers scattered to form a 1000-kilometer-square array that would be marched around the country. Embedded within the 1000-kilometer array would be a higher powered “telescope” of 2400 instruments targeted on individual faults, magma chambers, and mountains. After the seismic waves from earthquakes and explosions are formed into three-dimensional images and combined with geology, geochemistry, and topographic measurements, researchers might see how North America has been put together, what's holding up the Rockies, or how the Cascade volcanoes are being fueled from below. At a far smaller scale, the San Andreas Fault Observatory (SAFOD) would drill down 4 kilometers into the central San Andreas to find how continental blocks grind past each other to produce earthquakes.

    Both SAFOD and USArray had been knocking around as separate concepts for 5 years or more with bleak funding prospects, according to Herman Zimmerman, acting director at NSF's Earth Science division; even one of these projects was too much for the division's $100-million-a-year budget. Then, last year, division staff decided to bundle them under the EarthScope banner and seek support via NSF's Major Research Equipment account, which each year typically contains four to six projects. Since 1995 the account has funded large facilities beyond the reach of any division or even directorate, such as the $290 million LIGO, the Laser Interferometer Gravitational-Wave Observatory in Washington State and Louisiana, which was dedicated last week. EarthScope “would be an observatory for the entire community,” says Zimmerman. A presentation to the White House Office of Management and Budget earlier this month “went very well,” Zimmerman told a recent EarthScope town meeting. The $75 million over 4 years would cover the hardware and its deployment; the geosciences directorate, of which earth sciences is part, has committed to providing funds for operating costs and science support.

    In future years, NSF would like to expand EarthScope with two instruments that would give an even broader view of Earth. The Plate Boundary Observatory (PBO) would place a dense concentration of instruments along North America's major tectonic plate boundary from Alaska to Mexico, looking for the stress buildup that drives earthquakes. And over it all would be InSAR, a satellite-borne Interferometric Synthetic Aperture Radar that would check strain accumulation every 8 days with 100-meter resolution. EarthScope planners hope PBO might get under way in 2002 or so and InSAR soon after that.

    Support for EarthScope ranges from enthusiastic among geophysicists to guarded among geologists. “We're beginning to sense that, for some of our problems, the only solution is complex, multidisciplinary studies,” says seismologist David Simpson of IRIS, a consortium of seismological research institutions in Washington, D.C., that is expected to put in a bid to build and operate USArray. “These are big problems; they've got to be attacked in an integrated big-science way. EarthScope engages a much, much larger community than just the seismologists.” Despite his reservations, Burchfiel agrees that “there's a lot of great science to be done, [but] it's science in a somewhat different mode than some people are used to. The geophysics community is clearly trying to integrate geology and geophysics for better science. That's the way it has to go.”

    Whether it goes that way as soon as the project's backers hope depends first on winning a spot in the president's budget that appears in February, followed by a congressional nod later in the year. In the meantime, everyone would probably agree with Zimmerman's bottom line: “This is not an easy thing to pull off.”


    Scientists Decry Antipiracy Bill

    1. Jocelyn Kaiser

    Responding to a furious lobbying campaign, the House last week put off a vote on a bill that critics say could severely hinder how everyone from molecular biologists to environmental scientists uses electronic databases. Scientific groups are hoping a less restrictive proposal emerges when Congress returns in January.

    The issue arose 3 years ago, when the World Intellectual Property Organization floated a draft treaty that would impose civil and criminal penalties for using information in a commercial database without the database owner's approval. The initiative was put on the back burner, however, after the U.S. National Academy of Sciences and other organizations complained that the treaty might undermine “fair use,” a legal privilege that has long allowed open access to many kinds of data for educational and research purposes (Science, 25 October 1996, p. 494). Most troubling to these groups was the prospect that companies which repackage data freely available from the government—weather statistics or gene data, for example—could claim ownership of the raw information.

    Congress has since struggled to forge a consensus on how to protect commercial databases without overly restricting academic access (Science, 14 May, p. 1129). The latest overture, Representative Howard Coble's (R-NC) Collections of Information Antipiracy Act (HR 354), would prohibit for 15 years or more the use of data in a way that would harm a database's market. Backing the bill, which was approved by the House Judiciary Committee in May and was headed for a possible floor vote last week, are groups such as the National Association of Realtors, which wants to protect its Multiple Listing Service, and Reed Elsevier, which owns LEXIS-NEXIS and many scientific journals.

    University, library, and scientific groups, however, contend that Coble's bill is deeply flawed, particularly its definition of databases as “collections of information.” That sweeping term, critics say, could encompass tiny collections such as a handful of species names or even individual facts. And that could allow database owners to impose fees or other constraints on researchers hoping to create new data sets or manipulate the information—for example, by plugging weather data into a climate model. Another problem, they say, is that the bill would permit nonprofit uses of data “that do not materially harm the primary market,” without explaining what would constitute “harm.” According to a 1 November letter to House members from Association of American Universities (AAU) president Nils Hasselmo and signed by 12 other groups (including AAAS, Science's publisher), HR 354 “would place a shroud of uncertainty over today's customary and accepted practices.” An investigator who drew on a commercial database—which could mean any of Reed Elsevier's journals, for instance—could wind up violating copyright law if he or she let postdocs and grad students incorporate the data into their work, says AAU executive vice president John Vaughn. “We don't want to have to bring lawyers into the lab,” he says.

    The AAU and other groups have thrown their weight behind an alternative bill, HR 1858, crafted by the House Commerce Committee. HR 1858 would, among other differences, protect collections of facts but not discrete facts themselves; and it would allow more leeway for researchers, penalizing them only if they misuse data as part of “a consistent pattern engaged in for the purposes of direct commercial competition.” The bill's approach is more in line with an academy report released last month, “A Question of Balance: Private Rights and the Public Interest in Scientific and Technical Databases.” However, the Judiciary Committee bill, which is favored by House Majority Leader Dick Armey (R-TX), has dominated discussions so far.

    With HR 354 failing to pass before the House adjourned, some observers expect members to try to work out a compromise bill. The Senate also appears eager to move on database protection: Orrin Hatch (R-UT), chair of the Senate Judiciary Committee, last January signaled his intention to open debate by introducing several proposals into the Congressional Record. “We think if something happens, there could be fairly quick action,” says Skip Lockwood of the Digital Future Coalition.


    EU Confronts the Gender Gap

    1. Michael Hagmann

    At the University of Lisbon, being a woman does not seem to be a huge impediment to a successful career in science: Almost 60% of all assistant and associate professors and 30% of full professors there are female. But in most other European research establishments, that's far from the case. Throughout the European Union (EU), the situation for women scientists is dire—on average, men outnumber women by around 20 to 1. This bleak picture emerges from the pages of a new European Commission report that, for the first time, pulls together statistical data from all over Europe. Besides fueling the gender debate in the EU with hard data, the report also sketches out several recommendations to offset the imbalance, such as more meticulous bookkeeping for gender-disaggregated statistics, better access to public records, and an affirmative action approach similar to that in the United States.

    The report,* presented to EU research commissioner Philippe Busquin this week, is one of the outcomes of a conference on women in science held in April 1998. In the wake of the meeting, then-research commissioner Edith Cresson asked Mary Osborn, a cell biologist at the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany, to assemble a group of experts and look in detail at the situation female scientists face in the EU's 15 member states.

    The first obstacle the group—consisting of 12 top women scientists and science policy-makers—faced was a profound lack of sound statistical data. Osborn says that, especially in industrial research, “it's almost impossible to get good numbers.” Once the group had collected all the available data, however, a more or less consistent picture emerged. Although the science community in some southern European countries, such as Portugal, seemed to be a little less lopsided, the proportion of women in senior research positions was extremely small—in Austria, for example, only 4% of full professors are female, compared to almost 14% in the United States. The situation is even worse in independent research institutions and private granting organizations. “In some charities women didn't play any role at all,” says Osborn.

    This is in striking contrast to the gender distribution among science undergraduates, where every other student is female. “Women are not staying in science. They're not being promoted to the same level as their male colleagues,” says Osborn. “This is a huge waste of resources. Society, which is paying for the training [of female scientists], is not getting a good return.” Busquin agrees: “Women's potential is seriously underused. Many highly trained women are lost to science during their career.”

    Osborn's first take-home message is that “we need to push for better statistics, broken down by gender but also by academic rank. And a monitoring system, because if you don't have the numbers you can't really assess any progress.” Also, given the severity of the problem, the group calls for a concerted action plan across the EU instead of piecemeal projects in individual member states. European legislators should mandate target ratios for gender balance in public bodies such as universities, grant assessment panels, and policy-making committees. Osborn points out that some countries, including Finland and Italy, already have such gender equality acts in place.

    For the Sixth Framework Program, the next round of the EU's rolling multibillion-dollar research effort starting in 2002, the group suggests, among other things, that the commission should aim for a gender balance no greater than 60:40 on key scientific committees and evaluation panels by 2005, monitor grant applications and success rates by gender, and create a new European prize for excellent female researchers.

    The report will also be presented at a meeting of national civil servants from across the EU in Helsinki at the end of the month, where “it may serve as a catalyst to kick off national debates in the member states,” says Nicole Dewandre, the head of the Women and Science section of the EU research directorate. “This gives us a solid, quantitative argument for opening up the European science system to women,” she says.


    Learning Visualized, on the Double

    1. Marcia Barinaga

    Researchers have long believed that when the brain learns, the synapses, the connections between neurons, get stronger. For years, neuroscientists focused on chemical changes that boost synapse strength, but more recent work suggests that synapses change structurally, too. Now, in this week's issue of Nature, a team led by neuroscientist Dominique Muller of the University of Geneva in Switzerland reveals one dramatic change: Some strengthened synapses actually double, with a second synapse quickly forming right next to the one that was active.

    The Geneva team first stimulated rat brain slices to produce a form of synapse strengthening called long-term potentiation (LTP), which may mimic some events in learning. Then, with an electron microscope (EM), they looked at synapses where LTP had occurred. Researchers had tried to see physical changes at the strengthened synapses before, but those synapses were hard to find because they are only a small percentage of the total. To get around that problem, the Geneva group took advantage of a synaptic change known to happen during LTP.

    When the presynaptic neuron fires, it releases neurotransmitter molecules, which cross the synaptic gap and are picked up by a structure sticking out from the receiving neuron, called a spine. If the receiving neuron has already been activated in a way that primes it for LTP, the arrival of the neurotransmitter triggers LTP by causing calcium ions to flood into the spine. Muller's team treated the brain slices with a chemical that precipitates calcium, forming deposits that can be seen in the EM and serve as tags for spines that had undergone LTP.

    Team member Nicolas Toni found that when he looked at electron micrographs made an hour after inducing LTP, 20% of the tagged synapses had double spines, both contacting the same presynaptic neuron, a configuration that he very rarely saw in synapses that hadn't undergone LTP. The authors conclude that LTP triggers “a duplication of the active synapse,” presumably strengthening it, says Muller.

    Neuroscientist Tobias Bonhoeffer of the Max Planck Institute for Neurobiology in Munich, Germany, calls the work a “nice addition” to the growing story of how synapses reshape when they strengthen. It complements findings earlier this year by his team and one led by Roberto Malinow and Karel Svoboda at Cold Spring Harbor Laboratory on Long Island. Using a technique called two-photon microscopy, those teams watched synapses in living tissue. Within an hour after inducing LTP, the researchers saw what looked like new spines popping out of neurons near the strengthened synapses.

    “The question that was totally unresolved” in that work, says Bonhoeffer, was whether the new spines form synapses with the presynaptic neurons. If the double spines captured by Muller's group in EM images represent those new spines, Bonhoeffer says, the answer to that question would be yes.


    DOE Gives Up on Brookhaven Reactor

    1. David Malakoff

    Researchers lost a major tool for probing the structure of matter last week when Energy Secretary Bill Richardson announced that he will permanently close the mothballed High Flux Beam Reactor (HFBR) at Brookhaven National Laboratory in Upton, New York. The surprise move stunned both opponents and supporters of the facility, who were preparing for a battle over the safety of restarting the controversial reactor.

    The HFBR, opened in 1965, is a 60-megawatt nuclear reactor that provides scientists with neutron beams. Researchers use the particle streams to probe the atomic structures of everything from metals to tissues and to produce radioactive isotopes for use in medicine and in biomedical studies. The reactor has been on indefinite standby since January 1997, when workers discovered that radioactive tritium gas had leaked from the reactor into nearby groundwater (Science, 5 September 1997, p. 1431). The revelation ignited local opposition to restarting the reactor and prompted the Department of Energy (DOE) to replace the lab's management. The agency also announced that it would undertake a full-scale review of the reactor's potential threat to public health and the environment.

    A first draft of that review was due to be released next month. But Richardson short-circuited the process by announcing that a lack of support in Congress for restarting the reactor and his view that the funds could be better spent elsewhere led to the decision. “While I don't believe the Brookhaven reactor is a threat to the public or the environment, we need to focus our limited resources on productive research,” Richardson said in a 16 November statement. DOE officials estimate that the agency has spent $23 million per year keeping the HFBR on standby, but declined to estimate how much it will cost to decommission and dismantle the reactor. Brookhaven officials earlier had estimated closing costs at nearly $200 million.

    While environmentalists praised the decision, researchers mourned their loss. “The cost to national science effectiveness is likely to be far greater” than the cost of restarting the reactor, said Brookhaven director John Marburger in a statement decrying the HFBR's “untimely demise.” Richardson “pulled the rug out from under us—we weren't given a fighting chance,” added Brookhaven physicist Steve Shapiro, who noted that close to 300 scientists used the reactor the year before it was shut down. Now, he says, they will have to fight for time at two other facilities—one at Oak Ridge National Laboratory in Tennessee, the other in Grenoble, France—that produce neutron beams of similar energies. Both “run 24 hours a day, 7 days a week, and they still are oversubscribed,” he says.

    DOE officials hope to relieve the overcrowding with upgrades to several other neutron sources and the completion of Oak Ridge's new Spallation Neutron Source in 2005. Those sources, they note, may benefit from equipment scavenged from Brookhaven's abandoned reactor.


    Risks and Benefits: GM Crops in the Cross Hairs

    1. Dan Ferber*
    1. Dan Ferber is a writer in Urbana, Illinois.

    As controversy builds over the safety of genetically modified crops, the evidence so far hasn't pinpointed any specific problems—but also can't dispel the doubts

    An American entomologist publishes a study in Nature showing that pollen from genetically modified corn kills monarch butterfly larvae; two of his colleagues denounce him in a commentary for publishing “preliminary results” and imply that he is spreading rumors. A British food-safety expert writes in Nature that a concept that underlies regulation of genetically modified food in most of the developed world is “pseudoscientific”; an opponent fires back in a letter calling his commentary “a mish-mash of old-hat sociology and poor science.” A British scientist announces on television that genetically modified potatoes stunt the growth of rats and damage their immune system; his supervisors suspend him 2 days later. It would be hard to find a scientific debate more polarized than the one now being waged about the safety of genetically modified (GM) crops.

    But while biotech opponents talk of Frankenfoods and terminator genes and industry groups minimize safety concerns, a small group of investigators has been taking a serious look at GM crops to see what health and environmental risks they might pose. What they are finding is in many cases reassuring—but not always. The plants, most of which have been modified to resist pests or weed-killing herbicides, seem to pose minimal risks to human health, say experts. But environmental concerns such as the possibility that the novel genes might spread to wild plants and produce new strains of weeds, although hard to substantiate, are also proving hard to dispel.

    Complicating the weighing of risk is the question of how much any potential hazards are offset by the crops' potential benefits, such as reducing the use of chemical pesticides, lowering costs, and improving nutritional value. Part of the problem is that, unlike drugs or pesticides, plants have never been subjected to a risk analysis, says plant pathologist James Cook of Washington State University in Pullman, who chaired an international panel to devise risk assessment methods for GM crops. “We have to ask what are the safety issues raised by plants, then apply that to crop plants with transgenes,” he says.

    Food-safety concerns have stirred the most passionate debate among the public, prompting boycotts, bans, and protests. But few accept the conclusions of the report that sparked the furor over GM potatoes in Britain (Science, 22 October, p. 656). And there's little other research that might raise concerns that the transgenic crops now on the market threaten human health. “There's something wrong with the perception of risk here,” says microbiologist Abigail Salyers of the University of Illinois, Urbana-Champaign.

    For example, GM food critics worry about plant genetic engineers' practice of attaching the genes they are trying to introduce into plants to an antibiotic-resistance gene. They can then readily select those plants that have acquired the genes by treating them with the antibiotic, which kills any nonresistant plants. The critics charge that the antibiotic-resistance genes, which sometimes remain in the transgenic crops, could spread to pathogens in the body and make antibiotics less effective. But several panels of antibiotic-resistance experts have concluded otherwise. “Unanimously, the verdict has been that the chance of antibiotic-resistance genes getting into intestinal bacteria is minuscule,” Salyers says. And if they did get in, “the virtually unanimous verdict is that it wouldn't matter” because the same resistance genes are already present in many of the bugs.

    A more plausible—though still unlikely—threat to human health from transgenic foods comes from food allergies. An allergic reaction to food can be serious, even life-threatening, if it leads to anaphylactic shock. “That's one you certainly want to worry about,” says food microbiologist Bruce Chassy of the University of Illinois, Urbana-Champaign, a former food-safety adviser to the U.S. Food and Drug Administration. Indeed, in a study reported in 1996 in The New England Journal of Medicine, Steve Taylor and his colleagues at the University of Nebraska, Lincoln, showed that people allergic to Brazil nuts are also allergic to soybeans that have been engineered to express a Brazil nut protein to make them more nourishing.

    To Chassy, the outcome was reassuring: The results led the producer of the transgenic bean, Pioneer Hi-Bred International, to discontinue the soy line voluntarily before it was commercialized. What's more, the producers of GM foods screen their products for allergenicity, he says. Among other methods, they can check to see if the amino acid sequences of the proteins made by the genes they put into crop plants resemble those of known food allergens.

    Critics say that because many proteins that trigger allergic reactions have not yet been sequenced, the sequence comparison test will fail to detect some allergens. “If you find a match, then you have a problem,” says Rebecca Goldburg, senior scientist at the Environmental Defense Fund in New York City. “If you don't, it doesn't say anything.” But Chassy notes that conventional foods already on the market, such as peanuts and Brazil nuts, pose much higher risks of allergies than GM foods, as do plants produced by classical breeding methods, which introduce many potential allergens into the product. “If a zero-risk standard prevails, we shouldn't put any new food on the market and we should get rid of a lot of old ones,” he says.

    Bt or not Bt?

    It's the potential environmental effects of GM crops that stir deeper scientific debates, as was evident at a recent meeting, held near Chicago on 2 November, that examined whether pollen from so-called “Bt corn”—corn containing an insecticidal protein from the bacterium Bacillus thuringiensis—could harm monarch butterflies in the field. The colorful monarch became the poster child for the anti-GM movement last May, after entomologist John Losey and colleagues at Cornell University published a short laboratory study in Nature showing that Bt corn pollen could kill monarch butterfly caterpillars in the laboratory.

    View this table:

    Out of a group of caterpillars that had munched on milkweed leaves—the larvae's only food source—dusted with Bt corn pollen, 44% died within 4 days, while larvae eating leaves dusted with ordinary pollen all survived. Although perhaps not surprising—researchers had known for years that Bt bacteria, which are themselves widely used as pesticidal sprays, could harm a variety of butterflies and moths—the Losey study was the first one published showing that a Bt plant could directly harm a nontarget butterfly.

    The study attracted widespread media attention and alarmed biotech observers throughout the world. The resulting hubbub caused European regulators to place a moratorium on the approval of additional Bt crops and prompted jitters among biotech investors. Even so, it was not clear whether monarchs outside the lab, developing on milkweed plants growing near fields of Bt corn, are in fact in harm's way. To find out, major biotechnology companies, including Monsanto Co., Novartis Seeds Inc., and AgrEvo USA, formed an unusual consortium called the Agricultural Biotechnology Stewardship Working Group (ABSWG) that dispensed $100,000 to eight researchers at U.S. and Canadian universities to conduct further studies. The U.S. Department of Agriculture (USDA) and individual universities funded an additional 12.

    The study participants presented their early results at the Illinois meeting, where they did agree on one point. “The worst case scenario of a toxic pollen cloud saturating the Corn Belt and wiping out all the Lepidoptera” is clearly not going to happen, says entomologist Stuart Weiss of Stanford University. But Bt pollen might still have less dramatic harmful effects—although a press release put out by the ABSWG early in the meeting suggested otherwise (see sidebar on p. 1663).

    At issue in the new monarch studies is just how far pollen might drift from cornfields, and how toxic it might be to any monarch larvae that eat it. The potential for harm is certainly there, says entomologist John Obrycki of Iowa State University in Ames. Because corn pollen is relatively heavy, it is likely to settle near cornfields. What's more, Obrycki says, “we do find lots of milkweeds growing near cornfields, and they are being used by monarchs.”

    At a meeting of entomologists held last March, he and graduate student Laura Hanson reported results suggesting that enough pollen might collect on nearby milkweeds to harm the larvae. The work, which has not yet been published, showed that about 20% of monarchs that fed for 2 days on potted milkweed plants left at the edge of Bt cornfields died, compared to 3% of monarchs that fed on plants left near non-Bt cornfields. At the Illinois meeting, the industry- and USDA-funded researchers presented similar results, but their interpretation was more optimistic. In one study, for example, botanist John Pleasants of Iowa State and entomologist Richard Hellmich of the USDA's Agricultural Research Service and Iowa State first determined the levels of Bt pollen that are toxic to monarch larvae, then measured how much pollen they could trap on sticky slides left near cornfields.

    The results showed that even milkweeds within 1 meter of the cornfield were unlikely to be dusted with toxic levels of Bt pollen from two of the most widely planted corn varieties, AgrEvo's CBH 351 and Monsanto's Mon810, Hellmich said at the meeting. The researchers did find that pollen from the same line that Obrycki tested, Novartis Seeds' 176, is sufficiently toxic to threaten monarchs feeding on milkweeds up to 2 meters away, thus confirming Obrycki's results. But the more toxic Bt line represents just 2.5% of the corn planted in the United States. Overall, Hellmich says, his team's results and similar data presented by others at the meeting revealed a minimal risk to the monarch. “A lot of the data presented were overwhelmingly positive,” he concludes.

    Still, monarch experts were not entirely reassured. One problem, says insect ecologist Orley Taylor of the University of Kansas, Lawrence, who directs the conservation group Monarch Watch, is that even if Bt exposure doesn't kill monarchs, it could make them less fit for their long migration to Mexico, where they overwinter en masse. At the meeting, Taylor presented a model, based on current Bt corn acreage and the butterfly's migration patterns and reproductive behavior, that predicted a worst case scenario in which 7% of the North American monarch population would die. Although the real effect would undoubtedly be less, he says, “there's plenty of indication that there's going to be an impact. It's a matter of degree.”

    Bt toxins might also threaten beneficial insects indirectly, by entering the food chain. For example, in work published in 1998 and 1999, Angelika Hilbeck and her team at the Swiss Federal Research Station for Agroecology and Agriculture in Zurich, Switzerland, showed that green lacewing caterpillars—a beneficial pest-eating predator—were more likely to die when they ate European corn borer caterpillars that had fed on Bt corn than when the borers had fed on non-Bt corn. “It's interesting science because of what it says about the toxicology of Bt,” says entomologist Richard Roush of the University of Adelaide in Adelaide, Australia. But “a lot of us wonder whether it's really important in the field.” He and others note that Bt bacteria have been sprayed on farm fields for 3 decades, and that earlier studies had shown that beneficial predator insects were unaffected.

    Hilbeck argues, however, that because the toxin is expressed at high levels throughout GM crop plants, rather than just sprayed on their surfaces, plant-eating insects could receive a much bigger dose. She has begun field trials, and she says others should monitor the effects of Bt crops on lacewings and other insect-eating predators before a problem develops. “Anything is possible,” she says. “There may be no effect, but there may be a slow and chronic effect on green lacewing larvae. Then you might find, ‘Whoops, where did all the lacewings go?’”

    Flowing genes and superweeds?

    Ecologists also worry that genes such as those conferring resistance to herbicides or insect pests might pass from the crops into wild relatives and create so-called superweeds—invasive plants with the potential to lower crop yields and disrupt natural ecosystems. They note that a variety of crops, including canola, squash, sunflower, and sorghum, can outcross with weedy relatives growing nearby.

    Plant geneticist Val Giddings, a spokesperson for the Biotechnology Industry Organization, downplays the risk, saying that even if such outcrossing allowed a weed to pick up a gene, it would not persist for long in the wild. A herbicide-resistance gene, for example, would disappear from weeds outside the confines of farm fields because there would be no herbicide to select for plants containing it. “There is abundant literature that demonstrates that in the absence of selection pressure, a neutral trait will be lost over time,” Giddings says.

    Sometimes, but not always, answers plant ecologist Allison Snow of Ohio State University, Columbus. In a study published in April in Molecular Ecology, Snow, with Rikke Jørgensen and Bente Andersen of the Risø National Laboratory in Roskilde, Denmark, crossed canola plants carrying the gene that encodes resistance to the herbicide glufosinate with a weedy relative called field mustard. They found that the gene persisted in the weed even when no herbicide was applied. What's more, the weed produced equally fit offspring whether or not it had the herbicide-resistance gene. That means that the gene will probably stick around, Snow says.

    Another type of gene that might move to weeds are virus-resistance genes, such as those that have been engineered into yellow squash and zucchini, says Alison Power of Cornell University. If populations of the weedy relatives of these crops are kept in check by viruses, a virus-resistant weedy squash could potentially outgrow ordinary plants and become more aggressive. Researchers won't know until someone does field tests to find out, however. “It could be a significant issue,” Power says, but “we don't have good information to go on.”

    Benefits of biotech

    The backers of GM crops say that all this talk of their potential risks overlooks their benefits to consumers, farmers, and the environment. But although the risks remain hypothetical, it's also too early to tell whether GM crops are a proven boon, because only a few independent studies have been conducted, and those show clear benefits for some crops but not for others, agriculture experts say.

    Cotton, for example, is notorious for needing heavy doses of pesticides, so Bt cotton should offer substantial savings and environmental benefits. Indeed, by planting modified rather than conventional cotton on 2.3 million U.S. acres (nearly 1 million hectares) in 1998, farmers reduced chemical pesticide use by over a million pounds (450,000 kilograms), according to a report released earlier this year by Leonard Gianessi and Janet Carpenter of the National Center for Food and Agriculture Policy, a think tank in Washington, D.C., that is funded by industry and the USDA. What's more, cotton farmers increased their yields by 85 million pounds (39 million kilograms) and made $92 million dollars more than farmers who did not use the technology.

    The report says, however, that not all Bt crops fared as well. Although 14 million acres (5.7 million hectares) of U.S. cornfields—about one-fifth of the total corn acreage in the United States—were planted with Bt corn in 1998, the increased profits from higher corn yields did not cover the extra cost of the Bt corn seed. In addition, the Bt crop saved only 2 million of those acres (800,000 hectares) from chemical insecticides because most farmers don't bother to spray for corn borers because spraying often doesn't protect the corn. Researchers also worry that pest insects could develop resistance to the Bt toxins over the next several years because the bacteria is now so widespread. That would make Bt sprays ineffective, eliminating one of the few effective pest-control strategies available to organic farmers, who forswear chemical pesticides.

    Another recent report takes a look at the pros and cons of Roundup Ready soybeans—a herbicide-resistant line from Monsanto—and concludes that the results were mixed. On the plus side, says report author Charles Benbrook, an independent consultant to consumer and environmental groups in Sand Point, Idaho, and a former executive director of the National Research Council's Board on Agriculture, Roundup Ready soybeans allow farmers to substitute Roundup for more hazardous and long-lasting herbicides like acetochlor. And they reduce the need for farmers to till the soil to ward off weeds, which reduces soil erosion.

    But Benbrook's findings did not support industry claims that the Roundup Ready beans reduce herbicide use by allowing farmers to kill weeds with one dose of Roundup after the soybean plants have sprouted instead of dosing the fields with a variety of herbicides before and during the growing season. Instead, the Benbrook reported concluded, farmers applied two to five times more herbicides of all kinds to their GM soybean fields than to fields growing conventional soybeans. And in contrast to industry claims, a recent study by agricultural economist Michael Duffy of Iowa State University showed that Roundup Ready beans made Iowa soybean farmers no more money than farmers growing ordinary beans. Despite the increased herbicide usage, applications costs were lower, but so were yields from the GM soybeans. “You had lower income and lower costs, so it was kind of a wash,” Duffy says.

    Even if the technology has yielded few clear-cut benefits in the developed world, agbiotech backers say that in the developing world, new crops in the pipeline could improve yields for farmers and make tremendous strides toward reducing malnutrition and environmental degradation. A genetically engineered line of rice reported earlier this year, for example, can make more vitamin A precursor and accumulate more iron, which could prevent infections, blindness, and anemia in people in the developing world (Science, 13 August, p. 994). Other researchers are developing plant-based vaccines to prevent diarrheal and other diseases in the developing world, says plant biochemist Charles Arntzen, president of the Boyce-Thompson Institute for Plant Research in Ithaca, New York.

    And a Cornell group is engineering a virus-resistant papaya plant that could save crops in Brazil, Puerto Rico, and Jamaica. A version of the plant, which resists the papaya ringspot virus, has already revived Hawaii's papaya groves, devastated by the virus in the mid-1990s, says plant pathologist Dennis Gonsalves, who leads the effort. “You should go back and look now—it's beautiful,” he says.

    But before farmers sow GM crops around the world, researchers and regulators need to do a better job assessing the ecological risks, says Ohio State's Snow: “We shouldn't just be waving our hands. There really are not enough ecologists doing this research,” in part because research funds are scarce. And even biotech backers acknowledge the need for better data. “I would say that the benefits totally outweigh the risks, but we can't ignore the risks,” Washington State's Cook says.


    Monarch Press Release Raises Eyebrows

    1. Dan Ferber*
    1. Dan Ferber is a writer in Urbana, Illinois.

    Rosemont, Illinois—The 1-day conference, held here on 2 November, was not yet over, and researchers were still heatedly debating whether corn that had been genetically modified to make Bt, a protein toxic to insects, harms monarch butterflies. Yet a headline that day in the hometown newspaper, the Chicago Tribune, seemed to give the meeting's conclusion: “Monarch Butterfly So Far Not Imperiled.” Similar stories appeared in the Los Angeles Times and the St. Louis Post-Dispatch. How could the newspapers have known the upshot of the conference before the researchers themselves did?

    In fact, they didn't. The stories illustrate how eager interest groups are to spin even preliminary and debated results in the continuing war of words over the risks and benefits of genetically modified (GM) crops.

    The conference, which was sponsored by an industry group called the Agricultural Biotechnology Stewardship Working Group (ABSWG) and the U.S. Department of Agriculture (USDA), was the outgrowth of research reported last May showing that monarchs fed Bt pollen in the lab often died. In the wake of the uproar the report caused, the ABSWG and the USDA funded new studies to see whether the butterflies are at risk in the field. The conference brought the researchers together so they could present their early results (see main text).

    But the day before the conference began, the ABSWG had held a conference call between reporters and a small group of researchers whose results mostly seemed to show that the butterfly was safe. The ABSWG also issued a press release on the morning of the conference—before most of the researchers had presented their results—stating that the conference would “dispel doubts raised last spring about the safety of the monarch population.”

    The ABSWG's actions did not sit well with many meeting participants, including some whose results supported the industry claims. The press release “took me totally by surprise. I thought it was premature,” says one such researcher, entomologist Galen Dively of the University of Maryland, College Park. And insect ecologist Orley Taylor of the University of Kansas, Lawrence, director of the conservation group Monarch Watch, describes what the ABSWG did as a “manipulation.” Taylor, who remains to be convinced that Bt pollen is safe for monarchs, adds, “This steals the possibility of having a fair and deliberate discussion … by dictating what the interpretation of the meeting should be before it was held.”

    ABSWG spokesperson Val Giddings responds: “I think that's nonsense. … This was about as open and untrammeled a meeting as you could have hoped for.” Entomologist Richard Hellmich of Iowa State University in Ames agrees: “The intention of the meeting was to talk about science, and that really didn't disrupt the discussion.”

    Giddings also defends the accuracy of the press release, saying that the majority of the researchers concluded that the potential harm to the monarch was minimal. “It was virtually, although not completely, a consensus view,” Giddings says. But at the close of the conference, most researchers said more work was needed to show the true effect of Bt corn on the butterfly. “It was inappropriate to conclude there's no impact on the monarch butterfly,” Taylor says. “That was not a fair conclusion of any of the commentary we heard.”


    Biotech Critics Watch the Watchdogs

    1. Dan Ferber*
    1. Dan Ferber is a writer in Urbana, Illinois.

    Although genetically modified (GM) foods have been in the spotlight in Europe for several years, the U.S. public is just now waking up to the fact that such foods—corn, canola oil, and soy, to name a few—are already widespread on supermarket shelves. With that awareness has come increased scrutiny of the government's system for regulating the safety of these crops—and charges that the system is lax.

    The U.S. government divvies up oversight duties among three agencies: the Food and Drug Administration (FDA), the Department of Agriculture (USDA), and the Environmental Protection Agency (EPA). That situation, says Jean Halloran of the Consumer's Union, an advocacy group that is lobbying to require mandatory safety tests and labeling of GM foods, has produced a dizzying array of overlapping regulations that, despite their complexity, sometimes fail to offer sufficient safeguards. “Sometimes I think our regulatory process is designed to have a lot of smoke and mirrors. It's designed to look like it's a stringent process when it isn't,” Halloran contends.

    Regulators and industry representatives dispute that, maintaining that the U.S. system for regulating the foods is scientifically based and rigorous. “We are confident that the current policy does protect the public,” says James Maryanski, biotechnology coordinator for the FDA's Center for Food Safety and Applied Nutrition. Indeed, although some studies have pointed to potential hazards of GM crops (see main text), so far there's no evidence that they cause any health or environmental problems.

    In the current U.S. regulatory system, the USDA sets up the first hurdle. Companies often do field tests on promising transgenic crop lines to see whether they perform as expected. To ensure that the crops can't escape during the field tests, the companies are supposed to set up buffer zones around the test plots to keep the transgenic pollen from nearby fields, and to destroy transgenic seeds and plant tissue after the test. “It's like you grew it in a greenhouse,” says Sally McCammon, science adviser for the agency.

    Later, when a company wants to commercialize a crop, it's supposed to prove to the USDA that it won't have any significant effect on the environment, such as passing genes to nearby weeds and making them more aggressive. But critics charge that the USDA is more of a lapdog than a watchdog when it comes to protecting the environment. For example, in a 1995 study reported in Trends in Ecology and Evolution, ecological geneticist Joy Bergelson of the University of Chicago and Colin Purrington, now at Swarthmore College in Pennsylvania, showed that in approving new transgenic crops, the USDA often overlooks their own recommendations for performing field tests. “A lot of [their arguments] relied on no data whatsoever,” Bergelson says.

    Michael Schechtman, the agency's acting biotechnology coordinator, argues that field tests are unnecessary for crops that can't grow outside of cultivation and can't outcross with any weeds in the United States. He says the agency has required additional studies from companies whose GM crops can outcross with nearby weeds: “We think our review process has been thorough and has addressed all of the questions.” Nevertheless, Dan Glickman, secretary of agriculture, asked the National Academy of Sciences in September to conduct an outside review of the agency's GM-crop review process.

    The EPA, which comes into play only for those GM crops that produce insect-killing proteins, such as Bacillus thuringiensis (Bt) toxins, has also come under fire. In February, several environmental and organic farmers' groups filed a lawsuit, which is still unresolved, to force the agency to revoke the approval of all Bt plants on the U.S. market and run more extensive environmental tests on the plants. The groups' concerns include the possibility that pests would develop resistance to Bt toxins, making Bt bacterial sprays—a key pest-control tool of organic farmers—ineffective.

    In addition, Joseph Mendelson, legal director for the International Center for Technology Assessment in Washington, D.C., which is representing the plaintiffs, maintains that in approving Bt crops, the EPA ignored evidence that the toxins could kill a broad range of moths and butterflies. “The agency basically threw up its hands instead of taking the proper precautionary approach,” he says. But Steve Johnson, associate deputy assistant administrator for the agency's Office of Prevention, Pesticides, and Toxic Substances, says that Bt toxins did not harm several beneficial insects in toxicity tests, and Bt sprays have been used safely for decades. After assessing the risk, he says, “we felt that we were OK.”

    Some critics also doubt the aggressiveness of the FDA, which oversees the safety of most GM food in the United States. The agency does not mandate premarket safety tests, although before the food gets to market, companies voluntarily share with FDA officials the results of any toxicology, nutrition, or allergenicity tests they conduct. Rebecca Goldburg of the Environmental Defense Fund says that is not adequate, given that “the consultation process is voluntary and it's secretive.” The FDA's Maryanski responds that although companies could lie about the safety data, “it's not in their interest.” If the food that companies sell is not safe, he notes, they are legally liable under federal law, and the FDA has the authority to seize the product and order criminal prosecution.

    The FDA has also resisted efforts by activists to require labeling of GM foods, as is now done in the European Union. Currently, Maryanski says, the agency doesn't have the legal authority to do that, although that could soon change. A bill was introduced in Congress earlier this month that would require labeling of all foods containing GM products. Moved by continuing protests against their products, ag biotech companies are coming around to the idea as well (see p. 1666). With advocacy groups cranking up the pressure to tighten regulation of GM foods, and Congress beginning to listen, the FDA and other regulators may be forced to change the way they regulate GM crops, whether they like it or not.


    Industry Response: Ag Biotech Moves to Mollify Its Critics

    1. Martin Enserink

    As protests continue, the developers of genetically modified crops contemplate steps, such as labeling GM foods, once considered anathema

    When two of Monsanto's top executives boarded a jet this summer to take them from St. Louis to London, it wasn't just a routine business trip. They were headed for a secret meeting with the leaders of the British environmental movement—the very people who had branded the company's genetically modified (GM) food products as potential health hazards and ecological time bombs, and whose actions had helped trigger tabloid headlines like Frankenstein Foods and Farmageddon. These, the executives knew, had led an entire nation to avoid their products like poison. In short, they were going to confront their worst nightmare.

    Monsanto was in a predicament—which is far from over—that called for drastic action. Although some studies have raised concerns about GM foods (see p. 1662), so far, there is little evidence to suggest that those currently on the market are harmful, either to human health or ecosystems. Even so, the resistance to GM foods, which largely originated in Britain, is spilling into other European countries and the developing world. Companies such as Monsanto that have bet billions of dollars—and perhaps their futures—on GM crops are suddenly looking vulnerable, as are farmers who have staked their livelihoods on the new seeds. And development experts who are counting on the new technology to feed a growing world population are looking on nervously.

    “The opposition is astonishing. There's no way you can sell products in Britain that contain genetically modified organisms anytime soon. Forget it,” says Julian Kinderlerer, a researcher at the Institute of Biotechnological Law and Ethics at the University of Sheffield in the United Kingdom. Even in the United States, which has seen far less furor over the issue, leading baby food manufacturers Gerber and Heinz announced that they would permit no GM foods in their products. Worried by these developments, U.S. farmers, who have largely been embracing the new technology, are starting to balk. “Some of them are going to go back to traditional varieties next year,” predicts Charles Benbrook, an independent agricultural policy analyst in Sand Point, Idaho.

    Indeed, most agree that the next couple of years will be crucial for the future of GM crops—and that in the end consumers, rather than the farmers that the industry has long considered its primary customers, will decide the fate of GM foods. “It's a different ball game today,” says Mike Phillips of the Biotech Industry Organization (BIO), a lobby group in Washington, D.C. “It's finally dawning on Monsanto, as well as other companies, that it's what the consumer wants [that counts].” And to placate that consumer, some companies are contemplating taking steps, such as separating biotech and nonbiotech foods and labeling those that have been modified, that the industry has always opposed.

    Until recently, GM foods have been a success story. In the United States, over 40 transgenic crops have been approved for marketing, and farmers have planted an area larger than Great Britain with transgenic soy, corn, canola, potatoes, and cotton. Among U.S. consumers, the revolution has caused nary a ripple—partly, perhaps, because most people aren't aware that they're eating GM foods, as labeling isn't required. And worldwide, land area planted to GM crops grew 40% this year, to over 40 million hectares, according to industry figures.

    But as GM products found their way around the globe, resistance grew, especially in Britain, where the bovine spongiform encephalopathy crisis, as well as several Salmonella outbreaks, have eroded public trust in food safety regulation (Science, 7 August 1998, p. 768). A controversial study by food scientist Arpad Pusztai of the Rowett Research Institute in Aberdeen, Scotland, which claimed to show that GM potatoes could stunt rats' growth, further fueled the flames this year (Science, 19 February, p. 1094), as did a May statement by the British Medical Association, which called for a moratorium on the release of new GM crops, pending further study of their health effects.

    Reacting to the escalating public concern, several European supermarket chains banned GM products from their house brands, or even from their shelves. In Britain, subsidiaries of two major European food producers, Unilever and Nestlé, announced that they would phase out genetically modified ingredients in their products, and big fast-food chains like McDonald's, Burger King, and Kentucky Fried Chicken took GM food off their menus. Meanwhile, the European Union (EU) has decided that products in which more than 1% of one of the ingredients is transgenic should be labeled; and in June of this year, the EU dealt the industry a major blow by suspending the introduction of new GM crops for several years.

    Monsanto and other biotech companies have also heard rumbles of unrest from the financial world. Two gloomy reports, issued by Deutsche Bank analysts last May and July, even advised investors to back out of biotech companies. Although GM crops might be perfectly safe, they may soon “be perceived as a pariah,” said one of the reports, entitled “Genetically Modified Organisms Are Dead.” According to the bank, a two-tier market system will likely arise, with non-GM organisms the more desirable, and thus more valuable, commodity. Indeed, one of the largest traders in corn and soybeans, Archer Daniels Midland (ADM) in Decatur, Illinois, started offering farmers a premium of 18 cents per bushel for non-GM soybeans this spring.

    For years, Monsanto, backed by the U.S. government, had insisted that the European resistance was irrational and unscientific, and that there was no legal basis for stemming the flow of GM products. But those reassurances did little to win hearts and minds. On the contrary; a confident ad campaign touting the marvels of biotechnology in Britain last year backfired, says Neil Verlander, a spokesperson for Friends of the Earth, because it didn't seem to take the concerns seriously. “They got it wrong, and it hurt their image,” says Verlander. The fact that the campaign coincided with a piece in The Daily Telegraph, in which Prince Charles declared that genetic engineering “takes mankind into realms that belong to God and God alone” didn't help Monsanto either.

    But this summer, with the protests mounting, Monsanto shifted gears. Some credit Gordon Conway, president of The Rockefeller Foundation—a U.S. charity that has invested $100 million in genetic research benefiting the developing world—for pointing out to Monsanto executives that they had to change their tactics, lest biotech food become unmarketable altogether. Monsanto's trip to London, where executives met representatives of organizations such as Friends of the Earth and the Soil Association, was one of the first signs that something had changed. The trip resulted in a “healthy exchange of ideas,” says Verlander. And on 6 October, Monsanto CEO Robert Shapiro personally put on the hair shirt when he addressed a Greenpeace business convention in London through a satellite link. The company's attitude had “widely been seen, and understandably so, as condescension or indeed arrogance,” Shapiro admitted. “Because we thought it was our job to persuade, too often we forgot to listen.”

    That confession came 2 days after Monsanto had taken another step to pacify opponents. The company renounced the so-called “terminator technology,” which renders the seeds produced by transgenic plants sterile—forcing farmers to buy new seed every year.

    But just how much effect such conciliatory gestures will have on the market is uncertain. In early September, just before the harvest, ADM and another company, Consolidated Grain and Barge, started encouraging farmers to keep conventional and transgenic crops segregated, to make sure their products wouldn't be shut out of the market. The announcements rattled farmers, who worried that they might have bet on a doomed technology. “For a farmer, whose crop is his lifeblood, that's pretty hard to take when you're about to climb on the combine,” says Tamara White, director of commodities at the Illinois Farm Bureau.

    As a result, some predict that as early as next year, many growers may switch back to non-GM varieties. For instance, the National Corn Growers Association, which unites a minority of U.S. corn growers and has taken a stance against the introduction of biotech, predicts a big backlash. Some farmers are already ordering their soybeans to plant in the spring, says Lynn Clarkson, a corn and soy trader in Serro Gordo, Illinois, because they're afraid that non-GM seeds will have run out by January, when they would normally order. They will do the same to avoid corn engineered to produce a natural pesticide, the Bacillus thuringiensis toxin, he says. Policy analyst Benbrook, too, predicts that sales of GM seeds will plunge for the first time next year.

    The threat of falling sales has led some companies to rethink more than just their PR strategy. For years, they have resisted mandatory labeling of GM products, arguing that there was no scientific basis for concern, and that consumers might interpret the labels as indicating that the products are unsafe. Together with the U.S. government, the companies branded the European insistence on labeling a form of protectionism. The issue is on the agenda of the next ministerial meeting of the World Trade Organization, starting 29 November in Seattle.

    But the tide may be turning. Novartis, for instance, doesn't object to mandatory labeling, a position that was once seen as maverick within the industry but is now gaining acceptance, says Willy De Greef, head of regulatory and government affairs at Novartis Seeds. Labeling, says De Greef, “is also a way to show confidence … in the safety and quality of our products.” And it may not be the consumer turnoff that many fear, he says. In the Netherlands, GM foods have carried the neutral phrase “produced with modern biotechnology” since 1997. “There were some jitters at first, but eventually sales have stabilized,” De Greef says.

    Within the U.S. government, too, there are signs that a compromise on the thorny issue may at least be up for discussion. “I have a sense that the consumers have spoken, and they say: ‘We want the damned stuff labeled,’” said U.S. Undersecretary of State for Global Affairs Frank Loy at a recent meeting at the New York University School of Law, “so one ought to discuss labels.”

    But there's a catch: Farmers and traders will have to segregate their crops. And although that may work for small markets, it will pose problems for crops such as soy and corn, which are brought together in huge quantities and then shipped by rail or barge. Keeping GM and non-GM crops apart on a large scale, the BIO's Phillips says, would require huge investments in infrastructure. “The Europeans will have to pay for that,” he adds.

    Meanwhile, the industry is hoping that a new wave of GM products receives a warmer welcome. Most transgenic crops so far have made life easier for farmers and seed producers, but offer little to the consumer. A “second generation” of products in the pipeline may be better accepted. Some plants will lack allergenic proteins, for example, or have a healthier oil composition. They may also provide benefits for developing countries, such as the pro-vitamin A and iron-enriched rice produced earlier this year (Science, 13 August, p. 994).

    The big question, however, is whether developing countries will carry out their own risk analysis or simply adopt the European angst, says Sheffield's Kinderlerer, who has acted as a biotechnology consultant to governments in Asia, Africa, and Latin America. Already, “people are saying, if Europe is scared, shouldn't we be?” he says. “That's worrying, because we don't really need the technology. They do.”


    Duchamp and Poincaré Renew an Old Acquaintance

    1. Barry Cipra

    What did the groundbreaking modernist painter learn from the father of chaos? Art historians and mathematicians debate the question

    It was not your usual scientific conference. Talks on algebraic topology took turns with passages from Mallarmé's poems. Lectures on Duchamp's Large Glass shared an auditorium with sessions on celestial mechanics. But that's what you get when mathematicians and historians of science lock horns with art historians and postmodern theorists, as they did at Harvard University, 5 to 7 November.

    Some 200 scholars crossed higher-than-usual disciplinary walls to attend “Methods of Understanding in Art and Science: The Case of Duchamp and Poincaré,” a conference organized by Rhonda Roland Shearer, a New York City- based artist, and her husband, Harvard biologist Stephen Jay Gould. (Gould is also the president of AAAS, which publishes Science.) The conference was a coming-out party of sorts for Shearer's recent findings—or flights of fancy, as skeptics see them—regarding the pioneering modern artist Marcel Duchamp and his take on the writings of the mathematician Henri Poincaré. Shearer and Gould, who co-authored a recent essay in Science (5 November, p. 1093) on the relationship of art and science, founded the Art Science Research Lab in their New York home to take a fresh look at Duchamp's oeuvre. With colleagues including Richard Brandt, a physicist at New York University (NYU), they have gathered evidence that Poincarean ideas lurk behind several of the artist's most famous works—and as a result, these works are not what they appear to be.

    In a way, that's not surprising. Duchamp (1887-1968), widely regarded as the founder of modern art, loved to foil his viewers' expectations. A work formally titled “The Bride Stripped Bare By Her Bachelors, Even,” is actually what its nickname, the Large Glass, implies: a huge pane of glass. Rather, it's two panes, with designs painted on each. The top half, which Duchamp designated the bride, is dominated by a triptych of rough squares inside a dark cloud and a cascade of junk meticulously copied from one of Duchamp's earlier paintings. The bottom, “bachelor” half shows perspective drawings of several mechanical devices, including a chocolate grinder surmounted by an arc of conical sieves.

    The Large Glass took up a large chunk of Duchamp's career, from 1915 to 1923. In 1934, he published the Green Box, a collection of cryptic notes and sketches pertaining to the Large Glass. But he is most famous for what he called ready-mades: ordinary, commercial objects such as a coat rack, snow shovel, bicycle wheel, and, most notoriously, a porcelain urinal, which Duchamp claimed became art when he selected them.

    Shearer thinks Duchamp may have gotten the idea for his ready-mades from a surprising source: Poincaré (1854-1912). Poincaré is best known today for laying the mathematical foundations of chaos theory (more technically called nonlinear dynamics), in a prizewinning paper on celestial mechanics. But he was also widely known for popular essays on mathematics, science, and the mind. And, like many artists and writers in the early 20th century, Duchamp took a keen interest in such scientific ideas. References to Poincaré in the Green Box and elsewhere indicate that Duchamp was familiar with the mathematician's writings.

    Shearer traces Duchamp's term “ready-made” (tout fait, in French) to Poincaré's italicized use of the same word in a famous essay on mathematical creativity. “[I]t never happens that unconscious work supplies ready-made the result of a lengthy calculation,” Poincaré noted, but he argued that the unconscious plays a crucial role, as a ceaseless sifter of ideas. Shearer thinks the Large Glass can be viewed as a Poincarean creativity machine, with the ready-mades as ironic end products.

    Poincaré also wrote about non-Euclidean and four-dimensional geometry, and Duchamp's notes indicate that these ideas intrigued him. He especially liked the notion of getting a three-dimensional perspective on four-dimensional objects, rather like the way a set of 2D representations, such as photographs taken from different angles, can be used to visualize 3D objects. Shearer thinks that these geometrical ideas influenced Duchamp's ready-mades—or, rather, his photographs of them, as most of the originals have been lost.

    She and colleagues have analyzed these photographs and concluded that the objects shown involve tricks of perception and perspective. The bicycle wheel, for example, was mounted on a deceptively ordinary kitchen stool—in fact, they claim, one of the stool's legs pointed awkwardly inward and its rungs didn't connect. Moreover, the wheel was not attached at its center point, so that it would have wobbled as it spun. Similarly, the researchers found that a photograph of the four-hook coat rack shows each hook from a different perspective. Either Duchamp bent the hooks, or he doctored the photograph—or both. By combining the different perspectives, Duchamp is giving more information than a single perspective would provide, albeit in a way that isn't immediately obvious.

    One of Duchamp's more playful ready-mades, a postcard reproduction of the Mona Lisa on which he drew a beard and mustache, is titled LHOOQ: Pronounced aloud in French, the letters sound like the sentence “She has a hot ass.” Far from simply anointing an existing postcard, Shearer thinks, Duchamp created his own and even substituted his own face in the enigmatic portrait! She and NYU's Brandt have compared measurements of facial features on LHOOQ with those on other reproductions; their analysis exposes the Duchamp Lisa as a solid outlier.

    The ready-mades “are altered in much more extensive ways than he let on,” Shearer concludes. No one's noticed before, she explains, only because interpretation trumps perception: “You see much more with the mind than you see with the eye.”

    Most Duchamp scholars remain dubious. “All of these photographs [of the ready-mades] are faded and blurred,” notes Michael Taylor, curator of 20th century art at the Philadelphia Art Museum, which houses the Large Glass and other Duchampiana. “Rhonda's theories are theories, not facts,” adds Dickram Tashjian, an art historian at the University of California, Irvine.

    The stakes are high. By challenging the view of art as something created by the artist, Duchamp's ready-mades brought about a profound change in art, with repercussions that continue to this day. Shearer's theory that he fabricated the objects “turns Duchamp back into a craftsman,” Taylor says.

    But even her critics think Shearer has done something worthwhile. “She is making us look at Duchamp's works again,” Taylor says. In particular, he thinks, her analyses will focus attention on the artist's use of photography. “Duchamp had more of an interest in the camera than we thought,” Taylor says. And if she's right about the ready-mades, Tashjian says, “then we have a delicious ironic twist.”


    Stalking a Killer in Russia's Prisons

    1. Constance Holden

    A program to vanquish tuberculosis from an entire Russian region may provide a new model for battling an old scourge

    Two years ago, when microbiologist Alex Goldfarb launched a program in Russia to treat prisoners infected with tuberculosis, he got a nasty surprise. He and his colleagues at the nonprofit Public Health Research Institute (PHRI) in New York City thought their effort, funded with a $12 million grant from financier George Soros, would face mostly routine, easily treated cases. But “when the first lab data began to accumulate, we were shocked,” Goldfarb says. About 25% of prisoners were infected with strains resistant to two or more front-line drugs—several-fold higher than had been assumed.

    Alarms over a global resurgence of TB have been sounding for nearly a decade, and a thick report ( issued last month by Harvard Medical School and Soros's Open Society Institute documents one of the epidemic's most alarming aspects: the global spread of drug-resistant strains. Nowhere is the problem more acute than in Russia, particularly in its teeming prisons—what Goldfarb calls “the epicenter of a worldwide epidemic of multidrug resistance.”

    In a fresh approach to tackling the nightmare, PHRI, working with the World Health Organization (WHO) and the British nonprofit Medical Emergency Relief International (MERLIN), is combining a traditional treatment program with a targeted attack on drug-resistant strains, the largest ever mounted. The effort, which will treat both civilians and the prison population throughout the Russian region of Tomsk, will provide a model for other wider campaigns against TB in Russia, say public health experts. “The new approaches piloted in Tomsk,” predicts Paul Farmer of Harvard Medical School, “will have broad application throughout the region and beyond.”

    After the disintegration of the Soviet Union in 1991, the public health system collapsed, opening the door to a resurgence of TB. Russia was poorly equipped to deal with the epidemic. The standard treatment is a 6-month course of four drugs; because symptoms can disappear after a couple of months, fooling people into thinking they're cured, the protocol calls for health workers to stand over patients while they take their pills, a system called DOTS, for Directly Observed Therapy Short-Course. But in Russia, because of a drug shortage and the health care breakdown, patients often fail to see treatment regimens through to the end, allowing resilient bugs to flourish—particularly in the country's prisons.

    “If you purposely designed a program to show the world multidrug-resistant TB and spread it, this is it,” says Lee Reichman, director of the National Tuberculosis Center at New Jersey Medical School in Newark. Prisoners become infected even before they are tried as they are kept in crowded holding cells, often for years. Convicts with TB are removed to a Soviet-built network of 60 “TB prisons,” but not before they've spread the bug. “This is Siberia; it's cold. They keep the windows closed,” conditions that help the airborne bacterium get around, notes Reichman. PHRI's Barry Kreiswirth, who runs the institute's TB molecular biology lab, says overcrowding is so bad that prisoners often sleep in shifts. There's also lots of turnover to speed disease transmission: People often are incarcerated for petty offenses, says the medical director of the Tomsk TB project, epidemiologist Michael Kimerling of the University of Alabama, Birmingham, so the government occasionally offers a general amnesty to reduce the crowding, creating a constant flow of TB-ridden ex-convicts. As the PHRI people are fond of putting it, the prison system is an “epidemiological pump” that pours out about 300,000 people a year, of whom 10,000 have active TB.

    About 20% of the Russian prisoners are thought to carry drug-resistant varieties, particularly the prominent “W” family, which Kreiswirth first identified in New York during the epidemic of TB among AIDS victims in the early 1990s. Scientists have yet to determine how the W strains have evolved and spread, but “at the very least,” says Kimerling, “it shows the potentially global nature of drug-resistant strains.”

    In the meantime, Tomsk—a region about 5000 kilometers east of Moscow—is being prepped as the largest proving ground yet for a new strategy against multidrug-resistant TB. Called DOTS-Plus, it was first tested in a small program run by Farmer in Peru; WHO officially endorsed it last year. The regimen involves hammering drug-resistant cases with a battery of so-called “second-line” drugs for as long as 2 years. Targeted by the Tomsk program will be about 800 civilians with TB among Tomsk's population of 1 million as well as 1200 patients in the region's TB prison. Of the new cases in the prisons, sputum samples so far show that about 30% are caused by multidrug-resistant strains. Funded for 2 years with $4 million from Soros and the European Union, the Tomsk program is equipping local prison and civilian labs to perform duties from looking at sputum smears to bacterial cultures to drug testing, and to pipe samples directly to labs in Moscow and Boston. Several groups of Russian doctors have been sent to Reichman's center in Newark to learn the latest treatment protocols.

    Scheduled for launch last month, the program now won't get off the ground until March. “The main reason for delaying is to make damn sure it works properly,” says microbiologist Tim Healing of MERLIN. More time is needed to round up an adequate drug supply; sloppy treatment could spawn superbugs resistant to everything. “We have only a tiny, tiny handful of drugs that can potentially cure these patients,” says Nancy Bankin, an epidemiologist at the Centers for Disease Control and Prevention in Atlanta. “If we lose those, we'll have strains that are totally incurable.”

    The Tomsk TB Project is seeking additional support from other TB initiatives in Russia, such as a $150 million campaign against both TB and AIDS that the World Bank is about to launch. Kimerling hopes the program will run at least 5 years—enough time, he says, to gauge its effectiveness against the most vicious TB strains.


    CAS President Engineers Major Reform of Institutes

    Lu Yongxiang's job is to prod the crown jewel of Chinese science into embracing the type of research needed to sustain economic growth

    Beijing—One month after the People's Republic of China celebrated its 50th birthday with a vast military parade, the Chinese Academy of Sciences (CAS) took a very different approach to mark its golden anniversary: a symposium at which half a dozen Nobelists pondered the challenges facing science in the next millennium. The idea came from CAS President Lu Yongxiang, who oversees the country's premier network of research laboratories. And the look ahead was particularly appropriate as Lu leads CAS through the most ambitious reorganization in its history.

    The three-stage, 12-year reform effort will consolidate more than 120 institutes into 80 or fewer, and cut in half a payroll of 50,000 permanent positions (Science, 8 January, p. 150). “There was quite a bit of redundancy,” Lu says about the structure that grew up over half a century. His aim is a leaner, more flexible, and more productive network of institutes, with greater support for those whose ideas survive competitive review.

    An engineer trained at Aachen University in Germany, the 57-year-old Lu is the youngest president in the academy's history, and his reforms have produced a cadre of institute directors in their early 40s. His own field is fluid mechanics, but he gets high marks from CAS scientists for taking a broad view of science. Yang Huanming, director of the Human Genome Center of the Institute of Genetics in Beijing, says Lu was quick to grasp the importance of linking China's fledgling human genome efforts to the international Human Genome Project, for example. “Without his support, [China's participation] would not have been supported by other governmental departments,” Yang says.

    Mild-mannered and soft-spoken, Lu is a good listener. But he's not afraid to act in the cause of reform. He's eager to implement new guidelines from the Ministry of Science and Technology that give scientists a big slice of any revenue from commercializing technology developed in their labs as an incentive to focus on applied as well as basic research. He also has control over a $2.5 million director's fund to support high-risk but high-payoff projects that have not received sufficient funding through the usual channels.

    Although it will take years to judge the results of the current reforms, researchers say they like what they have seen so far. “This [reform] movement will really create a better research environment,” says Yuan Yaxiang, director of the Academy of Mathematical Sciences in Beijing, which was created by consolidating four previously separate math institutes. Lu says modestly that it hasn't been hard to win support for his ideas. “Everyone realizes the need for reform, and even the older scientists have come around,” he says.

    Lu laid out his vision for CAS in a 2-hour interview with Science's Tokyo correspondent, Dennis Normile, and Li Hui, a correspondent for China Features, at the conclusion of the anniversary symposium, held here from 1 to 3 November. Here are excerpts from that conversation:

    On the need for reform: “The basic concept is to find a way to promote research that suits the needs of science and also reflects Chinese characteristics. We need to get rid of redundancies and correct problems that have resulted from cultural practices and the implementation of a planned economy. Science advances very quickly, but our scientists and our scientific organizations did not keep pace with scientific developments.

    In the past, few institute directors did a good job of encouraging the mobility of scientific talent. Once people got into the system, they just worked and waited for retirement. And once a group formed and a research topic was finalized, it would just go on. There was no flexibility, there was no adjustment to reflect scientific or technological developments. This is not good for science and technology.”

    On its implementation: “The reform will be done in three phases. The first phase lasts 3 years, and about one-third of the [previously 123 CAS] institutes are being consolidated into 12 research centers as a pilot program. The second phase, from 2001 to 2005, will see another 30 to 40 institutes restructured into about 18 centers. The last phase, from 2006 to 2010, will be to consolidate the reforms and restructure the remaining institutes.

    The [additional] money is not a lot by international standards. We give our institutes [the equivalent of $20,000 to $25,000] per person per year. But even so, it is better than before, and I believe that the government will continue its support [for restructured institutes] at the same level.”

    On staffing: “The goal is to optimize the personnel structure. At the same time that we are reducing permanent staff, we are increasing the number of doctoral students, postdocs, and visiting scholars. Right now we have 11,000 graduate students. In 3 to 5 years, we will increase this to 25,000. Right now we have 1000 postdocs; we hope to increase that number to 2000 to 3000. We are not only a research organization, we're also a training organization. We have also started a visiting scholar project, to invite up to 300 senior scholars annually, both from within China and from overseas, to join CAS institutes temporarily.”

    On peer review: “We have introduced peer review, using not only domestic experts but also international experts. We need to provide consistent support for free, fundamental research. However, we just cannot support everything suggested by scientists. We have to be selective. For basic scientific research, we need to rely on international peer review or evaluations to guarantee that the quality of the science is up to international standards.

    For long-term projects to develop technologies critical to the nation's economic and social development [products that China badly needs but cannot easily obtain from the industrial world, such as microelectronics and supercomputers], we have to take a strategic approach. And here we feel we don't have to resort to the international community. Chinese scientists know better what their country needs for development, and we can maintain high standards even using purely domestic peer review.”

    On CAS's mission: “In terms of our research and development mission, CAS's role is different from the universities, different from private enterprises, even different from the National Science Foundation of China. [Not only do] we have to do better basic science, we also have to explore the areas of technology that will be critical for the nation in the future.

    For example, we think we should contribute to promoting the health of the Chinese people. But this should be focused on understanding basic phenomena related to health. This will involve an understanding of gene functions and the basic functioning of the neurological system to provide the scientific basis for the treatment of human disease.”

    On commercializing results: “In the past, if a project had commercial potential we'd keep it to ourselves. Now we want to get other people involved in the development. A second point is that previously any innovation or patent [from publicly funded research] belonged to the government and the institutes. The innovator was not allowed to profit from it. Now we think it is more important to respect human resourcefulness. [A 1996 law] allows the researcher to take the lion's share of any profits.

    We also want to develop multiple channels for development. We will collaborate in various ways not only with state-owned enterprises but also privately owned enterprises and foreign companies. For instance, if a research result appears to have potential for commercialization, the entire research team could join a commercial enterprise, or they could cooperate with a private entity, or form their own independent company.”

    On setting priorities for basic research: “We do not plan to repeat what is being done in other countries. But we have our unique attributes. For instance, we have unique genetic resources—both fauna and flora. And we have the well-established traditional Chinese medicine. After the human genome is sequenced, the emphasis will be on functional genomics, which will play an important role in drug development. In addition to genomic drug development, we should be able to produce drugs based on the long history of the use of traditional herbs. We will use modern methods to refine the active compounds and produce new pharmaceuticals.”

    On cross-disciplinary research: “In the first half of this century, science tended to become more narrowly focused. For instance, there was particle physics, and then condensed matter physics. And even condensed matter physics was further divided into semiconductor physics [and other subdisciplines]. This limited the generalization of science and also cross-disciplinary cooperation. But the modern approach to science is to emphasize integration and synthesization. Particularly over the past 50 years, the most outstanding scientific accomplishments have occurred at the intersections of various disciplines.

    Lots of people say that it is very important to emphasize cross-disciplinary cooperation, but once they get money they are very reluctant to carry it out. Cross-disciplinary cooperation is not an easy thing to do, but we have to try our best.”

    On funding risky research: “In basic scientific research, particularly in emerging areas, which are the most risky areas, we're giving institutes more autonomy in terms of how they use their resources. We're also giving project leaders more autonomy in deciding how to spend project funds. CAS headquarters cannot dictate what to do, but we will review progress.

    But CAS headquarters does have a role to play in the most risky areas. There may be proposals that institutes think are too risky and are very unwilling to support. The scientists can come to headquarters for help. The president has a special budget for more risky projects. They can get support to start the project, and, depending on results, the president will continue the support or decrease the funding.”

    On winning political support: “The 1997 Asian financial crisis really woke us up. The government started to discuss with scientists and with other leaders what economic development really depends on. The conclusion was that it depends on scientific innovation. The globalization of the economy also demands that we improve our innovation skills and ability.

    After the Asian financial crisis, we produced a report on knowledge innovation and economic development. That report was sent to all high governmental leaders and all members of the National People's Congress. And we plan to produce three more reports, one on sustainable development, one on advanced technology development, and one on scientific development. We don't ask for money. There are no specific projects or ideas. We just give the background on the necessity of scientific development. After the first report, I received personal letters from Premier Li Peng and other political leaders. They were very appreciative.”

    On the pace of reform: “On one hand, I'm satisfied with what we've achieved. On the other, I'm dissatisfied and hope for more. Part of the satisfaction is that the support for reform from both the government and the research institutes has been greater than anticipated. But there is still room for improvement in terms of the research direction and implementation, and the improvement of mechanisms and structure.

    Chinese culture has a lot of strong points, but some elements are very conservative. People are not ready to do anything that is totally different from what others do. There is a certain lack of independence in fields like science. Researchers tend to follow research trends.

    Personally I'm interested in the different innovative experiments of Germany, the United States, and Japan. In the first half of this century, Germany achieved a great deal by gradually accumulating talent and strategic knowledge. The United States has done very well, particularly in the second half of this century, by being very innovative in entrepreneurial terms. America has attracted talent from all over the world, in part because of the [flexibility of] American culture. Japan, of course, has taken a different approach, being very successful in industrial technology innovation. By learning from the experiences and lessons of other nations, China will have to find its own way forward.”