# News this Week

Science  22 Nov 2002:
Vol. 298, Issue 5598, pp. 1530
1. SCIENCE PHILANTHROPY

# Hughes Cuts Researcher Grants As Endowment Takes a Hit

1. David Malakoff

The U.S. economic slump has hit the lab bench. After enjoying years of soaring research spending fueled in part by an economic boom, some life scientists are being told to tighten their belts. A major blow landed last week, when the Howard Hughes Medical Institute (HHMI), one of the world's largest private research philanthropies, confirmed that it will trim spending by about 10%, or $100 million, over the next 2 years. “The great expansion is over,” says HHMI president Thomas Cech. “We're spending too much, so we have to make some hard decisions.” Other research institutions are also feeling the pinch. But the picture isn't uniformly bleak: Diversified fundraising and low interest rates have allowed some institutions to weather—or at least delay—the financial storm. “We're still on track to grow the research program,” says Ray Bye, vice president for research at Florida State University in Tallahassee. Thanks to an infusion of federal funds and patent licensing fees, the school's research budget will hit$175 million this year, double its 1998 level.

Much of the financial woe is due to nearly 3 years of falling stock prices. Overall, U.S. universities have seen the value of their endowments and other investments drop by an average of 10% since 2000, analysts estimate, with some faring far worse. Foundations are also hurting, with about half of 225 major charities planning to cut spending this year, according to the Center for Effective Philanthropy in Boston, Massachusetts.

At HHMI, a shrunken endowment (see graph) no longer produces enough income to cover the institute's annual spending, up 60% since 1996 to nearly $650 million for the fiscal year that ended 30 September. To pare back, HHMI's governing board started at home. It has cut this year's administrative budget by about 6%, or$3.5 million, and frozen hiring at its Chevy Chase, Maryland, headquarters. “You have to clean your own house before you ask others to do the same,” says Cech. It also trimmed a $100-million-plus-a-year grants program, eliminating a$22 million program serving medical schools.

But most of the savings will come out of the institute's prestigious $442 million biomedical research program, which currently supports about 330 investigators and their 3000 staffers. The investigators, who are employed by HHMI but work at universities, will have to cut spending by up to 10% annually in 2003 and 2004. The average investigator receives$500,000 to $1 million a year in support for 5 years, renewable after a rigorous review. To soften the blow, HHMI is allowing investigators to squirrel away spare cash saved over the next 8 months. Researchers will also be able to plead their case to HHMI officials, who will decide budgets on a case-by-case basis. “I felt an across-the-board cut was a mindless approach,” say Cech. “It might be a mistake to make an early-career investigator take as big a cut as a more mature investigator.” Flexibility, however, will be limited by Cech's overall goal of lowering HHMI's spending from the current 6% of its endowment to 5%, based on a rolling, 3-year average. If successful, Cech says, the result should be a budget that can accommodate a new class of investigators within a few years. But he expects the steady-state number of investigators to be about 300, down from a high of about 350 last year. Researchers are bracing themselves. Organic chemist Carolyn Bertozzi, an HHMI investigator at the University of California, Berkeley, says she has already cancelled some expensive service contracts, has stopped paying some travel costs for job candidates, and plans to reduce the size of her 34-member research group through attrition. “I may have to eliminate some projects as well,” she adds, but she won't decide until next year. Bertozzi says she could lose up to$100,000 in salary and supply funds.

Bertozzi and HHMI aren't alone. At Stanford University in Palo Alto, California, administrators are trying to close a $40 million budget gap by, among other actions, freezing hiring; the school has added more than 1200 staff over the last 5 years, boosting the total to 7900. It is also slowing a planned$1.6 billion construction program. Other science powerhouses planning reductions include Duke University in Durham, North Carolina, where officials plan to reduce faculty through attrition but say they might have to lay off professors if the economy doesn't improve. The Massachusetts Institute of Technology in Cambridge and the California Institute of Technology in Pasadena are eyeing cuts.

Institutions that depend on narrow funding sources face special problems. The Palo Alto-based David and Lucile Packard Foundation, a major backer of marine science, might lay off up to half of its 160 staff members next month because the value of its endowment, made up mostly of beleaguered Hewlett-Packard stock, has sunk to $4 billion from$13 billion in 1999.

There is some good news. Low interest rates have made it easier to sustain construction projects, including HHMI's $500 million Janelia Farm research campus in Loudoun County, Virginia. And a growing stream of government research dollars, led by a 5-year doubling of the National Institutes of Health's budget, has helped some campuses grow despite declines in other income streams. Even with cutbacks, notes Cech, who spent 22 years at the University of Colorado, Boulder, before joining HHMI in 2000, many academic research programs will end up ahead of where they were just a few years ago. “It just may take a little longer to fill those buildings,” he says. -DAVID MALAKOFF 2. U.K. RESEARCH # Courting Universities Break Off Engagement 1. Keri Page* 1. Keri Page is an intern in the Cambridge, U.K., office. With reporting by John Bohannon. LONDON—To some observers, it was shaping up as a marriage of necessity: London's two leading research universities uniting to pose a more potent challenge to the United Kingdom's academic powerhouses, Cambridge and Oxford. But mounting resistance to a plan to merge Imperial College and University College London (UCL) forced administrators earlier this week to call off the wedding. The decision is a stunning retreat for Imperial rector Richard Sykes and UCL interim provost Derek Roberts, who when announcing the engagement on 14 October had argued that joining forces was the only way to compete in the knowledge economy. Despite needing parliamentary approval, Sykes had predicted last month that the two universities would “start sharing resources by December.” That vision is shattered. In a terse, unsigned statement on 18 November, UCL said that “the best interests of the two institutions are not served by a formal merger.” Roberts told Science that “there were very strong opinions both for and against … but overall there were not enough people giving strong support.” Sykes did not respond to requests for comment. Although the architects of the failed plan were circumspect, many faculty members—particularly at UCL, where opposition ran high—aren't hiding their glee. “I'm completely delighted,” says UCL biologist Steve Jones, a comment echoed by several others contacted by Science. The climb-down is all the more remarkable considering that Sykes, before coming to Imperial, had orchestrated the megamerger of GlaxoSmithKline, now the world's largest pharmaceutical company (Science, 16 November 2001, p. 1443). He and Roberts, formerly managing director of General Electric Co., found common ground and agreed on a merger in a private meeting last month. They created a committee to report to their councils on 19 December about how a merger would affect operations. The committee's initial “vision” statement portrayed the combined university as a world-beater that would attract more funding for research in part by eliminating some competition for grants. Existing funds would also be spent more efficiently by not duplicating purchases of expensive equipment, and amalgamating departments would forge new collaborations and attract new blood. The new institution would have had a research budget of$600 million a year.

But within days of the proposal, many academics started balking. Some argued that the merger was far too slanted toward business interests. UCL immunopharmacologist John Foreman, dean of students and leader of the Committee for UCL, a group that voiced doubts about the merger, speculated that Sykes and Roberts might have been “blinkered by their extensive industrial experience.” His concern was that the new university would be governed by market forces, not educational needs. There was also a feeling that the merger was being “pushed through,” says UCL neurochemist John Clark. Adds UCL biologist Adrian Lister: “We'd been asked to subscribe to a great vision without being given any of the details.” Dissent also emerged at Imperial, where 160 staff members had signed a petition requesting an all-staff referendum on whether the merger should proceed. The petition was presented to the university senate at a 6 November meeting that Sykes chaired. According to Tom Pike of Imperial's electrical engineering department, Sykes subsequently denied the request.

Many scientists expressed fears that the merger would narrow the range of subjects taught and studied, triggering staff cuts and a reduced scope of research. And the Committee for UCL claimed that some departments might have to relocate. Roberts insists that no such relocation was in the works and lashed out at the committee, which he claims was “behaving in a malignant way and deliberately stirring up fears.”

Stung by the criticism nevertheless, Roberts and Sykes offered in an 8 November statement to UCL and Imperial staff members to “clarify the process” and assured them that a final decision would not be reached at the next month's meeting. But following what the UCL statement described as “intense deliberation,” the universities shelved the plans altogether. UCL has resumed its search for Roberts' replacement, who will take the helm in October 2003.

All the soul-searching triggered by the merger hasn't been for naught, researchers say. The discussions “highlighted the advantages and disadvantages of the current system,” says Jones. “We can now take these deficiencies on board and deal with them.”

3. RESEARCH MISCONDUCT

# German Inquiry Finds Flaws, Not Fraud

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

BERLIN—A paper claiming a spectacular remission of tumors is marred by shoddy scientific practices, but investigators aren't saying whether the results are also too good to be true. Last week the University of Göttingen said that its investigative committee had found evidence of sloppiness that constitutes misconduct, but not fraud, in a disputed paper about an experimental cancer vaccine. But with only a brief statement to go on, scientists following up on the work still don't know whether the data are valid.

The paper “was not prepared according to good scientific practice,” according to the Göttingen panel. First author Alexander Kugler, a urologist who has since left Göttingen, drafted the manuscript so sloppily that inaccuracies made their way into the published paper, the committee said, faulting his selection of subjects and the documentation of illustrations and techniques. None of the other 14 authors, the committee found, was guilty of scientific misconduct. The university says it will release the full report when the authors have resolved the paper's fate with Nature Medicine, which published it in March 2000.

Lawmakers opted not to give DHS control of other major science programs, as President George W. Bush had originally proposed, apparently agreeing with research lobbyists that the new department will lack the necessary expertise. A $1.5 billion bioterror research program will stay under the control of the National Institutes of Health, for instance, although DHS will have a say in setting its course. Similarly, the Centers for Disease Control and Prevention and USDA will continue to regulate laboratories working with potential bioweapons, although DHS can nominate new organisms to be regulated. Congress also nixed moving a cybersecurity program from the National Institute of Standards and Technology. “The science lobby is happy with what [Congress] did but even happier about what [it] didn't do,” says one congressional aide. As Science went to press, the Senate rejected a proposal to strip seven controversial provisions from the bill, including one that gives vaccinemakers protection from lawsuits. But Republican leaders agreed to revisit several of the measures next year, including the one creating university-based centers. 5. NUCLEAR PHYSICS # TESLA Accelerates; ESS Falls Back 1. Gretchen Vogel BERLIN—European physicists this week got mixed news from an eagerly awaited review of a pair of high-profile projects. As anticipated, Germany's science council on 18 November backed plans for a massive new linear collider, the$3.5 billion TeV Energy Superconducting Linear Accelerator (TESLA). But the council disappointed proponents of a $1.4 billion European Spallation Source (ESS), demanding a rewritten proposal before the machine would be considered for government funding. In fall 2000, Germany's science ministry asked the independent science council to evaluate proposals for nine major projects—with a combined price tag of more than$6.7 billion—to help it allocate a limited pot of research funding. In a preliminary report last July, the council recommended speedy funding for two smaller projects: a $25 million laboratory for very high magnetic fields in Dresden, and a$97 million airplane for atmospheric research. The council said that three big-ticket projects required a few revisions but were worthy of funding. TESLA, based at the DESY synchrotron in Hamburg, is a 33-kilometer-long machine that would complement the Large Hadron Collider, now under construction at CERN, the European laboratory for particle physics near Geneva. The council also liked a companion project to TESLA, a $673 million free-electron laser, and a$675 million accelerator at the Heavy Ion Research Center in Darmstadt, which would, among other things, allow high-energy physicists to probe how stars cook fundamental nuclear particles into elements (see p. 1544).

Left out in the cold was ESS, which would produce high-energy neutrons for materials science and biology research. The council concluded that the proposal from the Research Center Jülich, one of several sites vying to host the project, had not made a strong enough case to merit funding. That assessment angered many in the neutron physics community, who protested that the review committee had underestimated the machine's potential research payoff (Science, 18 October, p. 543).

In its final report this week, the council kept ESS in the lowest of its three categories, along with a polar-drilling research ship and a free-electron laser proposed by the BESSY synchrotron in Berlin. But it offered them the chance to submit new proposals based on additional planning. These would be evaluated and considered as the government sets funding priorities in the coming years, says council chair Karl Max Einhäupl.

ESS backers are putting a brave face on the disappointing news. Peter Tindemans, chair of the ESS council, insists that the council's decision is actually a welcome sign. “There is broad support for neutrons, and I am certain the final assessment will be positive,” he says. Others are less sanguine. ESS “is not dead in the water, but it certainly missed a major opportunity,” says nuclear physicist Claus-Konrad Gelbke of Michigan State University in East Lansing.

The council's recommendations leave TESLA and other highly rated projects with one last hurdle: the German government's final decision on funding, which is expected in 2003. In contrast, Gelbke notes, ESS “is scrambling to get its feet on the ground.”

# Agricultural Pumping Linked to Arsenic

In Bangladesh, groundwater has been both a blessing and a curse. Irrigation wells have helped end deadly famines. Yet millions of other wells dug to provide safe drinking water are laced with arsenic from ancient sediments, endangering human health. Now one study suggests that pumping for irrigation might be at least partly to blame for the poisoned water, although the finding is controversial.

On page 1602, a team led by hydrologist Charles Harvey of the Massachusetts Institute of Technology concludes that agricultural pumping might influence the release of arsenic into drinking water. That could signal the need for deeper drinking-water wells. “This is really important” if true elsewhere in the country, says physical chemist Stephan Hug of the Swiss Federal Institute for Environmental Science and Technology (EAWAG) in Dübendorf. But Hug and other experts caution that the finding might not be broadly applicable.

Arsenic levels in some drinking-water wells are high enough to thicken and discolor skin and raise the risk of various cancers. One explanation for the presence of dissolved arsenic, suggested in the late 1990s, was that irrigation pumping lowered the water table, leading to oxidization of the arsenic-bearing pyrite. Researchers at the British Geological Survey and University College London (UCL) later disproved this idea. UCL researchers favor another geochemical mechanism: Organic material from buried peat has been reducing iron oxides and releasing arsenic into the water ever since the last ice age.

But Harvey suspected that irrigation must play a role. During the dry season, a tremendous amount of water is pumped from the ground; this water is later replaced by monsoonal rains and local surface water. The heightened circulation “clearly brings in and transports chemicals through the aquifer,” Harvey explains. These compounds—say, carbon from sewage—could change water chemistry in a way that might trigger the release of arsenic from the sediments. To test the idea, he and colleagues at the Bangladesh University of Engineering and Technology in Dhaka and other institutions studied the groundwater chemistry in the Munshiganj District, outside Dhaka in southern Bangladesh, where many drinking-water wells are seriously contaminated.

The researchers drilled 15 new wells and then set out to alter groundwater chemistry as they suspect pumping does. In one case they injected water containing molasses, which is rich in organic carbon; arsenic levels increased substantially within days. Harvey suspects that the increase occurred because the organic carbon reduced and then dissolved the iron oxides that bear arsenic. In another experiment, injections of nitrate caused arsenic levels in the aquifer to plummet 80%, also within days. Nitrate oxidizes dissolved iron, Harvey explains, which then precipitates along with arsenic. The team believes that irrigation pumping might lower or raise arsenic levels by either mechanism, for example, by pulling in oxygenated water from sandy sediments or by drawing down organic carbon-rich water from ponds and channels.

At the study site, the researchers believe that this latter mechanism has spiked the drinking water with arsenic. In the upper part of the aquifer, inorganic carbon and methane—byproducts of carbon-based reactions that liberate arsenic—are roughly 40 years old, about the same age as irrigation pumping. “The message is clear,” comments Michael Berg, an environmental chemist at EAWAG. “If you pump a lot of groundwater in such areas, arsenic release can be triggered.” He has observed a similar pattern in Vietnam.

Elsewhere in Bangladesh, however, other factors appear to be more important in releasing arsenic than irrigation pumping. Geochemist Alexander van Geen of the Lamont-Doherty Earth Observatory in Palisades, New York, and his colleagues have found high levels of arsenic in water that's more than 40 years old, suggesting that irrigation pumping hasn't been involved. And arsenic contamination is less of a problem in the northwestern part of the country, where much farm water is pumped, adds John MacArthur of UCL. Harvey chalks up the inconsistencies to different sediment chemistry and says that his study area in Munshiganj is typical of southern Bangladesh: “I see no reason why the same process can't happen in other places.”

Arsenic levels at the study site begin to pass muster at about 160 meters, which suggests that deeper wells could reduce the arsenic problem. But that's an expensive option in one of the poorest countries in the world. Other near-term strategies include developing filtration techniques and trying to persuade villagers to switch to more distant shallow wells that are still safe.

7. ENERGY RESEARCH

# Industry Invests Big in Stanford Project

1. Andrew Lawler

An international consortium of energy companies intends to pump up to $225 million over the next decade into a climate change and energy project led by Stanford University in Palo Alto, California. Researchers say they are stunned by the size and scope of the effort to study ways to reduce global warming, which will examine everything from carbon sequestration to the economics of substituting hydrogen fuel for oil, coal, and natural gas. “This is one of the grand challenges of the century,” says Lynn Orr, a petroleum engineer at Stanford, who will lead the project. Although energy companies have long funded academic research programs, the scale and structure of the effort are unprecedented. Stanford and industry officials say that the data derived from the effort will be publicly available and that an independent advisory board will help chart the project's direction. “Absolutely nothing is off the table; we want all areas addressed,” says Frank Sprow, vice president for safety, health, and environment at ExxonMobil, which will provide the single largest chunk of funding. Even skeptics of industry welcome a broad research effort. “This is an acknowledgement that global warming is a problem they can no longer ignore,” says Dan Lashof of the Natural Resources Defense Council in Washington, D.C. ExxonMobil will contribute$100 million to the project, and General Electric and E. ON, an energy provider based in Düsseldorf, Germany, will provide $50 million each. Schlumberger, a global oil-drilling equipment company, will pitch in$25 million. University officials will be in charge of handing out $20 million during the project's first 3 years, roughly half to Stanford researchers and the remainder primarily to other academic scientists; company researchers are not eligible. The university will hold title to any patents, although the funding sponsors will have a short period to negotiate licenses before the discoveries are up for grabs. The first funding likely won't begin flowing until the end of next year. The project grew out of discussions between Stanford and Schlumberger about geological sequestration, or the injecting of carbon into the ground to prevent its release in the atmosphere. “This could be a big operation, potentially almost the same size as the oil industry today,” says Philippe Lacour-Gayet, a physicist and chief scientist at the Schlumber-Doll Research division of Schlumberger. The project's scope grew as other corporations became involved. Orr says that the scientific and engineering agenda has yet to be finalized but that the focus will be on ways to lower greenhouse emissions in the short run while exploring how to convert the world's energy system to less polluting fuels and technologies. That includes cheaper methods of generating hydrogen, more efficient burning of hydrocarbons, and other alternatives ranging from solar to fusion energy. Companies were attracted to Stanford because of its strengths in earth sciences and engineering and its tradition of interdisciplinary work, say industry representatives. Outside energy experts add that the university's stature should ease fears that the project will be tilted toward a hydrocarbon-biased approach. “If you wanted to buy a university to do your bidding, you wouldn't pick Stanford,” says John Holdren, an environmental science and policy professor at Harvard University. Orr agrees: “We will never give up the right to decide what we work on. We're not at all concerned about undue influence.” ExxonMobil managers say they hope the research lessons can be applied to developing as well as developed countries. But Sprow adds that the project doesn't mean oil has no future. “This is a terrific opportunity to see if oil can be used in a way that's more benign,” he says. Whatever turns up, Sprow and his consortium colleagues are betting big bucks that the research will help them cope with changes in their business as well as in the global environment. 8. NATIONAL SCIENCE FOUNDATION # Congress OK's Budget Doubling, At Last 1. Jeffrey Mervis Some straightforward political horse-trading paved the way for the National Science Foundation (NSF) to achieve one of its most cherished goals last week: a congressional promise to double the agency's budget in 5 years. Science lobbyists have spent years arguing that the recent ramp-up for the National Institutes of Health should be balanced by a similar boost for NSF. Last month Congress appeared ready to sign off on the idea as part of a reauthorization of NSF's programs, but then Senator Jon Kyl (R-AZ) applied a last-minute hold on the bill as it was about to go before the full Senate (Science, 25 October, p. 719). The real objection, however, came from the White House Office of Management and Budget (OMB), which felt that doubling was a crude budgeting tool and clashed with its efforts to hold down domestic spending. The parliamentary maneuver infuriated Senate Democrats, who complained that they had been blind-sided. But House members who had passed a similar bill in June didn't give up. They spoke with OMB officials, who quickly offered a compromise: a 5-year bill that made the last 2 years contingent on a review by OMB of NSF's progress in meeting a series of management goals that are part of a presidential good-government initiative. That allowed the White House to maintain that it hadn't handed NSF a blank check and to enshrine the concept that bigger budgets were a reward for good management. At the same time, congressional supporters of doubling could say that they had taken a big step toward raising NSF's budget from its current$4.8 billion to $9.8 billion in 2007. The bill (H.R. 4664), now awaiting the president's signature, doesn't actually give NSF a dime, however. Annual spending is set by appropriators, who have yet to complete action on any domestic spending bill for the 2003 fiscal year that began 1 October. But “we think it's great,” says NSF's David Stonner, head of legislative affairs. “It demonstrates strong congressional support for NSF.” The bill is loaded with congressional demands, too, including more than a dozen reports on topics ranging from improving math and science education to building big research facilities. 9. CELL BIOLOGY # Chaos Reigns in RNA Transcription 1. Jennifer Couzin The critical job of transforming raw genetic information into proteins seems to call for a well-oiled machine. But one research team, pushing the boundaries of imaging technology and computer modeling, argues that this machine is the picture of inefficiency. Rather than smoothly assembling on a gene, the proteins that form a major transcription tool, called RNA polymerase I, collide without sticking and zoom off if their companions are seconds behind schedule. The research, reported on page 1623, is not without critics, who contend that the technology used in the study has not advanced enough to support such a model. But the work reflects an increasingly sophisticated effort to delineate the dance performed by transcription machinery. Two papers analyzing the other main transcription tool, RNA polymerase II, will be published next month. Although the three home in on different aspects, all find similar chaos. “What they're saying is that things are just flying around, and they happen by accident to come together,” says Joseph Gall of the Carnegie Institution of Washington's branch in Baltimore, Maryland, of the Science paper. “That's an extreme view …, [but they're] such good data that you have to sit up and listen.” To gather these data, Tom Misteli and his colleagues at the National Cancer Institute (NCI) in Bethesda, Maryland, first conducted imaging experiments on animal cells. RNA polymerase I consists of at least a dozen different proteins; Misteli's group focused on nine of these that together make up the bulk of the polymerase. Using in vivo microscopy, they tagged one at a time with a fluorescent marker and followed each through the nucleus to the DNA. By watching how long each protein loitered by the gene and then overlaying that with the behavior of the eight others, the researchers could begin tracing polymerase assembly. But imaging technology reveals only so much. The biologists were curious about a protein's chance of being welcomed into the polymerase if it surfaced in the right place at roughly the right time. For that, they turned to Robert Phair, a computer modeler at BioInformatics Services in Rockville, Maryland. The team plugged imaging data into a model Phair built to simulate the known stages of polymerase assembly. The model suggested that joining the polymerase was quite a challenge: A polymerase protein would wait for only 2 seconds for another to show up and bind to it before darting off. Furthermore, the team discovered, a polymerase breaks apart once it has transcribed a gene, forcing reassembly to start from scratch. Despite this stunning inefficiency, the group found, a polymerase assembles every 1.5 seconds. Misteli theorizes that the system works because the polymerase proteins are so abundant. But several researchers question whether imaging and mathematical models can provide such an unambiguous picture of assembly. NCI's Gordon Hager wonders whether the polymerase always comes together the way the model predicts. And other researchers point out that it's tricky with imaging to tell whether a protein is joining the polymerase. Misteli agrees that imaging and modeling a living cell isn't foolproof, but he still considers it superior to previous in vitro work. Although Hager questions some of the details of protein motion reported by Misteli's team, his own paper, which will appear in December in EMBO Reports, supports the general theory that “everything is dynamic.” It examines regulatory proteins for RNA polymerase II; although not part of the polymerase, these enzymes help launch transcription. His group reports that these proteins spend just seconds in transcription locales. Another paper, by Oxford University's Peter Cook and his colleagues, will be published in the December Journal of Cell Biology. Cook's group studied a subunit of RNA polymerase II and saw many of the same inefficiencies as Misteli. This growing body of evidence might shift the debate about polymerase assembly and the stability of whole polymerases, says Cook: “A lot of what's driving everything is random chance events.” The purpose scientists seek in cellular machinery, he adds, might be nowhere to be found. 10. EVOLUTIONARY BIOLOGY # Bacteria Shared Photosynthesis Genes 1. Elizabeth Pennisi Historically, sun-loving microbes that convert solar energy to biomass, it seems, were quite promiscuous: They readily swapped DNA. Since then, they have been basking in the light for hundreds of millions of years, adding life-supporting energy and oxygen to the environment and making possible the variety of organisms on Earth today. Early on, these species were remarkably free, as researchers explain on page 1616, in sharing the photosynthesis genes that enable them to draw energy from sunlight—so free that it's hard to use these genes to trace the microbes' ancestry. “There's been massive horizontal gene transfer” among these organisms, says co-author Robert Blankenship, a biochemist at Arizona State University in Tempe. Until about 5 years ago, researchers considered the transfer of genetic material from one species to another an oddity. Since then, genome studies have shown that some genes have moved around quite a bit. Even so, microbiologists assumed this would not be true for genes involved in translating DNA to RNA, for example, or sunlight to biomass; they couldn't see how genes of such mixed ancestry could possibly coordinate these complex processes. But that assumption “doesn't seem to be true,” says W. Ford Doolittle, an evolutionary biologist at Dalhousie University in Halifax, Nova Scotia. The new work “clearly shows that photosynthesis genes have moved from one organism to another,” adds Carl Bauer, a biochemist at Indiana University, Bloomington. Five groups of bacteria use light as an energy source. To understand how photosynthesis genes could have evolved multiple times in these bacteria, Blankenship and others spent years studying the individual genes. But when bacterial genome sequences began pouring into public databases, they decided to take a global approach. In the summer of 2001, graduate student Jason Raymond and his colleagues began to analyze the genome sequences of one organism from each of the five photosynthetic groups: a cyanobacterium, a filamentous green bacterium, a purple bacterium, a green sulfur bacterium, and a heliobacterium. Comparing the five genomes using several computer programs, including one called BLAST, they found 200 genes that were common to all. Among those 200 shared genes, Raymond and his colleagues found about 50 photosynthesis genes. They compared the sequence differences of each gene among the five species; from those differences they built family trees that represented the relationships of the bacteria to one another. The approach is “very valuable,” says Radhey Gupta, an evolutionary biologist at McMaster University in Hamilton, Ontario, because it takes into account all the available genetic information instead of just a few genes to determine which species are ancestral. Had there been no gene swapping among the species, family trees based on each gene should have been the same. Instead, the researchers came up with 15 sets of relationships, the maximum possible with five species. “That suggested that different genes had different evolutionary histories,” says Blankenship. These histories could differ only if the various genes had spent time in other organisms. “What this does is give us the first good data that genes were shuttled from one species to another,” says Bauer. The photosynthesis genes the researchers identified provided other clues to the microbes' photosynthetic past. For one, researchers learned about new support genes that might help repair or assemble photosynthetic machinery. Also, because photosynthesis requires many more proteins than the 50 genes can provide, it's likely that other genes have taken on double duty and help with photosynthesis. In looking for photosynthetic microbes' earliest ancestor, the best these data can advise, Blankenship thinks, is to lump together the cyanobacteria, green filamentous bacteria, and heliobacteria. “It's going to be very hard to pin down whether any one group was the first” to do photosynthesis. But this doesn't bother Doolittle. For him, “to find that [photosynthesis] is very extensively patched together from pieces is very exciting.” 11. WILDLIFE RESEARCH # New Rules Ease Specimen Shipments 1. Philipp Weis* 1. Philipp Weis is an intern in the Cambridge, U.K., office of Science. CAMBRIDGE, U.K.—To the relief of scientists, an international trade body has decided to eliminate much of the red tape that has hindered the shipment of biological samples for research on endangered species. Although its action last week is not binding for individual nations, scientists say it will raise awareness of the pressing need for improved handling of the material. The strict regulations of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) aim to prevent smuggling of animal parts. But as a side effect, they also hamper research on endangered species. Scientists often wait weeks or even months before being allowed to send blood, hair, or feathers from the field back to their home labs—no matter how urgent the need for diagnostic tests. The first proposal to simplify the procedure was rejected 2 years ago at the last CITES meeting in Nairobi (Science, 28 April 2000, p. 592), but it has since been refined in the organization's committees. The new resolution, adopted during the parties' meeting in Santiago, Chile, lays out what kinds of samples, quantities, and purposes will qualify for a simplified and expedited permit. Biological samples must be “urgently required in the interest of an individual animal” and have a “negligible impact on the conservation of the species concerned.” Every country participating in CITES must provide a list of eligible institutions. The proposal covers shipments of blood, secretions, hair, feathers, and tissues but excludes reproductive tissues—ova and sperm—and embryos. Nevertheless, the proposal had encountered strong opposition from countries such as Mexico, Brazil, and China, which feared that it could allow uncontrolled access to genetic resources. “This is astonishingly far-reaching,” beams elephant researcher Thomas Hildebrandt of the Institute for Zoo and Wildlife Research in Berlin. The proposal, he says, will greatly simplify the process of obtaining samples. Even so, the declaration is just a recommendation to participating countries, warns Thomas Althaus of the Swiss Federal Veterinary Office, one of its authors. Many countries such as Thailand and the United States impose their own restrictions. But according to Hildebrandt, “the resolution gives us a stronger tool to pressure the authorities” to adopt compatible rules. 12. CANINE EVOLUTION # A Shaggy Dog History 1. Elizabeth Pennisi Biologists chase down pooches' genetic and social past ## A Shaggy Dog History Two-kilogram teacup poodles; 90-kg mastiffs; slender greyhounds; squat English bulldogs: For a single species, canines come in a vast array of shapes and sizes. Even more remarkably, they all come from the same stock. Many millennia ago, humans took in a few primitive wolves and made them man's best friend. Or so the story goes. For centuries, researchers have doggedly pursued the evolutionary and social history of canines, with mixed success. Only subtle differences distinguish dogs from coyotes, jackals, and other canids, making family trees difficult to construct and the timing of the transition from wolf to dog hard to pinpoint. Archaeologists find both wolf and dog remains near ancient human camps, which leaves the date of domestication open to debate. What seems certain is that dogs have been part of human history longer than cows, horses, or goats. And during that time, dogs have somehow adapted to their role as companions, developing sophisticated social skills not seen in other domesticated beasts. “Dogs have undergone a lot of selection to be compatible with humans,” says Jennifer Leonard, now an evolutionary biologist at the Smithsonian National Museum of Natural History in Washington, D.C. “And the selection has really worked,” she says. Just ask any dog owner. In this week's issue of Science, three research teams chase down some of the age-old issues surrounding the evolution of dogs. Using genetic studies, one offers new evidence about where dogs were first domesticated; another employs DNA comparisons to show that New World pooches aren't from the New World at all; and the third evaluates the ability of dogs to follow human cues. Some researchers think the results of these efforts clear up some key questions about dog evolution. “I'm very excited to read these articles,” says John Olsen, an archaeologist at the University of Arizona in Tucson. But others are skeptical. “I am not sure I believe them,” says Raymond Coppinger, a behavioral ecologist at Hampshire College in Amherst, Massachusetts, about the trio of reports. An upcoming project might help resolve some of the continuing debates. In September, the National Human Genome Research Institute (NHGRI) put dogs high on the list of species whose genomes it will sequence. The sequence could provide new data not just for genetic research but also for evolutionary studies. The project “will certainly give us more information and will bring more attention to dogs,” says I. Lehr Brisbin, a wildlife ecologist at the University of Georgia's Savannah River Ecology Laboratory in Aiken, South Carolina. “I am so excited that the dog has been picked.” ## Grandpaws Dog researchers, whatever their pet theory, know they're in for a fight. “Everything that anyone publishes about the origin of the dog is controversial,” explains Brisbin. “That's because everyone, even the man on the street, feels he is an expert on the dog.” Most enthusiasts agree with the standard story that dogs evolved from wolves. But a few insist that dogs stemmed, for example, from one of several jackal species, some hybrid canid, or even a contemporary of ancient wolves that has since gone extinct. Others have suggested that dog domestication took place more than once with more than one species, which might explain the great diversity seen in dog breeds. Then there's the question of how domestication occurred. Some researchers think that early humans raised wolf puppies or tamed wolves as pets or possibly assistant hunters, selecting for ever-more-docile animals. But Coppinger and others think wolves, even as pups, don't have the right temperaments for a role in such a scenario. Coppinger and Brisbin assert that wolves became ever less fearful of people as they adapted to scavenging food from their two-legged neighbors. Thanks to this easy source of food, wolves born with greater boldness around humans thrived, eventually parting company with their more wary companions. The date and place of domestication continues to be a mystery as well. Doglike jaws and other skeletal parts from 14,000 years ago have been discovered in central European and German sites. However, Italian researchers have suggested that their country is the dog's first home, citing DNA studies of 10,000- and 14,000-year-old wolf bones and 3500-year-old dog bones that show both these species had a genetic makeup similar to that of modern dogs. Perhaps the most dramatic find comes from Israel: A woman was buried 12,000 years ago with what many believe is a puppy in her hands. Nearby, archaeologists found a man from the same era buried with two small canids, also presumably dogs. Coppinger is not swayed by these tableaux because the bones are too wolflike. But Tamar Dayan, an archaeologist at Tel Aviv University, points out that the specimens have some key dog characteristics, such as crowded teeth and shorter jaws. Furthermore, unlike other archaeological finds, “this is the one place where we have a whole group of animals all in the [right] cultural context” as companions to humans, she points out. She believes that truly domesticated dogs showed up first in Israel, 12,000 years ago. This approximate date was questioned some 5 years ago but is now coming back into favor. ## Taming the DNA Robert Wayne and Carles Vilà, evolutionary geneticists at the University of California, Los Angeles (UCLA), and their colleagues stepped into this fray with a publication in 1997. They hoped their genetic data would settle any controversy about both the ancestry of dogs and the date of their domestication. They succeeded—partially. The researchers assessed differences in a section of the mitochondrial genomes of 140 dogs of different breeds from around the world: 162 wolves, five coyotes, and 12 jackals. “We showed very clearly that the dog is very close to the wolf and comes from several lineages of wolves,” says team member Peter Savolainen, a molecular biologist at the Royal Institute of Technology in Stockholm, Sweden. Not everyone was convinced, but the work did tip the scales in favor of the wolf. However, based on the number of differences between the sequences of wolves and dogs, the researchers estimated that dogs arose some 135,000 years ago—a conclusion that has quite a few colleagues growling. The date couldn't be right, opponents argue, given that the earliest accepted dog fossils date from just 14,000 years ago. They also suggest that very early humans were probably not sophisticated enough to keep wolves from interbreeding with dogs, a prerequisite for domestication. While canine researchers were still debating Wayne and Vilà's 1997 results, Savolainen decided to pinpoint where domestication first occurred and perhaps take a second look at the earlier results. For this work, he studied mitochondrial DNA from 426 dogs from across the globe. In addition, he obtained data from studies of Chinese dogs: 100 samples analyzed and provided by Ya-Ping Zhang and Jing Luo of the Chinese Academy of Sciences in Kunming. The researchers also gathered DNA from 38 wolves from Europe and Asia. As the previous study had found, most of the dogs and wolves fell into a single large genetically related group, and other dogs and wolves sorted into two medium-sized groups and several smaller ones. The three larger groups were distributed throughout Eurasia, suggesting that their ancestors had traveled extensively and mingled early in canine history. Furthermore, the data showed that similar breeds didn't arise from the same groups. Mastiffs and other large breeds didn't all fit, as one might have thought, into a single group that contained DNA from particularly large wolves. Despite the different groups, the DNA samples were all similar enough that “we can say now there was probably one geographic origin,” Savolainen concludes. That place was East Asia, he and his colleagues report on page 1610. The data aren't precise enough to identify a specific country, but “a good guess would be China,” Savolainen says. Several lines of evidence led Savolainen to East Asia. For one, he took a close count of the number of differences between the DNA of each group. As expected, he found that these differences had accumulated over time and had divided each group into subgroups. When he factored in the number of dogs in each group, he calculated that the East Asia pool had the most variety. “The high frequency of diversity in the East versus the West makes the [evidence] overwhelming,” comments Brisbin. Furthermore, a large number of genetic sequences were found nowhere else but East Asia, suggesting that this population is ancient enough to have accumulated unique genetic signatures. With these data, Savolainen and his colleagues also took a fresh look at the date-of-domestication question. Their estimate is 110,000 years later than that of Wayne and Vilà. But “we can't say for sure that one or the other is the right date,” Savolainen points out, as even he can calculate a much earlier date depending on how he processes his data. ## From the Old Country Early dogs quickly became world travelers, new evidence suggests. When the first humans walked across the Bering Strait 10,000 to 15,000 years ago, dogs were by their sides, claims Leonard, who did this work at UCLA with Wayne, collaborating as well with Vilà, who is now at Uppsala University in Sweden. Until now, many people thought that dogs in the Americas were domesticated from New World gray wolves, but mitochondrial DNA studies tell a different story, she and her colleagues report on page 1613. They decided to examine the origin of New World dogs because early genetic studies of supposed New World breeds showed rich European bloodlines. “It looked like the only way to address this was to look at archaeological specimens,” she explains. With the help of local researchers, the team studied 37 dog bones found at pre-Columbian archaeological sites in Mexico, Peru, and Bolivia. They extracted DNA from those samples and also looked at 11 DNA samples from dog remains deposited in Alaska before the arrival of the first European settlers. They compared these samples to DNA from 140 dogs and 259 wolves from around the world. The ancient DNA was just like modern Eurasian dog DNA, the team found. New World dogs fell into the same branch of the canine family tree as three-quarters of the Old World dogs, a branch that includes so-called primitive dogs such as the Australian dingo, the African basenji, and the New Guinea singing dog. The American gray wolf proved to be just a distant cousin. It appears that “dogs accompanied humans into the New World,” says David Hillis, an evolutionary biologist at the University of Texas, Austin. Moreover, the data suggest that five lineages of dogs came over the Bering Strait and became the predecessors of the Americas' dogs. Finally, the results show that a second wave of fresh blood flooded into the New World canine community with the arrival of colonists millennia later. Even the Mexican hairless, Alaskan huskies, and the Newfoundland and Chesapeake Bay retrievers—all considered to be breeds that were developed in the Americas—have DNA sequences that are indistinguishable from those of modern European dogs, Leonard and colleagues report. ## Best friends DNA studies can tell only part of the dog's tale. Along with genetic and morphological changes, substantial behavioral modifications were produced over the course of domestication, and these likely cemented the dog's place by the fire. “To be able to live with humans, it [was] evolutionarily beneficial to be able to read humans,” Savolainen points out. On page 1634, Brian Hare, an anthropologist at Harvard University, and his colleagues demonstrate that a cognitive skill that dogs have—but nonhuman primates don't—evolved during domestication. This finding is important not just for understanding dog evolution but also for assessing how smart animals can be. “We tend to look at the primate work and if [primates] can't do it, we [assume] all animals can't do it,” says Nicola Clayton, an ethologist at the University of Cambridge, U.K. But that just isn't so, says Hare's collaborator Michael Tomasello, a developmental and comparative psychologist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. Our primate cousins can follow the gaze of other chimps or of humans and use that clue to find food behind a barrier. But other cues go right by them: After a researcher hides food in one of two containers, the chimp can't figure out the food's location if the researcher points to or taps on the container with the food. That's not the case with dogs: Many take the hint the first time around, says Hare, who decided to see where this skill came from. Working with Christina Williamson of the Wolf Hollow wolf sanctuary in Ipswich, Massachusetts, Hare compared the success of seven human-reared wolves with that of seven dogs in picking the right container when he looked at, tapped, or pointed to it. All the containers smelled of food, so odor was not a cue. The dogs did significantly better than the wolves, he and his colleagues report. “I am quite convinced by their case that domestic dogs are absolutely expert at this thing,” says Peter Marler, an ethologist at the University of California, Davis. Next the researchers tried the experiment on puppies to determine whether the behavior was innate or learned. They used 32 puppies, aged 9 to 26 weeks. About half lived with families; the rest lived with one another in kennels and had little exposure to people. Many did quite well, and “there was no difference between those with a fair amount of experience in a home and those [with little experience with humans] in a kennel,” says Tomasello. He and Hare conclude that these skills were selected during the transition from wolf to pet pooch and are now an innate part of the canine personality. But not everyone is convinced. Coppinger and others worry that the researchers can't control for how individual dogs or wolves react to the test situation, although Tomasello counters that they tested for relevant differences and found none. Nonetheless, Clayton is eager to see more work. “If it's the result of domestication that dogs have become particularly good at understanding human signals, then we expect there would be a whole battery of tests that they would be better at [than primates],” she points out. ## Dogged pursuit While Hare and Tomasello work out new tests of canine craftiness, their more genetically oriented colleagues are eager to pin down genes contributing the many different behaviors that dogs exhibit. This pursuit has a long history but until recently had seemed to stall. Almost 50 years ago, two geneticists at Jackson Laboratory in Bar Harbor, Maine, began systematic studies of behavioral traits ranging from how well dogs get along with other dogs to their favorite play activity. John L. Fuller and John Paul Scott spent 20 years interbreeding basenji, cocker spaniels, Shetland sheepdogs, beagles, and wire-haired fox terriers. In one experiment, for example, the puppies were raised with minimal human contact, observed daily for 16 weeks, and evaluated according to their wariness toward people. From their observations, the researchers demonstrated that at least some aspects of behavior, such as aggressiveness, had a genetic basis. Moreover, they discovered that puppies passed through critical periods during which they learned specific behaviors, a realization that has guided dog training ever since. Since then, behavioral studies have had their ups and downs. In 1990, Jasper Rine of the University of California, Berkeley, began trying to track down the genes involved in a Newfoundland's love of water and a Border collie's obsession with herding. He began building a genetic map to help with this quest. The breeding studies were discontinued for lack of funding, but Rine's colleagues continued the mapping project and now have a genetic map with 3400 landmarks on it, a resource that should speed the discovery of new genes. Now mappers Elaine Ostrander of the Fred Hutchinson Cancer Research Center in Seattle and her colleagues have convinced NHGRI that the dog warrants more attention from the genome-sequencing community. This next step will enable researchers to explore why members of one species look and act so differently. “Of all the domesticated animals, the dog has been more artificially selected for divergent behavior than any other animal,” Brisbin points out. “Having the genome sequenced is going to help us learn how those diverse behaviors are controlled genetically.” Such studies might also have biomedical benefits. Karl Lark, a geneticist at the University of Utah in Salt Lake City, is tracking down skeletal genes and their regulatory proteins in order to understand the vast array of canine sizes and shapes. He might uncover genes important in human skeletal abnormalities. But for Lark and others, the fascination lies in understanding the dog for the dog's sake. As Wayne points out, and every dog lover seconds, “there's really no other species like it.” 13. PROFILE: HUSSAIN AL-SHAHRISTANI # The Very Model of a Modern Iraqi Dissident 1. Andrew Watson* 1. Andrew Watson is a writer in Norwich, U.K. With reporting by Richard Stone. Once Iraq's chief nuclear chemist, Hussain Al-Shahristani endured torture and 10 years of solitary confinement after refusing to work on the bomb LONDON—In the autumn of 1979, nuclear chemist Hussain Al-Shahristani made a decision that would rob him of his freedom and imperil his life, transforming him into one of the world's highest-profile dissident scientists. Twenty-three years later, United Nations weapons inspectors are hoping to find more scientists like him as they return to Baghdad after a 4-year hiatus. Shahristani's principled journey began shortly after Saddam Hussein ascended to the presidency and ordered the Iraqi Atomic Energy Commission to shift from peaceful research into “strategic applications,” a euphemism for work on an atomic bomb. It was also a time when the Iraqi government, unsettled by the revolution in neighboring Iran, had begun arresting thousands of people. The result, recalls Shahristani, was “mass executions and serious violations of human rights.” Shahristani was then one of two chief scientific advisers to Iraq's nuclear program. He and his fellow chief adviser, nuclear physicist Jaafar Jaafar, confided their misgivings to each other, but only Shahristani spoke out publicly against the program and the human rights violations. Soon he was arrested and tortured, then jailed for more than a decade. Jaafar, who was imprisoned briefly after suing for leniency for his colleague, went on to mastermind a nuclear program that has brought a cold sweat to the brows of Western leaders. In the decade since his daring escape from prison during the Gulf War, Shahristani has become a formidable nemesis of the Iraqi government. He spoke recently with Science from his office above a furniture store in North London, where he lives in exile. “He's a great scientist, and he should be honored for resisting Saddam Hussein's demands to work on nuclear weapons,” says David Albright, a physicist who heads the Institute for Science and International Security in Washington, D.C. Shahristani is also precisely the sort of individual whom United Nations weapons inspectors hope to contact now that they are back in Baghdad. The inspectors are empowered to bring willing scientists out of Iraq for debriefings, along with their families to avoid retribution from the Iraqi government. The hope is that such individuals will provide independent and credible information that will help inspectors better assess the full disclosure of its weapons of mass destruction programs that Iraq must deliver to the United Nations by 8 December. A solitary hero. Shahristani's career began like those of other young Iraqis in the scientific elite: He was singled out for a scholarship in Moscow and then at Imperial College in London, where he graduated in chemical engineering in 1965. Nuclear science was “fashionable” then, he says, and he jumped at the chance to work at the research reactor at the University of Toronto, where he earned a Ph.D. in nuclear chemistry. There he also wooed and married the typist of his dissertation, Bernice Holtom, who would be his pillar in the harrowing years to come. In 1970 Shahristani joined the Nuclear Research Centre at Tuwaitha, south of Baghdad, home to a newly supplied French research reactor, and introduced neutron activation analysis to Iraq. This technique is useful for measuring trace elements at sub-parts per million by flooding a sample with neutrons. Shahristani used it successfully to respond to an epidemic of mercury poisoning in Iraq from imported grain treated with a mercury-based pesticide. “The country was desperate to find out what was safe to eat,” he says. His analyses provided a means of assessing food safety. Such work marked him as a leading figure in the Iraqi scientific establishment. In 1978 he was appointed chief scientific adviser to the Iraqi Atomic Energy Commission, the most senior scientific post in the country. Shahristani claims that until the end of the 1970s the nuclear program was strictly peaceful—an assertion that “puzzles” Albright, who says the French reactor, which used highly enriched uranium, was “ideally suited” to a nuclear weapons program. He speculates that Shahristani may have been deliberately kept in the dark until 1979, when Hussein, who had been involved in negotiations with French nuclear officials, became president and signaled that his aim was to produce weapons. At a meeting of the commission attended by Ba'ath Party members, Shahristani denounced the nuclear aspirations and human rights violations. He says he thought that such a statement would encourage the government to simply move him out of the nuclear program. “I thought our scientific status would basically protect us from being arrested,” he says. He was wrong. “His arrest made him a national hero,” says Adel Sharif, a chemical engineer at the University of Surrey, U.K., who was a student in Iraq at the time. In the academic world “he was a source of inspiration,” Sharif says. “Everybody was talking about him privately.” Shahristani says he was tortured for 3 weeks, during which time he was suspended upside down from the ceiling for hours at a stretch and subjected to electric shocks. He counts himself lucky compared to other prisoners who had holes drilled into their bones and their hands dissolved in acid. Jaafar attempted to come to his rescue by petitioning Hussein for Shahristani's release, but that backfired: He too was arrested. “Jaafar was not tortured himself, but they brought other prisoners and tortured them in front of him until they died,” Shahristani says. He claims that broke Jaafar, who eventually became the scientific linchpin of Iraq's nuclear weapons program. While in prison, Shahristani says he was visited by Hussein's stepbrother and head of security, who tried to persuade him to recant. Shahristani refused. That rejection earned him 10 years in solitary confinement, in a room with no windows, no reading or writing material, and a single 15-minute chaperoned visit per month from his wife. He did not want to give the regime the pleasure of seeing him go crazy. “It sounds silly now, but I tried to make puzzles and then solve the puzzles that I'd just made myself,” Shahristani says. A devout Muslim, he prayed and recited sections of the Koran from memory to have “conversations.” Shahristani eventually was moved out of solitary confinement, and during the Gulf War in 1991, he seized an opportunity for escape: During a nighttime bombing raid, he stole a car and uniform of the prison's chief security officer and simply drove out past the guards. He and his family, along with a million other Iraqis, fled over the border that March into Iran. Iconoclastic views. Shahristani's refugee experience has shaped his activities ever since. In 1995 he set up the Iraqi Refugee Aid Council, which has helped tens of thousands of Iraqis in camps in Iran by setting up clinics, schools, and self-help programs. Two years ago he moved from Iran to London, the center of Iraqi political opposition and a focal point for the United Kingdom's estimated 250,000 ethnic Iraqis, where he has continued his work with refugees. “Unlike others who defected, he risked his life to continue to try and do something, to stay as close as he could to Iraq, to help the refugees, to document the abuses,” says Shelley Saywell, who in 1995 directed a Canadian documentary of Shahristani's life. What also sets Shahristani apart are his views on Iraq's weapons programs. He downplays concerns that Iraq is on the verge of acquiring a nuclear bomb. “Iraq basically has the know-how to assemble a crude nuclear device, but it lacks the fissile material,” he says, basing that conclusion on information from resistance cells and well-placed scientists in Iraq as well as his contacts with recent defectors. He discounts the recent revelation by the U.K. government that Iraq has been trying to purchase uranium ore from Africa, claiming that the regime lacks centrifuges and other equipment to enrich it. Others are more cautious. Albright, a longtime Iraq analyst, says Shahristani may be underestimating his former employer. “You have to worry that Iraq is reconstituting its uranium-enrichment program or even dabbling in plutonium,” he says. “It's very hard to detect these activities.” But Shahristani is far from dismissive of Hussein's biological and chemical ambitions. Concerns are running high about possible covert work on botulinum, anthrax, gas gangrene, and aflatoxin (Science, 16 August, p. 1110), and Shahristani says that his own sources suggest such concerns are justified. He has also raised disturbing new questions about Iraq's chemical weapons program. U.N. inspectors know that Iraq started working on mustard gas in 1982, followed by sarin and tabun. Shahristani backs claims from defectors that prisoners were used as guinea pigs. “Thousands of people were taken from prisons for experiments,” he alleges. He also asserts that much of the R&D on chemical and biological weapons has ended: Most scientists in these programs “were sent back to the universities. The regime has decided it has enough know-how to use its inner core of security officers to do the production work.” His most explosive allegation, however, is that the Iraqi military has placed tons of chemical weapons, including the devastating nerve gas VX, in Shiite villages in the southern half of the country and intends to detonate the stocks in the event of a U.S.-led invasion. Based on its suspected covert precursor stocks and available equipment, Iraq has the capability of producing “tens of tons” of VX, notes a former U.N. chemical weapons inspector. However, no experts have corroborated this scenario, and a few are dubious. The booby-trap scenario is “unlikely,” argues Kelly Motz, an analyst on Iraq at the Wisconsin Project on Nuclear Arms Control in Washington, D.C. It “would undermine [Hussein] in the eyes of Arabs and help justify the U.S. position.” Shahristani strongly disagrees, noting that Hussein has already used poison gas on his citizens, against Iraqi Kurds in the late 1980s. Sensing a coming confrontation, Shahristani fears “a potentially very serious human catastrophe” facing the Iraqi people—a suffering that he knows all too well. 14. NUCLEAR PHYSICS # Accelerator Aims to Find the Source of All Elements 1. Charles Seife Nuclear physicists hope that an expensive atom smasher will reveal the secrets of stellar alchemy, but first they have to secure funding We are all made of starstuff. The big bang created hydrogen, helium, and a little bit of lithium and other light atoms. But everything else—the carbon, oxygen, and other elements that make up animals, plants, and Earth itself—was made by stars. The problem is that physicists aren't quite sure how stars did it. The answer, they hope, will be revealed by an$840 million machine called the Rare Isotope Accelerator. RIA will smash stable atoms into fragments, producing rare, unstable nuclei that play a brief but crucial role in the creation of heavy elements. By studying these unstable nuclei—analyzing their half-lives, their ability to capture neutrons, and other properties—scientists believe they will finally be able to figure out where all the heavy elements are born. “RIA's the machine that will nail the entire issue,” says Claus-Konrad Gelbke, a nuclear physicist at Michigan State University in East Lansing.

If RIA is a nail, then the Department of Energy (DOE) seems to be a reluctant hammer. Although the agency's Nuclear Science Advisory Council recommends building RIA—at either Michigan State or Argonne National Laboratory in Illinois—its other committees covering fusion energy and high-energy physics are each pushing strongly for even more expensive projects. And that stiff competition is likely to produce losers as well as winners. “In times of tight budgets, you have to make tough decisions,” says James Decker, principal deputy director of DOE's Office of Science. In an effort to sway DOE, RIA's supporters point to growing European interest in building a rival facility in Darmstadt, Germany (see p. 1534). “They're moving on a very aggressive and assertive trajectory,” warns Gelbke, “but RIA has been on the table for more than 2 years.”

Scientists hope that RIA will focus on a crucial final piece of the puzzle of how stars create elements heavier than helium. Physicists already know in great detail how lighter elements such as carbon and oxygen are produced in the nuclear furnaces of stars, which take hydrogens and fuse them into helium and eventually into other elements. But fusion can't create elements heavier than iron, the most stable atom of all, meaning that elements such as gold, lead, and uranium had to be forged in some other way.

Much of it happens in dying stars. After a star exhausts its supply of hydrogen fuel, it flares briefly before burning helium for hundreds of thousands of years. The byproducts of this nuclear furnace are copious amounts of neutrons, which bombard light elements produced by fusion in the aging sun. Under the neutron assault, these atoms capture more and more of the neutrons and become heavier and heavier. When they stray too far from the realm of atomic stability, they decay by spitting out a particle or by converting a neutron into a proton. But the neutrons keep coming, and the nuclei get heavier still—far beyond what normal stars produce with fusion—in what astronomers call the s-process. “The s-process … accounts for roughly half of the heavy elements beyond iron,” says Hendrik Schatz, a nuclear astrophysicist at Michigan State University.

By knowing the properties of the elements involved in the s-process and analyzing elements sequestered in ancient meteorites, stellar winds, and other places, scientists have figured out that it occurs in the helium- burning phase of dying stars, says Michael Wiescher, a nuclear astrophysicist at the University of Notre Dame in Indiana: “You can use this information to pin down the site for the s-process.” Yet even this knowledge can't account for half the trans-iron elements.

Physicists believe that a different, more rapid form of transformation, known as the r-process, is needed to make the rest. The r-process requires a million billion times as many neutrons as a dying star can churn out, bombarding light atoms with an immense number of neutrons in a matter of seconds. Unlike the slow s-process, in which atoms accumulate neutrons at a leisurely pace over hundreds of thousands of years, the r-process so overwhelms atoms with neutron bombardment that they don't have a chance to decay before having to swallow one neutron after another. The atoms swell in size very rapidly, passing from unstable state to unstable state as they grow. After the bombardment ceases, the products decay into the stable and semistable elements (such as uranium) that dot our solar system.

That's the theory, but scientists are still uncertain what object or event triggers the r-process. The elements involved in the r-process are so neutron-laden that they are very unstable and short-lived, and scientists haven't been able to study them in the lab. “There's a lot of debate going on about where [the r- process] actually occurs,” says Wiescher. “You have to have a large neutron flux, a neutron-rich environment, and certain thermodynamic conditions of temperature, pressure, and entropy. Right now, there are two candidates.” One candidate is the violent collision of two neutron stars. But physicists think it is more likely that the r-process takes place in the fiery cataclysm of a supernova explosion: the product of either the superdense shock wave that ripples away from the supernova or the enormous “wind” of neutrinos that pushes matter away from the explosion.

Nuclear physicists hope RIA will fill in this knowledge gap. The accelerator will measure the basic properties of very unstable elements, including many of those involved in the r-process. “The r- process species are very far away from stability, but RIA has the intensity and selectivity to reach these,” says Schatz. “I think with RIA, we will have a pretty solid understanding of nuclear physics underlying the r-process.”

RIA is designed to create these elements in two ways. The first uses a beam of light atoms that strikes a big chunk of a heavy element such as uranium or thorium, shattering the nuclei in the target and creating unstable fragments. The target block is then heated to diffuse out the fragments, which are then sorted and measured. Unfortunately, this method, which is used by existing heavy-ion labs such as ISOLDE at CERN, the European particle physics laboratory near Geneva, and TRIUMF in Vancouver, Canada, can't analyze very short-lived species that decay before the extraction process is complete.

But RIA can use a second method—one pioneered by the National Superconducting Cyclotron Laboratory (NSCL) at Michigan State University—that shoots a beam of heavy elements at a thin target of light elements. The heavy nuclei fragment, fly through the target, and are immediately sorted into different species by their mass and charge. Because this method wastes no time with extraction from a thick target, scientists can measure very short-lived species quickly. Once they understand the properties of the elements involved in the r-process, nuclear physicists will be able to figure out what stellar conditions are needed for it to take place. “It has a chance of really solving the [r-process] problem,” says Donald Geesaman, the director of Argonne National Laboratory's physics division.

As an added benefit, RIA will be able to supply rare isotopes for other studies, including basic nuclear structure research, nuclear proliferation-related experiments, or even medical applications. “It'll open a whole new world,” says Geesaman. “Any isotope you want, you can have.”

But only if it's built, of course. DOE's Decker says that no decision on the project is imminent, assigning it a status that makes U.S. supporters uncomfortable. Last week, Germany's Science Council set priorities for major science projects, and a \$675 million heavy-ion laboratory is among the experiments that it deemed deserving of attention. This unnamed laboratory, which would be built at the GSI heavy-ion research center in Darmstadt, Germany, has a great deal of overlap with RIA, although Gelbke says it probably won't put the r-process problem to rest; its broader mission means that it wouldn't be able to study quite as many elements as RIA would.

“We're poised and ready to go,” he adds. “All we need is a decision.”

15. EVOLUTION

# A Trigger for the Cambrian Explosion?

1. Richard A. Kerr

Sediments in Oman provide evidence that an extinction 542 million years ago set the stage for a proliferation of wild and wonderful life forms

Before the Cambrian period began 542 million years ago, life was microscopic, vegetative, or just so odd that it now seems otherworldly. Then, in a geologic moment, an evolutionary explosion littered the fossil record with the recognizable remains of every basic form of animal that we know today. What caused this change is controversial. Some think of the lead-in to this explosion as a “slow fuse” of gradually accumulating genetic traits that finally produced large, complex animals; others believe a “trigger” of some sort set off the mechanism that suddenly produced Cambrian animals.

At last month's annual meeting of the Geological Society of America in Denver, Colorado, sedimentologist John Grotzinger of the Massachusetts Institute of Technology and his colleagues reported the latest evidence of a trigger for the Cambrian explosion: an extinction 542.0 million years ago, possibly brought on when the deep sea disgorged noxious waters. “We do have evidence for point-blank extinction,” says Grotzinger. But even in the data-sparse realm of early life, this one page from the fossil record of Oman isn't enough to prove that a near-knockout punch to primitive life set off the Cambrian explosion. Despite the rarity of sediment and fossils preserved from that time, more records must be found.

Forming the Oman record entailed some geologic happenstance; finding it required some lingering crude oil. Late in Precambrian times, what is now Oman on the far eastern tip of the Arabian Peninsula held a deep basin filled with water from the adjacent ocean, a sea much like the Mediterranean today. In the basin's shallower waters, great reefs formed as microorganisms helped precipitate millimeter-scale clots of carbonate, known as thrombolites. But the water level would sometimes fall enough to cut off the sea's shallow connection to the open ocean, the seawater would evaporate, and salt instead of carbonate would be deposited. Six pairs of salt and carbonate layers were laid down in Oman, and, to the Omanis' good fortune, oil eventually filled the spaces (blue in figure) between the carbonate clots.

Enter the age of fossil fuel. Drilling for oil has penetrated all six thrombolite layers. In a drill core provided by Petroleum Development Oman, Grotzinger found two of the late Precambrian's emblematic inhabitants —cone-shaped Cloudina and gobletlike Namacalathus—throughout the first three thrombolite layers. Apparently, these carbonate-shelled animals of uncertain affinities thrived attached to or lying on top of Oman's carbonate reefs. But in the next three reef deposits, Cloudina and Namacalathus were gone, even though the abundance of thrombolite would suggest that the living conditions were pretty much as they had been during earlier intervals. To Grotzinger, that's strong evidence that Cloudina and Namacalathus were gone from the world, not just missing from this little corner of it.

By the best measures of time in this distant era, the apparent extinction comes right at the jump from the Precambrian to the Cambrian. Grotzinger and his colleagues found that the carbon isotopic signature of the first thrombolite layer that lacks the Precambrian creatures is significantly lighter than the signatures of those below it. A similar isotopic shift marks the boundary between the Precambrian and the Cambrian elsewhere in the world. And radiometric dating of volcanic ash layers shows that the shift took less than a million years and occurred by 542.0 ± 0.5 million years ago, within the documented age range of the boundary's carbon isotopic shift elsewhere.

If Cloudina and Namacalathus were not alone in disappearing, the resulting extinction at the dawn of the Cambrian could have set off an evolutionary explosion, Grotzinger argues. Such an explosion might occur, he says, “if you cleared the playing field [through an extinction] and started over again.” Such a dramatic event could open up new possibilities for life in the same way the extinction of the dinosaurs opened the way for mammals. But rather than envisioning an asteroid impact, Grotzinger sees geochemical signs in the Oman cores—similar to those others have seen elsewhere—that oxygen-deficient, carbon dioxide-rich waters welled up into the shallow sea at the same time. That could have been enough to wipe out any marine species not adept at taking up oxygen or fending off the toxic carbon dioxide (Science, 1 December 1995, p. 1441).

No one, including Grotzinger, thinks the case for a global Precambrian-Cambrian extinction is closed. “It would be consistent with an extinction,” says paleontologist Sören Jensen of the University of California, Riverside, “but you wouldn't want to say it proves it.” First, the evidence so far involves only two species at a single place. Second, no extinction this abrupt has been proposed before, notes paleontologist Douglas Erwin of the National Museum of Natural History in Washington, D.C., but “the Omani data provides further support of there having been a biological crisis then. It's certainly an increasingly reasonable idea.” Major extinctions mark the other important turning points of evolution that have occurred since the Cambrian explosion, such as the end of the “old life” of the Paleozoic era 250 million years ago. Proving that a trigger set off the most fundamental evolutionary event since life's origin will take some more digging or perhaps drilling.

16. SCIENCE AND SECURITY

# Entering the Twilight Zone Of What Material to Censor

1. Martin Enserink

For scientists struggling to cope with “sensitive but unclassified” information, the National Academy of Sciences offers a provisional answer

You can't read it online. You can order a paper copy, but you won't receive what many say is the most interesting part—unless you have a good reason to see it. That's the status of a recent study on agricultural bioterrorism from the National Academy of Sciences (NAS), an entire chapter of which was excised and is now available only on a need-to-know basis (Science, 20 September, p. 1973). The academy doesn't particularly enjoy playing censor. But experts say its new role is a harbinger of what's to come for the scientific community.

The samizdat chapter falls under a rapidly growing category of information that the government wants to keep under wraps, even though, for one reason or another, it can't be classified. Scientific organizations are concerned about this “sensitive but unclassified” label, however, not only because it increases the administrative burden, but also because it crimps the free flow of scientific information. Its inherent murkiness can lead to arbitrary decisions and abuse, says Steven Aftergood, a secrecy expert at the Federation of American Scientists in Washington, D.C. “The classification system, with all its defects, at least has clear rules and procedures,” says Aftergood.

But the academy's approach to the agroterrorism report is being closely watched by those who suspect that other professional organizations might have to travel down the same path. Meanwhile, NAS says it would like clearer cues from the Bush Administration about how far to extend the veil of secrecy in the future. “We'd like the government to give us explicit guidance about what ‘sensitive but unclassified’ information is,” says chief executive William Colglazier.

Not writing a terrorist's cookbook was a priority for the members of the academy panel, says veterinary pathologist Harley Moon of Iowa State University in Ames, who chaired the group. Everything in the study was already out in the literature, says Moon, and as far as the group was concerned, the entire report could have been made public. The Office of Homeland Security reviewed the document but did not recommend classification, academy officials say.

Still, the U.S. Department of Agriculture, which paid for the report, strongly insisted that the academy withhold the entire thing. By way of compromise, NAS removed the third chapter, which contained a series of bioterrorism case studies, plus a few other bits and pieces, and placed them in an appendix. (In another unprecedented move, NAS also agreed not to post the study online.)

Academy officials then drew up guidelines as to who could see the appended material. The list encompasses federal, state, and local government workers, officials involved in homeland security, and animal and plant health scientists, but not members of the media or the general public. Anyone interested in the appendix has to file a written request, says Charlotte Kirk Baer of the academy's Board on Agriculture and Natural Resources. Academy staff members then call applicants, ascertain their identity, and ask why they need the report, she says.

So far, about 50 people have requested the document, most of them security officials from government agencies such as the Pentagon and the CIA. None has been denied a copy, says Kirk Baer—although one person has not yet responded to the academy's request for more information.

Legally, NAS is walking a fine line when it withholds documents from the public domain, says Howard Crystal, an attorney at Meyer and Glitzenstein in Washington, D.C. Under the Federal Advisory Committee Act, the academy must cite one of seven exemptions listed in the Freedom of Information Act when rejecting public requests for documents. Classified materials form one often-used exemption, but the censored chapter falls under a different one, explains Colglazier, which protects matters “related solely to the internal personnel rules and practices of an agency.” The provision protects the government from having to store and release trivial information, like employee parking rules, but it is also used to keep a variety of information—from law enforcement manuals to habitat maps of protected bird species—out of the hands of those who might use it to break the law.

Moon says he has “respect for the process” that vetted his report and has accepted the restrictions, although he was hoping for a different outcome. But the growth of the “sensitive but unclassified” category is worrisome to the academy. In an 18 October statement about science and security, NAS's three presidents urged the government to affirm the general principle that there should be no restrictions on reporting nonclassified research and to help “avoid creation of vague and poorly defined categories” of information.

Others say they are flatly opposed to the new category. “My bias is that information should be either classified or not classified,” says Steven Teitelbaum, president of the Federation of American Societies for Experimental Biology. A neither-fish-nor-fowl category will create “administrative nightmares” for research organizations, says Teitelbaum, and make it difficult to repeat and verify any new scientific results. That would ultimately be “bad for the country,” he says.

In a statement to the House Science Committee last month, presidential science adviser John Marburger said the Office of Homeland Security's designation of the new information category is still “in the formative stage” and is being shaped in “listening sessions” with many parties, including scientific societies. Marburger acknowledged, however, that open access to research findings is “critical to continued scientific advancement.”

Aftergood says he hopes the issue will soon be clarified. A somewhat vague class of restricted information—and an ad hoc system to guard it—might be “acceptable in the short run, while we try to develop more standardized procedures,” he says. “But it's not acceptable in the long run.”

17. RESEARCH ETHICS

# Planned Misconduct Surveys Meet Stiff Resistance

1. Constance Holden*
1. With reporting by Rebecca Spieler Trager of The Blue Sheet in Chevy Chase, Maryland.

Biomedical societies are criticizing a proposed poll for asking broad questions; an earlier survey was shot down by the White House

The government's Office of Research Integrity (ORI) has built its reputation on high-profile investigations into alleged fraud, attracting both praise and ridicule. Now the 10-year-old arm of the Department of Health and Human Services (HHS) is trying to blaze a trail in understanding, and then preventing, scientific misconduct. But its new direction seems equally controversial: One proposed survey has already been shot down by the White House, and another is under fire from two prominent biomedical research groups.

Last week the Federation of American Societies for Experimental Biology (FASEB) and the Association of American Medical Colleges (AAMC) sent a strongly worded letter to HHS attacking a proposed survey for straying beyond the bounds of misconduct. “This is a terrible instrument,” says FASEB president Stephen Teitelbaum of Washington University in St. Louis, Missouri, who considers the proposed ORI survey too broad. “The questions are in many ways outrageous [and would produce] uninterpretable and invalid data.”

ORI director Chris Pascal defends the proposed survey. It's important to cast a wide net to gain “empirical scientific evidence” on the problems that can undermine research integrity, he says. Speaking last weekend at an ORI conference on research conduct, Pascal suggested that the FASEB/AAMC letter “reinforces … the importance of reviewing these issues.”

The two societies are so far the only ones to react in writing to a notice in the 7 October issue of the Federal Register announcing ORI's plans to use a 13-page questionnaire designed by the Gallup organization. It would be sent out early next year to 3000 principal investigators. At its heart is a list of 19 practices: Respondents are supposed to characterize them as misconduct or not and to say whether they or their colleagues have done them. The letter charges that some of the questions are “ambiguous,” are “subjective,” or “do not in any way fall under the federal definition [of misconduct].” The organizations are particularly incensed by a question asking whether the respondent has ever had any direct evidence of a colleague “citing an article they had not read firsthand.”

Noting that federal agencies took years to agree on a terse definition of misconduct—“fabrication, falsification, or plagiarism”—FASEB and AAMC argue that pollsters should use it. “Have they made up another definition?” demands Teitelbaum. He thinks ORI should not be investigating “issues such as authorship and citation practices, which are the purview of research institutions and not the federal government.”

David Korn, AAMC's vice president for biomedical and health sciences, points out that his organization has been cooperating with ORI in encouraging professional societies to pay more attention to research ethics. “The problem is that ORI wants to involve itself in a broader way in what I call the morals of scientific behavior,” including authorship, materials sharing, and relationships between investigators and their students. For example, Korn objects to a question about whether respondents have seen anyone “inadequately supervising research subordinates or exploiting them.” He says, “These are all important issues, but we do not believe this should be regulated by the government.” Although ORI has not said how it plans to use the survey, Korn worries that it might “somehow define a code … involving all conceivable aspects of scientific behavior.”

Pascal acknowledges that FASEB and AAMC “have got a small point about the fact that this was labeled research misconduct [when] it's clearly more” than that. He promises to “fix the ambiguities” in the questionnaire. But otherwise ORI intends to hold its ground. “FASEB wants us to limit questions to the federal definition of misconduct,” Pascal says, “but we feel strongly that other issues are important as well.” He says that ORI's stance is backed up by a report from the Institute of Medicine this year that “made a big pitch that additional research is needed into research integrity issues.”

Science historian Nicholas Steneck of the University of Michigan, Ann Arbor, who has been working part-time at ORI, thinks scientific societies are in no position to criticize ORI for its attempts to develop guidance on research integrity. “I don't see any effort on FASEB's part,” he says, although he admits AAMC has been “supportive.” Steneck argues that ORI's responsibility goes far beyond the “narrow [list] of behaviors that fall under the [Office of Science and Technology Policy] definition of research misconduct.” Teitelbaum responds that “grant-holding institutions are responsible for policing scientific misconduct. … This is not, nor should it be, a mission of scientific societies.”

ORI has already had to curtail its plans to have a contractor interview people found guilty of research misconduct in hopes of learning more about the circumstances of their erring ways. Mark Davis, now at Kent State University in Ohio, and Michelle Riske of the firm Justice, Research & Advocacy in Amherst, Ohio, were funded in 1999 to do a two-part research project. They completed the first part, which involved examining the case files of 104 people found guilty of research misconduct. But the White House Office of Management and Budget (OMB) drew the line at a poll, saying that it did not include “a representative sample” and that the design was “inadequate.” According to Davis, OMB advised that it would be better to interview officials at the institutions involved.

Davis says he was “incredulous” at OMB's intervention. With a team of Kent State researchers, he has now applied for a grant from ORI and the National Institutes of Health to complete the interviews. OMB does not have the same jurisdiction over grants, he says, meaning that it cannot block such an award.