# News this Week

Science  01 Oct 2004:
Vol. 306, Issue 5693, pp. 26
1. EPIDEMIOLOGY

1. Jennifer Couzin

A panel of outside experts chosen by the Department of Veterans Affairs (VA) has concluded that there is a “probable link” between neurotoxins such as sarin gas and the mysterious ailments that struck veterans of the 1990–91 Gulf War. This conclusion—in a draft report obtained by Science and scheduled for release later this month—is at odds with other analyses of Gulf War illness, including an August report from the Institute of Medicine (IOM). The VA study also recommends that the VA invest at least $60 million over the next 4 years for additional Gulf War illness research. VA officials declined to comment prior to the report's release on how they might respond. The VA panel, chaired by former Defense Department official and Vietnam veteran James Binns, was formed in 2002, more than 3 years after Congress passed a law mandating both a new research panel to advise the VA secretary and an expansive IOM review of Gulf War research and treatments. The VA has been under pressure from veterans to de-emphasize the view that stress and trauma were chief drivers of Gulf War illness. “It's clear that something different happened to 1991 Gulf War veterans,” says veteran Stephen Robinson, executive director of the National Gulf War Resource Center in Silver Spring, Maryland, and a member of the VA panel. The authors of the new report argue that neurotoxins are the likeliest explanation for the fatigue, muscle and joint pain, memory loss, and dizziness that has plagued tens of thousands of Gulf War veterans. On the 11-member panel are several veterans and six physician-scientists, including a well-known advocate for this controversial theory: Epidemiologist Robert Haley of the University of Texas Southwestern Medical Center in Dallas. Haley says he was added to the panel after VA Secretary Anthony Principi learned of his views and spent a half-day with him in Texas discussing his work in May of 2001. But many scientists who study Gulf War cases are unconvinced that low levels of sarin gas, pesticides, or the pyridostigmine bromide pills that troops took to protect them from nerve gas can explain Gulf War illness. For one, they say, it's difficult to determine which troops were exposed to what. Furthermore, many animal and human studies have failed to show that low doses of neurotoxins can cause the kind of problems Gulf War veterans experience (Science, 2 February 2001, p. 812). “I don't know of any serious expert review that has come to these conclusions,” says Simon Wessely, director of the King's Centre for Military Health Research in London. Wessely, like many researchers in the field, believes that Gulf War illness arose from a combination of the stress of war, the use of experimental vaccines, and possibly exposures to environmental hazards such as oil-well fires. Because Gulf War ailments are spread evenly across different branches of the military, including both the Navy and the Army, Wessely says, the culprits ought to be factors that nearly all troops confronted. Some experts on Gulf War illness who asked to remain unnamed worry that tying Gulf War illness to neurotoxins overlooks a large number of studies that question the link. For example, a VA-funded study by Larry Davis of the New Mexico VA Health Care System and his colleagues surveyed 1000 Gulf War veterans and 1100 veterans not deployed to the Persian Gulf. The researchers found no evidence of damage to peripheral nerves that distinguished Gulf War veterans from the others. Haley says the panel considered alternative viewpoints before arriving at its conclusion. Neurobiologist and physician Beatrice Golomb, a panel member from the University of California, San Diego, adds: “There was surprising agreement among the people who put this report together.” But the panel appears to be largely on its own. In August, an IOM report reviewing literature on sarin gas and Gulf War illness concluded that there was “inadequate/insufficient evidence” to link low-dose exposure with persistent neurological symptoms. Still, Lynn Goldman, an epidemiologist at Johns Hopkins University and chair of yet another IOM panel on Gulf War illness, says that it may be too early to rule out any specific cause of this mysterious malady. 2. FUSION SCIENCE # Europe May Break Out of ITER Partnership 1. Daniel Clery CAMBRIDGE, U.K.—Europe is ready to scrap the planned collaboration on what is supposed to be a global fusion reactor. That's the message from a meeting last week of research ministers from the 25 European Union (E.U.) countries, who set a late-November deadline for deciding whether to press ahead with a French site for the$5 billion International Thermonuclear Experimental Reactor (ITER).

Last month, outgoing E.U. research commissioner Philippe Busquin expressed regret for not having “closed the file” on ITER, whose partners—the E.U., China, Japan, Russia, South Korea, and the United States—have been split for nearly a year over whether to locate the reactor in France or Japan. But in a parting shot, Busquin drafted a letter saying that several ITER partners have a “very strong preference” for the site of Cadarache in southern France and “would support an initiative from the Union to unblock the situation.” Last week the ministers appear to have followed his advice, calling on the European Commission to make every effort to negotiate an agreement to build at Cadarache involving “as many partners as possible” and to report back at the council's next meeting on 25–26 November.

The council also ordered the commission to figure out how to fund the project without taking any extra money from E.U. coffers. After the council meeting, French research minister François d'Aubert told reporters that France would double its ITER funding to $1.12 billion, accounting for roughly 20% of the costs. With the E.U. having pledged 40% and Russia and China likely to stake 10% each, that leaves 20% to make up through cost savings or by enlisting new members such as Canada, India, and Switzerland. The United States and South Korea have voiced support for building ITER at a site in northern Japan. And the E.U.'s solo approach carries increased risk that the success of the project could be compromised. “It would be a tragedy if this leads to an ITER without the United States and Japan,” says one European fusion scientist. Worse still, however, would be the possibility of two rival ITERs, one in France and one in Japan—or none at all. 3. CONFLICT OF INTEREST # NIH Proposes Temporary Ban on Paid Consulting 1. Jocelyn Kaiser Hoping to allay ongoing controversy about industry consulting by its staff, National Institutes of Health (NIH) officials plan to impose a 1-year ban on all outside paid activities for industry. NIH deputy director Raynard Kington, who announced the proposed moratorium last week, says it will allow NIH to sort out possible ethics lapses and devise a rigorous oversight system. But others worry that the move will further strain valuable ties with companies and make it tougher for NIH to keep top scientists. The proposed ban comes after months of congressional scrutiny of NIH policies, sparked by a Los Angeles Times story last December that reported that some high-ranking NIH scientists had received hundreds of thousands of dollars in payments from industry that posed at least the appearance of a conflict of interest. In June, the House Oversight and Investigations subcommittee announced that some 100 consulting activities reported by drug companies did not show up in NIH's own records (Science, 2 July, p. 25). After finding that some of these deals “probably were not appropriately reviewed,” NIH has decided it needs a 1-year pause to complete its overall review and make sure new procedures and training are in place, Kington said last week. His memo acknowledges that NIH has found “vulnerabilities in our system.” Kington says NIH will then determine whether to make the ban permanent or allow consulting on “a limited basis.” “Clearly, we believe there's value in some of these relationships,” Kington says. NIH already plans, however, to permanently ban industry consulting by senior staff members and those who oversee grants. The moratorium is not a huge shock, say some NIH scientists, because previously approved outside activities were suspended in February for another review. Those consulting arrangements that were reapproved and new ones can continue until the ban takes effect, which probably won't be for a couple of months because NIH first has to propose a new regulation. (NIH says there are 66 active arrangements.) After that, scientists can still advise industry—if they do it for free as part of their job. Some scientists say the temporary ban will bring welcome clarity, because the rules are confusing now. And scientific exchanges with industry will not end: “Science will move forward,” says Robert Desimone, intramural research director for the National Institute of Mental Health, who leaves this month to head the Massachusetts Institute of Technology's McGovern Institute. But others say the pause—which might end up being closer to 2 years—could be harmful. “You're going to end up losing people from the intramural program,” predicts Harold Varmus, president of Memorial Sloan-Kettering Cancer Center in New York City, who as NIH director loosened the rules on consulting in 1995. Several researchers at NIH who consult declined to comment for attribution but suggested that companies may drop their NIH advisers for specific projects and suspend the work while looking elsewhere for advice. This could both jeopardize ongoing research and damage NIH scientists' relationships with the companies, some say. National Academy of Sciences president Bruce Alberts, who co-chaired a high-level panel earlier this year that advised NIH to continue to permit some industry consulting, says the moratorium is appropriate. However, he warns against a permanent ban, noting that his panel concluded that certain interactions couldn't take place. For example, government employees on official duty are forbidden from signing a confidentiality agreement; companies prefer such agreements so that they can protect shared information. “I think it would be a mistake if this [the ban] were the long-term policy,” Alberts says. 4. # Parkfield Happens 1. Richard A. Kerr A scientific event nearly 20 years overdue occurred 28 September near the central California town of Parkfield (population 37) when a magnitude 6.0 earthquake struck. “It was much anticipated but long delayed,” says seismologist Ross Stein of the U.S. Geological Survey (USGS) in Menlo Park, California. Attracted by Parkfield's history of quakes every 20 or 30 years, seismologists installed millions of dollars of instruments starting in the 1980s—and then waited. “This is the most well-recorded earthquake in history,” says USGS's Michael Blanpied. 5. PLANETARY SCIENCE # Heavy Breathing on Mars? 1. Richard A. Kerr Planetary scientists probing the martian atmosphere through the Mars Express orbiter report that both methane and water tend to be concentrated over the same three equatorial regions of Mars, regions covered by water-enriched soils. The new find further stokes talk of life on Mars, which flared up last March (Science, 26 March, p. 1953) when the same researchers first spotted methane on Mars. The gas could be coming from life buried beneath the inhospitable surface. But the association with water raises a new possibility: that researchers are finally seeing wisps of the icy subterranean vault where much of the planet's long-lost water may be stored. At last week's International Mars Conference in Ischia, Italy, Vittorio Formisano of the Institute of Physics of Interplanetary Space in Rome—the principal investigator on the Planetary Fourier Spectrometer (PFS) instrument on the European Mars Express—refined the picture of methane on Mars. Last spring, he and PFS team members announced the first detection of martian methane at a concentration of about 10 parts per billion. This time, Formisano could say that the methane is concentrated over the same three equatorial regions—Arabia Terra, Elysium Planum, and Arcadia-Memnonia—where water vapor is concentrated by a factor of 2 to 3 in the lower atmosphere. And those are also three regions, Formisano says, where the U.S. Mars Odyssey orbiter has detected signs of water in the upper meter of martian soil, in the form of ice or hydrated minerals. The coincidence of atmospheric water, methane, and soil water “points to a common source underground,” says Formisano. “Then one can speculate as to what that source is.” The methane naturally calls to mind methane-generating bacteria that could live beneath a few kilometers of frozen crust. The accompanying water—a key prerequisite for life—supports that picture. On the other hand, an erupting volcano, a simmering hot spring, or even abiotic reactions between rock and cold ground water could produce methane and water vapor, too. But some researchers say another source may be more likely still: an exotic mix of methane trapped molecule by molecule in crystalline cages of water ice. Long known on Earth from beneath the deep seabed and within permafrost (Science, 13 February, p. 946), such hydrates could form anywhere between 15 meters and as much as several thousand meters beneath the martian surface, according to calculations published in 2000 by Michael Max of Marine Desalination Systems in Washington, D.C., and Stephen Clifford of the Lunar and Planetary Institute in Houston, Texas. On Earth, hydrate methane usually comes from bacteria decomposing organic matter; on Mars, either life or chemical water-rock reactions could be responsible. Either way, Clifford notes, the martian methane could have been generated and trapped eons ago, as the planet cooled and freezing temperatures crept down through a waterlogged crust. Planetary geologists have seen abundant signs that water shaped the surface of early Mars (Science, 6 August, p. 770), and most assume that at least some of that water sank beneath the surface and still resides there. But they've never detected any. Now, they could be seeing it leak out as the methane hydrate slowly decomposes. The methane-water coincidence “is a real neat observation,” says Clifford, even if “it doesn't uniquely point to life.” It does have some hurdles to clear yet, however. The details of the original PFS methane detection have yet to be published, leaving open the possibility that a small part of water vapor's spectral signature has been mistaken for a spectral line of methane. And planetary scientists find it curious that any regional concentration can be recognized at all, because martian weather mixes methane around the planet in a matter of months. Things may get clearer in the next couple of months as PFS data, as well as telescopic observations, come out. 6. U.S. SCIENCE BUDGET # NSF, NASA Meet 2005 Request After 'Bonus' From Senate Panel 1. Andrew Lawler, 2. Jeffrey Mervis A Senate spending panel has done some creative accounting to meet the president's request for NASA and the National Science Foundation (NSF) in a tight budget year. But the strategy comes at a price that many scientists may find objectionable, and there is no guarantee that the subterfuge will even hold up when Congress returns after the November elections to complete its work on the overdue 2005 budget. A bitterly partisan presidential campaign, a massive deficit, and the ongoing war in Iraq have made it harder for legislators to cut the deals normally required to pass the 13-piece federal budget, and the slice that includes NSF and NASA is one of the most contentious. Last week the Senate Appropriations Committee tiptoed through that minefield by declaring$2 billion in the $93 billion bill to be emergency funding and, therefore, exempt from a self-imposed spending cap. Some$800 million of that largesse went to NASA—for getting the shuttle ready to fly again and preparing a mission to rescue the failing Hubble Space Telescope. That raised NASA's budget to $16.4 billion, some$200 million more than the president's request and $1.2 billion above the level approved earlier by its counterpart panel in the House of Representatives. The emergency label also allowed legislators to meet the president's NSF request for$5.74 billion. That represents a 3% boost over current spending instead of a 2% cut, to $5.47 billion, adopted by the House panel. In another bit of good news, a separate Senate committee last week approved the nomination of acting director Arden Bement, raising hopes that he will be confirmed before the Senate recesses later this month. The larger Senate figure for NSF includes some unpleasant surprises, however. The most unsettling is the panel's rejection of three new starts in NSF's major facilities account. The panel “saved” a total of$82 million by blocking funding to begin construction of a high-energy physics project called RSVP, a refurbished ocean drilling vessel, and a network of ecological observatories. The House has funded the first two. At the same time, the Senate panel reminded NSF of its promise to request $50 million next year for an Alaska-based research vessel, a home-state project favored by panel chair Ted Stevens (R-AK). The legislators also cautioned NSF to follow a recent report from the National Academies on how it decides which big new projects to fund (Science, 16 January, p. 299). Congress ordered that report after scientists complained about a growing backlog of projects—a situation that, ironically, would recur if the panel's “no new starts” dictum prevails. NASA gets a$200 million increase over the president's request—but much of it is eaten up by congressional earmarks, projects not backed by the agency. The committee warned the agency not to forget science in its push to return humans to the moon and called for a National Academy of Sciences panel to examine the role of science in the new exploration effort. This action came the same week that a new study by the National Academies warned NASA not to sacrifice solar physics for its new exploration initiative.

7. SCIENTIFIC PUBLISHING

# Suit Seeks to Ease Trade Embargo Rules

1. Yudhijit Bhattacharjee

Journals should be free to edit and publish articles by scientists and other authors living in countries under U.S. trade embargoes, says a suit filed this week by a coalition of publishers and authors. Current regulations require U.S. publishers and authors to seek a government license before working with authors in Iran, Cuba, and Sudan; these rules violate trade laws and the freedom of speech, according to the suit, filed 27 September in U.S. federal court in New York City.

The issue has been simmering since October 2003, when the Treasury Department's Office of Foreign Assets Control (OFAC) ruled that U.S. journals needed prior government approval to publish work from embargoed countries (Science, 10 October 2003, p. 210). After a heated discussion with publishers, OFAC reversed that ruling 6 months ago but asserted that activities leading to “the substantive or artistic alteration or enhancement” of materials from the embargoed countries were still prohibited without a license. In a 2 April letter to the Institute of Electrical and Electronics Engineers, OFAC Director Richard Newcomb explained that the agency was enforcing the Trading with the Enemy Act and the International Emergency Economic Powers Act.

But OFAC's regulations are illegal, say the Association of American Publishers, Association of American University Presses (AAUP), PEN American Center, and Arcade Publishing. The plaintiffs argue that OFAC has violated 1988 and 1994 revisions to these laws that exempt “information and informational materials” from trade embargoes. OFAC maintains that the 1988 and 1994 revisions do not apply to informational materials “that are not fully created and in existence.”

The restrictive regulations “should be stricken from the books because they violate the very statutes that OFAC is purporting to enforce,” says Peter Givler, executive director of AAUP. OFAC's rulings have already had “a chilling effect” on the publishing climate, says Givler, citing a recent decision by the University of Alabama Press to suspend plans for publishing archaeology and history books by Cuban scholars.

Publishers were compelled to take the legal route because of OFAC's “double-talk,” says Mark Brodsky of the American Institute of Physics. “Sometimes they say editing that involves changing syntax will require a license; when pressure is put on them, they say it's not necessary. Publishing should not be subject to the whims of the bureaucracy.”

OFAC spokesperson Molly Millerwise says the agency has no comment on the suit, which asks the government to remove the publishing restrictions.

8. GENETICS

# DNA Reveals Diatom's Complexity

1. Elizabeth Pennisi

Diatoms are an enigma. Neither plant nor animal, they share biochemical features of both. Though simple single-celled algae, they are covered with elegant casings sculpted from silica.

Now a team of 45 biologists has taken a big step toward resolving the paradoxical nature of these odd microbes. They have sequenced the genome of Thalassiosira pseudonana, which lives in salt water and is a lab favorite among diatom experts. The work should prove useful to ecologists, geologists, and even biomedical researchers, says Edward Theriot, a diatom systematist at the University of Texas, Austin: “We've just jumped a generation ahead by having this kind of understanding of this genome.”

Diatoms date back 180 million years, and remnants of their silica shells make up porous rock called diatomite that is used in industrial filters. Today diatoms occupy vast swaths of ocean and fresh water, where they play a key role in the global carbon cycle. Diatom photosynthesis yields 19 billion tons of organic carbon, about 40% of the marine carbon produced each year; thus, by processing carbon dioxide into solid matter, they represent a key defense against global warming.

Many marine organisms feast on diatoms. When conditions are ripe, the algae can multiply at astonishing rates, creating ocean “blooms” that are sometimes toxic. These blooms can suffocate nearby marine life or make a toxin that harms people who eat infected shellfish. “This is a group of organisms that has amazing importance in global ecology,” says Deborah Robertson, an algal physiologist at Clark University in Worcester, Massachusetts.

Since 2002, Daniel Rokhsar, a genomicist at the DOE Joint Genome Institute in Walnut Creek, California, and his colleagues have been unraveling the genome of T. pseudonana. They were aided by a technique called optical mapping, in which stretched-out chromosomes are nicked by enzymes and viewed through a light microscope. Those nicked pieces of DNA stay in order and enable the sequencers to assemble almost all the bases in the correct place on the right chromosomes.

The draft genome consists of 34 million bases, Rokhsar, E. Virginia Armbrust, an oceanographer at the University of Washington, Seattle, and their colleagues report on page 79 of this issue. They ultimately found about 11,500 genes along the diatom's chromosomes and along the DNA in its chloroplast and mitochondria.

Analyses of these genes and the proteins they encode confirm that diatoms have had a complex history. Like other early microbes, they apparently acquired new genes by engulfing microbial neighbors. Perhaps the most significant acquisition was an algal cell that provided the diatom with photosynthetic machinery.

Some biologists hypothesize that diatoms branched off from an ancestral nucleated microbe from which plants and animals later arose, a theory supported by the identification of T. pseudonana genes in some plant and animal genomes. As diatoms, plants, and animals evolved, each must have shed different genes from this common ancestor. As a result, diatoms were left with what looks like a mix of plant and animal DNA, plus other genes that are remnants of the engulfed algae.

The new data support this complex scenario, says Robertson. Some 182 T. pseudonana proteins are related only to red algae proteins; another 865 proteins are found just among plants. About half the proteins encoded by the rest of the diatom's genes are equally similar to counterparts in plants, animals, and red algae.

The newly analyzed genome has also begun to shed light on how a diatom constructs its intricately patterned glass shell. So far, Rokhsar and his colleagues have uncovered a dozen proteins involved in the deposition of the silicon and expect to find more. Such progress could be a boon to materials scientists. “Being able to understand [silica processing] should have a payoff in nanofabrication,” says Robertson.

Currently, a mere 100 or so researchers call themselves diatom specialists. With the genome in hand, interest in diatoms is going to expand, Theriot predicts: “It will help put diatoms on everyone's radar.”

9. NONPROFIT WORLD

# Santa Fe Institute Seeks President

1. Jeffrey Mervis

SANTA FE, NEW MEXICO—Barely 15 months into a 5-year term, Robert Eisenstein has stepped down as president of the Santa Fe Institute (SFI) here. His sudden departure last month has reopened debate about how to run the $7 million institute, which has done pioneering work on chaos theory and complex systems. “The chemistry didn't work,” says Robert Denison, a financier and chair of the institute's board of trustees. “It just wasn't a good fit.” Denison says that the twin issues of attracting scientific talent and funding were key factors in the board's decision. “I look forward very much to a return to life as a full-time research scientist and educator,” says Eisenstein, a physicist and former senior manager at the National Science Foundation who is remaining at SFI as a resident faculty member. Founded in 1984 by physicists George Cowan, Murray Gell-Mann, and others, SFI bills itself as a “unique environment for visiting and resident scientists.” The culture is shaped by a constantly changing cast of characters, the result of a strict no-tenure rule: Resident faculty members receive a 3-year appointment, renewable once, while hundreds of other scientists come for periods ranging from one day to several years. This spring, as three of SFI's core faculty members approached the end of their second terms, two accepted tenured academic jobs: Walter Fontana at Harvard Medical School's systems biology program, and James Crutchfield at a new Center for Computational Science at the University of California, Davis. The third, J. Doyne Farmer, had his contract extended this summer by a special action of the board of trustees. The personnel moves created anxiety about the next generation of SFI scientists and whether they would enhance the search for answers to the hard interdisciplinary problems that have attracted people to SFI. “This place runs on people and their ideas,” says resident faculty member Ellen Goldberg, an immunologist who stepped down at the end of 2002 after 6 years as president. “As president you try to bring in people familiar with how universities operate but frustrated by their inability to pursue their ideas within traditional academic boundaries.” “Bob took a lot of heat for what happened, even though it was board policy, and [the departing faculty] landed great jobs,” says Denison. “I might have acted sooner [to replace them], but Bob felt that he needed to know where we were headed before he could recruit and raise money.” Eisenstein's oft-expressed desire to apply SFI's science to societal problems and to inject more science into the local schools, Denison adds, bumped up against faculty members who saw those efforts as a possible distraction from SFI's primary mission to do fundamental research. Eisenstein plans to work on global sustainability, problems linked to scaling phenomena, and science education. Denison says that he hopes to name an interim president shortly and that SFI has begun an international search for someone who combines scientific achievement with fundraising and organizational skills. 10. CANCER RESEARCH # Pioneering Prevention Institute Declares Bankruptcy 1. Jocelyn Kaiser, 2. David Malakoff A small but influential U.S. research institute known for exploring links between lifestyle and cancer has closed its doors after 35 years. The Institute for Cancer Prevention (IFCP), the only center funded by the National Cancer Institute (NCI) that focused solely on prevention, declared bankruptcy last week and has laid off its roughly 100 employees. Researchers at the Valhalla, New York-based institute are devastated, and outsiders are lamenting the demise of a group that helped launch the field of cancer prevention—the idea that proper diet and behavior can ward off cancer. “I feel so angry, so unhappy. … Scientists here really put this place on the map,” says Karam El-Bayoumy, IFCP's director of research. Meanwhile, some employees want an investigation into what led to the institute's downfall. Originally called the American Health Foundation, the institute was founded in 1969 by physician Ernst L. Wynder, who 19 years earlier had published a landmark study linking smoking and lung cancer. The foundation's scientists and clinicians built an international reputation for research into everything from tobacco carcinogenesis to the protective effects of green tea. “It really was the flag bearer” for cancer prevention, says oncologist Steven Clinton of Ohio State University in Columbus. By the time Wynder died in 1999, however, the institute was in financial trouble. To rejuvenate the group, the board hired Donald W. Nixon of the Medical University of South Carolina, who changed its name and expanded clinical research. But its problems grew worse: In January, Nixon informed the board that IFCP had overdrawn funds provided by approximately 15 NCI grants to meet its$18-million-a-year budget. NCI subsequently calculated that IFCP owed it $5.7 million. “We were caught totally by surprise,” says Michael Epstein, chair of IFCP's board and an attorney with Weil, Gotshal & Manges in New York City. IFCP explored a number of possible solutions, Epstein says, including selling the lease on its building or merging with another group willing to take on the debt. But on 21 September, after NCI refused to advance the institute any more money and a biotech company rejected a last-ditch merger offer, IFCP filed for Chapter 11 bankruptcy. A federal judge has since appointed a trustee to liquidate its assets. Some employees accuse Nixon of mismanagement and question the cost of the institute's Manhattan office. They have asked New York officials to probe several of IFCP's actions, including its alleged failure to make some employee retirement payments over the past year. Nixon could not be reached. In the meantime, NCI has offered to help researchers move their grants and laboratories to other institutions; at least five of the 15 or so principal investigators are moving 315 kilometers to Pennsylvania State University's medical campus in Hershey. “Hopefully, science will continue to be served,” says Epstein, “albeit at other institutions.” 11. DIABETES # Islet Transplants Face Test of Time 1. Jennifer Couzin Will the Edmonton protocol, hailed as a major step toward a cure for type I diabetes, hold up in the long run? Ellen Berty was driving home from her special-education job when the call came, on the cell phone she'd bought expressly for this purpose. The caller spoke the magical words every person needing a transplant dreams of hearing: “We have a match.” In her Mazda convertible, Berty let out a yell of triumph. “I'd won the contest of my life,” she recalls thinking on that sunny June day 3 years ago. Ten hours later, Berty lay sedated in a radiology suite at the National Institutes of Health (NIH) in Bethesda, Maryland, while doctors delicately injected a yellowish green solution into a vein feeding into her liver. The mix held hundreds of thousands of islets, cells from the pancreas of a man who'd died suddenly. These cells were supposed to supply Berty with the critical hormone insulin she'd lacked for 40 years, ever since being diagnosed with type I diabetes at the age of 13. Berty's islet-cell transplant is part of a vast global experiment, a test of a therapy that's been hailed as the greatest hope for curing type I diabetes. Five years after physicians in Edmonton began transplanting islets under a new and widely celebrated protocol, the long-term results of this strategy are beginning to emerge. They paint a nuanced and still unfinished picture of a treatment that some doctors concede is riskier than they expected and less effective than they had hoped. The NIH trial in which Berty enrolled reflects the promise and peril of these transplants. Berty has been one of the lucky ones. She stayed off insulin injections for 2 years after her transplant. Today, she's back on a low dose, but she has relatively few side effects from the immunosuppressive drugs she takes to prevent islet rejection. Like most islet recipients, Berty also has none of the diabetes complications she suffered before. Still, Berty was NIH's last islet-transplant patient. After treating her and five others, NIH stopped accepting new volunteers, its physicians increasingly anxious that antirejection drugs, which must be taken for life, were spawning problems worse than those the transplanted islets were solving. Other centers disagreed. They continued testing the procedure, and today more than 300 patients have received islets under the protocol crafted by the Edmonton team. NIH, the Juvenile Diabetes Research Foundation (JDRF), other nonprofit organizations, and several European governments have poured hundreds of millions of dollars into coaxing these transplants to work. But as islet transplants expand and less experienced centers launch islet programs, it's become less clear what “work” really means. The original goal of islet transplants has been met: Lifelong diabetics receiving new islets have been able to abandon, at least for a time, insulin shots. According to an NIH survey published last month, 22 of 38 islet recipients were still off insulin a year after their transplant. Those numbers sag with time, though, and it's not known how long transplanted islets can thrive, or what's killing them when they fail. A more pressing question is whether insulin independence is enough. A sizable minority of islet recipients struggle with new health problems, from painful mouth ulcers to anemia to kidney disease, largely attributed to the combination of antirejection drugs prescribed by the Edmonton protocol. And no one knows whether patients given islets actually live longer than they would have without them. A controversial study from some of the NIH scientists who treated Berty hints that the risk of a shortened life span might be real. Physicians are launching clinical trials to improve the safety and effectiveness of islet transplants, but they're far from offering this experimental therapy to all but the most severely affected diabetes patients. For one, there aren't enough cadaver pancreases to go around. Although many are looking at stem cells as a renewable source of islets, that's still a distant prospect. Aldo Rossini, director of the diabetes division at the University of Massachusetts Medical School in Worcester, compares the current state of islet transplants to the Wright brothers' first flight. “They flew a couple hundred feet”—a remarkable accomplishment at the time, he notes. Still, says Rossini, “no one could have expected us to fly to California in that plane.” ## Measures of success Since 1972, when Paul Lacy, a researcher at Washington University in St. Louis, cured diabetic rats by giving them healthy islets, transplanters have sought to extend that success to humans. The approach seemed obvious: In type I diabetes, the body's immune system mistakenly attacks insulin-producing islet cells in the pancreas, and by the time the symptoms of diabetes surface, most of these islet cells are gone. But in more than 400 human islet transplants beginning in the 1970s, doctors couldn't get transplanted cells to stick. Many suspected that, ironically, the steroid drugs given to prevent islet rejection were also toxic to islet cells. Then in the summer of 2000, the dreary world of islet transplants changed forever. A team at the University of Alberta in Edmonton, Canada, reported in The New England Journal of Medicine that they'd given islets to seven diabetes patients under a new regimen, and after roughly a year, all seven were still off insulin. Unlike earlier islet transplants, the Edmonton protocol didn't involve steroids. Led by James Shapiro, the Edmonton team combined three antirejection drugs, one of which, sirolimus, had recently begun human testing. It also gave patients islet cells from multiple pancreases. The group's report instantly became medical legend. “Here,” says David Nathan, director of the diabetes center at Massachusetts General Hospital in Boston, “was this absolute miracle.” Research funders quickly responded to Edmonton's success. JDRF, one of the country's wealthiest and most powerful disease advocacy groups, declared islet transplants a top priority, and since 2000 it has poured$225 million into the field. Hospitals in the United States and Europe raced to set up islet-transplant centers, and patients flocked to them in droves. Emory University's 18-month-old islet-transplant program has fielded 5500 inquiries from patients, says surgeon Christian Larsen, its director. Constrained by strict entry criteria and a tight budget, Emory has given transplants to just six.

Like others in the field, Larsen believes that ideal islet-transplant candidates are patients who, despite their best efforts, cannot control their blood sugar. More dangerously, their bodies have lost the ability to sense blood sugar lows, resulting in sudden fainting spells, seizures, and even comas or death. For patients like Berty, who suffered middle-of-the-night seizures and blackouts while driving, the condition is terrifying and profoundly disruptive. It's these patients—maybe 1% of type I diabetics—who islet transplanters welcomed into clinical trials. “Every patient we take on, they're near death's door or in desperate straits,” says Shapiro.

Transplanters quickly found, however, that the success of the Edmonton protocol is tough to sustain; the new islets seem to fade over time. Experienced islet-transplant centers like Edmonton, the University of Miami, and the University of Minnesota, Twin Cities, boast insulin independence rates of 80% to 90% a year after transplant, far higher than the rates of many smaller centers. After 3 years, that falls to 60% among Miami's patients, says Camillo Ricordi, scientific director of the Diabetes Research Institute there. Mark Atkinson, a pathologist who studies diabetes at the University of Florida, Gainesville, and research chair of JDRF, recently reviewed unpublished data on patients from Edmonton, 3 to 4 years after their transplants. Between 12% and 25% were insulin independent, he says. Among the original Edmonton seven, only two remain off insulin, says Shapiro.

“Something is not going in the right direction long term,” says Ricordi. One possibility, he says, is that the antirejection drugs, although less toxic to islets than steroids, still harm the cells. Some nondiabetic patients taking the drugs after receiving liver, heart, or kidney transplants have developed diabetes, notes David Sutherland, chief of transplantation at the University of Minnesota.

A more fundamental problem may be that the immunosuppressive drugs can't erase the underlying autoimmune response that killed a patient's original islets. “These people don't like islets, no matter whose they are,” says Peter Senior, an endocrinologist at the University of Alberta.

Another explanation for islet failure is that patients may be receiving too few islets, even if they get cells from multiple donors. A normal pancreas has roughly 1 million islets, but current techniques allow only about 400,000, at most, to be extracted from a donor pancreas. Moreover, unknown numbers die soon after they're transplanted, forcing the rest to labor unusually hard to supply enough insulin. The islet cells may just “poop out” over time, says Sutherland.

Edmonton found that giving patients islets from as many as three pancreases could sustain insulin production longer. But pancreases are a scarce and costly resource. Fewer than 2000 are donated each year, and most go toward whole-organ pancreas transplants for diabetes. In the United States, they also cost from $15,000 to$25,000 each.

Increasingly, however, transplanters are wondering whether insulin independence, a goal pushed heavily by islet-transplant centers, funders, and many patients, is the only yardstick by which to measure islet-transplant success. Patients like Ellen Berty and others who have gone back on insulin have found that partial islet function can stave off the hypoglycemia they experienced before their transplants. This has doctors hoping that islet transplants might prevent long-term complications of diabetes, even if recipients still need some insulin. “Even if they're not off insulin,” says Shapiro, “their problems go away.”

## Walking a tightrope

But what if the therapy is as bad as the disease? Last month, the risky nature of these transplants was underscored by NIH's first report from its Collaborative Islet Transplant Registry. None of the 86 islet recipients NIH surveyed died from the procedure. But the agency cataloged 20 serious adverse events linked to islet transplants. They include four cases of life-threatening neutropenia, a depletion of white blood cells caused by antirejection drugs. “Islet transplants are still incredibly experimental,” says Ricordi.

Amy Parker learned that the hard way. Parker, who asked that her real name not be used, was diagnosed with type I diabetes as a teenager. As her disease became progressively more unmanageable, she began having seizures from low blood sugar, and blood vessels behind her eyes started to leak. She needed multiple laser eye surgeries to preserve her vision.

In 1999, soon after Edmonton began its revolutionary set of islet transplants for patients like her, she applied. In November and December 2002, Parker underwent two separate islet transplants.

Then, her new ordeal began.

Since receiving the transplants, her insulin requirements have dropped to a quarter of what they once were, and she no longer suffers seizures or hypoglycemia. But every day she experiences “deathly horrible” headaches, a result of the antirejection drugs, she learned. Two summers ago, she began having trouble breathing while on a family vacation in British Columbia. In July, she was switched from the drug sirolimus, a possible culprit, to mycophenolate, another immunosuppressant. If that fails to help her, says Parker, she may drop out of the study and lose her islets.

The experimental nature of islet transplants was further driven home last June at the American Diabetes Association meeting in Orlando, Florida, where the Edmonton team released troubling kidney function data on its first 45 islet-transplant patients. Of the five patients Edmonton has followed for 4 years, two have “quite bad renal outcomes,” including one who has required dialysis, says Senior. Overall, a third of the 45 have high levels of a protein in their urine that's normally a harbinger of declining kidney function.

On the other hand, about a fifth of diabetes patients typically develop kidney disease. Says Senior, “These people may well have ended up with kidney failure irrespective of transplant. The question is, are these drugs hastening that?”

## Changing course

It's mixed news like this that has dampened enthusiasm among a handful of doctors who once believed islet transplants were ready for patients. One is David Harlan, a diabetes specialist at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in Bethesda, Maryland, who treated Berty. Like his colleagues around the world, Harlan was enthralled by the Edmonton protocol when it first appeared. In late 2000, he pulled together a transplant team and more than $1 million in NIH funding to launch an islet- transplant program at NIH. From 29 December 2000 through 14 June 2001—the date of Berty's transplant—he and his colleagues performed transplants in six women with severe type I diabetes. The team quickly grew troubled by what it was seeing. Looked at through the lens of diabetes, the picture was relatively rosy: Four of six patients became insulin independent, and three stayed that way for at least a year and a half. Even those who still needed some insulin no longer suffered the hypoglycemic episodes that had driven them to this experimental trial in the first place. But problems abounded. Two patients, including one off insulin, had to discontinue immunosuppressants because of the intolerable side effects, such as deteriorating kidney function, and their bodies rejected the islet cells. Even Ellen Berty, the NIH success story, ran into some trouble. In her first year after the transplant, the antirejection drugs contributed to a severe foot infection and caused mouth ulcers so large that NIH dentists photographed them for use in a textbook. For Harlan, the price NIH islet recipients were paying didn't seem worth it. “When you expand the experience, you find problems that were not expected,” says Antonio Secchi, head of the transplant program at Milan's University Vita-Salute San Raffaele, one of about four major European islet-transplant centers. Two of his center's 10 islet recipients who became insulin independent have since dropped out of the program because of drug side effects. One central question that preoccupies Harlan is whether islet recipients will live longer than those in comparable health who don't receive transplants. It's too early to answer that question directly, so Harlan turned to data on pancreas transplants. They have been used for years in much the way islet transplants are now, although most are given to diabetes patients who also need kidneys. Harlan and his colleagues examined data from 124 transplant centers in the United States from 1995 to 2000 and arrived at an unsettling conclusion: Patients receiving a solitary pancreas or a pancreas after a kidney transplant were more likely to die within 4 years than those still on the waiting list. Published last December in the Journal of the American Medical Association, the article touched off a furor. Many transplant surgeons disputed its results. Minnesota's Sutherland and his colleague Rainer Gruessner have reanalyzed the data, and Sutherland says they've arrived at a conclusion opposite to Harlan's. Some patients in Harlan's study, says Sutherland, were on the waiting list of more than one hospital and ended up being counted twice. The study also excluded patients awaiting pancreas transplants who had very poor kidney function; Harlan worried that that might produce misleading results, but Sutherland believes those patients should be included. Concerns about long-term survival after an islet transplant, however, must be weighed against the improved quality of life that many transplant recipients experience, at least initially. “The psychological benefit of insulin independence is potentially enormous,” says Emory's Larsen, “and it's hard to understand for a nondiabetic.” Rita Hart, 46, is off insulin after undergoing three transplants at Miami over 2 years, the last in July 2003. Before her transplant, diabetes was consuming her life and complications were piling up. “I was losing hope,” she says. Now, despite drug side effects that include anemia, she feels vastly more optimistic. “It's striking how many patients ask for a third transplant,” says Senior. “Even with all the side effects and all the downsides, they still think it's a good thing.” And so Edmonton, like many other islet-transplant centers, continues to grow. Today, more than 25 hospitals have performed islet transplants that hew closely to the Edmonton protocol. NIH will soon announce$75 million in awards for a new clinical islet transplantation consortium in which centers will collaborate on islet studies. Although Harlan ended his islet-transplant trial early, the agency believes the treatment is worth pursuing. “This is not a black-and-white issue,” says Allen Spiegel, director of NIDDK.

New money, however, will go only so far: Islet transplants are extraordinarily expensive, costing up to $200,000 in the United States for one patient in the first year. Antirejection drugs add another$30,000 annually after that. At centers like Miami, where most patients remain part of a protocol, the price of success—of supporting patients for years after a transplant—is becoming prohibitive, says Rodolfo Alejandro, an endocrinologist and director of the clinical islet-transplant program at the University of Miami. (Costs in Canada are somewhat lower because there's no charge for organs, and the Alberta health care system agreed in 2001 to pay for transplants for Alberta residents.) Because they're still considered experimental, most United States islet transplants are funded by NIH, JDRF, and sometimes by pharmaceutical companies that manufacture immunosuppressants.

Costs are one roadblock to performing the kind of large, controlled studies that some say are needed before islet transplants can shift from being an experimental therapy to being one approved by the U.S. Food and Drug Administration (FDA). Some islet transplanters, like Alejandro, believe that one option is for FDA to approve the therapy under its existing “orphan drug” category, making it available to essentially the same patients getting islets now—those with uncontrolled diabetes. That way, it could be covered by insurance. A year ago, FDA held a public advisory committee meeting in Gaithersburg, Maryland, and agency officials made clear they want certain issues addressed first. Those include consistency in how islets are processed and a better assessment of the risk-benefit balance.

No matter how FDA rules, major hurdles stand in the way of islet transplants going mainstream. First, the shortage of donor pancreases means scientists must find a renewable source of islets. One popular option would involve using some type of stem cell. This year, JDRF has committed more than $8 million to stem cell research, more than$6 million of it to human embryonic stem cell work. Yet creating islets from stem cells isn't imminent, according to Larsen and other transplanters.

Milder immunosuppressive regimens might come more rapidly. One study that's gearing up at Miami calls for giving islet recipients a dose of bone marrow cells culled from the donor's vertebrae, to try to help patients better tolerate the islet cells.

Current islet recipients, and the many more people with diabetes hoping for a transplant, are eagerly awaiting the day when islet transplants are easier to come by and gentler to receive. But Berty remains upbeat. A book she's written chronicling her experience came out this spring. Its title: I Used to Have Type 1 Diabetes: Kiss My Islets.

12. RESEARCH COMMUNITY

# Science Weathers the Storms

1. David Grimm*
1. With reporting by Sean Bruich.

Researchers struggle to keep their work on track in the wake of recent hurricanes

On a small beach in southeastern Florida near Fort Lauderdale, marine biologist Jeanette Wyneken races to collect as many loggerhead sea turtle nests as possible before the full brunt of Hurricane Frances hits. She fills her car with all she can carry and records the GPS coordinates of the nests she must leave behind, hoping that they will still be there when she returns. Her efforts are not entirely selfless, though: She's also guaranteeing that, while the storm wreaks havoc outside, her research on a threatened species can continue in the lab.

Wyneken—like many scientists at southeastern universities and institutions—faced a rare challenge in this season's record string of hurricanes. Many had to battle power outages, flooding, and even police barricades to keep their work on track. Not all succeeded. The hurricanes—Charley, Frances, Ivan, and Jeanne—destroyed sensitive equipment and reagents, set back research, postponed conferences, and forced the extension of grant deadlines. This chain of storms “has been a huge disruption,” says University of South Florida oceanographer Frank Muller-Karger, whose St. Petersburg lab had to move its computers into bathrooms to avoid losing data when Charley hit. “It's been an incredibly stressful period.”

At Cape Canaveral, even before Frances began pounding the beaches, scientists at the Kennedy Space Center faced some tough choices. “Packing our spacecraft up would set the launch date back at least 2 weeks and cost a couple million dollars,” says Neil Gehrels, who heads NASA's Swift gamma ray observing satellite project. But he was loath to take a chance, because “NASA is very cautious with its equipment.”

In the end, Gehrels instructed his team to seal the satellite in an airtight metal container and move it to a secure hangar. His prudence proved correct. The space center took a direct hit from Frances, suffering the worst damage since it was established in 1963. Even though the launch date was delayed by the move and subsequent evacuation of personnel, Gehrels says the alternative would have been much worse. “Swift would have taken 5 years to rebuild,” he says, “to say nothing of the cost.”

Packing up and evacuating wasn't the preferred option for all southeastern scientists, however. When Hurricane Ivan looked like it was on a collision course for New Orleans, Tulane University parasitologist Paul Brindley decided to move his wife and 9-year-old daughter into his lab on the fifth floor of the university's environmental research building. “We thought we'd be safer hunkered down there than at home,” he says. Brindley brought beans for his family to eat and air mattresses for them to sleep on and kept his daughter calm by letting her play games on his office computer. Meanwhile, he ventured into his workspace to transfer his schistosomes to liquid nitrogen and plug his freezers into backup generator outlets—just in case.

A backup generator was the first thing to go at the University of Florida, Gainesville, biochemist Arthur Edison discovered when he got a frantic call at 3 a.m. on the morning Frances struck. Edison runs the university's Advanced Magnetic Resonance Imaging and Spectroscopy Facility, which relies on a \$2 million system of superconducting magnets to study everything from structural biology to Alzheimer's disease. “The magnets need power to stay cold,” he says; otherwise, they can fail in 8 hours. Edison had to wait until morning to check on the magnets because the town was flooded and under curfew. When he entered the building under police escort, he discovered that the entire institute was on the fritz. “The whole place was beeping,” he says.

Edison's magnets were fine because they never lost power, but other equipment had failed. He spent several hours plugging powerless machines into working outlets and moving his colleagues' sensitive reagents from dead freezers into working ones. Still, it could have been worse. Remembering how Tropical Storm Allison drowned more than 35,000 lab animals at Baylor College of Medicine in Houston, Texas, in 2001, Edison and others had spent the days before the hurricane sandbagging doors and taping windows shut.

While some were trying to keep water out of their labs, Wyneken was trying to bring it in—hoping to save her loggerhead turtles. Hurricane Frances had knocked out the power to the pumps in her building at Florida Atlantic University in Boca Raton, stopping the flow of fresh seawater to the turtle tanks. Rather than risk using contaminated water from the nearby beach, Wyneken made a 72-kilometer trek up the coast to fill the 50-kilo containers in her truck with water from the Juno Beach Marine Life Center. On the way back, she had to get special permission to cross closed bridges and hiked through a carpet of downed ficus trees.

Many graduate students undertook similar physical risks to keep from losing thesis projects they had spent years working on. When Hurricane Ivan veered toward the Alabama shoreline, Charlyn Partridge, a biology Ph.D. student working at the University of South Alabama in Mobile, ignored her parents' pleas to seek shelter at their home in Louisiana. Instead, she headed straight for the basement of the university's life sciences building. While the Federal Emergency Management Agency set up shop on the first floor, Partridge dissected her pipefish to collect the daily readings she needed for sexual selection studies. “If I had missed a day, I would have lost a month of work and may not have been able to finish my project on time,” she says. Partridge acknowledges that she took a risk by going to the lab. “But you need to make sure everything that's important to you is safe,” she says. “That also includes the research.”

Although no one welcomed the storms, some research actually benefited from them. Hurricane Charley damaged sensors on marine research buoys being used by University of South Florida oceanographer Robert Weisberg, but he left equipment running when Frances hit. “As a result, we got a really nice data set,” he says. “And it was totally unplanned.” Weisberg says that, although Frances caused some damage, sensors recorded changes in water temperature and current that will eventually be assimilated into models that may help improve hurricane forecasting.

Wyneken is beginning to see a bright side as well. The first eggs she saved on the beach have begun to hatch, and she believes she will be able to collect good data on how young turtles adapt to their environment. “Sometimes you have to do some crazy things for science,” she says. “But when you see a whole nest of baby turtles hatching … with their big brown eyes and big floppy feet, it makes all of your efforts and hassles seem worthwhile.”

Wyneken's turtles are still going to need some luck. In the coming weeks, she will tag them for further study and release them onto the now-damaged beach where she rescued them. Once they make their way back to the water, they'll contend with predators, starvation, and—as Hurricane Jeanne made clear last week—a storm season that is far from over.

13. PALEOANTHROPOLOGY

# Dressed for Success: Neandertal Culture Wins Respect

1. Michael Balter

Neandertals made jewelry and must have worn clothing—but were they as sophisticated as modern humans? Researchers gathered at a high-level meeting to find out

GIBRALTAR—One day in 1848, when workers were blasting in a quarry on the Rock of Gibraltar, out of the dust and rubble tumbled a strange-looking human skull. It had a jutting, prognathous face, thick brow ridges, and an elongated brain case. The skull was presented to the Gibraltar Scientific Society, which had no idea what to make of it and put it in storage. Eight years later, miners working in a limestone cave in Germany's Neander Valley came across a similar skull. This time, scientists concluded that it was a sort of primitive human, and so in time “Neandertal” rather than “Gibraltarian” became an epithet for brutish behavior.

But today respect is growing for the Neandertals, whose brains were slightly bigger than those of our own species and who survived more than 100,000 years of sharp fluctuations in climate. Last month, when more than 100 archaeologists and anthropologists gathered here for the third triannual meeting on Neandertals and modern humans,* much of the discussion centered on the Neandertal's abilities and culture.

For example, although Neandertals had always been considered cold hardy, some researchers now conclude that Neandertals must have relied chiefly on their material culture, rather than their cold-adapted biology, to brave the chill of Ice Age Europe. Other researchers made controversial claims that Neandertals were full partners in the cultural innovations that swept through Europe beginning about 45,000 years ago, creating their own original tools and jewelry. Although not everyone at the meeting was willing to go this far, most agreed with anthropologist Jean-Jacques Hublin of the Max Planck Institute of Evolutionary Anthropology in Leipzig, Germany, that “Neandertals were complex hominids doing complex things.”

## Feeling the chill

One fact that is not in contention is that Neandertals, who first appeared in Europe and Western Asia about 150,000 years ago and apparently thrived until their extinction about 25,000 years ago, were well adapted to cold northern latitudes. The Neandertal body was chunkier and more muscular than that of modern humans, and their limbs were somewhat shorter—all features thought to help reduce heat loss. In Gibraltar, however, University College London anthropologist Leslie Aiello presented new data that challenge this conventional wisdom. In collaboration with physiologist Peter Wheeler of Liverpool John Moores University, Aiello set out to determine “what it really felt like to be a Neandertal living in Ice Age Europe.”

Aiello and Wheeler first tested the hypothesis that the Neandertal's stout body would have kept it significantly warmer. They calculated a parameter called the “lower critical temperature,” the limit at which a human must increase its internal heat production (usually by eating more) to maintain a body temperature of 37°C. Using formulas that factor in the thermal conductance of the skin, body surface area, and estimated basal metabolism rate, Aiello and Wheeler compared Neandertals, modern humans, and the tall, slim form of Homo erectus found in Africa. To their surprise, the lower critical temperature differed very little among all three: 27.3°C for Neandertals, 28.2°C for modern humans, and 28.5°C for Homo erectus. “I find this astounding,” Aiello said. “The Neandertal body form will keep it a bit warm, but not enough to live in a very cold environment.”

But just how cold was it? Aiello and Wheeler addressed this question with the help of a pioneering research effort known as the “Stage 3 Project,” led by Cambridge University geoarchaeologist Tjeerd van Andel. This work has generated a wealth of new data about climatic conditions in Europe between 60,000 and 24,000 years ago, the period of Oxygen Isotope Stage 3 (Science, 6 February, p. 759). Because modern humans arrived in Europe around 40,000 years ago, Stage 3 includes the crucial period during which Neandertals and modern humans coexisted.

One of the major achievements of the Stage 3 Project is an estimate of the wind-chill factor—a much better indicator of conditions than temperature alone—at hundreds of sites known to have been occupied by prehistoric humans. The project was able to achieve excellent resolution, creating a Europe-wide grid of 60-kilometer-by-60-kilometer squares and time slices that vary between 3000 and 10,000 years in duration.

Aiello and Wheeler looked at the wind-chill factors for 457 Neandertal and modern human sites. They found that as the last Ice Age approached, a large number of the Neandertal sites would have turned positively frigid. For example, Neandertals living at Kulna Cave in Moravia about 25,000 years ago would have faced winter wind chills of −24°C. Aiello and Wheeler next calculated how much insulation the Neandertals would have needed using a unit of insulation called the “clo.” One clo is roughly equal to wearing a modern Western business suit or having 1 centimeter of body hair or 2 centimeters of body fat. They found that even if Neandertals had worn one clo of insulation, for example in the form of animal skins, toward the latter half of Stage 3, many Neandertal sites would still have been unbearable. Despite their supposed cold-hardiness, Neandertals would have needed a great deal of clothing and shelter to survive in these places, probably calling forth all of their cultural and material resources.

Thus, it is perhaps not surprising that Neandertals usually chose to live in areas where winter wind-chill temperatures were warmer than those occupied by the culturally more sophisticated modern humans. For example, Aiello and Wheeler found that during the period 37,000 to 22,000 years ago, Neandertals faced median winter wind chills of −16°C at their sites, while at sites associated with modern cultures the wind chills ranged from −20°C to −23°C. That suggests that the culturally advanced moderns were even better equipped to fight the cold—and so might have had a competitive edge against the Neandertals during the coming Ice Age. “Neandertals did extremely well for a long time,” Aiello concluded. “The only difference was that now they had modern humans to compete with them.”

This argument made sense to many researchers at the meeting. Anthropologist Chris Stringer of the Natural History Museum in London, for example, suggests that Neandertal clothes were probably less effective insulators than those sported by modern humans. “There is no evidence of sewing needles from any Neandertal sites,” Stringer points out, whereas many modern human sites have such needles.

But some participants argued that Neandertals, at least during the earliest periods of coexistence with modern humans about 40,000 years ago, were just as capable of making clothes as their supposed competitors. “Needles do not appear until much later” —after 25,000 years ago—even at modern human sites, notes archaeologist Francesco d'Errico of the University of Bordeaux in France. “We know from use-wear analysis [of bone and stone tools] that Neandertals were working and scraping animal skins.” And some of their bone tools, d'Errico says, could easily have been used to make holes in animal skins, even if they did not have actual needles.

Inferences about Neandertal tailoring abilities quickly led to a broader debate about whether Neandertals overall were culturally inferior to modern humans during the short time that the two groups coexisted. At the meeting, d'Errico, along with University of Lisbon archaeologist João Zilhão, sparked fierce debate with arguments to buttress their view that Neandertals and moderns were cultural near-equals.

The debate is tied closely to the chronology of several archaeological “cultures” (Science, 2 March 2001, p. 1725). For most of their history, Neandertals made stone flakes, scrapers, and axes collectively known as the Mousterian culture. When modern humans arrived in Europe, they began producing a different culture called the Aurignacian, consisting of more sophisticated stone and bone tools as well as personal ornaments such as beads. The later Aurignacian was also characterized by the beginnings of cave art, and these dramatic developments are sometimes referred to as the “Upper Paleolithic revolution.” Right around the time that modern humans arrived, however, the Neandertals underwent a cultural shift, creating beads and tools, called “Châtelperronian,” that closely resemble the early Aurignacian. Most archaeologists have assumed that the Neandertals were copying the modern humans through a process of acculturation, but d'Errico, Zilhão, and their co-workers have argued insistently that the Châtelperronian represented an independent cultural achievement.

At Gibraltar, d'Errico and Zilhão continued their attack on the acculturation theory. D'Errico proposed an alternative “multispecies” model for the rise of modern behavior, in which both Neandertals and moderns fully participated in the Upper Paleolithic revolution. In a sweeping review of the archaeological evidence across Europe, d'Errico maintained that modern behavior “appeared at different times and at different places.” And he challenged the notion that the Neandertals had simply copied the moderns. His own study of beads from Châtelperronian sites, carried out with postdoc Marian Vanhaeren, showed that Neandertals often made beads from perforated animal teeth, whereas moderns usually made beads from bone and shells and used different perforation techniques. And at Grotte du Renne, a French site occupied first by Neandertals and later by modern humans, d'Errico argued that the Neandertals made sophisticated bone awls earlier and in much greater numbers than their supposedly more “modern” successors.

Zilhão attempted to drive the point home with a review of the radiocarbon dating for sites across Europe. In one of the meeting's most hotly contested talks, he dismissed on technical grounds dates of 40,000 years or earlier at two key central European Aurignacian sites and concluded that there was no reliable evidence for any Aurignacian artifacts before 36,500 years ago. If true, this could mean that the Châtelperronian, which most archaeologists agree can be dated to at least 40,000 years ago, arose in Europe before the arrival of modern humans and that the Neandertals might have launched Europe's Upper Paleolithic revolution all by themselves. “The Châtelperronian comes before the Aurignacian by many millennia,” Zilhão concluded.

These arguments received a hostile reaction from some researchers at the meeting. Hublin points out that this time period is right at the limit of radiocarbon dating's capabilities. It makes “no sense” to “ask if the Aurignacian was 36,000 years ago or 38,500 years ago when we have such big margins of error,” he says.

Nevertheless, despite the vigorous debates, most researchers at the meeting agreed that the Neandertal's long, successful reign in Eurasia probably means that the cognitive gap between them and modern humans was not as great as many experts once thought. “The Neandertals had big brains, and they must have been using them for something,” says Aiello. “The gap is closing, but we haven't fully closed it yet.”

• * Perspectives on Human Origins, Gibraltar, 26–29 August 2004.

14. ENGINEERING OF SPORT MEETING

# In Volleyball, Crafty Players Serve Up an Aerodynamic Crisis

DAVIS, CALIFORNIA—From 13 to 16 September, researchers from many disciplines discussed sports from curling to skydiving, from table tennis to boxing, at the 5th International Conference on Engineering of Sport.

Ever since Isaac Newton noted that spinning tennis balls follow curving trajectories, scientists and engineers have puzzled over the flight of spherical balls. Now, a new analysis suggests that volleyball is the oddest ball game of all, as the big, light orb regularly enters a curious state in which one half experiences much greater aerodynamic drag than the other does.

The observation explains why a volleyball can swerve unpredictably by as much as a meter—if it's moving slowly enough. It also puts a new spin on a bit of common wisdom about ball sports, says Ken Bray, a physicist at the University of Bath, U.K. “Everybody always argued that all ball sports are played in this comfortable regime where the drag is constant [with velocity],” Bray says. “But it turns out in volleyball that's not the case.”

When a ball moves through the air, a long tangle of swirling air trails behind it. Flapping like a flag in the wind, this “turbulent wake” pulls straight back on the ball and slows it down—the phenomenon known as drag. At low speeds, the wake is large and the drag is high, but if a ball moves faster than a certain speed, the wake suddenly shrinks and the drag plummets. The speed range in which the drag changes rapidly is known as the drag crisis, and balls moving in it can behave unpredictably.

In most sports, the balls hurtle so fast that the drag has bottomed out and the drag crisis never comes into play. But not so for volleyball, reports Thomas Cairns, a mathematician at the University of Tulsa in Oklahoma who coached the women's volleyball team there for 17 years. Cairns and his students videotaped volleyballs launched from a serving machine and then analyzed their trajectories with a computer. In some serves the balls moved with topspin, in which the top of the ball rotates toward the oncoming air and the bottom rotates away from it. When that happens, the top of the ball effectively moves faster through the oncoming air than the bottom half does. Cairns found that the trajectories of some serves made sense only if the top of the ball was moving fast enough relative to the air to avoid the drag crisis, while the bottom half was moving so slowly it dipped into it.

This unusual half-and-half state played havoc with the ball's trajectory and could reverse another key effect of spin: the aerodynamic lift force that can make a ball swerve up or down or side to side. In spite of its name, the lift ordinarily pushes a ball with topspin down, as the spinning ball turns against the turbulent wake like a gear turning against a toothed rail. That means a serve with topspin ordinarily sinks faster than a similar serve with no spin. But Cairns observed a serve with topspin that floated farther than a matching spinless serve. He also saw spinning serves that swerved sideways, but in the direction opposite to the way spinning balls normally curve. Cairns even spotted a few serves that swerved first one way and then the other.

Ultimately, Cairns hopes to figure out how to predict and control those effects. “We'd like to get to the point where you can say to the player, ‘Hit it this fast if you want it to do this or that,’” he says. But certain competitive players already seem to take advantage of the strange aerodynamic effects, says Rabindra Mehta, an aerodynamicist at NASA's Ames Research Center in Moffett Field, California. “The men get up there and try to hit the ball as hard as they can,” he says. “But if you watch the women, they hit it at about 15 meters per second, which is where this effect comes in.”

15. ENGINEERING OF SPORT MEETING

# To Throw Farther, Waste Energy

DAVIS, CALIFORNIA—From 13 to 16 September, researchers from many disciplines discussed sports from curling to skydiving, from table tennis to boxing, at the 5th International Conference on Engineering of Sport.

When throwing, the arm works against itself and wastes energy. But a new mechanical analysis suggests that such seemingly profligate efforts actually enable the limb to fling things farther.

In throwing and other physical activities, the first step forward is often a step back. For example, to jump straight up, a person first crouches toward the ground. “The downward motion is kind of strange when you think about it,” says Sam Walcott, a doctoral student in theoretical and applied mechanics at Cornell University in Ithaca, New York. “I'm moving in the direct opposite direction that I want to go.”

The body briefly continues to move downward even after the muscles in the legs and torso begin to pull it upward, which means it works against itself. As muscles don't store energy like springs, that “negative work” essentially goes to waste. Similarly, in throwing, the forearm momentarily moves backward even as the upper arm pulls it forward, again squandering energy. Biomechanists aren't sure what purpose this “countermovement” serves.

But Walcott believes that wasting a little energy lets the body use what energy it has left more effectively. Walcott used a computer to study an idealized arm consisting of two straight segments—representing the upper arm and forearm—that hurled a virtual ball. The upper arm could move about a pivot, but only in a plane; the forearm could then move so that it swept out a cone perpendicular to that plane, creating a throwing motion that resembled the whipping action of a baseball player's arm. Torques at the “shoulder” and the “elbow” set the arm in motion. Walcott gave the stick-figure limb a fixed amount of energy to expend and then let the computer search for the arm motion that produced the longest throw.

If the computer program allowed the arm to work against itself, it threw the object farther. The design of the arm doesn't allow it to chuck the object at any old angle and speed, Walcott explains, but “doing this negative work somehow allows us to get closer” to the optimal angle and speed.

It's an interesting argument, says Michele LeBlanc, a biomechanist at California Lutheran University in Thousand Oaks, but the abstract analysis probably isn't the entire explanation of countermovement. The details of how specific muscles, bones, and sinews interact will also play a role, she says. Jill McNitt-Gray, a biomechanist at the University of Southern California in Los Angeles, says that the precise function of countermovement will probably vary even from person to person: “You and I can jump together, and how you get your vertical impulse and how I get my vertical impulse might be different.”

16. ENGINEERING OF SPORT MEETING

# Pulling Straight to the End of the Pool

DAVIS, CALIFORNIA—From 13 to 16 September, researchers from many disciplines discussed sports from curling to skydiving, from table tennis to boxing, at the 5th International Conference on Engineering of Sport.

For decades, competitive freestyle swimmers have been taught to make an S-shaped path when pulling their hands through the water. But measurements and calculations now show that to generate the maximum thrust, swimmers should pull their hands straight back through the water, reports a mechanical engineer whose research was inspired by his previous study of turtles.

Swimmers have been purposely doing the “S-pull” since the early 1970s, when famed swimming coach James (“Doc”) Counsilman used underwater cameras to film elite swimmers and found that they were moving their hand first out to the side and then back under their bodies. By moving side to side, hands acted like little airplane wings or propeller blades, Counsilman argued, generating hydrodynamic lift that pulled the swimmer through the water. That lift would supplement the force generated by simply pushing against the water with the palms. In recent years, researchers have questioned just how large and important the lift forces are, but the S-pull has remained a standard technique among competitive swimmers.

However, the S-pull may not be the best pull for all races and circumstances, says Shinichiro Ito of Japan's National Defense Academy in Yokosuka. Using measurements of the lift and drag coefficients of manikin hands and a computer model of a swimmer, he found that the S-pull makes the most efficient use of energy, as it maximizes the ratio of lift to drag. It does not, however, generate the most thrust. Instead, Ito found, a straight “I-pull” yields more pure power.

Ito had already observed something similar in his study of freshwater turtles. When paddling about leisurely, turtles wave their feet in flourishes, doing a reptilian version of the S-pull. When frightened, however, terrified terrapins pull their feet straight back to swim away as fast as possible. Analysis showed that for turtles, the sinuous movement was more efficient, Ito says, but the straight movement produced greater thrust.

Other familiar creatures also provide living examples of the advantages of the I-pull. Underwater video shows that Australian swimming sensation Ian Thorpe snaps his elbow and pulls his hand straight through the water, Ito says. Other swimmers are following the nine-time Olympic medalist's lead, says Yuji Ohgi, a professor of physical education at Keio University in Fujisawa, Japan. “At the Sydney Olympics [in 2000], only Ian Thorpe had the I-shaped pull,” he says. But now, “many, many Australian swimmers do it.”

Switching from S-pull to I-pull isn't easy, says Ohgi, who is also a swimmer. Good swimmers generate power by rolling from one side of their bodies to the other, he says, and that makes their hands move side to side almost automatically. “The I-shaped pull is rather more difficult than the S-shaped pull because of the rolling motion” of the body, Ohgi says. Still, to shave every fraction of a second from their times, more swimmers are tackling the challenging technique and learning to swim like a frightened turtle.

17. ENGINEERING OF SPORT MEETING

# Snapshots From the Meeting

DAVIS, CALIFORNIA—From 13 to 16 September, researchers from many disciplines discussed sports from curling to skydiving, from table tennis to boxing, at the 5th International Conference on Engineering of Sport.

R2D2 meets K2. A robot standing 45 centimeters tall and weighing 3 kilograms swishes down a 10-meter artificial ski slope much like a human skier, report engineer Takeshi Yoneyama of Kanazawa University in Japan and colleagues. The mechanical downhiller isn't completely lifelike, because it doesn't generate nearly as much force with its legs as humans do. Still, the robot has already provided insights into why skiers move their joints the way they do.

The camber of least resistance. The tops of the wheels of racing wheelchairs are tilted toward each other to make them more stable. But such “camber” also reduces the amount of rolling friction, reports Nick Hamilton, a sports engineer at the University of Sheffield, U.K. Hamilton figured that the friction must be least when the wheels are perpendicular to the ground. To his surprise, his measurements showed that the friction was smallest when the wheels leaned by 8 to 14 degrees, presumably because the tires deform to reduce the amount of contact with the ground.