News this Week

Science  20 Jan 2006:
Vol. 311, Issue 5759, pp. 314
  1. AVIAN INFLUENZA

    Amid Mayhem in Turkey, Experts See New Chances for Research

    1. Martin Enserink

    ANKARA—It's Turkey's turn to wage war against H5N1. More than 2 months after it first emerged in this country, the feared avian influenza strain has suddenly exploded in the past 3 weeks: Twenty people are assumed to have been infected, and four have died—including three children from one family. Across the country, massive and at times chaotic culling operations are in full swing in an attempt to prevent the virus from becoming endemic.

    But amid the devastation, scientists also see a unique opportunity to study questions about H5N1 whose answers may benefit not just Turkey but also the entire world. Members of an international team of experts, flown in 2 weeks ago to assist the government in investigating and controlling the outbreaks, say Turkey has been exceptionally open and has welcomed studies that may help prepare for a possible pandemic. Although he's cautious not to criticize other countries, epidemiologist Guénaël Rodier of the World Health Organization's (WHO's) European office in Copenhagen, who heads the team, says, “we do have better access here.”

    Turkey's struggle.

    Quashing the large avian influenza outbreak in Turkey will require international assistance, scientists say.

    CREDIT: MURAD SEZER/AP PHOTO

    In an interview last week, Rodier rattled off a series of proposed studies to which the Turkish government has reacted favorably. They include a detailed epidemiological investigation to establish the virus's potential for human-to-human transmission; a so-called serosurvey—a study looking for antibodies—among patients' family members, poultry cullers, health care workers, and the rest of the community in affected areas; and a study to find out risk factors for severe disease among those infected. Completing them all would take months, Rodier says.

    Some have suggested that Turkey is opening up in order to further its candidacy for E.U. membership; others say the country realizes it needs all the help it can get. Juan Lubroth of the U.N. Food and Agriculture Organization, who was in Turkey last week, credits the government with “mature, good governance” and notes that FAO has had good relations with Turkey in the past.

    The international team, which includes epidemiologists, microbiologists, lab experts, and veterinarians, swarmed out last week to visit hospitals, stricken villages, labs, and health authorities to help collect information and control the outbreak. Roughly half of the experts have set up camp in Van, a city in the eastern part of the country that has been hit the hardest; the other half is based closer to the Turkish government, in a heavily fortified U.N. off ice building in a hilly suburb of the capital.

    Several factors, in addition to the hospitality, make Turkey a valuable site for research, experts say. For instance, Turkish doctors appear to record more elaborate histories of their patients than do those in East Asia, which can be invaluable for understanding viral exposure, says pediatrician Angus Nichol, former head of the U.K.'s Communicable Disease Surveillance Centre. (Nichol is currently seconded to the European Centre for Disease Prevention and Control in Stockholm.)

    The large number of human cases in a short period is another factor that makes the outbreak particularly interesting. The first recorded poultry cases in Turkey occurred on a turkey farm in the western province of Balikesir in early October; for 2 months after that, no new outbreaks were reported. But in late December, the number of poultry outbreaks started to skyrocket, and human cases followed quickly. As of Tuesday, the agriculture ministry had confirmed outbreaks in 12 of the country's 81 provinces, situated in the western, northern, and eastern parts of the country, and was investigating reports in 19 others. Human cases have occurred in nine provinces.

    Researchers are not certain why the country is seeing so many cases, whereas East Asia has had fewer than 150 over the past 2 years. So far, they have not seen any signs of human-to-human virus transmission, the feared overture to a pandemic. Sequencing of the virus from one Turkish patient at the National Institute for Medical Research (NIMR) in London—one of four WHO collaborating centers for flu—has shown a genetic mutation, previously seen in patients in China and Vietnam, that makes the virus bind more easily to human cells. But whether that makes any difference for epidemiology is unclear, says NIMR Director Alan Hay, who was in Ankara last week.

    The human cases may have occurred in the cold, mountainous eastern part of the country simply because many villagers brought their animals indoors when the winter began in earnest, Rodier says. Rural dwellings there are often simple, one-room structures where people and animals live together, which might create conditions conducive to transmission. But this needs to be investigated further, Rodier says.

    Researchers are asking another question: Why does the disease appear to be milder here than in eastern Asia? The death rate of about 25% is half that of previously known outbreaks, and there have been five mild or completely asymptomatic cases. One theory holds that milder cases have been occurring elsewhere but aren't being recorded. Indeed, a study among 45,000 Vietnamese by Anna Thorson and colleagues at the Karolinska Institute in Stockholm, published recently in the Archives of Internal Medicine, showed that those who lived in households where poultry became sick or died had an increased risk of influenza-like symptoms, especially after close contact with the birds.

    Such studies can suffer from so-called recall bias, however; people who had sick chickens may just remember their symptoms better. A broad serosurvey—among patients' contacts, those exposed on the job, and the community in general—would be a better gauge of the true extent of H5N1's spread. Several such studies have been carried out in affected Asian countries, but the results have not been published, to the frustration of many flu experts. “Serological studies are often very hard to get out of countries—they're politically sensitive, even in Western countries,” says Nichol. But from what he has heard about completed H5N1 serosurveys, they do not point to widespread infection beyond the recorded H5N1 cases, he says.

    Yet another possible explanation for the milder cases may be that worried Turkish parents, exposed to wall-to-wall media coverage, take their children to a hospital earlier. Once there, they are immediately given oseltamivir, an antiviral drug known to work best when given early in infection. Indeed, oseltamivir efficacy against H5N1 is another important topic to be studied, says Rodier.

    Early this week, experts weren't ruling out that some of the milder cases might actually be false positives. Flu testing in Turkey is done by the National Influenza Centre, based at the Refik Saydam Hygiene Institute in central Ankara.

    Although the first four positive tests there were confirmed by NIMR and have been added to WHO's official tally, the others, which included the milder cases, were not. Kurban Bayrami, a major 4-day religious festival, brought the country to a standstill last week, making sample shipments impossible. Although patients with flu are well cared for, even in remote areas, and a vigorous education campaign is now under way to prevent more infections, reining in the poultry outbreak remains a daunting task. A top priority now is to establish exactly where the virus is and isn't present in birds, says Stefano Marangon, director of science at the Istituto Zooprofilattico Sperimentale delle Venezie in Padua, Italy, who also visited Turkey last week. Massive culling in affected areas may prevent the disease from becoming endemic.

    But to succeed, Turkey needs help from the international community, Marangon adds; for instance, several of the nation's eight regional animal health labs don't have equipment for rapid testing and need to be upgraded. Turkey was set to offer a battle plan and make a request for international support at a large donor meeting for avian influenza scheduled for this week in Beijing.

  2. AVIAN INFLUENZA

    WHO Proposes Plan to Stop Pandemic in Its Tracks

    1. Dennis Normile

    Ever since the H5N1 avian influenza strain began racing through Asia 2 years ago, the World Health Organization (WHO) has been urging the world to prepare for a possible pandemic. Now it is going a step further, planning a rapid response that just might quash a pandemic before it starts. To work, any country and WHO would have to recognize that the virus had acquired the ability to be transmitted easily among humans while its spread was still limited. Then, with international support, that country would have to impose quarantines and launch massive campaigns to administer antiviral drugs to contain the virus.

    Rapid response.

    The outbreak in Turkey has underscored the need for bold interventions. Above, Minister of Health Recep Akdag visits a child being treated for a possible H5N1 infection.

    CREDIT: REUTERS/ANATOLIAN NEWS AGENCY

    “Clearly, there is no guarantee that we would stop a pandemic,” admits WHO virologist Keiji Fukuda. “But if successful, this could prevent enormous [amounts] of illness and death.” At the moment, however, few of the developing countries hardest hit by H5N1 have the necessary capabilities, and it is unclear whether developed countries will offer sufficient technical and financial support.

    WHO proposed the plan at a Japan-WHO Joint Meeting on Early Response to Potential Influenza Pandemic in Tokyo on 12 and 13 January, announcing that it will form a new Global Task Force for Influenza. The 20 or so outside experts in virology and public health will be on standby to help the agency assess the signals that may presage a pandemic.

    Two modeling studies published late last summer gave weight to the idea that early intervention was at least theoretically possible, says Fukuda. One, from a team led by Ira Longini of Emory University in Atlanta, Georgia, appeared in Science (12 August 2005, p. 1083). The second team, led by Neil Ferguson of Imperial College London, published its results in the 8 September issue of Nature. Both concluded that, under the right circumstances, early intervention could stop a pandemic in its tracks (Science, 5 August 2005, p. 870).

    But the gap between the ideal and current reality was apparent at the Tokyo meeting. The first step in this rapid-response scenario would be spotting a virus soon after it has acquired human-to-human transmissibility. This would be extremely difficult in the remote mountainous areas of Laos where technical capabilities are weak, said Baunlay Phommasack, a Department of Health official from that country. His views were borne out by an analysis of some 70 human cases in Asia in the past 2 years. As Hitoshi Oshitani, a public health specialist at Tohoku University in Sendai and consultant to WHO, described, on average, it took 2 weeks after the onset of symptoms for cases to be identified and notification sent to WHO. Lab confirmation of suspect H5N1 samples can add several days to 2 more weeks. “This is too late to contain the virus,” he said. He also noted that imposing an effective quarantine would be logistically difficult and could well run into opposition on human-rights grounds. Wide-scale administration of the antiviral Tamiflu, generically known as oseltamivir, also hinges on having sufficient stockpiles readily available. And even if supplies are on hand, recent studies have raised questions about proper dosing for H5N1, several meeting participants pointed out.

    All these unknowns mean that an early response “is not a panacea,” says Shigeru Omi, director of WHO's Regional Off ice for the Western Pacific. But Omi and other WHO officials emphasize that even if it fails to thwart a pandemic, early intervention might slow the spread of disease, providing precious days or weeks for other countries to put pandemic plans into action and for drug companies to start developing a vaccine.

    At the meeting Oshitani pointed out that few countries, if any, currently include early response as part of national pandemic-preparedness plans. Fukuda adds that the next step for WHO will be to launch “intensive discussions to develop plans reflecting each country's needs.” Most developing countries, he said, will need to upgrade both local surveillance and lab capabilities to deal with agricultural and human health threats. But that won't come cheap, cautioned World Bank official Jacques Baudouy, who reported bank estimates that globally between $1.2 billion and $1.5 billion will be needed over the next 3 years. Issues of international support for building such capacities in developing countries were due to be taken up at an International Donor Conference in Beijing on 17 and 18 January.

  3. COSMOLOGY

    Astronomers Push and Pull Over Dark Energy's Role in Cosmos

    1. Robert Irion

    WASHINGTON, D.C.—The claim was a headline writer's dream: Dark energy, a hidden force that is blowing the universe apart, had varied dramatically over time and at one point even reversed direction. But while science reporters at the astronomy meeting* rushed to file their stories, most researchers were saying, “Not so fast.”

    The debate revolves around whether gamma ray bursts (GRBs), enormous explosions deep in space, can help astronomers measure distances in the universe. In the late 1990s, two research teams used the less-violent explosions of supernovae as “standard candles” of known brightness to illuminate how quickly the cosmos grew in the past. The results pointed to an accelerating universe, powered by a repulsion that seems to arise from space itself. But supernovae are too faint to shed light on cosmic expansion just a few billion years after the big bang. “Gamma ray bursts can fill in the gap,” says astronomer Bradley Schaefer of Louisiana State University in Baton Rouge.

    Schaefer studied a database of 52 GRBs detected by various satellites. Although GRBs differ wildly in their energy outputs, Schaefer claims that a careful accounting of up to five burst properties—such as their peak wavelengths of energy and their patterns of brightening and fading—enabled him to calibrate GRBs as rough standard candles and thus ascertain their distances. He found that nearly all of them—including the 12 farthest—were brighter than expected if dark energy had been constant throughout cosmic history.

    Tug of more.

    Dozens of distant gamma ray bursts (artist's view, inset) suggest that the repulsive force of dark energy is not the “constant” that many believe.

    CREDITS: B. SCHAEFER/LSU; (INSET) D. AGUILAR/HARVARD-SMITHSONIAN CENTER FOR ASTROPHYSICS

    To explain the discrepancy, Schaefer maintains that the expansion of space after the big bang slowed down much more markedly than predicted, because dark energy exerted an attractive pull at that time. The force first dwindled and then, in the past 10 billion years or so, became increasingly repulsive. But Schaefer notes there's a 3% chance his conclusion is a statistical fluke. “This is not high enough confidence to make any claims that I have formally rejected the cosmological constant,” he says. “I don't want to push the results too much.”

    Reaction to the presentation was decidedly mixed. “It's absolutely worth pursuing,” said astronomer George Ricker of the Massachusetts Institute of Technology in Cambridge. “It's the germ of a very productive idea.” And a key figure in the dark energy quest, cosmologist Michael Turner of the National Science Foundation in Arlington, Virginia, offered his guarded blessing. “The history of standard candles is extraordinarily checkered,” Turner said. “But it's a very intriguing result.”

    Others objected that Schaefer was overreaching. GRBs, they point out, arise from giant stars across a vast range of masses, spins, and compositions. When such stars create black holes at their cores and erupt with gamma rays and x-rays, the blasts are so different from one another that many observers doubt Schaefer's calibrations can succeed. What's more, several astronomers said, that variability makes GRBs ill suited to detect changes in dark energy when the universe was small, because its force at that time was nearly negligible. “It's a blunt tool to do a problem that's kind of delicate,” says supernova expert Robert Kirshner of Harvard University.

    Cosmologist Adam Riess of the Space Telescope Science Institute in Baltimore, Maryland, has even deeper qualms. Nearly all GRBs are billions of light-years away. Without nearby points of known luminosity to anchor it, Riess says, Schaefer's distance curve is mathematically unreliable and creates the illusion of a shifting constant. “I believe it is a calculation error, and he will recognize that,” Riess says.

    Schaefer intends to press onward. “Supernovae have been tremendously improved in their accuracy of standard candle-ship” in the past decade, he notes. “I expect the same will happen with GRBs.” At the very least, tracking dark energy will be the field's one constant for years to come.

    • * 207th meeting of the American Astronomical Society, 8–12 January.

  4. PSYCHOLOGY

    Hunter-Gatherers Grasp Geometry

    1. Constance Holden

    Are triangles and other geometric shapes embedded in the brain? The question of whether scientific concepts are innate is a tantalizing one for cognitive scientists. Now scientists studying villagers in a remote area of the Amazon report on page 381 that core geometric concepts are part of basic human cognitive equipment.

    Several research teams have probed the inherent mathematical sense of hunter-gatherer groups, documenting, for example, that in the absence of words for numbers, number sense grows hazy after 3 or 4 (Science, 20 August 2004, p. 1093, and 15 October 2004, p. 499). A team led by cognitive scientist Stanislas Dehaene of the Collège de France in Paris has now delved into the less-studied area of geometric knowledge. The researchers tested children and adults in an Amazonian group called the Mundurukú to see if Euclidean geometry dwells in the minds of a people who have little or no schooling, and no artifacts, such as rulers or maps, that employ geometric or metric concepts.

    Anthropologist Pierre Pica of Paris VIII University tested 14 Mundurukú children aged 6 and up and 30 adults, getting them to point to shapes displayed on his solar-powered laptop. They were shown sets of six figures and asked to point to the one in each set that diverged from a geometric figure such as a triangle or a basic concept such as parallelism or symmetry. The subjects overall got about two-thirds of the answers correct.

    For a more interactive test, the researchers concocted a map-reading task. Three containers, one holding a hidden object, were set out in a right-angled triangle in a room-sized area. After looking at a map representing the three containers, with one marked to indicate the object, the subjects were asked to find it. This required several abilities: translating two-dimensional information into three dimensions; perceiving the same pattern in a 10-fold change in scale, and locating the object based on the relationship of the three points. The success rate averaged 71%.

    On both tests, the Mundurukú children and adults performed at about the same level as a control group of 26 U.S. children tested by Harvard cognitive scientist Elizabeth Spelke. (A group of 28 U.S. adults did better.) The tests presented the same profile of difficulty in both cultures, says Dehaene, showing that “even without education, and living in isolation without artifacts such as maps, you can have a developed geometrical intuition.” As for why the Mundurukú adults, despite their experience, did no better than the children, Dehaene speculates that “they have no language for these concepts, so they stay where they are in the state of core knowledge.”

    Harvard University cognitive scientist Steven Pinker calls the paper “a nice addition to the literature on cognitive universals.” The map study, he says, “may show that everyone applies a sophisticated analysis of visual shape and configuration” even if it's not part of conscious reasoning.

    Euclid in the Amazon.

    Anthropologist Pierre Pica tests Mundurukú children on geometric concepts (top). Other villagers read a map to identify a hidden object (bottom).

    CREDITS (TOP TO BOTTOM): PIERRE PICA/CNRS PHOTOTHÈQUE; S. DEHAENE ET AL., SCIENCE

    Linguist Daniel Everett of the University of Manchester, U.K., who studies another Amazon tribe, the Pirahä, calls the work “very significant” and says he plans to test related abilities in the Pirahä. But he cautions that interpretation of such results is difficult “unless one has done a grammar of the language and a fairly thick ethnography.”

    Rosalind Arden, who has tested cognitive abilities in a South American tribe, the Aché in Paraguay, has stronger reservations about the research. Arden, a doctoral student in behavioral genetics at King's College London, contends that the tests used in the study have less to do with a “shared core of geometric knowledge” than with “general reasoning ability.” In other words, she says, the Mundurukú were simply taking a “garden-variety, nonverbal intelligence test.”

  5. NONPROLIFERATION

    India Struggles to Put Its Nuclear House in Order

    1. Richard Stone*
    1. With reporting by Eli Kintisch in Washington, D.C., and Pallava Bagla in New Delhi.

    Last year, the United States set out to bring India into the fold with a landmark agreement that would end the country's pariah status as a nonsigner of the Nuclear Nonproliferation Treaty (NPT). But that deal is now at risk as U.S. and Indian officials in New Delhi wrangle over a plan to split up India's vast nuclear establishment into distinct civilian and military programs. The thorniest issue, Science has learned, is that India's draft separation plan designates several key facilities—including all R&D centers—as military installations, placing them off-limits to nonproliferation safeguards.

    India's stance could scuttle the deal, nonproliferation experts warn. The two countries are racing to find a compromise before U.S. President George W. Bush visits India for a summit with Indian Prime Minister Manmohan Singh in early March.

    Sweeping aside decades of animosity over India's nuclear ambitions, Bush and Singh last July signed an agreement that would end an embargo that forbids NPT signers from trading with India in nuclear materials and technology. In exchange, India would allow the International Atomic Energy Agency (IAEA) to inspect civilian facilities. India pledged to erect a firewall between these installations, which would acquire nuclear know-how from abroad, and military ones beyond the IAEA's reach. This separation is “arguably the most important of [India's] commitments,” the U.S. State Department's lead negotiator, R. Nicholas Burns, under secretary for political affairs, testified in Congress last November.

    Under lock and key.

    India's draft plan to fission its nuclear establishment designates the majority of installations as noncivilian, including controversial facilities such as Kalpakkan (inset) and the CIRUS reactor, putting them outside international control.

    SOURCE: INSTITUTE FOR SCIENCE AND INTERNATIONAL SECURITY; (PHOTO INSET) P. BAGLA

    It's also deeply challenging to India's government—and a political lightning rod. In India, “the hard-liners do not want this agreement, because they feel it will impinge on the military effort,” says Kenneth Luongo, executive director of RANSAC, a nonproliferation think tank in Washington, D.C. As part of the agreement, India would forswear further nuclear weapons tests, thus freezing development of its arsenal.

    Also disconcerting to hawks within India is that the separation plan would unravel the deliberate ambiguity around India's nuclear program. “For historical reasons, no facilities are clearly demarcated as civilian or military,” says T. S. Gopi Rethinaraj, an arms-control expert at the National University of Singapore. Hundreds of nuclear specialists divide their time between civilian and weapons R&D. Like an operation to separate conjoined twins who share vital organs, splitting the nuclear establishment will be complex. “In identifying civilian nuclear facilities, we have to determine that they are of no national-security significance,” Anil Kakodkar, chief of India's Atomic Energy Commission, told reporters at a recent press conference. “We will do this in a phased manner.”

    Other concerns divide U.S. policymakers, the nuclear industry, and the nonproliferation community. The United States stands to gain lucrative contracts to supply fuel and technology to India's fast-growing nuclear energy sector, and India has pledged not to export enrichment or reprocessing technologies to states without such a capacity. But some have doubts: What if India were not a reliable partner? What if it diverted new technology to weapons R&D, either on the sly or by reneging on the deal? “India may well become another source for illicit nuclear trade,” asserts nonproliferation expert David Albright, president of the Institute for Science and International Security, a think tank in Washington, D.C.

    As Burns explained to Congress, “We concluded we had a better chance to have India meet international nonproliferation standards if we engaged rather than isolated it.” He added that he has urged India “to craft a credible and transparent plan.”

    Its outlines are now emerging. In December, a delegation to Washington, D.C., led by Indian Foreign Secretary Shyam Saran shared with U.S. officials the first draft of a separation plan. It fell short of U.S. expectations, with several supposedly civilian facilities on the military list, says a U.S. State Department official. The tug of war includes CIRUS, a reactor in Mumbai presumed to have produced plutonium for weapons; a centrifuge hall in Mysore that enriches uranium for naval reactors, analysts claim; and fast-breeder reactors and a fuel reprocessing plant in Kalpakkam (see map).

    CIRUS is burdened with Cold War baggage. When India purchased the heavy-water research reactor from Canada in 1956, it pledged to use it only for peaceful purposes. But analysts assert that CIRUS cranked out plutonium for India's first fission devices, tested in 1974. Despite claims that the devices were for peaceful uses, like oversized sticks of dynamite, the United States assumed the worst and spearheaded a 30-year drive to choke off the flow of nuclear technologies to India. India declared itself a nuclear power after a second round of tests in 1998.

    CIRUS was the sole source of plutonium for India's stockpile until Dhruva, a larger heavy-water reactor, came on line to augment production in 1985. India's December opening bid places CIRUS on the military list, excluding it from inspection. But U.S. officials argue that declaring it civilian would dissipate lingering bitterness over India's failure to keep its “peaceful uses” pledge in the past. If India were to acquiesce and declare CIRUS civilian, it might build an upscale version of Dhruva or convert a power reactor into a weapons facility, says Rethinaraj. Construction of new military facilities is not prohibited under the U.S.-India deal. Further complicating matters, CIRUS is located in the heart of the Bhabha Atomic Research Centre (BARC), much of which, including Dhruva, is on the military list.

    Kalpakkam represents a different kind of headache. The fast-breeder reactors there are testing a blend of uranium and plutonium fuel for civilian power reactors. But the reprocessing facilities that extract plutonium from spent fuel could just as well produce nuclear material for bombs. India's breeders are meant to be a bridge from its current power plants, which draw on India's dwindling uranium reserves, to future reactors that tap the country's vast supplies of thorium (Science, 19 August 2005, p. 1174). (India has placed its thorium facilities on the military list as well, it says, to protect the intellectual property of its designs.)

    Some observers hold that the nuclear pact undercuts Kalpakkam's economic rationale because India could import uranium, postponing the use of thorium reactors. Kakodkar insisted that India will stick with the development of fast breeders, not only for electricity generation but also because thorium reactors would benefit from the design experience. The bottom line, he said, is that India will not submit any of its R&D centers to safeguards, including the Indira Gandhi Centre for Atomic Research in Kalpakkam.

    A third flash point is the Rare Materials Project (RMP) in Mysore. At this facility, uranium hexafluoride gas is fed into a centrifuge cascade that boosts the concentration of the fissile isotope uranium-235. Analysts link this enrichment facility to India's classified program to develop naval reactors; they point out that it could just as easily churn out bomb-grade uranium for weapons. Last month, A. N. Prasad, a former BARC director, insisted in The Hindu newspaper that the RMP “cannot even be discussed, let alone safeguarded.”

    Whatever happens to the facilities, some experts argue that by pledging to uphold a moratorium on testing, India has in effect sworn not to refine its nuclear arsenal. “That's the greatest achievement of the deal,” asserts Rethinaraj. It's unclear whether the U.S. Congress will buy that if it has qualms over the separation plan. Burns and his team were in New Delhi earlier this week for further negotiations. Engagement with India—or continued isolation—is still on the table.

  6. CNRS SHAKEUP

    France's Basic Science Agency Hopes New Lineup Will Resolve Crisis

    1. Barbara Casassus*
    1. With reporting by Martin Enserink.

    PARIS—France's leading basic research agency, CNRS, is struggling to get back on course after the abrupt loss of two top managers. CNRS President Bernard Meunier resigned on 5 January; 4 days later, the number two, Director Bernard Larrouturou, was fired. This ended a damaging standoff at CNRS over the selection of department directors, according to Research Minister François Goulard, who told Science that Prime Minister Dominique de Villepin approved his decision to replace Larrouturou. It had been an open secret for months that the two Bernards were at loggerheads (Science, 27 May 2005, p. 1243).

    Larrouturou, meanwhile, vigorously defended his tenure at a press conference on Tuesday and in a letter to the CNRS staff. (A handout for reporters listed 12 frequent criticisms of the agency and declared each of them “FALSE!”) In the letter, Larrouturou said that the decision to fire him was “reactionary” and that the disagreement between Meunier and him was “deliberate and organized” to thwart the reform plans (www.cnrs.fr/Lettre_aux_personnels_01051.pdf).

    Most of the CNRS management team backed Larrouturou in a public statement last week. The research unions and the protest movement Sauvons La Recherche (SLR) also objected to his ouster, even though they had opposed his plans for CNRS and continue to oppose the government's science reform bill that will become law this month. SLR decried the government's “hostile decision” to remove Larrouturou, saying that it was illogical to approve the reform and then fire its architect. But Goulard rejects that argument: “One can agree with a director's reform but not necessarily agree with all his policies.”

    Moving swiftly, the government last week installed a new president: Catherine Bréchignac, a physicist and CNRS director from 1997 to 2000. Arnold Migus, a physicist and director of the French Institute of Optics in Orsay, was set to take Larrouturou's place, but Goulard intends to merge the two top CNRS positions by decree. Bréchignac will be the first to hold the new post, he says. Migus will remain second in command.

    Return engagement.

    Catherine Bréchignac gets a second tour as CNRS president.

    CREDIT: E. LEGOUHY/CNRS PHOTOTHÈQUE

    Jacques Fossey, general secretary of SNCS, the leading research union, says that despite previous disagreements with Bréchignac, “we were able to work with her.” Whether Bréchignac will heed calls to scrap Larrouturou's reform plan and start over remains to be seen. “It is up to the management to decide on the agency's internal organization,” says Goulard. It's not likely to be thrown out, he adds, although he doesn't rule out some improvements.

  7. SOUTH KOREAN SCIENCE

    Armed With Cash, Institute Chief Launches an Education 'Blitzkrieg'

    1. Richard Stone*
    1. With reporting by Ahn Mi-Young, a freelance writer in Seoul.

    DAEJEON, SOUTH KOREA—For months, Robert Laughlin has talked up plans for transforming one of South Korea's top science universities into an academic powerhouse able to compete with the likes of the Massachusetts Institute of Technology. Now the Nobel laureate physicist has a war chest to make it happen. South Korea's legislature has approved the first installment of a $97 million “globalization package” for the Korea Advanced Institute of Science and Technology (KAIST) in Daejeon, a science city 150 kilometers south of Seoul. “It's time for a blitzkrieg,” Laughlin says.

    In December 2004, a few months after being appointed KAIST president, Laughlin roiled the campus with a proposal to triple KAIST's enrollment and shift the balance toward undergraduates, quadruple tuition charges, and transform in-house research from an industry subsidy into a money spinner. Critics denounced the plan as disruptive (Science, 25 February 2005, p. 1181). “It was such a shock,” says nuclear engineer Chang Soon Heung, a KAIST vice-president. “We were afraid he would mess up our efforts to raise funds and attract students.” Science ministry officials repeatedly ruled out tuition hikes. “They said, ‘No, no, no,’” Laughlin says, but promised support. “I said, ‘Show me the money.’”

    Bold moves.

    Robert Laughlin says he aims to “internationalize” the Korea Advanced Institute of Science and Technology.

    CREDIT: COURTESY OF KAIST

    Now they have. The ministry has set up a special fund of 20 billion won ($19.4 million) per year over the next 5 years to make KAIST more competitive; on 30 December 2005, the National Assembly approved the 2006 allotment. Although the increase is less than 10% of KAIST's $200 million budget, it will allow the university to raise the fraction of foreign faculty to 15% and aim to teach all graduate courses in English by 2010, among other changes. (Currently, about one in three are in English.) “We're trying a bold experiment to internationalize students,” Laughlin says. “It's what the parents want.”

    Top science students tend to enroll at Seoul National University, Laughlin says, unless they flunk SNU's tough English entrance exam. That means that the best KAIST students often have poor English skills. Many KAIST faculty members, however, are SNU grads proficient in English. Last year, Laughlin canvassed faculty members to see who would lecture in English rather than Korean. “They didn't want to do this at first,” he says, “but I got big smiles when I mentioned they'd be paid a bonus.” The fund will also strengthen KAIST's R&D, allowing Laughlin to award seed money for innovative projects and lure talent with handsome start-up packages.

    Although Laughlin now has more spending power, the blunt-talking reformer also has fences to mend. He has made enemies in prodding professors to compete for grants and for failing to aggressively court corporate R&D sponsors, such as the semiconductor giant Samsung Electronics. “He just pushes his way without listening to us and thus lowers our morale,” claims one senior professor.

    Even Laughlin's fiercest critics, though, admire the accomplished scientist as a role model for Korean students and credit him for attracting more top-notch students to KAIST. “This is a conflict between two different visions,” says Kim Sang-Soo, KAIST's vice president of operations. Laughlin agrees—and vows to press ahead with implementing his vision. The “real reforming,” he says, “hasn't happened yet.”

  8. SCIENTIFIC PUBLISHING

    Hwang Aftereffects Reverberate at Journals

    1. Jennifer Couzin,
    2. Constance Holden,
    3. Sei Chong

    As Science announced its retraction last week of two fraudulent papers by teams led by Woo Suk Hwang of Seoul National University, other journals that had published papers by the disgraced Korean scientist or his colleagues at MizMedi Hospital in Seoul were investigating whether phony or misleading data had appeared in their pages, too.

    Hwang and his co-authors published a flurry of papers in at least nine journals within the past 2 years. Molecules and Cells, a Korean journal that published several papers last year on human embryonic stem (ES) cells and cloning by the MizMedi co-authors, told Science it would formally retract three papers on 28 February. Associate Editor Ahn Kwangseog said photographs used in those papers also appeared in papers submitted to Science, Stem Cells, Reproduction, and Biology of Reproduction.

    Biology of Reproduction has already retracted one paper—on an animal-free culture system for human ES cells—because of apparent duplication of images that also appeared in the 2004 Science paper. Judith Jansen, managing editor of the journal, says she does not know whether additional papers have problems; the journal has published at least four co-authored by either Hwang or the MizMedi group. “We're looking at everything that we have,” Jansen says.

    The journal Stem Cells has expressed “concern” about a technical paper from MizMedi researchers on the cultivation of human ES cells, citing apparent duplications of images within the paper as well as use of an image that also appeared in the 2004 Science paper. Editor-in-Chief Curt Civin of Johns Hopkins University in Baltimore, Maryland, says the authors have acknowledged “mistakes.” The journal is awaiting results of investigations under way in Korea to determine whether the paper is still valid.

    At Molecular Reproduction and Development, editors are sifting through at least six Hwang-authored papers, all of them involving research with animals, while they await results of investigations under way in Korea and at the University of Pittsburgh, according to Susan Spilka of the publisher, John Wiley & Sons.

    No end in sight.

    More papers by the Hwang team are under investigation.

    CREDIT: LEE JAE-WON/REUTERS

    Several other journals published papers detailing animal studies by Hwang or the MizMedi group. Anthony Trioli of Elsevier, publisher of Theriogenology, says it is looking into an unspecified number of papers; the results aren't expected for several weeks.

    A spokesperson for the publisher of the Korean Journal of Veterinary Science, said the journal is not investigating a Hwang paper from last year.

  9. DRUG DEVELOPMENT

    Drugs Inspired by a Drug

    1. Jean Marx

    Endocannabinoids, substances in the brain and body mimicked by marijuana's active ingredient, are inviting therapeutic targets for conditions from obesity and pain to addiction and osteoporosis

    CREDIT: CORDELIA MOLLOY/PHOTO RESEARCHERS INC.

    Whatever one's view of its legality, there's no denying that marijuana is a potent drug that has a strong impact on the brain and the rest of the body. In addition to producing an intoxicating “high,” marijuana can ease anxiety and pain, stimulate hunger, and impair memory. The drug also has a long history in folk medicine. Over the centuries, it's been used for ills such as menstrual pain and the muscle spasms that afflict multiple sclerosis sufferers and others.

    Now, medicine may be on the doorstep of a new era of drug development, one centered not on marijuana itself but instead inspired by the discovery more than a decade ago that its primary active ingredient, a chemical called tetrahydrocannabinol (THC), mimics natural chemicals acting in the brain and elsewhere in the body. Like many other drugs, THC exerts its effects by binding to receptors, proteins located on the surface of neurons and other cells that are the targets of naturally occurring regulatory molecules—in this case, ones dubbed endocannabinoids, after the marijuana-producing plant Cannabis sativa.

    In the past few years, a torrent of research has pointed to the endocannabinoids and their receptors as major targets for drug development. “Endocannabinoids apparently act in just about every system people have looked at,” says THC discoverer Raphael Mechoulam of Hebrew University Medical Faculty in Jerusalem, Israel. The systems include those controlling learning and memory, appetite and metabolism, blood pressure, emotions such as fear and anxiety, inflammation, bone growth, and even the growth of certain cancers. Consequently, depending on the condition they aim to treat, drug developers are rushing to identify compounds that either turn up endocannabinoid function or dampen it.

    The drug closest to the clinic is rimonabant, an endocannabinoid blocker under development by the French pharmaceutical company Sanofi-Aventis. Clinical trials reported last year showed that the drug can aid in controlling obesity, as well as metabolic syndrome, a constellation of conditions including high blood pressure and elevated blood lipids that often accompanies obesity and predisposes individuals to cardiovascular disease. Researchers from Sanofi-Aventis and elsewhere are now exploring whether rimonabant can be used to help smokers and alcoholics kick their habits.

    Although efforts to develop agents that enhance endocannabinoid activity are less advanced, such compounds are undergoing preclinical testing for the treatment of several conditions, including epilepsy, pain, anxiety, and diarrhea. “There are several possible therapeutic strategies we can use to exploit our knowledge of how endocannabinoids are regulated,” says Vincenzo Di Marzo of the University of Naples, Italy.

    Target identified

    Endocannabinoid research got off to a slow start. The modern era began in 1964 when Mechoulam and his colleagues isolated THC and determined its structure, which proved to be lipidlike. That may have been one reason why interest in THC lagged early on. Lipids are “greasy, messy little molecules that are hard to do anything with,” says Bradley Alger, an endocannabinoid researcher at the University of Maryland School of Medicine in Baltimore.

    Most known signaling molecules, such as neurotransmitters and hormones, are amino acids and peptides: substances that need to interact with specific receptors to exert their effects. But lipids can pass directly into cell membranes, and some researchers thought that THC might exert its effects by simply dissolving in, and disrupting the function of, nerve cell membranes. Such a nonspecific mechanism of action would make it very difficult to design drugs that mimic THC's desirable effects without causing the psychoactive ones as well.

    In the mid-1980s, however, the tide turned in favor of a distinct THC receptor when Allyn Howlett's team, then at St. Louis University Medical School in Missouri, linked THC activity to adenylate cyclase, an enzyme well known to help transmit signals from receptors to the cell interior. In 1990, Lisa Matsuda, Tom Bonner, and colleagues at the National Institute of Mental Health finally cloned a THC receptor, from a rat brain, although it's since been found in many peripheral tissues as well.

    The discovery of this receptor, now called CB1, meant that the brain must have its own THC-like molecules, as the body doesn't maintain receptors just for the components of psychoactive weeds. Mechoulam's group identified the first of these endogenous cannabinoids, called anandamide, in 1992, and a few years later followed up with a second, 2-arachidonylglycerol (2-AG). These compounds have more than one target: In 1993, Muna Abu-Shaar and colleagues at the Medical Research Council Laboratory of Molecular Biology in Cambridge, U.K., cloned a second cannabinoid receptor, CB2, which occurs mainly on cells in the body periphery.

    Stopping the munchies

    The endocannabinoid field began to take off in the years that followed. “We have made a lot of progress, mainly due to the fact that we've discovered the receptors and their endogenous ligands,” says Daniele Piomelli of the University of California (UC), Irvine. Researchers began to pursue several strategies for exploring the functions of the endocannabinoids. For example, they designed chemicals that either mimic endocannabinoid action at their receptors or block it.

    Rimonabant, which was identified in 1994 by a team of Sanofi-Aventis scientists, was one of the first inhibitors to come out of these efforts. The researchers found that it preferentially binds to CB1, thereby blocking endocannabinoid action at that receptor but not at CB2. They also found that rimonabant promotes weight loss.

    Marijuana users have known for years that smoking a joint causes the “munchies,” stimulating their appetite for food. Indeed, people suffering from debilitating diseases such as AIDS sometimes use marijuana as an appetite aid. It therefore hasn't been a huge surprise that several teams have shown that THC and endocannabinoids stimulate food intake by mice. In contrast, mice administered rimonabant eat less.

    Endocannabinoids may be part of the system by which the hormone leptin controls food intake and metabolism. One hint of this came in a 2001 study on mutant mice that don't make leptin and therefore overeat and become extremely obese. George Kunos, Di Marzo, who was then on sabbatical in the Kunos lab, and their colleagues at the Medical College of Virginia in Richmond found that in such mice, endocannabinoid levels are much higher than normal in the hypothalamus, a brain region involved in appetite control. Treating the rodents with leptin brought the levels down.

    In the 22 December 2005 issue of Neuron, Lorna Role and her colleagues at Columbia University College of Physicians and Surgeons in New York City provided a possible mechanism to account for how leptin suppresses endocannabinoids: Endocannabinoid production is stimulated by the influx of calcium ions that occurs when nerve cells respond to appropriate neurotransmitters, and leptin inhibits this influx.

    Even as the evidence linking endocannabinoids to appetite control was building, Sanofi-Aventis embarked on a series of clinical trials designed to test rimonabant's effectiveness as an antiobesity drug. The promising results from two of these, one including 1507 subjects, most of whom live in Europe, and the other, including 1306 North American subjects, were published last year. (The European study appeared in the 16 April 2005 issue of The Lancet, and the North American study was in the 17 November 2005 issue of the New England Journal of Medicine.)

    In both studies, which produced similar findings, all the patients were on a reduced-calorie diet. But whereas controls lost only 2 to 3 kilograms of weight over the year's course of treatment, individuals who also took 20 milligrams of rimonabant a day lost 8 to 9 kilograms. Perhaps even more important, says Jean-Pierre Després of the Laval Hospital Research Center in Montreal, Canada, who directed the North American study, those taking the drug showed greater reduction in abdominal fat deposits, which are a known risk factor for diabetes and heart disease. “To me,” he adds, “rimonabant is more of a cardiovascular drug than a weight-loss drug.”

    Major player.

    CB1 receptors (red) are widely distributed in the brain.

    CREDIT: K. MACKIE/UNIVERSITY OF WASHINGTON

    Indeed, rimonabant appears to have benefits beyond simple weight loss. In order to be eligible for the trials, the subjects also had to have additional risk factors for heart disease, such as high blood pressure or elevated levels of blood lipids including cholesterol. Those risk factors also showed greater improvement in the treated subjects than in controls, apparently even more than could be expected from the weight loss alone. “Only about 50% of the metabolic effects were due to weight loss,” says Di Marzo. “There seems to be some direct effect on fat cells.”

    There is support for that idea from animal work. For example, Beat Lutz's team at the Max Planck Institute of Psychiatry in Munich, Germany, working with that of Uberto Pagotto at Sant Orsola-Malpighi Hospital in Bologna, Italy, found that mice lacking the CB1 receptor stay very lean throughout life. This can't be totally due to reduced feeding: Although the animals do eat less while young, they eventually eat more food—but still maintain their sleek physiques.

    Researchers, including the Sanofi-Aventis team and that of Kunos, now at the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in Bethesda, Maryland, have found that endocannabinoids can act directly on both fat and liver cells in ways that lead to increased synthesis of fatty acids. “Blocking this promotes fat-burning,” Kunos says. This may be another way rimonabant keeps weight down.

    Diet drugs, which typically have to be taken long term, have had a checkered history, so researchers will be closely watching the safety of rimonabant. So far, it appears to be well tolerated. Robert Anthenelli of the University of Cincinnati College of Medicine in Ohio, who has conducted clinical trials with the drug, describes its side effects, including nausea, diarrhea, and depression, as generally “mild and transient.”

    Smoke signals

    Anthenelli directs an effort aimed at finding out whether rimonabant can help with another major cardiovascular risk factor: smoking. About 3 years ago, Caroline Cohen, Philippe Soubrie, and their colleagues at Sanofi-Aventis showed that the drug reduces self-administration of nicotine by rats. Nicotine, like other addictive drugs, hooks its users by triggering release of the neurotransmitter dopamine in the brain's pleasure centers, and the researchers found that rimonabant reduces that release. These results suggested that the drug might aid smoking cessation and, given its other effects, help prevent something that is often a bane for smokers trying to quit: weight gain.

    None of the results from the smoking trials have yet made it into print, but about 2 years ago, Anthenelli described early findings from STRATUS-US (Studies with Rimonabant and Tobacco Use in the United States) at the annual meeting of the American College of Cardiology. The 787 participants were divided into a control group whose members received a placebo and two treatment groups, one of which got 5 milligrams of rimonabant a day whereas the other got 20 milligrams. The quit rates of people in those two groups were about double those of the controls, Anthenelli says, “and they had less weight gain, at least in the short term.”

    NIAAA is also currently sponsoring a phase II trial to see whether rimonabant curbs alcohol consumption in heavy drinkers. And although the work is not yet nearly as advanced as that on obesity and smoking, rimonabant and other CB1 inhibitors are being tested as possible therapies for a number of additional conditions in which endocannabinoids are implicated. Last year, for example, Di Marzo, working with Jonathan Brotchie at Toronto Western Research Institute in Canada, reported results indicating that endocannabinoid activity contributes to Parkinson's disease symptoms.

    The researchers created a nonhuman primate model of the disease by treating marmosets with the chemical MMTP, which destroys the same brain area that degenerates in Parkinson's disease. They found that treating these animals with rimonabant improved their ability to perform voluntary movements, which are impaired in Parkinson's disease. In addition, when administered together with levodopa, the standard Parkinson's drug, rimonabant ameliorated the abnormal involuntary movements that are a distressing side effect of levodopa treatment.

    CREDIT: COURTESY OF RAPHAEL MECHOULAM

    The actions of endocannabinoids outside the brain are also stirring clinical interest. In the late 1990s, Kunos and his colleagues showed that the chemicals underlie the low blood pressure of hemorrhagic shock. As a result of hemorrhagic bleeding, Kunos says, “the macrophages of the immune system are activated. They produce anandamide, which attaches to the linings of the blood vessels and heart. This causes vasodilation and thus decreased blood pressure.”

    Since then, the Kunos team has shown that endocannabinoids also contribute to low blood pressure associated with cirrhosis of the liver and with septic shock, which is induced by the toxins produced by certain pathogenic bacteria. In those instances as well, activated macrophages are apparently releasing anandamide. In all these cases, rimonabant blocked the drop in blood pressure, suggesting that the CB1 inhibitor might be useful for treating the conditions.

    Strong bones, no high

    In many other conditions, the goal is not blocking endocannabinoids but the somewhat more difficult task of enhancing their activity. One way to do this is with compounds that mimic endocannabinoid actions on their receptors, as long as this can be done without also causing the high that marijuana is famous for.

    This may be easier to accomplish with the CB2 receptor, which is found mostly on peripheral cells. In 1999, for example, Mechoulam and his colleagues came up with a compound dubbed HU-308 that specifically triggers CB2 receptors. HU-308 produces no behavioral effects, at least in mice. In this week's issue of the Proceedings of the National Academy of Sciences, Itai Bab (also at the Hebrew University of Jerusalem), Mechoulam, and colleagues describe results indicating that a CB2 activator might help combat osteoporosis, the common bone-thinning disease. They found that if CB2, but not CB1, is knocked out in mice, the animals show bone loss much like that in osteoporosis patients. HU-308 can counteract that by stimulating the activity of bone-forming cells while at the same time turning down the activity of cells that degrade bone. The drug also prevented most of the bone loss that ordinarily occurs in female mice whose ovaries have been removed to mimic the osteoporosis that occurs in women after menopause.

    Stimulating CB1 receptors could be more problematic. They are so widely distributed throughout both the brain and body periphery that activating them indiscriminately could cause a host of unwanted side effects. So instead of turning up the receptors, researchers are taking a different tack: blocking the enzymes that inactivate endocannabinoids after they've done their job. Drug developers have an advantage here in that the compounds are not made all the time, but only when and where needed, and then are quickly destroyed. “These lipid signaling molecules are probably made and broken down ‘on demand,’” says Benjamin Cravatt of the Scripps Research Institute in La Jolla, California.

    So even though an inhibitor of a degradative enzyme would be present throughout the body, it should only buttress an endocannabinoid's action at the sites where it is actually being produced. The Cravatt team has discovered an enzyme called fatty acid amidohydrolase (FAAH), which breaks down anandamide. Cravatt, Piomelli, and others have identified inhibitors of FAAH and also of monoacylglycerol lipase, the enzyme that degrades 2-AG. These inhibitors may have several therapeutic applications given that endocannabinoids seem to protect against a variety of ills.

    One such ill is high blood pressure. Two years ago, the Kunos team found elevated levels of both anandamide and CB1 receptors in the blood vessels and hearts of rats that spontaneously develop hypertension. Given that anandamide is known to lower blood pressure, Kunos speculates that the changes are an effort by the body to counteract the blood pressure rise, even though it does not return the animals' blood pressures to normal. Consistent with this idea, Kunos and his colleagues found that an FAAH inhibitor lowers the blood pressure of the hypertensive rats.

    Recent research suggests that tissue-damaging inflammation might also be treated with agents that bolster endocannabinoid activity. In 2004, for example, Lutz's group showed that mice lacking CB1 receptors developed much more severe inflammation of the intestines when treated with a chemical irritant than did normal animals. In contrast, animals unable to make FAAH were protected from the irritant's effects—an indication that drugs that inhibit the anandamide-degrading enzyme might treat inflammatory bowel conditions such as Crohn's disease.

    Endocannabinoid protection against inflammation extends into the brain. In the January issue of Neuron, Oliver Ullrich of Otto von Guericke University in Magdeburg, Germany, and his colleagues report elevated anandamide concentrations in the brains of multiple sclerosis patients. Further work with mouse brain tissue in lab cultures suggests that the anandamide increase is an effort by the brain to ward off the damaging effects of immune cells called microglia.

    By causing inflammation, microglia ordinarily worsen the damage caused to brain neurons by the excitatory neurotransmitter glutamate. But the researchers found that anandamide suppressed that inflammation whereas CB1 and CB2 inhibitors increased it. Such data may help explain why the drug Sativex, a standardized extract of marijuana plants produced by GW Pharma in the United Kingdom, seems effective against MS spasticity.

    Skeleton preserver.

    Bone from a mouse lacking CB2 receptors (right) is much less dense than bone from a normal mouse (left).

    CREDIT: O. OFEK ET AL., PNAS 103, 696 (2006)

    Endocannabinoids may also protect brain neurons directly against excitotoxic damage. About 2 years ago, Lutz, now at the University of Mainz in Germany, and his colleagues genetically engineered mice so that they lacked CB1 receptors in the main neurons of the forebrain, but not in the mossy neurons that feed them inhibitory signals. The researchers then injected the excitotoxin kainic acid into the brains of both those animals and of normal mice. They found that anandamide levels went up in the hippocampus of all the mice, but those lacking the CB1 receptors in their forebrain neurons suffered much more severe seizures and neuronal damage than did the controls.

    Gut protector.

    An irritating chemical causes much more severe inflammatory changes in the colon of a mouse lacking CB1 receptors (right) than in a normal colon (left).

    CREDIT: F. MASSA ET AL., JOURNAL OF CLINICAL INVESTIGATION 113, 1202 (2004)

    “The endocannabinoid system is like a brake in the brain so as not to have excessive neuronal activity,” says Lutz. Drugs that boost endocannabinoid action by inhibiting their breakdown might therefore be useful for treating epilepsy, which occurs when neurons fire excessively, and neurodegenerative conditions such as Alzheimer's and Parkinson's disease, where excitoxicity is thought to play a causative role.

    Combating pain and anxiety

    If drug companies can develop safe and effective ones, endocannabinoid boosters might also tackle pain. Several years ago, UC Irvine's Piomelli and his colleagues showed that injecting anandamide into the paws of mice before injecting the noxious chemical formalin ameliorates the pain responses the animals would otherwise show. In contrast, injections of both CB1 and CB2 receptor inhibitors exacerbated those responses.

    In that case, the endocannabinoid was acting to block the initiation of pain responses in the periphery. But about 6 months ago, the Irvine group showed that anandamide and 2-AG also contribute to something called stress-induced analgesia, in which the brain's pain-suppressing pathways are activated by an acute stress, such as an injury. They found that inhibitors of the degradative enzymes for both endocannabinoids enhance this pain suppression. Such inhibitors have also shown promising results in animal models of depression and anxiety.

    Even phobias and posttraumatic stress disorder (PTSD) may be amenable to treatment with endocannabinoid boosters. When animals are repeatedly subjected to a noxious stimulus, such as a mild shock, that is paired with a innocuous stimulus, such as a tone, they will eventually learn to react with fear, by jumping, say, in response to the tone alone. Over time, that response will be lost in the absence of further shocks. About 3 years ago, Lutz and his colleagues showed this “extinction” of an aversive memory requires endocannabinoids. For example, they found that extinction did not occur in mice lacking CB1 or given rimonabant.

    About a year ago, a team led by Kerry Kessler of Emory University School of Medicine in Atlanta, Georgia, extended these results, showing a similar involvement of endocannabinoids in extinction of aversive memories in rats. The Emory team also demonstrated that they could enhance that effect by giving the animals a compound that inhibits endocannabinoid breakdown. Because there are parallels between fear conditioning in animals and PTSD, phobias, and other types of human anxieties, the researchers suggest that these conditions might be among those that would benefit from enhancing endocannabinoid activity.

    And if all that hasn't been enough to draw the attention of basic scientists and drug developers, evidence from Di Marzo's group indicates that the chemicals even limit the growth of cancer cells. About 3 years ago, the researchers found that anandamide and 2-AG levels are elevated in samples of human colon cancers. This again appears to be a defensive response, as work with cultured human cancer cells, and more recently with thyroid tumors implanted in mice, shows that endocannabinoids inhibit tumor cell proliferation.

    “There's an overwhelming flood of literature on endocannabinoids,” Lutz says. “If you go to MEDLINE, almost every day you find a nice paper.”

  10. ARCHAEOLOGY

    Rising Water Poses Threat to Egypt's Antiquities

    1. Andrew Lawler

    Crop irrigation and inadequate sewers may sink Egypt's famed ancient temples and burial sites into a watery grave

    LUXOR, EGYPT—The god Amun created the first solid ground, pushing back the waters of the primeval sea, according to Egyptian mythology. But his formidable powers may not be enough to save his own temple and other famous archaeological sites from rising waters along the Nile River. Amun's temple complex of Medinet Habu, which has survived 21 centuries in the desert, is now threatened by salty groundwater eating away at its foundations. “See this deterioration?” says University of Chicago epigraphist Brett McClain, pointing at flaking stone along the base of a temple wall. “This was not happening a few years ago.”

    Crumbling splendor.

    A rising water table threatens Luxor Temple.

    CREDIT: GAVIN HELLIER/GETTY IMAGES

    Although officials disagree about the prime culprit, a combination of agricultural practices and inadequate sewers have combined to raise the water table several meters around Luxor, posing a silent threat to scores of temples and tombs critical to scholars such as McClain as well as to the tourism industry. “When I found out that the Temple of Luxor and the Temple of Karnak were going to completely fall apart because of the rising water table, I was shocked,” says Zahi Hawass, director of Egypt's Supreme Council of Antiquities.

    Hawass is overseeing efforts to reduce the damage, including digging huge channels around the threatened monuments. “Because the rising water table can damage everything, this project is my top priority,” he says. But bureaucratic intransigence may stall longer term solutions, such as convincing nearby farmers to switch crops.

    In 2004, as damage reports came in from sites such as Medinet Habu, Hawass commissioned SWECO, an engineering firm based in Stockholm, to come up with a plan to protect the Luxor region. Luxor, an important religious and political center in ancient Egypt, is the source of thousands of inscriptions and images—many with their original paint still intact—that reveal the details of Egyptian life 3 millennia ago. The area also is critical for generating tourism revenue for Hawass's organization; it is second only to the Giza pyramids in popularity among visitors.

    The study found that the temples' soft sandstone is absorbing rising groundwater, and with it, high levels of salt. When the water evaporates, the salt crystallizes, filling the porous rock. For an immediate fix, a Cairo-based firm, Egypco, is building drainage canals around both temples to drain the water west to the Nile; the project is under SWECO's supervision and uses $7 million in funding from the U.S. Agency for International Development (USAID). The work began a year ago and is due for completion this summer, says USAID official James Harmon. The projects should lower the groundwater around both temples by 2 meters or so, protecting the massive foundations that support thousands of tons of stone.

    Hawass blames most of the groundwater problem on inadequate sewers, particularly on the crowded East Bank near the temples of Luxor and Karnak. A new sewage system at Karnak has led to a half-meter drop in groundwater levels, agrees Raymond Johnson, field director at the University of Chicago's center in Luxor. But Johnson and others point to the cultivation of sugar cane as the prime culprit, especially on the West Bank, home to Medinet Habu and a host of other temples and tombs. There, irrigation canals suck water from the Nile into what was once desert. Johnson notes that farmers regularly flood fields to speed the growth of sugar cane, thus keeping the ground saturated. “The canals never dry out, so the groundwater remains high,” he says.

    Flawed foundation.

    Epigraphist Scott McClain finds water damage at Medinet Habu.

    CREDIT: A. LAWLER/SCIENCE; K. BUCKHEIT/SCIENCE (MAP)

    Johnson and other foreign experts argue that the best solution is to stop growing sugar cane near monuments. “Plant beans or flowers instead—something which uses less water—with the help of economic incentives,” urges Johnson. But that would require cooperation among several ministries, and the Egyptian government strongly subsidizes the sugar industry, says one foreign expert who declines to be named. All the same, “given that priceless antiquities are a key part of the GDP [gross domestic product], I don't think this is a good tradeoff,” the foreign official adds. But Hawass isn't optimistic about influencing farmers: “It would be pretty much impossible to change agricultural practices, so we will focus on engineering solutions.”

    The problem on the West Bank of Luxor—where sugar cane cultivation is pervasive—is increasingly acute. Standing water can be seen in what remains of Amenhotep III's mortuary temple; Medinet Habu lies just a kilometer or two away on what once was desert. Johnson fears that the water is creeping west toward the Valley of the Queens and even the Valley of the Kings, home to Egypt's most spectacular—and vulnerable—tombs. Hawass insists those areas will remain high and dry. But plans are on the drawing board to build large drainage systems to move water on the West Bank back to the Nile, although the cost remains uncertain.

    For researchers such as Johnson, who runs the University of Chicago's cataloging and restoration effort at sites such as Medinet Habu and the Luxor Temple, the rising groundwater is not the only threat. He notes an ominous increase in humidity and rainfall that threatens the fragile carvings and paintings, the bread and butter of current Egyptology. “In the last 20 years, we've watched the monuments age,” he says.

    Hawass and foreign archaeologists agree that the crisis requires immediate action. “If you don't start lowering the water table now, we'll start losing these monuments,” says Johnson. If the effort fails, a large portion of Egypt's illustrious past may sink back into the primordial waters.

  11. ARCHAEOLOGY

    Archaeological Pharaoh Sets Determined Course for Egypt

    1. Andrew Lawler

    Zahi Hawass is arguably the most famous archaeologist in the world, as well as one of the busiest. Trained in his native Egypt and at the University of Pennsylvania in Philadelphia, the 58-year-old Hawass took over as secretary general of Egypt's Supreme Council of Antiquities in 2002. But he has been the public face of Egyptian archaeology for years, appearing in dozens of documentaries in his trademark Indiana Jones-style hat to lead viewers into dusty tombs.

    Behind the scenes, he controls access to thousands of archaeological sites and also keeps his hand in several excavations; he administers $5.2 million to $7 million in tourist revenues annually. With 37 years in the field and a Western Ph.D., Hawass is reshaping Egyptian archaeology, raising standards and demanding respect from outsiders. Unlike many of his predecessors, Hawass drives a hard bargain with foreign researchers and museum officials, forcing excavators to publish promptly, pressuring museums not to buy looted antiquities, and demanding hefty fees for traveling exhibits.

    While taking phone calls, signing documents, and joking with a visiting archaeologist in his Cairo office, Hawass recently spoke in his rapid-fire manner about his strategy for Egypt's archaeological future.

    Q: How do you reconcile tourism—and the need for revenue—with archaeology?

    We put the monuments first. We stopped the proposed ring road by the pyramids. We stopped the western paved road that was going to Abydos. And we have a program to close the pyramids at Giza—a different one every year [for restoration]. We plan to limit tourists to a certain number [to limit damage to sites].

    Q: Are you placing tighter controls on archaeological work?

    For the first time, we are applying very strict rules. Egypt used to be a place where foreigners and Egyptians could do anything at anytime. Now for the first time, you cannot discover anything without restoring it. Number two, no one can excavate anything new in upper Egypt at all. You can only do restoration, conservation, GIS [Geographic Information Systems], and epigraphy. If you want to excavate, you go to the Delta, because the water and agriculture are damaging critical sites, and to the desert, because no one knows what is there.

    Also, [archaeologists] have to publish a report 3 months after finishing [a season]. Every 5 years, if you don't have a final publication, you will be stopped. We stopped 35 expeditions run by amateurs. We stopped a French expedition at Saqqara that had been working for 10 years excavating tombs but with no publications.

    CREDIT: MOHAMAD AL SEHETY/ASSOCIATED PRESS

    Q: Are you seeking to have artifacts that were taken illegally returned?

    When I came to this position, I opened a new department called the department for the return of stolen artifacts. We actually stopped [artifact sales at] auctions in England and New York. And if you buy [stolen] artifacts, you will never be permitted to work in Egypt.

    We are restoring the tomb of Amenhotep III [in Luxor]. We discovered the head of the king['s statue] is in five locations, all taken out of the country in the last century. The director of the Louvre refused to return their piece. How can we cooperate with them in the future? If you don't want to help us, we won't help you. I'm not asking for all artifacts to come back, just the unique ones which should be in their homeland.

    Q: Some argue that Egypt can't keep track of the artifacts it has, such as in the basement of the Egyptian Museum in Cairo.

    This was the past. We are building 13 museums now. I cannot find the artifacts to go into these museums. Sure, the basement of the Cairo Museum is full of thousands of artifacts—such as stone vases, things that cannot be displayed. And within a year, the basement of the Cairo Museum will be better than any museum in the world. We started a database 6 months ago to record every piece. Renovation of the basement is under way.

    Q: What's your biggest challenge?

    Training the people I need. I'm opening a school in Cairo dedicated to training [curators and archaeologists]. If you don't know what you are doing, people can deceive you.

  12. BIOMEDICAL TRAINING PROGRAMS

    NIH Told to Get Serious About Giving Minorities a Hand

    1. Jeffrey Mervis

    A National Academies' report says that these controversial programs can't be assessed without better data—and better management

    After more than 3 decades of trying to increase the number of minority biomedical researchers, officials at the National Institutes of Health (NIH) have a raft of anecdotal evidence that its training programs are working. One favorite success story is Erich Jarvis, a neuroscientist at Duke University in Durham, North Carolina, who, as an African-American student from Harlem, was supported by some of those programs and who in 2002 was named the nation's top young scientist. The program managers themselves exemplify NIH's goal of diversifying the nation's biomedical research workforce. Clifton Poodry, head of the division of Minority Opportunities in Research at the National Institute of General Medical Sciences (NIGMS), was born on the Tonawanda Seneca Indian Reservation in Buffalo, New York, for example, and spent 2 decades as a successful academic researcher before joining NIH.

    SOURCE: NIH

    But personal success stories aren't the same as hard data. And good data, says a recent report* by a National Academies' National Research Council (NRC) panel, don't exist. Asked to assess the programs, the panel threw up its hands. It is devilishly difficult to track participants through their training and into the workforce to find out if they have indeed achieved the gold standard of becoming biomedical researchers, the panel concluded. NIH hasn't invested the time, money, or high-level interest needed for a proper evaluation, it added, nor shared what data do exist.

    “There's no good way to track the success of these programs,” says John Bailar, emeritus University of Chicago statistician and co-chair of the panel, part of NRC's Board on Higher Education and Workforce. “We were asked to find out what works, and we couldn't do it because of serious problems with the data.” NIH can't even say how many participants are actually minorities, it noted, much less how well its programs are doing in churning out minority scientists.

    The report's list of flaws is long and damning. Panel members deplored the lack of coordination among the programs, which are run by one or more of NIH's 27 institutes and centers. They questioned NIH's definition of success—the production of Ph.D. biomedical researchers good enough to win NIH funding—given the considerable opportunities open to those with less training and the importance of raising the level of public scientific literacy. They also pointed to a lack of commitment from the top. A meeting of minority-training coordinators convened by the panel, Bailar noted, was the first time all had been together in the same room. And even the report's most basic recommendation—that NIH convene such a group and have it draw up guidelines for a thorough evaluation—has yet to be implemented more than 6 months after NIH officials were briefed on the report.

    “The root problem is that these programs have suffered from a lack of sustained high-level interest,” Bailar asserts. Despite dedicated administrators such as NIGMS's Poodry and John Ruff in, who heads NIH's National Center on Minority Health and Health Disparities, Bailar says that “a lot of senior managers view these programs as an obligation and don't give them the attention they deserve.”

    Data deficit.

    NIH contractors got information from only one in seven former trainees they had hoped to interview.

    SOURCE: NIH

    Even so, the paucity of good data didn't prevent the panel from concluding that the programs are essential. Indeed, it recommended that “NIH should commit to the continued funding of minority-targeted research training programs.” At a time when programs that favor members of a particular race or gender are under assault (Science, 25 July 2003, p. 455), supporters worry that the lack of an adequate assessment could be a serious problem.

    Stinging rebuke

    NIH has a long history of addressing the serious underrepresentation of African Americans, Hispanics, Native Americans, and Pacific Islanders in biomedical research. Some 79 programs serve populations from community college students (see sidebar) to postdoctoral fellows. Despite some gains, the current output is tiny—108 blacks, 175 Hispanics, and 11 Native Americans earned biological science Ph.D.s in 2003, for example—and their 7.3% share of the total number of degrees awarded is a far cry from the group's 25% presence in the general population (see graphic).

    The NRC panel examined 49 programs that ran between 1970 and 1999. After spending more than 4 years and $1.5 million, the panel delivered a stinging rebuke of NIH management practices.

    One problem, according to the panel, is NIH's narrow definition of success. What the agency wants, in the words of veteran NIH training administrator Walter Schaffer, is “people who can do research and sit on our review panels and advisory boards.” But although few participants make it through the doctorate—nobody has a clue what percentage—many still contribute to the biomedical sciences after earning a lesser degree. “Many of these programs serve quite a different population than the typical NIH training program, so a lower rate of success isn't very surprising,” says Bailar. As a result, the panel concluded, NIH should consider a “broader definition of success.”

    Another sticking point is the inaccessibility of relevant data. Project directors submit annual progress reports, but the data generally do not include longitudinal information on a student's entire academic career. “Once a student leaves, what's the motivation for an institution to track them?” asks Ruffin. And even when grantees dig out that information and submit it to NIH in their annual reports and renewal applications, the agency hasn't found a way to compile it and use it effectively. “We had an electronic database that was also supposed to serve as a tracking mechanism,” says Adolphus Toliver, who runs both the Bridges to the Baccalaureate Degree program and the Minority Access to Research Careers program for upper-level honors students. “But it didn't work, so we stopped using it.”

    A third problem is that students don't necessarily remain in minority-training programs throughout their education. Even programs that link different types of institutions—such as the Bridges to the Baccalaureate Degree from community colleges to 4-year institutions, and the Bridges to the Doctoral Degree from master's to doctoral programs—don't promise students a slot as they advance. That undermines the program's effectiveness, not to mention making it harder to track students.

    One of the biggest complaints from the NRC panel is that NIH officials were unwilling or unable to make program data available for a rigorous analysis. NIH shared the data with a private contractor, who surveyed participants and project directors. The response rates were as low as 8%, however. “The NIH data contract achieved a very low response rate,” the panel concluded. “As a result, there is a high likelihood of bias among the survey results.” The restriction also prevented the NRC panel from doing its own analyses, Bailar adds.

    In the long run, the failure to support claims of success could hurt these programs, which are already under threat from those who disapprove of race-based preferences. In November, for example, the U.S. Justice Department threatened to sue Southern Illinois University for running three such programs, one a “bridges” effort for underrepresented minorities pursuing science degrees, funded by the National Science Foundation (Science, 25 November 2005, p. 1263). Even agencies that support minority preference may balk because the evidence for these programs is weak. “When I briefed NIH on the report,” says Bailar, “some of the institute directors said: ‘You haven't shown any evidence that it produces a lot of Ph.D.s. So why should I bother to fund it?’”

    Jarvis and Poodry harbor no doubts about the value of the training programs. “I wouldn't be where I am today without these programs,” says Jarvis, who this fall won a prestigious NIH Director's Pioneer Award.

    Poodry feels likewise. But he also thinks that the NRC panel is right in calling for clear and measurable outcomes. “We need a doubling [of minority Ph.D.s] every 8 years to shift the [participation] curve to where it should be,” he says. “If that doesn't happen, then 20 years from now we'll probably be looking at the same results and wondering why things haven't improved.”

    • * Assessment of NIH Minority Research and Training Programs, Phase 3, NRC (2005).

  13. BIOMEDICAL TRAINING PROGRAMS

    Will This Bridge Take Me to the Lab?

    1. Jeffrey Mervis

    The National Institutes of Health's (NIH's) “Bridges to the Baccalaureate Degree” tries to help underrepresented minority students become scientists. But measuring its impact—and, by extension, all of NIH's minority-training programs—may be a bridge too far.

    The Bridges program links community colleges with research universities at dozens of sites around the country. Working with students more likely to have grown up on an Indian reservation, in an urban ghetto, or with parents speaking a language other than English than are their undergraduate peers attending research-intensive universities, the Bridges program supplements coursework with academic assistance, career counseling, paid lab jobs, lectures, and other activities.

    It's an excellent way to expose them to a life in research. But it's a long way from fulfilling NIH's dream of turning them into biomedical researchers capable of winning federal grants. Even following what happens to the thousands of students who try to cross that bridge has so far proven impractical.

    Why are the students so hard to track? The main reason is their educational peregrinations. Even if students earn their associate's degrees, they may not head to a 4-year school. If they do, they may not win a spot in another NIH-sponsored minority program, if one exists on campus. They may not major in science. Even if they graduate, they may not attend graduate school. And so on.

    Hard to calibrate.

    NIH's “Bridges” program helps minority students transfer from community colleges to research universities, but there are few data on what happens to them later.

    CREDIT: COURTESY OF BRIDGES PROGRAM

    The available data are both impressive and sobering. California State University, Los Angeles (CSU-LA), has had a Bridges grant since the program's inception, giving project director Linda Tunstad an unusually long perspective on what happens to her students. From a 12-year pool of 148 students, she says, some 76% continued their education at a 4-year school, two-thirds of them at CSU-LA. At least 37%—55 and counting—have earned bachelor's degrees. Of the 75 who attended CSU-LA, 39 have earned bachelor's degrees, mostly in the biological and chemical sciences, and 22 have gone on to graduate programs.

    Even if institutions take the trouble to follow their students, however, the significance of the journey may not be clear. When NIH's Adolphus Toliver told Bridges directors recently that the program has a 23% transfer rate—the share of community college students who advance to a 4-year school—the group's first question was: “Is that good or bad?” recalls biologist Thomas Landefeld of CSU Dominguez Hills, past president of the project directors' group. Toliver's answer? “We don't know.”

    The group would also like information on how their participants stack up against the general student population in terms of completing a bachelor's degree, entering graduate school, and earning a Ph.D. “We think that our programs are adding value,” says Landefeld. “But without comparative data, it's hard to know for sure.”

  14. SOCIETY FOR INTEGRATIVE AND COMPARATIVE BIOLOGY MEETING

    Sea Slug Inks Its Way to Safety

    1. Elizabeth Pennisi

    SOCIETY FOR INTEGRATIVE AND COMPARATIVE BIOLOGY MEETING, 4–8 JANUARY, ORLANDO, FLORIDA

    Like squid and octopi, the shallow-water invertebrates known as sea hares eject ink when startled. Quick-moving squid and octopi use their inky clouds as a smokescreen, distracting potential predators while they attempt to escape. Now Charles Derby, a neuroethologist at Georgia State University in Atlanta, is discovering that the slow-moving sea hare's ink contains a host of protective compounds, some tailored to deter or confuse specific enemies.

    Magic potion.

    The ink released by sea hares is full of chemicals that drive predators away—and sometimes into a feeding frenzy.

    CREDIT: GENEVIEVE ANDERSON

    By testing the chemical makeup of inks secreted by two sea hare species facing different predators, Derby and his colleagues have found a complex defense system of deterrents, alarm calls, and feeding stimulants within the milky purplish and pink fluid. “The ink mixture allows the sea slug to persist in the presence of multiple predators through a simultaneous array of surprising mechanisms,” says Erik Sotka, a marine ecologist at the College of Charleston, South Carolina, Grice Marine Laboratory.

    Although researchers have long studied chemical defenses in the sea hare's skin and digestive glands, they have not looked in depth at the ink, says Derby. Sea hare “ink” actually consists of two substances, each secreted by a different organ into the mantle cavity, where they intermingle before being ejected. The ink is colorful and thin, whereas the other substance, opaline, is viscous. Each contains its own repertoire of compounds, and Derby finds that when ink and opaline meet, innocuous enzymes and amino acids react to form noxious substances. “This animal uses ‘common’ biological chemicals in novel ways,” notes Esther Leise, a marine biologist at the University of North Carolina, Greensboro.

    At the meeting, Derby described how sea hares ward off giant sea anemones. An anemone's tentacles may snare a sea hare, but the predator immediately spits out the potential meal and vigorously retracts its tentacles once the hare ejects its inky weapon, Derby reported. His postdoc Cynthia Kicklighter has found that opaline alone has no repulsive effect: If anything, it stimulates feeding behavior by the anemone. But the ink contains all sorts of anemone-repulsing chemicals, says Derby.

    In contrast, when Derby, Kicklighter, and their colleagues tested opaline and ink separately against spiny lobsters, another sea hare predator, the opposite proved true: Opaline was more protective than the ink, they reported last year. The lobster work also suggests that feeding stimulation is actually a defensive strategy. The sea hare's ink-opaline mixture contains substances, such as the amino acid taurine, that set off a feeding frenzy in a lobster—it grabs at the ground and ink cloud as if to ingest it, enabling the sea hare to slink away.

    As an added bonus, the ink mixture spreads the word among sea hares when danger approaches. Kicklighter and her colleagues have recently presented either ink or opaline to juvenile sea hares. The animals drew in their heads and moved away from either substance. The sea hares did the same when exposed to ink from an octopus and a squid, suggesting a common warning system for all these species. The researchers have identified three of the sea hare's warning compounds, two of which also exist in the squid and octopus inks. Paul Moore, a sensory ecologist at Bowling Green State University in Ohio, calls the sea hare's arsenal “a case of deceptive chemical signaling strategy not seen before [in animals].” Such research “will open up a new avenue of thought for aquatic chemical ecology,” he predicts.

  15. SOCIETY FOR INTEGRATIVE AND COMPARATIVE BIOLOGY MEETING

    Was Lucy's a Fighting Family? Look at Her Legs

    1. Elizabeth Pennisi

    SOCIETY FOR INTEGRATIVE AND COMPARATIVE BIOLOGY MEETING, 4–8 JANUARY, ORLANDO, FLORIDA

    The fossil Lucy is the most famous example of Australopithecus afarensis, a hominid that lived between 3.9 million and 3 million years ago. Since her discovery in 1974, anthropologists have been arguing over how she moved, because although she looks a bit like a chimpanzee, her pelvis, legs, spine, and skull suggest she walked upright. Nonetheless, her short legs, long arms, and other features indicate that she spent a lot of time in trees.

    Now David Carrier, a comparative physiologist at the University of Utah in Salt Lake City, has jumped into the fray with a provocative idea about Lucy's legs. In earlier studies with dogs, he had found that short legs provide mechanical benefits during fights. Pit bulls' short limbs, for example, aid stability and are tough enough to sustain attack without breaking.

    Carrier contends that Lucy and other australopithecines also had bodies built for defense against each other: Their short legs may have provided a competitive edge when males battled rival suitors.

    There's no fossil evidence of ancient hominid battles, so Carrier tested his idea indirectly, by analyzing living apes. In great apes, males square off over females, and natural selection has favored large size in these males, with females being more diminutive. Fossil data indicate that males were likewise the brutes of A. afarensis. Other researchers have established that the more competitive the males, the larger the overall size differences between the sexes.

    So Carrier used size sexual dimorphism as a proxy for aggression within a species. Using data in the literature, he was able to analyze nine primate species, including gibbons, chimps, gorillas, orangutans, African monkeys, and humans. He found that the greater the body size difference between males and females, the shorter the relative leg length. To Carrier, this confirms that apes with more male competition tend to have shorter legs. He argued at the meeting that australopithecines' short legs may have helped body stability when males fought each other for females. Thus male-versus-male competition may have outweighed the need for efficient walking or running.

    But others say that so far the evidence is slim. “It's just storytelling,” says comparative biologist Frank Fish of West Chester University in Pennsylvania. The work “should generate a lot of controversy,” agrees Roshna Wunderlich, a physical anthropologist at James Madison University in Harrisonburg, Virginia. “He has a fairly strong correlation, but he needs to establish causality.” Nonetheless, the notion that limbs are shaped by more than locomotion “is a really creative idea,” says Elizabeth Brainerd, a comparative morphologist at Brown University.

  16. SOCIETY FOR INTEGRATIVE AND COMPARATIVE BIOLOGY MEETING

    Water Launches Spores Like a Rocket

    1. Elizabeth Pennisi

    SOCIETY FOR INTEGRATIVE AND COMPARATIVE BIOLOGY MEETING, 4–8 JANUARY, ORLANDO, FLORIDA

    It takes just a little water to send mushroom spores flying—and fast. Using a video camera that records 100,000 frames per second to capture a process never before witnessed, Nicholas Money, a mycologist at Miami University in Oxford, Ohio, has figured out the pivotal role water plays in the moments leading up to a fungal spore's rapid takeoff. The liquid can accelerate a spore more than 10,000g, the equivalent of almost instantaneously propelling a human 600 kilometers per hour. “The spores look like little cannonballs,” says Elizabeth Brainerd, a comparative morphologist at Brown University, who has seen the video.

    Vroom!

    Surface tension in water droplets makes mushroom spores fly.

    CREDIT: GETTY IMAGES

    Money studies how honey fungus (Armillaria mellea), a pathogenic mushroom that infects about 500 woody plant species, spreads. To do that, he has begun with the first step in dispersal: the launching of spores. His graduastudent Jessica Stolze has found that once formed, the spores secrete sugars and sugar alcohols, which suck water out of the air. A drop then forms on a stalk at the base of the spore and expands until it makes contact with the rest of the spore surface. At that point, the water “rockets over the spore, and its motion pulls the spore off its perch,” says Money.

    Surface tension supplies the energy for this ballistic event, he explained. If someone disturbs the drop, say, with a micropipette, the spores stay put. Bigger drops move faster over a spore and shoot it farther, he notes.

    This rapid-fire ejection is critical for spore dispersal. Taking off “is relatively difficult to do because small things have high drag,” Brainerd explains. A spore's water-propelled flight may barely be a millimeter long, but on a good day, that distance gets the spore into an air current that whisks it away to a new home.

    Of the 74,000 fungi, about 40% depend on water droplets to propel spores. But there are other innovative launch strategies. Money is beginning to study fungi that shoot spores out of tubes akin to pressurized cannons. The speeds attained this way can be remarkable; Steven Vogel of Duke University in Durham, North Carolina, estimates that spores can travel 34.5 meters per second, with accelerations of 870,000 times gravity.

  17. SOCIETY FOR INTEGRATIVE AND COMPARATIVE BIOLOGY MEETING

    Crab, Raccoon Play Tag Team Against Turtle

    1. Elizabeth Pennisi

    SOCIETY FOR INTEGRATIVE AND COMPARATIVE BIOLOGY MEETING, 4–8 JANUARY, ORLANDO, FLORIDA

    Attempts by wildlife managers to help endangered Florida sea turtles may be backfiring. A field study on four beaches has shown there is a tradeoff between turtle-egg predation by raccoons and by ghost crabs that live in burrows along the beach. Management programs that remove raccoons from beaches have led to population booms in ghost crabs and even greater damage to sea turtle nests, says Brandon Barton, a graduate student in environmental studies at Yale University.

    While examining the stomach contents of raccoons as part of an evaluation of the effectiveness of removal programs, Barton realized that the mammals ate more than just turtle eggs: Ghost crabs made up more than 10% of the raccoons' diets. Wondering whether fewer raccoons resulted in more turtle nest raids by ghost crabs, Barton and James Roth, a community ecologist at the University of Central Florida in Orlando, surveyed raccoon and ghost crab populations and monitored turtle-egg predation at four sites: one where wildlife managers had trapped the mammals for the past 25 years; another where cages over turtle nests thwarted raccoon raids; and two where there was no raccoon control.

    Crime scene.

    Ghost crabs and raccoons can take quite a toll on sea turtle eggs and hatchings.

    CREDIT: BRANDON BARTON/YALE UNIVERSITY

    Active removal reduced the raccoon population, but the crab population was about double that at the other study sites, Barton reported at the meeting. At the trapping site, the mean body size of the crabs increased as well. Moreover, nest predation was 50% higher there—with about 30% of the turtle eggs disappearing.

    How much of this increased egg loss was due to ghost crabs is unclear, says Barton. Ghost crabs burrow into the sand to do their dirty work, and visits by raccoons obliterate telltale signs of crab activity. Barton also suspects that the crabs' burrows vent fumes from turtle egg and hatchling remains, helping the raccoon home in on nests.

    This work “will force people to rethink programs to remove raccoons from nesting beaches,” says Alessandro Catenazzi of Florida International University in Miami. Brent John Sinclair, a functional ecologist at the University of Nevada, Las Vegas, agrees: “It's another one of the classic examples of something that's not making any difference or making [a situation] worse.”

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