News this Week

Science  04 Mar 2005:
Vol. 307, Issue 5714, pp. 1386
  1. PALEOANTHROPOLOGY

    Small but Smart? Flores Hominid Shows Signs of Advanced Brain

    1. Michael Balter

    The startling announcement last October of an 18,000-year-old skeleton of a new species of human posed a paradox: Despite having a brain no larger than a chimp's, the diminutive hominid from the Indonesian island of Flores showed signs of advanced intelligence, including hunting with sophisticated stone tools. That paradox may now be solved. A detailed study of the cranium of Homo floresiensis, published online this week by Science (www.sciencemag.org/cgi/content/abstract/1109727), reveals that the hominid apparently managed to pack a number of features of more advanced brains into its very small skull. Brain features preserved in its cranium suggest that the Flores hominid may have been able to perform advanced cognitive tasks, says lead author Dean Falk of Florida State University in Tallahassee.

    That finding may overturn long-held ideas about the evolution of the human brain and also raises some provocative notions about how the Flores people evolved in the first place. “If they are correct, this is really a stunner,” says anthropologist Leslie Aiello of University College London (UCL). Evolutionary anatomist Fred Spoor, also of UCL, adds that the new study “upsets one of our main concepts of human evolution, that brain size has to increase for humans to become clever.” The work also undercuts the notion proposed by some critics that the Flores bones are those of a microcephalic modern human rather than of a new species.

    To study the hominid's brain, Falk and colleagues, including anthropologist Charles Hildebolt of the Mallinckrodt Institute of Radiology in St. Louis, Missouri, analyzed a cast of the inner surface of its skull, or endocast, which preserves the surface features of the brain. Because the skull was too fragile for the usual method of pouring liquid rubber inside it, the team made a virtual endocast from computerized tomography scans. The original discovery team, including co-authors Michael Morwood and Peter Brown of the University of New England in Armidale, Australia, had the skull scanned at a hospital in the Indonesian capital of Jakarta before the bones were temporarily moved last fall to Yogyakarta (see sidebar).

    Thinking ahead?

    The highly convoluted frontal lobes of Homo floresiensis may indicate advanced cognition.

    CREDIT: D. FALK ET AL., SCIENCE

    The researchers compared the endocast to virtual endocasts of the skulls of a microcephalic modern human, a modern woman, a Homo erectus, a pygmy, and a chimpanzee, as well as latex endocasts of other humans, primates, and extinct hominids. They found that, relative to its overall size, the brain of Homo floresiensis has very large temporal lobes, brain regions associated in living people with understanding speech and hearing. Even more dramatically, the hominid has highly folded and convoluted frontal lobes, areas of the brain just under the forehead that are implicated in higher cognition. “There are two huge convolutions,” Falk says. “I haven't seen swellings like this before in any [extinct] hominid endocasts,” including those of Homo erectus. The most convoluted region is in the most forward-projecting part of the frontal lobe, called the frontal pole. Falk identifies this region as Brodmann's area 10, which is expanded in modern humans and is involved in undertaking initiatives and planning future actions—key components of higher cognition.

    This enlarged area suggests that the little Flores people may well have been capable of creating the stone tools that were found near them, which are more typical of those made by prehistoric modern humans than earlier hominids including Homo erectus. “The real take-home message here is that advanced behaviors, like making sophisticated stone tools, do not necessarily require a large, modern, humanlike brain,” says Spoor. “It can be done by reorganizing a small brain, with convolutions and rewiring, and this goes to the heart of our understanding of human evolution.”

    Not everyone is ready to discard the importance of brain size, however. Anthropologist Katerina Semendeferi of the University of California, San Diego, who has studied area 10 extensively, cautions that “many would argue that absolute size is of paramount importance”; she adds that stronger evidence linking the stone tools with the small Flores people would strengthen the case for their cognitive abilities.

    No match.

    The brain of Homo floresiensis (top) bears little resemblance in shape to that of a modern human microcephalic.

    CREDIT: D. FALK ET AL., SCIENCE

    Whatever the hominid's capabilities, the endocast results argue against the notion that it was a pathological case of microcephaly, the authors say. In overall brain shape, the Flores hominid least resembles the microcephalic, and it also bears little resemblance to the pygmy. “The skull is totally the wrong shape” to be a microcephalic, Falk says.

    But anthropologist Alan Thorne of the Australian National University in Canberra counters that the single European microcephalic analyzed “tells us virtually nothing about the global range of microcephalic virtual endocasts.” Others agree that the paper alone does not completely rule out microcephaly. “The case [against microcephaly] is increasingly less likely but not entirely closed,” says Aiello. Spoor notes, however, that few researchers are convinced by the microcephaly argument at this point. “Colleagues advocating that [the Flores hominid] is a modern human microcephalic should start publishing hard evidence in peer-reviewed journals to underpin their claims,” he says.

    Assuming that Homo floresiensis is a new hominid species, the question remains why its brain is so small. In the original Nature papers, Morwood, Brown, and their co-authors suggested that an ancestral population of larger Homo erectus shrank in body and brain, in the first case of island dwarfism seen in hominids. But the new paper urges reconsideration of an alternative hypothesis, that a small-brained, small-bodied, pre-erectus hominid managed to get to Flores in the distant past, and then, in a case of parallel evolution with modern humans, evolved a relatively advanced brain on its own. “Some of [the hominid's] traits indicate that the ancestral population may predate Homo erectus,” says Morwood. He adds that his team is now preparing to look for just such an ancestor on the Indonesian islands of Java and Sulawesi. Says Falk: “Maybe there are even more surprises waiting out there.”

  2. PALEOANTHROPOLOGY

    "Hobbit" Bones Go Home to Jakarta

    1. Michael Balter

    While scientists debate the evolutionary lessons to be drawn from the discovery of Homo floresiensis (see main text), a bitter custody battle over the tiny hominid's remains (Science, 25 February, p. 1179) may be almost over. Late last week, Indonesian paleoanthropologist Teuku Jacob gave most of the remains of up to eight individuals of the claimed new human species to members of the Center for Archaeology in Jakarta, the bones' official repository. Jacob had been studying the bones since November, when a center researcher helped him pack them into a leather bag and take them to his laboratory at Gadjah Mada University in the Indonesian city of Yogyakarta.

    Some members of the original Australian-Indonesian team that discovered the hominid on the island of Flores protested loudly that the hominid had been in effect kidnapped, in violation of a memorandum of understanding between the Australian and Indonesian institutions involved. Jacob insisted that he had full permission from the archaeological center and in turn charged the Australians with interfering with long-standing arrangements among Indonesian laboratories.

    According to center director Tony Djubiantono, Jacob has now returned all the hominid remains except two leg bones—a tibia and a femur—to Jakarta. Djubiantono says he is not sure when the rest of the bones will be reunited at their Jakarta home, but says that he will call Jacob “next week and every week” until they are returned.

  3. PLANETARY SCIENCE

    A Strange Little Saturnian Ice Ball Gets Stranger Still

    1. Richard A. Kerr

    When the Cassini spacecraft approached Saturn's icy-bright satellite Enceladus (en-SELL-uh-duss) last month, “we knew it was going to be weird,” says camera team member Torrence Johnson. “We just didn't know how weird.” The misfit satellite turned out to be even stranger than scientists thought in 1981, when Voyager 1 first visited. Voyager images showed the supposedly long-dead primordial ball of ice to have been geologically refreshed in recent times. Some unidentified geologic process had smoothed its battered surface in places. Now, says Johnson, it appears “some areas on Enceladus have to be very young, possibly younger than on Europa,” the ice-covered ocean moon of Jupiter.

    The Cassini camera, which returned 20 times the fine detail of Voyager images, imaged three sorts of terrain as it swept within 1180 kilometers of Enceladus, says Johnson, who works at the Jet Propulsion Laboratory in Pasadena, California. As seen in Voyager images, large parts of the 500-kilometer-diameter moon are cratered by comet impacts, although the craters appear “softened.” Presumably, this geologically older surface ice has been warm enough to flow and “relax.” A second sort of terrain that in Voyager images looked completely blank now appears to be fractured by repeated squeezing and stretching of a brittle crust.

    A third terrain looks “scallopy, twisted, taffylike,” says Johnson. Absent are the smooth plains formed by once-fluid water that were assumed to have spewed onto the surface in “cryovolcanic” eruptions. “You don't see the flat, flooded picture of cryovolcanism” discussed after Voyager, says Johnson. “Something flowed there, but it was very viscous.” All in all, large parts of Enceladus have suffered “fairly energetic events fairly recently,” perhaps less than 100 million years ago.

    Wrinkled youth.

    Something has more than once crumpled this part of icy Enceladus. Judging by the dearth of impact craters, it happened in the geologically recent past.

    CREDIT: JPL/NASA

    The missing piece of the puzzle is an energy source that could have warmed and melted ice as well as fueled tectonic forces on Enceladus. Cassini may have found one. As the spacecraft flew by, its radio signal's frequency shifted more than expected. That means the moon was gravitationally tugging on Cassini harder than a ball of pure ice would, says camera team member Joseph Veverka of Cornell University. “It's definitely got some rock in there,” he says. And rock would carry radioactive elements such as potassium-40 whose decay would have heated the interior, perhaps melted ice with the help of some naturally occurring ammonia antifreeze, and churned the interior to deform the surface.

    Rock would help, notes planetary physicist David Stevenson of the California Institute of Technology in Pasadena, but, he adds, “I don't understand why Enceladus is doing something different from other moons.” Neighboring Tethys, for example, is twice the diameter of Enceladus and has perhaps six times the mass, yet it is covered by ancient cratered terrain. Unlike watery Europa, Enceladus does not presently orbit in step with other moons, which could pump tidal energy to it from Saturn, although it might have done so in the past (Science, 29 July 1983, p. 449). More clues to Enceladus's energetic lifestyle could come next week (9 March), when Cassini makes an even closer pass.

  4. COMPUTER SECURITY

    Flaw Found in Data-Protection Method

    1. Charles Seife

    Cryptographers are making a hash of things again. Last month three code breakers demonstrated a way to break the Secure Hash Algorithm (SHA-1), a government-approved standard cryptographic function crucial to many electronic transactions, including digital signature schemes and password verification. Although the finding doesn't mean that SHA-1 is unusable, it has prompted the cryptographic community to suggest finding more secure versions of SHA. “The research community is going to have to think very hard about this,” says Massachusetts Institute of Technology cryptographer Ron Rivest. “We clearly have to replace SHA-1.”

    A hash function is a mathematical device that takes a chunk of text (which can be huge) and, through a series of arithmetic manipulations, turns that text into a number (which is small). Hash functions allow computer programs to verify that large blocks of text or data are unaltered without needing to store the large files themselves. For example, you might know that a particular hash function spits out the number 634,331,206 when given the authentic text of War and Peace. If someone gives you a file of text, you just run the hash function on it. If the number 634,331,206 doesn't come out, the file can't be an unaltered copy of War and Peace.

    Hashed Hancock.

    A digital signature scheme using hash functions (such as SHA-1) and ciphers may be vulnerable to forgery.

    That is what many operating systems do with passwords: Rather than storing passwords in an easy-to-steal file, they store the passwords' hash values instead. Even if hackers get hold of the list of hash values, they don't know how to turn those values into valid passwords and get into the system. Of course, this is true only if the program can't be run backward. To guarantee a one-way hash function, the National Institute of Standards and Technology (NIST) in the early 1990s introduced SHA-1.

    Now, more than a decade later, three researchers from China and the United States have devised the first successful attack on SHA-1. Although they don't force the algorithm to run backward, in an unpublished paper circulating among computer-security experts they show how to do a related trick. “What we have done is shown something called a collision,” says Yiqun Lisa Yin, an independent consultant in Greenwich, Connecticut. “Two different messages map to the same outcome.” In other words, Yin and her two colleagues, Xiaoyun Wang and Hongbo Yu of Shandong University in East China, came up with a way to find different blocks of text that have identical hash values. In theory, hackers could use the trick to forge stamps of authenticity for electronic documents.

    An attacker, by pure brute force, would expect to find one such collision in 280 attempts. The team shows how to reduce that value to 269 tries—still out of the range of supercomputers, but close enough to worry experts. Rivest thinks NIST should hold a competition to design a next-generation hash algorithm. NIST has no plans for such a competition, says Edward Roback, chief of NIST's Computer Security Resource Center, but is encouraging users to switch to beefed-up versions of SHA: “It's not like SHA is completely broken, but any time the security of an algorithm is less than expected, it's a concern.”

  5. PLANETARY SCIENCE

    Ice or Lava Sea on Mars? A Transatlantic Debate Erupts

    1. Richard A. Kerr

    The déjà vu was palpable when U.S. planetary scientists heard the news last week that a frozen sea the size of the North Sea had been found on Mars. “We went through all this 7 years ago when [Mars Global Surveyor] first imaged these terrains,” says planetary geologist Alfred McEwen of the University of Arizona, Tucson. “Our immediate reaction then was, ‘Gosh, that looks like frozen ice.’ But we quickly realized it had to be lava.”

    “It can't be lava,” says volcanologist John Murray of the Open University in Milton Keynes, U.K. He and his teammates running the High Resolution Stereo Camera (HRSC) onboard the European Space Agency's Mars Express orbiter reported at the First Mars Express Science Conference last week that the “lava” is actually an ice floe-covered sea frozen in place. That would make the Elysium Plains a fetching place to land and look for microfossils of martian life, Murray notes.

    Everyone agrees that both water and lava have gushed from the ground in the vicinity of Elysium (Science, 30 November 2001, p. 1820). McEwen and others had traced lava and water flows back to the great ground cracks of the 1000-kilometer-long Cerberus Fossae. Apparently, rising magma intersected subterranean water and drove it through the cracks to the surface, carrying with it any debris of life past or present. Murray and his colleagues now see signs that about 5 million years ago such a gusher did not just seep into the ground but pooled to a depth of 45 meters over an area about 850 kilometers across. Once its surface froze, they say, the waters moved again, breaking the ice into floes now locked into a frozen sea that has become buried under a protective layer of volcanic ash and sediment.

    Sea ice or lava sea?

    No doubt parts of Mars look like a frozen sea off Antarctica, but looks can be deceiving, say many U.S. planetary scientists.

    CREDIT: ESA/DLR/FU BERLIN (G. NEUKUM)

    In a paper to be published 17 March in Nature, Murray and his colleagues will detail the ice signs they see in the images, which are among the first European data returned from another planetary body. A pivotal claim is that the level of the putative sea has dropped since its surface froze. Mapping elevations using HRSC stereo imaging as well as laser altimetry from Mars Global Surveyor, they find that flood material inside as well as outside some craters has sunk about 15 meters below the crater rim. Floodwaters could have seeped or sublimated away, says Murray, but lava could not. In addition, “the edge [of the flow] ties in well with a sea rather than lava,” says Murray. Where HRSC has looked, he sees a beach swept by turbulent flows, a high-water mark, and the final sunken level with pack ice at the bottom.

    American Mars geologists, who have dominated the field by dint of returning almost all the previous data from Mars, aren't persuaded. “I think it's unlikely they're right,” says Michael Carr, planetary geologist emeritus at the U.S. Geological Survey (USGS) in Menlo Park, California. McEwen and many others feel more strongly than Carr that they were right the first time. “We've been studying these lavas for 7 years,” McEwen says. “Put aerial photos of Iceland [lava flows] side by side with Mars, and you can't tell the difference.”

    Martian lavas could look so much like sea ice because similar processes shape both. But on Mars, McEwen sees—among other volcanic features—small edifices that disgorged the lavas and steep-sided levees at the flow edges like the ones lavas form on Earth. “What we're talking about is a sea of lava,” says planetary volcanologist Laszlo Keszthelyi of USGS in Flagstaff, Arizona. The apparently sunken lava may just be the result of lava withdrawing beneath a solid crust, he says.

    Resolution of the matter will likely require targeting the exact areas HRSC imaged with the camera and ground-penetrating radar on Mars Reconnaissance Orbiter, due for launch this August. Until then, water or rock may remain in the eye of the beholder.

  6. CONFLICTS OF INTEREST

    NIH Scientists Raise Fuss About Scope of New Rules

    1. Jocelyn Kaiser

    Scientists at the National Institutes of Health (NIH) are rallying to challenge strict new ethics rules that many feel go much too far. A group of intramural leaders met with NIH Director Elias Zerhouni last week to air their concerns. Meanwhile, NIH officials say they have cleared many of those on a list of scientists who apparently had failed to report ties to drug companies.

    The new ethics rules, imposed last month, came in response to revelations in the press and in Congress that some NIH scientists have had lucrative consulting deals that weren't always publicly disclosed or even reported to NIH. In addition to barring all consulting for industry and nonprofit health-related organizations, the regulations prohibit senior staff members and their families from owning stock in drug and biotech companies. Everyone else can own no more than $15,000 in holdings from any one company (Science, 11 February, p. 824).

    The rules have outraged NIH scientists. Among their worries are their own stock portfolios and how the rules might affect the recruitment of fellows, who spend only a few years at NIH. Last week, a newly elected, 18-member executive committee of the Assembly of Scientists—a revival of a defunct body—shared their views with Zerhouni. He “clearly understand how difficult some of these issues are,” says committee member Cynthia Dunbar of the National Heart, Lung, and Blood Institute. NIH officials were sympathetic to recommendations to craft exemptions for fellows and to extend the 150-day deadline for divesting stock, she says. But Zerhouni advised them to send their concerns to the Department of Health and Human Services, which developed the rule along with the Office of Government Ethics.

    Dunbar says the Assembly of Scientists is now working on a set of proposals more in line with the recommendations of a blue-ribbon panel last year that urged Zerhouni to ban consulting by senior leaders but allow limited consulting by others (Science, 14 May 2004, p. 936). Other scientists are weighing a legal challenge to the stock ban, says Abner Notkins of the National Institute of Dental and Craniofacial Research.

    Meanwhile, NIH clarified a press report regarding the status of about 100 scientists accused by a congressional committee of not telling NIH about their consulting activities. The committee compiled its list from information supplied by drug companies. As many as 80% of those on the list have been exonerated, according to a 23 February story in The Washington Post. But NIH Deputy Director Raynard Kington says only about half have been cleared, and investigations of the rest are still under way.

  7. FRENCH SCIENCE

    Report Puts Pasteur Move on Hold

    1. Martin Enserink

    PARIS—Scientists at the Pasteur Institute here were elated last week after a report by British mediator John Skehel scuttled a controversial plan to move part of the lab to a commercial site outside Paris. But decisions about the Pasteur's future accommodation—and the fate of its embattled director, Philippe Kourilsky—are on hold until the election of a new board of directors in the next few weeks.

    Loath to leave their historic campus in the heart of the city—the site of Louis Pasteur's original lab and now his resting place—the staff vehemently opposed moving several units to a building donated by Pfizer in the suburb of Fresnes. Kourilsky said the move was necessary to renovate key buildings on the Paris campus. Seeking to help resolve the crisis, Pasteur's board of directors resigned en masse on 12 January (Science, 21 January, p. 333).

    But Skehel, director of the Medical Research Council's National Institute for Medical Research (NIMR) in London, has concluded that the building posing the biggest renovation problem, called Daclaux, can be upgraded in two stages, each taking about 6 months. Uprooted staff could be temporarily relocated to Biotop, an on-campus building that's now home to biotech start-ups. Biotop residents, in turn, should be offered temporary housing in a Paris science park, Skehel and NIMR assistant director John Wills conclude in their report.

    The directors of Pasteur's 12 scientific departments, to whom Skehel presented his conclusions on 17 February, are generally “very pleased,” says Brigitte Gicquel, director of the Microbial Pathogenesis department. “The recommendations are very precise, very clear, and they are feasible,” she says.

    Under fire.

    Philippe Kourilsky's abrasive style has angered Pasteur staff.

    CREDIT: GAILLARDE RAPHAEL/GAMMA

    Some scientists say Kourilsky, already under fire for his abrasive management style, may have to step down. A Pasteur spokesperson says Kourilsky will not comment, but a short statement issued on his behalf says a study group would be formed soon to analyze the report and its consequences. Gicquel says it seems inconceivable that the recommendations would not be heeded. For the moment, however, all decisions are on hold until Pasteur's 100-strong General Meeting—made up of staff and outsiders—elects 16 new members to the 20-member board of directors on 15 March.

    If the move to the 17,000-square-meter complex in Fresnes is abandoned, it's not clear how the building would be used. One option would be to rent it, a spokesperson says. Complicating matters further, the French government has recently floated yet another plan: to lure the entire Pasteur Institute to Palaiseau, 22 kilometers southwest of Paris. There, it would become part of a “Competitivity Pole”—regional centers of scientific expertise and innovation being promoted by the government—along with the prestigious École Polytechnique and other institutions.

    This choice may be less controversial than Fresnes because the location is easier to reach, has more scientific prestige, and would not split the campus in two, notes Pasteur's Patrick Grimont. Although, as a private institution, Pasteur could not be forced to move, the spokesperson says the option is “being considered.”

  8. INFECTIOUS DISEASES

    Experts Dismiss Pig Flu Scare as Nonsense

    1. Martin Enserink

    It could be the result of an embarrassing lab escape or a vaccine study gone awry; it could even be the smoking gun from a secret biowarfare program.

    But then, it could be nothing at all.

    For 4 months now, a series of strange influenza sequences has been sitting in GenBank, the U.S. National Institutes of Health's DNA database, that seems to suggest that pigs in South Korea have become infected with a flu strain used for research in labs around the world but not known to occur in nature. The World Health Organization (WHO) in Geneva has dismissed the snippets as the result of a lab error. But the Korean scientist who posted them insists they are real—and troubling—and he is hoping that two renowned flu labs will prove him right.

    Meanwhile, speculation about the case has been fueled relentlessly on the Internet by an outsider to the influenza world. Henry Niman, the president of a Pittsburgh, Pennsylvania-based company called Recombinomics and the operator of a mailing list about flu, believes that the virus, called WSN/33, poses a grave danger to human health. Recently, his views have begun to draw attention—much to the chagrin of those scientists who think the whole story is nonsense.

    The bizarre case started on 24 October when Sang Heui Seo, a researcher at Chungnam National University in Daejeon, deposited in GenBank partial RNA sequences from a series of viruses isolated from pigs. Niman, a molecular biologist and former Harvard surgery instructor with an intense interest in virus evolution, discovered them soon after they were made public in late November. He noticed that six of the viruses appeared to be hybrids; in addition to genes from H9N2, an avian flu virus that previously circulated in Korean pigs, they had between three and seven genes with WSN/33-like sequences.

    WSN/33 was produced in 1940 by infecting mice with the first human flu virus ever isolated, in London in 1933. It's a mystery how it got into the pigs, says Niman, who proffers scenarios ranging from a lab accident to illicit experiments to create a deadly flu strain for biowarfare—neighboring North Korea comes to mind, he says. Niman believes the spread of the virus should be thoroughly investigated, because WSN/33, which infects mice's brains, is distantly related to the 1918 pandemic virus, and if it infects pigs, it may infect humans as well. That's why he immediately alerted WHO in December.

    Agitator.

    Henry Niman (right) is worried that pigs on Korean farms (shown here being sanitized for foot-and-mouth disease) may harbor a strange flu virus, posing a threat to human health.

    CREDITS: YUN SUK-BONG/REUTERS; (RIGHT) H. NIMAN

    But WHO is unimpressed. The agency discussed Niman's claims by e-mail with its flu advisers in December, says Klaus Stöhr, WHO's global influenza coordinator. They quickly concluded that the results were lab contamination. Such mix-ups can happen easily when researchers use the polymerase chain reaction to amplify bits of genetic material, says Robert Webster of St. Jude Children's Research Hospital in Memphis, Tennessee, one of Stöhr's advisers. Contamination was likely, says Webster, because Seo had previously received WSN/33 from Webster's own lab. (Seo also worked at Webster's lab between 1999 and 2002, and the two published seven papers together.)

    But in an interview, Seo denied ever having received the WSN/33 from Memphis or anywhere else. What's more, “I have many scientific data that can rebut WSN contamination,” he wrote in a follow-up e-mail. But he declined further comment until his results are published. Seo says Science rejected his paper describing the discovery of WSN in pigs but may reconsider the manuscript if the findings are backed up by a well-established flu lab.

    Seo hopes that Malik Peiris at the University of Hong Kong and Yoshi Kawaoka at the University of Wisconsin, Madison, who both have samples from Korea, can confirm WSN's presence. Both Peiris and Kawaoka declined to comment for this story, but Stöhr says the results from the Kawaoka lab will be out soon. The Korean National Veterinary and Quarantine Services also told Science it has been unable to replicate the findings, despite testing hundreds of pigs.

    Molecular biologist and flu expert Ron Fouchier of Erasmus University Medical Center in Rotterdam, the Netherlands, says the sequences definitely contain WSN's genetic signature. But he says the fact that the six controversial isolates have varying numbers of WSN fragments points to lab contamination: “If this was an endemic pig virus, I'd expect all viruses to have the same WSN gene segments.”

    Even if WSN were circulating in Korean pigs, Stöhr says, that wouldn't spell disaster. There's no evidence that WSN is still dangerous to humans, he says; indeed, Fouchier adds, many labs use it without taking special safety precautions.

    Determined to draw attention to the case, Niman, who has also criticized WHO extensively for its handling of the severe acute respiratory syndrome and avian influenza outbreaks, has posted more than 50 messages about the case on his site since December, with some success: Infectious-disease specialist Laurie Garrett of the Foreign Relations Council in New York City wrote about the case in an online article on 16 February—although she dismissed it as a “scary near-miss”—and last week, Nature reported Niman's claims.

    That attention irks Stöhr, who points out that Niman has not published in the scientific literature since 1996 and is not a flu expert. WHO will not issue an official statement about the case, he says: “We're not going to bother 6.5 billion people with something that's of no public health importance.” Webster, too, says any publicity is too much: “It's so easy these days for somebody with a Web site to create a lot of panic.”

    Being an expert doesn't always mean being right, counters Niman, who adds that when the truth comes out, “WHO and Webster will look very ridiculous.”

  9. CANADA

    Grants Councils Say More Isn't Nearly Enough to Keep Science Healthy

    1. Wayne Kondro*
    1. Wayne Kondro is a freelance writer in Ottawa.

    OTTAWA—Research no longer carries the political cachet it once did. That's the message Canadian science policy makers are taking from a new budget put forward last week. The Liberal Party's promise to double Canada's research effort by 2010 and put science at the top of its agenda has been undermined by disappointingly small increases for the country's three granting councils. The result, say the council chairs, is likely to be fewer grants, smaller awards, and less support for training the next generation of scientists.

    “The problem is that the [political] winds are different,” says Marc Renaud, head of the Social Sciences and Humanities Research Council (SSHRC). “Support for science and technology is not as strong as it used to be.”

    The minority government's blueprint for the fiscal year that begins on 1 April provides a little for everyone, although Prime Minister Paul Martin reserved the biggest increases for retooling the military and cutting taxes in an apparently successful bid to win over the opposition Conservative Party. Genome Canada gets $132 million over 2 years pending an assessment of long-term national genomics needs. The nonprofit agency had been due to expire this year after spending $300 million supporting genomics research of interest to industries such as agriculture, health, forestry, and fisheries (Science, 10 March 2000, p. 1732). Universities get a 6% boost in payments for indirect costs associated with research (Science, 27 October 2000, p. 687). And the government has reserved $24 million over 10 years for the new Canadian Academy of Sciences, once it becomes operational (Science, 22 October 2004, p. 589). The budget also provided $178 million over 5 years for the Vancouver-based TRI University Meson Facility (TRIUMF).

    Mixed news.

    Canada's new budget contains upgrades to TRIUMF but not money to send scientists to CERN.

    CREDIT: M. HAPKE/TRIUMF

    But Natural Sciences and Engineering Research Council president Thomas Brzustowski lamented his failure to obtain a larger increase. “I thought I made a good case” for a $64 million boost, he says; instead, the council received an increase of $18 million, or 3.3%, to its $522 million budget. That means Brzustowski will spend an unhappy last few months in office before retiring in July, trying to reconcile rising demand with few additional resources.

    For SSHRC, Renaud says a 5% boost translates into a declining success rate for applicants. And Alan Bernstein, president of the Canadian Institutes of Health Research, says that a one-time, 5% hike could jeopardize a planned expansion of clinical trials and an initiative in regenerative medicine. “It's hard to be strategic when you get these increases 1 year at a time,” he says.

    TRIUMF also received $44 million less than requested. The gap, says Director Alan Shotter of the University of Alberta, means that TRIUMF won't be able to send Canadian scientists to international facilities such as CERN, Europe's high-energy particle physics lab near Geneva, although it will continue to host visiting scientists. Still, the government's continued investment in the lab was welcome news to foreign collaborators. “That facility is going to make significant contributions to science,” says C. Konrad Gelbke, director of the National Superconducting Cyclotron Laboratory at Michigan State University in East Lansing.

  10. HUMAN EMBRYONIC STEM CELLS

    Getting the Mice out of ES Cell Cultures

    1. Constance Holden

    Researchers in Wisconsin have come a step closer to developing a culture for human embryonic stem (ES) cells that is free of animal products—a recipe that is essential for growing any cells that would be used for therapy in humans.

    Human ES cells are tricky to grow, and many regard their culture more as an art than a science. “In general, we don't understand what is going on here,” says stem cell researcher Ronald McKay of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland. But scientists have found that they need a combination of at least two animal-derived products: fetal bovine serum to nourish the cells and a layer of fetal mouse fibroblasts called feeder cells that inhibit differentiation into a variety of cell types.

    Because of that, there is a risk of contamination from animal pathogens, a fact confirmed by a study published in the January issue of Nature Medicine. Physician Ajit Varki and colleagues at the University of California, San Diego, identified a substance on the surface of cultured human ES cells, N-glycolylneuraminic acid, that is taken up from animal products and that would probably cause them to be rejected if transplanted into a patient.

    To circumvent such problems, many groups have been racing to develop stem cell culture media free of animal products—mouse feeder cells in particular—with some unreplicated reports of success. Now, a group led by developmental biologist Ren-He Xu of the WiCell Research Institute at the University of Wisconsin has found that in high doses, a synthetic human molecule known as fibroblast growth factor 2 (FGF2) can do what mouse feeder cells do: sustain stem cells in an undifferentiated—or pluripotent—state.

    Xu says his team, which includes James Thomson, who first successfully derived human ES cells, discovered a few years ago that when the culture medium they normally use is not conditioned by mouse cells, it promotes stem cell differentiation, mimicking the activity of bone morphogenetic protein (BMP). That meant that there must be molecules in the feeder cells that suppress BMP activity. They have now determined that FGF2, a protein routinely used in human ES cell culture, will, if administered in high quantities in combination with BMP antagonists, inhibit BMP activity, preserving the cells in the undifferentiated state. The report appears in the March issue of Nature Methods.

    Although Varki says the Wisconsin study is “a major step forward,” he and others point to several issues that remain to be resolved—including finding ways to remove bovine serum, which also appears to be a major source of contamination.

  11. RETROVIRUS MEETING

    Gut Assumes Sinister New Role in HIV Pathogenesis

    1. Jon Cohen

    BOSTON—It's the gut, stupid.

    That was one of the clearest take-home messages from the 12th Conference on Retroviruses and Opportunistic Infections, where 3900 researchers from 72 countries converged 22 to 25 February to discuss some of the most fundamental questions riddling the field. New insights emerged about everything from the forces behind Uganda's celebrated drop in HIV prevalence to the amount of benefit that anti-HIV drugs have provided. And on the basic research front, immunologist Daniel Douek of the Vaccine Research Center at the U.S. National Institutes of Health in Bethesda, Maryland, tied together new data with underappreciated older work that illuminate the guts of HIV pathogenesis.

    Despite 20 years of research into HIV, debates still rage about the path from infection to immunological mayhem. There is abundant evidence that HIV preferentially infects and decimates CD4 white blood cells, and some researchers have long argued that direct killing alone causes the profound CD4 loss that is the hallmark of AIDS. That prompted David Ho, chair of this year's meeting, to once wear a button saying, “It's the virus, stupid.” Another camp contends that HIV infects a relatively small number of CD4 cells and indirectly causes the massive death of uninfected “innocent bystanders” by activating them, a process that leads to their premature death.

    Before and after.

    An uninfected person's ileum contains mounds of protective immune cells (left); these are stripped bare after HIV infection.

    CREDIT: REPRODUCED FROM J. EXP. MED. 200, 749–759 (2004) BY COPYRIGHT PERMISSION OF THE ROCKEFELLER UNIVERSITY PRESS

    Daniel Douek indicted both direct and indirect killing, with the infection of CD4 cells in the gut playing an especially sinister role. Building on previous work done in monkeys by Ronald Veazey and Andrew Lackner of the Tulane National Primate Research Center, Douek charted how HIV blazes through CD4 cells, starting in the gut and then moving into lymph nodes and the blood. Regardless of the route of transmission, at infection, HIV selects CD4s that also have surface receptors known as CCR5. The vast majority of CD4+/CCR5+ cells reside in the gut. Douek showed a startling photograph taken during colonoscopies. Whereas an uninfected person's ileum had mountains of lymphoid tissue that contained CD4+/CCR5+ cells, the landscape of the ileum of a person recently infected by HIV was scraped clean. “You have absolutely no lymphoid tissue at all—it's completely wiped out,” noted Douek, who showed evidence that direct killing caused this loss.

    As the disease progresses to a chronic infection, said Douek, indirect killing explains much of the CD4 loss. Douek focused on lymph nodes, which repopulate the body with new CD4s. He proposed that when HIV destroys gut immunity, other pathogens flourish, which, in turn, overactivates the lymph production of CD4s, many of which will soon die even though they are uninfected.

    Just as the inflammation caused by hepatitis destroys the liver, chronic inflammation of lymph nodes—which Douek dubbed “immunitis”—destroys their architecture, leading to massive buildup of collagen, causing fibrosis. And his lab, working with a group headed by Timothy Schacker of the University of Minnesota, Twin Cities, indeed showed that the greater the amount of collagen in lymph nodes, the less able infected people were to respond to anti-HIV drugs. Douek says lymph node biopsies thus may help clarify differences in people's responses to treatment, and he suggests that antifibrotic agents like the cancer drug Gleevec might help HIV-infected people.

    The most important ramifications of this improved understanding of how HIV causes disease could be in vaccine research, said Douek. A vaccine that triggers immune responses in the gut may best thwart the initial infection. Similarly, measuring gut immunity after vaccination—no easy feat—may also guide researchers to specific responses that correlate with protection.

    Off message.

    New data ascribe Uganda's AIDS “success” to condom use rather than the abstinence and faithfulness promoted on this Kampala billboard.

    CREDIT: STAFFAN WIDSTRAND/CORBIS

    Douek's presentation received rave reviews. “It made it worth my coming here,” said Steven Deeks, a leading AIDS clinician at the University of California, San Francisco. “It's the best talk I heard,” agreed AIDS vaccine researcher Ronald Desrosiers, who heads Harvard's primate research center.

    Another highlight of the meeting was an epidemiologic study from Uganda. Maria Wawer of the Columbia University Mailman School of Public Health in New York City has led a study of HIV's spread in Uganda's Rakai district, conducting annual surveys of 10,000 people over the past 15 years. Uganda has been praised for its sharp declines in HIV prevalence, which some—including the Bush Administration—have attributed to increases in abstinence and monogamy. Wawer's new data challenge those assumptions, indicating that, at least in Rakai, drops in prevalence were due to deaths from HIV outnumbering new infections and an increase in condom use. Wawer noted that Uganda now has a shortage of condoms.

    Kevin DeCock, an epidemiologist who heads the U.S. Centers for Disease Control and Prevention's efforts in Kenya, cautioned against pitting one prevention strategy against another and contended that one of the most effective approaches is often overlooked: HIV diagnosis, an opportune time to encourage people to reduce risky behaviors.

    Diagnosis also frequently leads people to anti-HIV therapy, providing dramatic benefits that Rochelle Walensky, an infectious-disease specialist at Massachusetts General Hospital in Boston, has attempted to quantify. According to a mathematical model developed by Walensky, Kenneth Freedberg, and colleagues, anti-HIV drugs in the United States alone have saved over 2 million years of life. The model further shows that if a person starts potent treatment with an average of 87 CD4 cells—a state of destruction that typically occurs after about 11 years of untreated HIV infection—drugs available today will extend life by nearly 15 years. This “far exceeds the gains realized by many other disease interventions,” including treatment for breast cancer and lymphoma, she said. Now the challenge is to get the drugs to the more than 4 million people who most need them but still have no access.

  12. BIODEFENSE

    Has Biodefense Gone Overboard?

    1. Jocelyn Kaiser,
    2. Martin Enserink

    The 9/11 terrorist attacks and the anthrax letters triggered a vast program to protect the U.S. from bioterrorism. Three years later, some scientists complain that it is hurting basic microbiology—and ultimately, public health

    Patricia Kiley is wondering whether to hop on the bandwagon.

    As a young microbiologist at the University of Wisconsin, Madison, Kiley is making a name for herself studying some of the most basic life processes—for instance, how bacteria sense changing oxygen levels in their environment. But lately, she has felt the oxygen being sucked out of her own field, as funding has become increasingly scarce. Her dilemma: Should she trade her model organism, Escherichia coli, for a bioterrorism agent, to get a shot at the current U.S. biodefense bonanza? Scientifically speaking, switching would be “stupid,” Kiley says; progress is much easier in E. coli, a well-known lab workhorse. But she worries that she may have little choice.

    Kiley is not the only one who's concerned. More than 750 U.S. microbiologists—including the president-elect of the American Society for Microbiology in Washington, D.C., Stanley Maloy of San Diego State University, and seven past ASM presidents—sent an open letter to National Institutes of Health (NIH) Director Elias Zerhouni this week, complaining that the current spending spree in biodefense is threatening the very foundation of microbiology. While budgets have skyrocketed for exotic agents such as plague, anthrax, and tularemia—each of them negligible as human health threats—research on widespread and perhaps mundane pathogens is falling by the wayside, the letter says, as is work with traditional model organisms such as Kiley's E. coli.

    The letter by S. Altman et al., published in this issue, has circulated among more than 1100 reviewers for, and beneficiaries of, two NIH study sections for microbiology, and it has become a hot topic in recent weeks. “Researchers should never whine about a lack of funding for their research,” says David Walker of the University of Texas Medical Branch in Galveston, who did not sign it. “Biodefense is what Congress wants us to do,” adds Walker, whose university has thrived thanks to the new money. Walker also notes that the main organizer of the letter, molecular biologist Richard Ebright of Rutgers University in Piscataway, New Jersey, has an agenda that goes beyond advocating for microbiology; Ebright has been an outspoken critic of the biodefense buildup, arguing that it is creating new risks (see sidebar, p. 1397).

    NIH officials, meanwhile, say the numbers cited in the letter are misleading. Biodefense research spending—some $1.7 billion this year in NIH funding alone, almost entirely at the National Institute of Allergy and Infectious Diseases (NIAID)—has come on top of existing budgets, says NIAID Director Anthony Fauci, and nonbiodefense microbiology has fared no worse than NIH-supported research in general. “I wish those who signed it would take a careful look at the data,” says Fauci. Moreover, studying biodefense agents is yielding valuable insights that will help fight other, more prominent diseases as well, Fauci says.

    Even among those who did sign, opinions vary widely. Whereas some believe that the massive biodefense effort is unnecessary or even dangerous, others agree that it can help the fight against infectious disease—they just think the balance is skewed.

    Getting the boot?

    Biodefense grants have shot up but basic microbiology is suffering, the open letter complains.

    CREDITS (LEFT TO RIGHT): KENNETH LAMBERT/AP; SOURCE: RICHARD EBRIGHT

    Windfall for science

    Just how much money would go to biodefense was decided in the frantic months that followed 9/11 and the anthrax letters in 2001. Among several other measures aimed at protecting the nation from bioterrorism, the Bush Administration decided to radically ramp up research on biodefense. NIAID staff added up rough costs for new labs, put together a strategic plan, and persuaded the White House to propose $1.5 billion in new money for biodefense research and labs in NIH's 2003 budget.

    Congress agreed, and NIAID's overall budget rose 47% in 1 year, leaving it with a portfolio divided evenly among AIDS, biodefense, and other infectious diseases. Although the new money helped complete a plan to double the NIH budget over 5 years, many institutes other than NIAID saw their budgets rise only about 85% to 90%.

    Fauci takes pride in having made sure the research money landed at his institute. If two other contenders—the Department of Homeland Security, formed in 2002, and the Pentagon—had gotten their hands on the money, it would have been directed toward more concrete countermeasures, such as vaccines, drugs, and diagnostics, he says—giving the research community much more to grumble about.

    In a vigorous defense of the program during an interview last week, Fauci said he was able to strike a “deal” with the Administration that allows NIAID to spend about one-third of the money on basic research and so-called emerging infectious diseases. That includes components such as a genomics initiative and an $85 million, 5-year program on innate immunity that “is totally non-organism specific,” Fauci says.

    A large chunk of the money has gone to building 14 new biosafety level 3 and BSL-4 labs that can handle the most dangerous pathogens—a source of much debate in local communities. Fauci points out that these labs can also be used to study emerging diseases such as avian flu or severe acute respiratory syndrome. Broader than the Category A, B, and C list of biodefense pathogens of the Centers for Disease Control and Prevention, the NIH list includes agents such as dengue, influenza, West Nile virus, and drug-resistant tuberculosis.

    Besides, Fauci contends, even work on a potential bioterrorism agent can have broad applications—for instance, in the February issue of the Journal of Clinical Investigation, researchers report that mice can be partially protected from a poxvirus infection by a drug that targets a cell-signaling pathway needed by the virus, findings that could yield a new approach for antiviral drugs.

    Dueling data

    The current brouhaha hinges on two different analyses: one, by the letter writers, that suggests a steady erosion in funding for microbiology, and one from NIAID that purports to show that such support hasn't changed.

    Ebright and his colleagues have several gripes. One is that many of the biodefense grants were initially awarded through special competitions with pots of money set aside specifically for a handful of high-priority Category A or B agents. Unlike investigator-initiated grants, which are assigned to NIH-wide review panels by topic and receive funding only if they meet a certain quality level, the “requests for applications” are reviewed by panels created just for that competition, and proposals that fall below the usual quality standard may still receive funding. So, like other targeted research, these grants can be easier to get.

    The letter asserts that this funding strategy resulted in a steep decline in awards funded by the two main NIH study sections evaluating nonbiodefense, basic microbiology grants: Microbial Physiology and Genetics, and Bacteriology and Mycology. These two sections constitute the bulk of funding for basic microbiology, says Ebright, and are supported mostly by NIAID and the National Institute of General Medical Sciences (NIGMS). Ebright and his colleagues contend that in these two sections, the number of awards has fallen from 1117 between 1996 and 2000 to 746 since then, a drop of 33%. (The numbers come from CRISP, NIH's grants database.) In the same period, the number of grants for six bacterial diseases that are on the priority bioweapons list but are extremely rare in humans—tularemia, anthrax, plague, glanders, melioidosis, and brucellosis—shot up from 33 to 497. (The letter does not address viruses, but the developments in virology are similar, says Ebright.)

    Enough for everyone.

    NIAID's Anthony Fauci, whose budget rose by 47% after 9/11, says biodefense hasn't come at the expense of other fields.

    CREDIT: GERALD HERBERT/AP

    Data on success rates (the fraction of applications funded) provided by NIAID support the critics' contention that it has been harder to get grants for nonbiodefense work than for biodefense work (see table, above), although projections for 2006 suggest that the difference will disappear as biodefense funds get shunted from new grants into paying for existing grants and contracts.

    Not only is less money going to research on bacteria that cause thousands of infections each year, the protesters say, but fundamental research on model agents such as E. coli, Bacillus subtilis, and Salmonella is also in decline. Such basic work has led to vast advances in knowledge, paving the way for new antibiotics, says Stanley Falkow of Stanford University in California, who also signed the letter. “It will be very difficult to make the same basic discoveries working on the biothreat agents,” he says—not just because researchers barely know them, but also because studying them is restricted to high-containment labs subject to strict and cumbersome security measures.

    But Fauci counters with a different set of numbers. NIAID's analysis of nonbiodefense bacterial physiology grants since 2000—defined more broadly, not limited to two study sections—finds that the number of awards has been stable, hovering between about 120 and 150 per year since 2000. It's possible that the number of grants has fallen at NIGMS, Fauci says, but that could reflect tighter budgets at that institute: “If there wasn't biodefense money, they [investigators] would be suffering anyway.” NIGMS program director James Anderson says the institute has not done an analysis of trends in microbiology funding, which are also affected by reviewers' own preferences; lately, they have preferred mechanistic studies, for example. But if the numbers of applications and awards have dropped, “NIGMS is interested in the reasons.”

    The letter urges NIH to add basic microbial research to its biodefense program and to assess proposals for biodefense side by side with basic microbial research, which would give nonbiodefense researchers a better chance at competing.

    An exaggerated risk?

    The nitty-gritty of grant numbers aside, the letter does raise a broader issue: Does biodefense deserve all this money? Apart from the five anthrax deaths in 2001, there have been no known bioterrorism deaths in the United States. Natural deaths from many other biodefense agents—such as smallpox, tularemia, and plague—are also low if not zero. Is it worth spending billions of dollars on these agents, when flu alone causes more than 30,000 deaths a year in the United States and food poisoning some 5000?

    Countries other than the United States don't seem to think so. Although many European nations have taken some basic precautions, for instance, such as stocking up on smallpox vaccine, there isn't anywhere near the funding avalanche—nor the meetings, journals, and businesses—that have sprung up in the United States.

    But Fauci says he's seen intelligence that convinces him that the threat is all too real. Some researchers are worried too, even if they're not privy to secret information. “I'm personally very concerned,” says virologist Peter Palese of Mount Sinai School of Medicine in New York City, who considers the threat “underestimated.” If anything, he adds, more money should be going to biodefense.

    CREDITS (TOP TO BOTTOM): CDC/COURTESY OF LARRY STAUFFER MANFRED KAGE/PETER ARNOLD, INC.; SOURCE: NIAID

    But Milton Leitenberg, an arms-control expert at the University of Maryland, College Park, couldn't disagree more. No evidence suggests that any terrorist organization is able to produce an effective bioweapon, he says, and some of the grim scenarios outlining a bioterror attack appear primarily designed to scare people. As an example, he cites Atlantic Storm, a recent exercise in which politicians simulated an international smallpox attack that takes thousands of lives (Science, 28 January, p. 513) Many of its premises—for instance, that an Al Qaeda splinter group could produce a smallpox powder in a “small brewery in Klagenfurt, Austria”—are wrong, Leitenberg says.

    Abigail Salyers of the University of Illinois, Urbana-Champaign, who presided over ASM when the anthrax attacks occurred in 2001, also believes that much of the fear—and much of the research—is unnecessary. Public health officials know how to respond to crises, she says; even in 1947, when a smallpox case surfaced in New York City, millions were vaccinated against the disease almost without a wrinkle. The lesson: Dealing with a bioterror attack isn't rocket science, she says, and a powerful public health system and an effective communication strategy are the best preparation.

    Mark Wheelis, a biological arms-control specialist at the University of California, Davis, says he's delighted to see the discussions unfurl. A few people have been critical of the biodefense boom, he notes, but by and large, the three-and-a-half years since 9/11 have passed without an informed debate about exactly what's threatening the U.S. population and how much should be invested to avert those dangers. “This letter finally opens the debate,” he says. “We should welcome it.”

  13. BIODEFENSE

    Microbiologist on a Mission

    1. Jocelyn Kaiser

    The scientist who persuaded hundreds of his colleagues to sign a letter criticizing U.S. spending on biodefense research is not only worried about its impact on basic microbiology (see main text). Richard H. Ebright is also passionately opposed to the proposed expansion of biodefense labs. It might seem like a pacifist's argument, but far from it; as one former labmate puts it, Ebright is “complicated.”

    Ebright, 45, spent 6 years as an undergraduate and graduate student in the laboratory of Harvard geneticist Jon Beckwith, a left-leaning social activist on everything from the Vietnam War to genetic discrimination. As an outspoken conservative, Ebright “was unusual in my lab,” says Beckwith; “we would get into lots of debates.” Ebright held his own and also excelled academically, publishing his first paper in the Proceedings of the National Academy of Sciences while still in college. He is now a Howard Hughes Medical Institute investigator at Rutgers University in Piscataway, New Jersey, where he studies the initiation of DNA transcription.

    Speaking conservatively.

    Richard Ebright thinks the biodefense boom is making the country less safe.

    CREDIT: JENNIFER S. ALTMAN

    Since 9/11 and the anthrax letters, Ebright, like his former adviser, has taken on a cause. When the National Institutes of Health proposed a massive new biodefense program, Ebright began to worry that vastly increasing the number of labs and people working on bioterror agents would only raise the risks that a pathogen would accidentally escape or be deliberately released by a “disturbed, disgruntled, or adversarial” scientist, he says. As he argued in a letter to Nature he co-authored in January 2002, a better strategy would be to expand research on related, less pathogenic agents, while limiting work on bioterrorism agents to a few strictly controlled labs. It's a view shared by “most policy experts on bioweapons outside the government,” he contends. It also makes for some strange bedfellows: Ebright, still a registered Republican, shares information with Edward Hammond, a liberal Democrat and U.S. leader of the Sunshine Project, a weapons watchdog that is tracking the biodefense buildup (Science, 6 August 2004, p. 768). Hammond, who praises Ebright as “brave” for expressing what many scientists believe but don't say, calls it a “tactical alliance.”

    Ebright's views have often made him a lone voice amid the many researchers who are benefiting from the biodefense boom. Some of these scientists have now added their signatures to the open letter, which the media-savvy Ebright sent to reporters at major newpapers and journals. The signers share a concern about preserving basic microbial science, even though they “have different views on other aspects of biodefense,” Ebright says.

  14. CONSERVATION SCIENCE

    What's in a Species' Name? More Than $450,000

    1. Bijal P. Trivedi*
    1. Bijal P. Trivedi is a freelance writer in Washington, D.C.

    The German group BIOPAT has successfully raised funds for taxonomy and conservation science by selling the rights to name species

    Everyone in Stan Vlasimsky's family has an alter ego in the animal kingdom. A dainty Bolivian orchid, Epidendrum lezlieae, is named for his wife Lezlie. For daughter Claudia and son Liam, there are frogs in Panama and Madagascar, respectively. Daughter Magdeline has a Filipino butterfly carrying her name. And for the newest addition, toddler Caiden, there is a Peruvian lizard, Euspondylus caidenii.

    Vlasimsky is not a rugged biologist trudging through remote forests or swamps and naming newly discovered species. The business consultant was on a flight 5 years ago when he read about BIOPAT (Patrons for Biodiversity), a German nonprofit group offering naming rights to new species in exchange for donations to conservation science (Science, 21 January 2000, p. 421). “What a novel idea,” says Vlasimsky, whose namesake, Eupholus vlasimskyi, is a belligerent-looking black beetle. “It was a great way to support not just the scientist's research but also the species. And at the end of the day, it was a lasting gift.”

    BIOPAT isn't the only game in town. This week the New York City-based Wildlife Conservation Society (WCS) held an online auction for the right to name a new species of titi monkey—a rare find from the jungles of Bolivia's Madidi National Park. “Bolivia is one of the poorest countries in South America, and it's hard to raise money to protect these places,” says WCS primatologist Robert Wallace, the monkey's co-discoverer.

    The WCS auction was, in part, inspired by BIOPAT's success. Born to some controversy in December 1999—critics called for the group to abandon its plan—BIOPAT has so far facilitated more than 100 species sponsorships and raised more than $450,000 for research and conservation. The cost of naming a species ranges from $3500 for various insects to $13,000 for a hummingbird; the more attractive or rare the species, the higher the price. The proceeds are split between the institution of the species' discoverer and field research projects in the country of the species' origin. BIOPAT-raised money, for instance, has funded surveys of bat populations in Sri Lanka, taxonomic training programs for locals in Myanmar, and an inventory of Bolivian orchids in the Tariquia conservation area.

    Potential BIOPAT customers surf an online catalog of plants and creatures. About 40 species of slugs, bugs, flowers, frogs, and others are currently available. Customers can even request a species with specific traits—a yellow orchid with violet stripes, for example—and a call goes out to Germany's museums and institutions that are members of BIOPAT. The customer also works with scientists to craft an appropriate species name and publish its description, which brings official recognition.

    All in the family.

    A businessman paid for the rights to name these plants and animals after his family.

    CREDIT: COURTESY OF BIOPAT

    “We can arrange virtually any sponsorship,” says Claus Bätke, BIOPAT's president and an agrobiologist with German development agency Deutsche Gesellschaft für Technische Zusammenarbeit. Most large museums have drawers that have been stuffed for decades with species waiting for a taxonomist to describe, classify, and name them, Bätke explains. “We have several hundred unnamed insects here,” adds Gerhard Haszprunar, a professor of systematic zoology at the University of Munich and director of the State Zoological Collection in Munich, who first came up with the naming idea. “We are always happy to give BIOPAT new species.”

    Most donors choose charismatic species—orchids and frogs account for about 50% of sponsorships. For example, BIOPAT enabled a friend of Mikhail Gorbachev to sponsor Maxillaria gorbatchowii, a Bolivian orchid. Insects and other arthropods seem to spark little interest. An “ugly” spider from China has remained unnamed for 2 years, says Bätke.

    Corporations have gotten into the act. The German food company Vitaquell named a Columbian hummingbird Thalurania vitaquelli and plans to use it in ads for low-fat margarine. BIOPAT will veto requests that it deems inappropriate. One potential customer tried to name a particularly unattractive insect after his mother-in-law, and another wanted to memorialize Nazi propaganda filmmaker Leni Riefenstahl with an orchid.

    Not every group selling species' names is as successful as BIOPAT. The Immortals Program of the Australian Museum in Sydney, which funds biodiversity research, has attracted only eight donors since its launch in the late 1990s, raising approximately $31,000.

    BIOPAT itself got off to a rocky start, drawing fire from the U.K.'s International Commission on Zoological Nomenclature (ICZN), which suggested that “name selling would spread to those whose intention is simply their own financial gain” (Science, 18 February 2000, p. 1203). ICZN added that such a scheme could lead to fraudulent species descriptions and muddy the scientific naming system. No such abuses have arisen, however.

    Still, Neal Evenhuis, the new president of ICZN, continues to share the concerns that his predecessors expressed. But he acknowledges that selling and auctioning species names is a symptom of how bad government funding is for taxonomy. “It's not as sexy to find a species anymore as it is to sequence its DNA,” Evenhuis says. “BIOPAT are not the bad guys. Raising $450,000 in this fashion in 4 years is a tremendous result in their effort to promote and further taxonomic research and conservation.”

    For Vlasimsky, the eponymous flowers, frogs, lizards, and bugs instill in his family a value for research and biodiversity. “My kids know they each have an animal and that this is important. They talk about this with their friends,” he says. Conservation scientists also hope that such personal links will spur donors to make sure their namesakes survive.

  15. U.S. POLAR RESEARCH

    Shift in Icebreaking Fleet Could Crunch NSF Budget

    1. Jeffrey Mervis

    Plowing a path to polar research stations is no longer a core mission of the U.S. Coast Guard. But can the National Science Foundation afford to do the job?

    Half a century after agreeing to help the National Science Foundation (NSF) serve up a banquet of polar research, the U.S. Coast Guard is getting up and walking away from the table. And NSF doesn't know if it can pay the bill.

    NSF is responsible for U.S. science at the poles, which includes three stations in Antarctica and a growing presence in the Arctic. But it can't do its job without the Coast Guard's help in clearing the sea ice. That's a perennial need at McMurdo Station, the logistical hub for U.S. activities on the Antarctic continent. Although NSF pays for the fleet's deployment—some $12 million last year—the Coast Guard has shouldered the much greater cost of building and maintaining two aging heavy-duty icebreakers that focus on McMurdo and a newer, less powerful research icebreaker that spends most of its time in the Arctic.

    But that relationship seems headed for the deep freeze. Last month the Bush Administration told Congress in its proposed 2006 budget submission that NSF would henceforth be responsible for the ships, two of which are desperately in need of major repairs or replacement after 30 years of ice-crunching. Officials at both the Coast Guard and NSF say the policy shift was presented as a fait accompli last fall during budget negotiations.

    The White House has tried to sweeten the deal with a one-time transfer of $48 million to NSF from the Coast Guard. But that's less than two-thirds of the $75 million the Coast Guard estimates it will cost to maintain the ships this year. And it's little more than a down payment on a possible $600 million tab to retrofit the 30-year-old Polar Sea and Polar Star—and even more to replace them. (The Sea is now undergoing an extensive inspection to determine what repairs are needed, and the Star is slated for the same major overhaul after next winter.) Not surprisingly, NSF officials fear that the agency's new duties could eventually wreak havoc with its overall budget, which shrank by 3.2% this year and has little chance of growing significantly next year. Three panels have been convened to study the issue from all angles.

    “We need to look at the whole system, both short-term and long-term, and figure out what makes the most sense,” says Karl Erb, head of polar programs at NSF. But some things—none of them good—are already clear to Sridhar Anandakrishnan, a glaciologist at Pennsylvania State University, University Park, and past chair of NSF's polar science advisory committee. “It's a huge crisis,” he says. “And I don't know how we can solve it without additional funding from Congress.”

    Cold welcome.

    The Polar Sea and Polar Star help an oil tanker reach McMurdo Station in Antarctica.

    CREDIT: PETER WEST/NATIONAL SCIENCE FOUNDATION

    The Administration says NSF should foot the bill because the icebreaking fleet mainly serves the academic scientific community. What's more, enabling science is a lower priority for the Coast Guard, now part of the Department of Homeland Security, than activities such as law enforcement, search and rescue, and fostering economic development. Accordingly, this year's 2006 budget request concludes that “it is unlikely that the Coast Guard could provide funding in future years for refurbishment or replacement of the icebreakers. That, in turn, threatens the research programs that depend on their services.”

    Indeed, funding lies at the heart of the problem. “We think that polar icebreaking is important,” says Cmdr. Thomas Wojahn, ice operations program manager for the Coast Guard. “And we think we should continue to operate the ships. But icebreaking needs to be properly funded.” Wojahn notes that soaring fuel bills, bigger repair bills, and recent extreme ice conditions in the Antarctic have boosted the cost of doing business without a commensurate rise in funding.

    The new arrangement gives NSF a chance to break that vicious cycle, the White House says. Once the Coast Guard transfers responsibility for icebreaking, according to budget documents, “NSF will have flexibility to pursue alternatives to current operations.” Those alternatives could include renting commercial or foreign icebreakers, as NSF did this winter to replace the Polar Sea (Science, 21 January, p. 338). A more radical approach would be to offload fuel, supplies, and other materials at a spot that remains ice-free throughout the year and then haul the material over land. But the savings in annual icebreaking might be swamped by the cost of building a new station and extending NSF's supply lines.

    Anandakrishnan agrees that it makes sense for NSF to ensure access to its research assets. But he says nobody anticipated the “perfect storm” that has built up in the past few years. “We've known for a long time that it would eventually come to the point where the Coast Guard would say, ‘You want us to do this? Then find the money!’ But NSF is also in a bad way, financially.”

    Although Congress could reverse the policy and block the transfer of funds, both the Coast Guard and NSF are proceeding on the assumption that it will take effect next year. A joint working group is drawing up a new agreement on how the three ships will be operated and maintained over the next few years, says Erb. At the same time, the National Academies' National Research Council is beginning a study of how the country's polar icebreaking fleet should be deployed, “including scenarios for continuing those operations and alternative approaches.” Although the $600,000 study will run until the end of 2006, Congress has asked for an interim report by September. Finally, Erb is assembling an NSF task force to weigh the agency's long-term prospects for operating in the polar regions. He hopes the panel will “at least start to narrow down the options” in time for NSF's 2007 budget submission to the White House in September.

  16. MATHEMATICS

    What in the Name of Euclid Is Going On Here?

    1. Dana Mackenzie*
    1. Dana Mackenzie is a freelance writer in Santa Cruz, California.

    Computer assistants may help mathematicians dot the i's and cross the t's of proofs so complex that they defy human comprehension

    In 1998, a young University of Michigan mathematician named Thomas Hales solved a nearly 4-century-old problem called the Kepler conjecture. The task was to prove that the standard grocery-store arrangement of oranges is, in fact, the densest way to pack spheres together. The editor of Annals of Mathematics, one of the most prestigious journals in mathematics, invited him to submit his proof to Annals. Neither of them was prepared for what happened next.

    Over a period of 4 years, a team of 12 referees wrestled with the lengthy paper and eventually raised a white flag. They informed the editor that they were only “99 percent” certain that it was correct. In particular, they could not vouch for the validity of the lengthy computer calculations that were essential to Hales's proof. The editor took the unprecedented step of publishing the article with a disclaimer that it could not be absolutely verified (Science, 7 March 2003, p. 1513).

    It is a scenario that has repeated itself, with variations, several times in recent years: A high-profile problem is solved with an extraordinarily long and difficult megaproof, sometimes relying heavily on computer calculation and often leaving a miasma of doubt behind it. In 1976, the Four Color Theorem started the trend, with a proof based on computer calculations so lengthy that no human could hope to follow them. The classification of finite simple groups, a 10,000-page multiauthor project, was completed (sort of) in 1980 but had to be recompleted last year. “We've arrived at a strange place in mathematics,” says David Goldschmidt of the Institute for Defense Analyses in Alexandria, Virginia, one of the collaborators on the finite simple group proof. “When is a proof really a proof? There's no absolute standard.” Goldschmidt thinks the traditional criterion—review by a referee (or team of them)—breaks down when a paper reaches hundreds or thousands of pages.

    The computer—which at first sight seems to be part of the problem—may also be the solution. In the past few months, software packages called “proof assistants,” which go through every step of a carefully written argument and check that it follows from the axioms of mathematics, have served notice that they are no longer toys. Last fall, Jeremy Avigad, a professor of philosophy at Carnegie Mellon University, used a computer assistant called Isabelle to verify the Prime Number Theorem, which (roughly speaking) describes the probability that a randomly chosen number in any interval is prime. And in December, Georges Gonthier, a computer scientist at Microsoft Research Cambridge, announced a successful verification of the proof of the Four Color Theorem, using a proof assistant called Coq. “It's finally getting to the stage where you can do serious things with these programs,” says Avigad.

    Mapping the way.

    Georges Gonthier's computer verified billions of calculations on “hypermaps” like the one shown.

    CREDIT: COURTESY OF GEORGES GONTHIER

    Even Hales is getting into the action. Over the past 2 years, he has taught himself to use an assistant called HOL Light. In January, he became the first person to complete a computer verification of the Jordan Curve Theorem, first published in 1905, which says that any closed curve drawn in the plane without crossing itself separates the plane into two pieces.

    For Hales, the motivation is obvious: He hopes, eventually, to vindicate his proof of the Kepler conjecture. In fact, three graduate students in Europe (not Hales's own) are already at work on separate parts of this project, two using Isabelle and one using Coq. Hales expects them to finish in about 7 years.

    But Hales thinks that computer verifiers have implications far beyond the Kepler conjecture. “Suppose you could check a page a day,” he says. “At that point it would make sense to devote the resources to put 100,000 pages of mathematics into one of these systems. Then the mathematical landscape is entirely changed.” At present, computer assistants still take a lot of time to puzzle through some facts that even an advanced undergraduate would know or be able to figure out. With a large enough knowledge base, that particular time sink could be eliminated, and the programs might enable mathematicians to work more efficiently. “My own experience is that you spend a long time going over and going over a proof, making sure you haven't missed anything,” says Carlos Simpson, an algebraic geometer and computer scientist at the University of Nice in France. “With the computer, once it's proved, it's proved. You only have to do it once, and the computer makes sure you get all the details.”

    In fact, computer proof assistants could change the whole concept of proof. Ever since Euclid, mathematical proofs have served a dual purpose: certifying that a statement is true, and explaining why it is true. Now those two epistemological functions may be divorced. In the future, the computer assistant may take care of the certification and leave the mathematician to look for an explanation that humans can understand. “Just because a proof is explanatory doesn't mean it's certain,” says Harvey Friedman, a logician at Ohio State University in Columbus. “Just because it is certain doesn't mean it's explanatory. They are two separate dimensions.”

    So far, Hales, Simpson, and Friedman are part of an extremely small minority: mathematicians who have taken the trouble to learn about proof assistants. “Mathematicians don't know about [computer proof verification], they're not interested in it, and they don't believe it,” says Freek Wiedijk, a computer scientist at the University of Nijmegen in the Netherlands who specializes in proof verification. Simpson says much of the mistrust may stem from a misimpression that computerized proof checkers are trying to automate mathematical creativity.

    In fact, an assistant can no more prove the Four Color Theorem than an online thesaurus can write Hamlet. In a typical session with a proof verifier such as Isabelle or Coq, the mathematician enters the hypotheses at the top of the computer screen and the “proof obligation”—the conclusion—at the bottom. She decides on a “tactic” to simplify the proof obligation—for example, subdividing it into simpler cases, performing a calculation, or applying a previously known theorem. Each time the user enters a tactic, the computer program executes it and updates the proof obligation. When there are no more obligations left, the proof is verified.

    One stumbling block is that published proofs never specify every step. Every math student is familiar with the dreaded words, “it is obvious that …” To the computer, nothing is obvious. It is up to the user to break the “obvious” step down into subtasks that the computer can check. Diagrams are particularly troublesome; the user must somehow parse the pictorial information into allowable tactics.

    Different languages.

    Machine proofs (right) can look very different from “human” versions.

    All in all, people who have used proof verifiers say they can formalize about a page of textbook mathematics in a week. Avigad says he reached a top speed of a page a day while working on the Prime Number Theorem—close to the break-even point at which it will be worth mathematicians' time. “When it becomes not too much harder to formally verify a proof than to write it up carefully, it starts looking like a win,” he says.

    Probably the most remarkable accomplishment so far by a computer proof assistant is Gonthier's recently completed verification of the Four Color Theorem. This theorem began as a conjecture in 1852, when a graduate student at University College London named Francis Guthrie asked his professor Augustus DeMorgan if he could prove that any map can be colored with four colors in such a way that no two adjacent countries have the same color. After more than a century of unsuccessful attempts, some by eminent mathematicians, two computer scientists, Kenneth Appel and Wolfgang Haken, finally proved it in 1976. Their computation-intensive argument raised an immediate furor. “Mathematicians over 40 years old couldn't be convinced that a proof by computer was correct, and those under 40 couldn't be convinced that a proof with 700 pages of hand calculations was correct,” jokes Robin Wilson, a graph theorist at the Open University in Milton Keynes, U.K. Enough questions remained about its validity that another team of graph theorists, led by Paul Seymour of Princeton University and Neil Robertson of Ohio State University, published a revised proof in 1995. Even this streamlined proof relies on a case-by-case analysis of more than a billion different maps, far more work than a human mathematician could do in a lifetime. The computer did it in 3 hours.

    Crunching through special cases also played a large role in checking the proof, Gonthier says. “From the point of view of someone using a formal computation system, those are really the easy parts. The hard part, in this case, was finding formal definitions that captured correctly the intuitions behind graph theory.” Gonthier had to revamp Seymour and Robertson's approach considerably, so that the proof assistant would understand what elementary ideas such as “the next edge on the left” meant. In his final proof script, he estimates that 19,000 lines came directly out of the Robertson and Seymour paper, and 19,000 lines were his own work. (Another 22,000 lines are white space, comments, and “infrastructure.”)

    Specialists in computer verification give Gonthier's work very high marks. “That guy is amazing,” says Wiedijk. “I can't compete with this kind of genius.” Hales calls it “a magnificent piece of work. What this means is that the proof is finally self-checking. You don't have to worry about whether the programmers introduced bugs into the computer code.” On the other hand, every graph theorist contacted for this article either had not heard of Gonthier's work or remained skeptical about it. “I have no serious doubts that computers have done their part flawlessly,” says Bojan Mohar, a graph theorist at the University of Ljubljana, Slovenia. “[But] I cannot confirm that Gonthier has made the correct translation of the [human] proof into computer form.” Others doubt the machines themselves. Coq may tell them that Gonthier's code is correct, but why should they trust Coq?

    “It's reasonable to say [Coq's code] has been verified experimentally,” Gonthier says. Coq is a program that has been developed (at INRIA in Paris) over a period of 20 years, boasts a community of about 100 active users, has source code that is open for inspection, and runs on several different computers and operating systems. Besides, he argues, “even traditional mathematical proofs use physical artifacts. You're relying on the fact that when you flip back to a previous page, the ink doesn't change. Your day-to-day experience is that the ink doesn't change. Similarly, our experience with computers is that once given a consistent set of instructions, they compute consistently. It's just hard to give them a consistent set. Proof-assistant technology makes sure that you do.”

  17. MATHEMATICS

    Have a Coq and a Smile

    1. Dana Mackenzie

    Why would hundreds of computer scientists devote more than 30 years to developing mathematical proof assistants that most mathematicians don't even want? The answer is that they are chasing an even more elusive grail: self-checking computer code.

    In a sense, the statement “this program (or chip, or operating system) performs task x correctly” is a mathematical theorem, and programmers would love to have that kind of certainty. “Currently, people who have experience with programming ‘know’ that serious programs without bugs are impossible,” Freek Wiedijk and Henk Barendregt, computer scientists at the University of Nijmegen in the Netherlands, wrote in 2003. “However, we think that eventually the technology of computer mathematics … will change this perception.”

    Already, leading chip manufacturers use computer proof assistants to make sure their circuit designs are correct. Advanced Micro Devices uses a proof checker called ACL2, and Intel uses HOL Light. “When the division algorithm turned out to be wrong on the Pentium chip, that was a real wake-up call to Intel,” says John Harrison, who designed HOL Light and was subsequently hired as a senior software engineer by Intel.

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