News this Week

Science  09 May 2003:
Vol. 300, Issue 5621, pp. 876
1. WEAPONS LABORATORIES

DOE Breaks With Tradition, Puts Los Alamos Up for Bids

1. David Malakoff

Six months after reluctantly agreeing to help the country's World War II effort by managing a new laboratory near Los Alamos, New Mexico, the University of California (UC) was surprised to learn from government officials that their charges were building a revolutionary weapon of unimagined destructiveness. Last week the university got another shocker: It will have to compete for the right to continue its 60-year relationship with Los Alamos National Laboratory.

The news came from Energy Secretary Spencer Abraham, who had asked for a review of the Department of Energy (DOE)-UC partnership in the wake of a string of security and financial scandals at the laboratory. It left the university in the awkward position of trying to decide whether to fight for a job that it didn't originally want and has traditionally said it won't compete for. “It is one thing to manage [Los Alamos] at the request of the federal government … and quite another to actively pursue what could now be interpreted as a business venture,” says UC President Richard Atkinson, who appeared before Congress last week to discuss the 30 April decision.

At stake, he and others say, is the government's ability to find a manager who can attract top technical talent for jobs ranging from maintaining reliable nuclear weapons without testing to developing better global climate models. “This is a big deal … [the lab] is at a crossroads,” says Representative Billy Tauzin (R-LA), head of the House Committee on Energy and Commerce, which held the 1 May hearing.

The laboratory is a $2.2-billion-a-year enterprise with 12,000 employees, of whom 7800 also work for UC. Although celebrated for its world-class science, it has drawn criticism for several management blunders. They include a 1999 firestorm over charges that lab physicist Wen Ho Lee mishandled classified weapons data and a more recent controversy surrounding the firings—and subsequent rehirings—of two investigators who documented lax financial practices. The scandals led to calls from Congress to cancel the contract, and starting in January the university ousted 16 top lab managers in a sweeping overhaul. DOE, meanwhile, began its own 4-month review (Science, 10 January, p. 184). In a 29 April report to Abraham, DOE officials recommended against a hasty divorce. In an 11-page analysis,* DOE Deputy Secretary Kyle McSlarrow and Linton Brooks, acting head of the department's National Nuclear Security Administration, lauded the university's reform effort and concluded that immediate termination “would be highly disruptive to the things that are going well at Los Alamos, especially science.” It also predicted a “devastating exodus of the most experienced employees” if the laboratory lost the UC's academic prestige and generous employment benefits, which include tuition breaks for the children of lab employees. The two officials concluded that an open competition—the practice at most other DOE laboratories—is needed to help fix a “Los Alamos culture [that] exalted science and devalued business practices.” But they went out of their way to encourage UC to compete. “I categorically reject the notion that competition is a repudiation of an incumbent,” Abraham said in a statement. The report also makes it clear that the lab's recruiting and retention efforts have benefited from the “prestige of association with a world-class university.” A “little-noted benefit of the university,” it adds, has been to “foster a culture of scientific skepticism and peer review” that has proved “absolutely crucial” to the lab's weapons work. Those conclusions could affect the competition, which DOE is now struggling to organize. A request for proposals could be issued in late 2004, with bids due in early 2005. The first clues to DOE's desires could come in July, when an advisory panel will deliver its thoughts on lab contracting in general. The National Academies is also expected to weigh in. At UC, Atkinson says his “instinct [is] to compete and compete hard.” But the final decision will be made by the university's 26 governing regents and his successor, as Atkinson is retiring in October after 8 years on the job. Several regents have already said the university should compete, but many faculty members want the university out of the nuclear weapons business. The list of potential bidders isn't long, DOE veterans say. “This is big science, so you need someone who understands how to run big science,” Brooks told lawmakers. One candidate is the University of Texas, which said in a statement that it is watching developments “with great interest.” Battelle, an Ohio-based nonprofit that already manages four other DOE laboratories, is another possibility, as is defense giant Lockheed Martin, which currently manages Sandia National Laboratories. Any bidder will have to swallow the cost of putting together a proposal, which some lawmakers peg at$10 million or more. That could be too steep a price for UC, Atkinson predicts. In addition, DOE is requiring the winner to keep Los Alamos's current workforce and maintain UC's benefits package for existing employees. The tuition benefit alone costs the university “a huge amount of money,” Atkinson notes.

DOE says it will wait until next year to decide if it will compete the contract to manage Lawrence Livermore National Laboratory in California, another weapons-related facility UC has managed since 1952. The department is, however, extending the university's contract to manage Lawrence Berkeley National Laboratory.

2. NATIONAL INSTITUTES OF HEALTH

A Call From Downtown to Shed Staff, Authority

1. Jocelyn Kaiser

A renewed push by the Department of Health and Human Services (HHS) to streamline staff and operations is stirring concern at the $27.2 billion National Institutes of Health (NIH). Anxious employees last month e-mailed around copies of a memo from Bob Wood, chief of staff for HHS Secretary Tommy Thompson, outlining plans for future staff cuts and consolidations across the department. Some NIH alumni and current staff members say they are worried that intramural research will get mired in paperwork if HHS centralizes authority, as the memo implies. Few NIH senior staff contacted by Science would comment on the record, but one administrator described it in an e-mail as “devastating.” After receiving “about 10” e-mails about the Wood memo, former NIH Director Harold Varmus told Science: “I find the whole thing pretty scary.” Varmus, now president of Memorial Sloan-Kettering Cancer Center in New York City, says: “As soon as you do things centrally, you can't run a research institution.” HHS spokesperson Bill Pierce maintains, however, that the proposed changes “will have no impact on research” at HHS. “We have the finest, best researchers in the world, and one of our priorities is to make sure this continues,” says Pierce. The 17 April memo appeared to be one of the last official actions by Wood, who is leaving HHS for a Washington, D.C., public affairs firm, Barbour Griffith & Rogers. Wood writes that the department needs to avoid “duplicative administration functions” and “redirect the dollar savings to our programs.” HHS will do so by freezing hiring in fiscal year 2005, possibly cutting staff by 5%, and trimming administrative staff 15% by 2004, the memo says. It also indicates that each HHS agency must fold all administrative functions into one office by October 2003. Most worrisome, say NIH staff members, is that HHS “will begin planning immediately” to consolidate procurement at an HHS support center. The agency is also looking at consolidating grants and budgets, the memo says. Although HHS has been merging some functions for 2 years, the memo has reignited old concerns. Procurement seems to be the biggest worry. During Varmus's tenure, NIH reorganized a cumbersome, NIH-wide procurement system into five service centers that dramatically improved efficiency, Varmus notes. The prospect of having HHS centralize all procurement—covering everything from paper supplies to transgenic mice, drugs for clinical patients, and 7-tesla magnets—“is of significant concern,” says Story Landis, scientific director for the National Institute of Neurological Disorders and Stroke. Some staff members grumble that intramural programs are already suffering from Thompson's efforts to centralize human resources at HHS. One scientist says that it now takes 3 months—instead of one—to hire a lab technician and that HHS, not the NIH lab chiefs, screens applications. Genome institute director Francis Collins has repeatedly questioned the human resources consolidation, describing it publicly last September as “damaging.” NIH officials are also worried about pressure to contract out scientific grants management jobs, a move some scientists say could threaten the peer-review system (Science, 21 March, p. 1823). NIH Deputy Director Raynard S. Kington, who is heading a task force examining the restructuring of NIH's administration, declined to comment on the memo but said: “We're exploring ways that we can improve the efficiency of NIH without compromising our research mission.” The task force expects to draft a plan “within the next several months,” Kington says. According to other sources, NIH hopes to avoid bad consequences by proposing efficiency moves on its own. 3. ANTHRAX VACCINE NIAID's Nasty Surprise 1. Jon Cohen The Bush Administration has ordered the National Institute of Allergy and Infectious Diseases (NIAID) to commit$233 million this fiscal year to buy millions of doses of a next-generation anthrax vaccine. This has caused NIAID, the second largest branch of the National Institutes of Health (NIH), to put a hold on funds for an untold number of new grant applications until it reshuffles its budget, sending shock waves through the research community. “It was a big surprise,” acknowledges NIAID Director Anthony Fauci, but he insists that the funds can be found without “a major impact on people's grants.”

The problem stems from disagreement over whether NIH should be in the procurement business. Last year, the White House asked Congress to allocate $250 million to NIAID to fund the procurement of an anthrax vaccine that would work better than the one now in use. But many inside and outside NIH sounded alarm bells. “Right from the get-go I said there's going to be misunderstandings because we at the NIH don't procure,” says Fauci. “We do research up to preadvanced development.” But the Office of Management and Budget (OMB) argued that it made sense to put the entire vaccine program under the same roof. Congress agreed with NIH and its advocates and removed the$250 million from NIAID's fiscal year 2003 budget request. But it didn't expressly say who should pay for the anthrax vaccine procurement.

After the budget became law in February, OMB had 30 days to submit what's known as its apportionment, which details how the funds should be disbursed. On the “11th hour of the 30th day,” one NIH insider says, NIH received the OMB apportionment with a footnote that obligated NIAID to spend $233 million ($250 million minus some general cuts) on anthrax vaccine procurement.

NIAID is currently funding development of a vaccine based on a genetically engineered version of an anthrax protein called recombinant protective antigen (rPA). If animal and human tests look promising, the Administration wants NIAID to buy 25 million doses for a national stockpile. Next week, NIAID will seek proposals from companies to manufacture the vaccine.

The bulk of NIAID's $3.73 billion 2003 budget is committed to funding existing grants and contracts; only$541.68 million is allocated to new and recompeting grants. That means the procurement program potentially represents “a huge hit” to investigator-initiated grant applicants, warns Patrick White, director of legislative affairs for the Federation of American Societies for Experimental Biology. Fauci says the institute plans to “minimize the damage” by cutting new grants from 4 to 3.5 years and restructuring payments on existing contracts. “We're still working out the numbers, but it's very unlikely we will be funding fewer people,” he says.

The building spree is a departure for the $10 billion HHMI, which today operates as a virtual institute, supporting more than 300 scholars at university-based laboratories. Two years ago, HHMI President Thomas Cech and other HHMI leaders decided they needed a bricks-and-mortar campus to bring together interdisciplinary teams of in-house and visiting scientists to develop new technologies for biology (Science, 2 February 2001, p. 803). Rubin, an HHMI vice president, says his planning group studied many top institutions before settling on two models they admired most: Lucent Technologies' Bell Labs in Murray Hill, New Jersey, known for pioneering work in solid state physics and electronics, and the Medical Research Council's Laboratory of Molecular Biology in Cambridge, U.K., a powerhouse in molecular biology where Rubin did graduate work. Both were noteworthy for their small working teams of no more than five people; high turnover; and internal funding, which allowed scientists to “take risks,” Rubin says. Like them, Janelia Farm will have no tenure system. Group leaders will do hands-on lab work, which is now “very rare” for tenured faculty at universities, according to Rubin. Setting an example, he will move his own Drosophila lab from the University of California, Berkeley, to Janelia Farm. Rafael Viñoly Architects in New York City came up with an airy, adaptable design. The main labs for 24 group leaders and visiting scientists will be housed in a long, curving building tucked into a hillside and walled on the north side with glass. The goal, says Rubin, is to make possible “anything we might want to do in the next 30 to 40 years.” 5. SPACE PHYSICS NASA Orders Make-or-Break Tests for Gravity Probe 1. Andrew Lawler A controversial space mission to test Einstein's general theory of relativity last week was given a reprieve—or enough rope to hang itself. NASA managers have drawn up three tests for the over-budget and behind-schedule Gravity Probe-B (GPB) mission and have decreed that failing any one will doom the$600 million project, which is just months from launch.

GPB is in essence a giant and delicate thermos bottle. It is designed to measure a slight rotation of space near the spinning Earth—a phenomenon called frame dragging that is predicted by Einstein's theory—as well as the tiny bending effect of gravity upon light. Technical problems have forced five launch delays in the past 4 years, boosting the mission's cost by $166 million. In March Ed Weiler, NASA's space science chief, ordered up a technical and scientific review to decide whether to cancel the program in light of the rising costs and continued delays (Science, 21 March, p. 1827). Its results were presented at a 30 April meeting that included officials from Marshall Space Flight Center in Huntsville, Alabama, and the mission's principal investigator, Stanford University physicist Francis Everitt. Weiler said afterward that he told the GPB team “we will terminate with no further reviews” if the instrument fails either of two thermal vacuum tests or the team fails to come up with a better mission operations plan. Everitt calls the decision “appropriate.” The technical review, chaired by Tom Fraschetti of NASA's Jet Propulsion Laboratory in Pasadena, California, concluded that GPB's hardware is “in fairly good shape” but that technical issues involving a heater, fuses, and a star sensor may require more work. The team was skeptical that the spacecraft will be ready for launch this fall and recommended that it undergo two more thermal cycle tests, which mimic the intense hot and cold of space, following troubles in a similar test late last year. Everitt says that those problems were “blown out of all proportion” and that the test actually was “extremely successful.” The team also recommended a more detailed plan for mission operations. The scientific review, led by University of Chicago physicist Michael Turner, found “some erosion” in the scientific value of the frame-dragging experiment because other missions now in the pipeline should produce results that have a bearing on Einstein's predictions and “more significant erosion” in measuring gravity's effect on light. Everitt says he “vigorously” disagrees with the reviewers, who did not go so far as to claim that GPB is scientifically redundant. The GPB team is confident that the experiment can be ready for a September launch, although NASA officials think that the end of the year is more likely. And time is money: A November launch adds$10 million to the latest overrun of $20 million to$30 million, and a 6-month delay would cost $30 million to$40 million more.

6. INFECTIOUS DISEASES

Smallpox Vaccination Campaign in the Doldrums

1. Martin Enserink

WASHINGTON, D.C.—Reality has caught up with the Bush Administration's ambitious plan to vaccinate between 5 million and 10 million Americans against smallpox by this summer. So far, fewer than 35,000 people have received the vaccine, and many states have halted vaccination, awaiting further guidance from the federal government. At a meeting of an Institute of Medicine (IOM) panel last week, several state and local health officials sharply criticized the campaign and urged the government to cancel its second and largest phase, which has begun in only one state, Florida.

Officials from the Centers for Disease Control and Prevention (CDC) in Atlanta say what counts is that states and cities are ready to face an attack—not the exact number of vaccinees. But they concede that it is hard to convince people to get the shots. Mustering momentum is likely to be even tougher now that the vaccine has caused unanticipated side effects, the war in Iraq has ended—without turning up any stockpiles of bioweapons so far—and the public health system is preoccupied with SARS.

The Administration spent months deliberating the magnitude of the preparedness campaign, unveiled on 13 December (Science, 20 December 2002, p. 2312). Up to 437,000 medical personnel expected to help contain an outbreak would be vaccinated within a month, starting in late January, top Administration officials said at the time, followed by another 5 million to 10 million other medical personnel, law enforcement agents, and firefighters in the next few months. Separately, the Department of Defense revealed a plan to immunize about half a million armed services members.

With 422,000 military personnel vaccinated, the latter goal is almost reached, says John Grabenstein, deputy director for military vaccines for the Army's surgeon general. But the civilian program has been beset by resistance from labor unions and a lack of volunteers. One of the foremost objections was solved last week, when Bush signed a law to compensate those hurt by the vaccine. But the program has also suffered from evidence that the vaccine can cause inflammation of the heart and its surrounding membrane.

Although the risk of myocarditis and pericarditis, which have struck 15 civilians and about 17 military personnel, was known from previous studies, its magnitude was “underanticipated,” concedes Grabenstein. CDC has also reported a higher-than-expected rate of heart attacks among vaccinees, but it's not yet clear whether they are linked to the vaccine. As a precaution, the agency now recommends that anyone with known heart disease or three or more risk factors for it forgo the vaccine.

In the last few months, the Administration has been backing away from the targets set last December. Having just 50,000 civilians vaccinated in stage one may be enough to contain an outbreak, says CDC's Joseph Henderson. (In Colorado, for example, officials think the 224 who have already been vaccinated will suffice, Denver public health director Franklyn Judson, an outspoken skeptic of the plan, told the IOM panel.) But some participants speculated that CDC's rapid shift has been driven more by politics than public health. “I'm concerned that this compromises the credibility of the CDC,” said panel member Ronald Bayer of Columbia University.

With the first stage of the project now drastically curtailed, it's unclear how many states will embark on the second. CDC was set to release additional guidelines this week, as part of a broader bioterrorism preparedness package, and states are expected to develop plans and apply for funding over the next 2 months. But several speakers at last week's meeting urged CDC to reconsider the scientific case for continued immunization. “Why are we doing this? Where are the data to support it?” asked Gianfranco Pezzino, president of the Council of State and Territorial Epidemiologists. Many expressed concern because even the modest first phase has drained resources and time from other public health programs.

Yet by increasing communication among health and law officials, the program has paid off in another way, said Mary Selecky, Washington state's secretary of health: “We're much better able to deal with SARS, there's no question.”

7. LONGEVITY RESEARCH

Single Signal Unites Treatments That Prolong Life

1. Evelyn Strauss

Many techniques can bestow Methuselah-like life spans on yeast and other lab creatures: heating their environments, tinkering with their genes, or restricting their food, for example. But the molecular mechanisms that translate these manipulations into longevity remain mysterious.

New work suggests that a yeast protein whose antiaging powers had been unrecognized until now could explain how diverse stimuli stall aging. “I think it's really exciting that … one gene seems to increase longevity in response to many stress signals,” says Leonard Guarente, a molecular biologist at Massachusetts Institute of Technology in Cambridge. No one knows whether the findings will extend to other creatures, but they support a theory of aging that has been proposed for mammals: Stress makes them endure.

Some yeast show their age by becoming infertile, and researchers commonly measure life span by counting how many times a new Saccharomyces cerevisiae cell can bud to create daughter cells. Dropping the growth medium's glucose concentration boosts yeast's reproductive capacity; this treatment is used as a model of calorie restriction, which enhances longevity in many animals, including rodents and possibly primates. An enzyme called Sir2 is a necessary part of the yeast food-restriction pathway: Without it, the yeast have normal life spans. Moreover, adding extra copies of the gene for Sir2 promotes longevity in yeast and worms. Sir2 removes acetyl groups from the protein spools around which DNA winds in cells; as a result, the DNA packs more tightly. This so-called silencing prevents DNA from reshuffling, which ages yeast.

Three years ago, Guarente's group showed that Sir2 has a penchant for the small molecule NAD, which channels energy from food into cellular power (Science, 18 February 2000, p. 1181). Quantities of Sir2 don't change when nourishment is scarce. Presumably, researchers reasoned, glucose restriction boosts the enzyme's activity rather than its production. Sir2's predilection for NAD suggested that extra dollops of it prod Sir2 to work overtime.

To test this idea, David Sinclair of Harvard Medical School in Boston and colleagues added NAD precursors to yeast. One day, says Sinclair, graduate student Kevin Bitterman “came into my office and said, ‘there's something really weird.’” Nicotinamide—a molecule that cells transform into NAD—was abolishing DNA silencing rather than activating it. The compound inhibited silencing at miniscule concentrations; Sir2's activity had apparently “evolved to be very sensitive to nicotinamide levels,” says Sinclair.

To test whether nicotinamide governs life span, the researchers engineered yeast to overproduce an enzyme called Pnc1 that breaks down nicotinamide. Draining nicotinamide slowed aging, but only in cells with intact Sir2. Furthermore, prolonging life by reducing glucose required Pnc1, the team reports in Nature this week.

The researchers then discovered that Pnc1 appears to participate in other life-extending treatments. Its production rose in cells exposed to low glucose concentrations, amino acid restriction, heat, or salt. Further tests demonstrated that Pnc1 enlivens Sir2 by consuming nicotinamide rather than by amplifying NAD abundance.

The results support a scenario in which diverse stressors induce Pnc1 to destroy nicotinamide, which in turn allows Sir2 to reinvigorate yeast. Sinclair doesn't rule out a role for an increase in NAD, the theory he was testing when he stumbled upon nicotinamide. But the newfound system “would provide the cell with a mechanism to control Sir2 without altering levels of a NAD, which is essential for basic metabolism.”

Guarente lauds the work and Sinclair's interpretations, but says that their opinions differ about “what's the most important signal in glucose-deprived cells.” His team has preliminary data suggesting that the ratio of NAD to a related molecule, NADH, underlies the change in Sir2 activity that comes with food deprivation in yeast. Perhaps, he proposes, Pnc1 controls the response to stress, whereas the ratio of NAD to NADH controls the response to food limitation.

Whether dietary restriction represents one of many forms of stress or acts through an independent mechanism holds relevance beyond yeastology. If Sinclair is correct and a single system can retard aging regardless of the stressor, the work supports a controversial theory for how calorie restriction prolongs life. In a phenomenon dubbed hormesis, modest assaults fortify an organism against destructive processes—such as those that underlie aging, says Edward Masoro, professor emeritus at the University of Texas Health Science Center in San Antonio, who pioneered the study of calorie restriction. “This is an important piece of work because it supports the hormesis view of calorie restriction, at least in yeast,” says Masoro.

In any case, the work reveals a new way to control Sir2 activity—and the findings will undoubtedly fuel efforts to find life-prolonging therapies for people. If they pan out, such treatments could transform old stories of ancient humans into future realities.

Twenty-One Women in 2003 Class

This year's new class at the U.S. National Academy of Sciences (NAS) contains a record number of women. Seventeen are part of the 72 newly elected regular members, with four among the pool of 18 new foreign associates. Those proportions are roughly twice the percentage of full professors at U.S. universities. Overall, women now make up 7.7% of the academy's 2015 living members.

“What began 4 to 5 years ago has borne fruit this year,” says NAS Home Secretary Stephen Berry of the University of Chicago. “People are clearly trying to identify women who have been overlooked, but the [nomination] process can take several years.” Even Nobelists sometimes have to wait their turn, he noted: It was 1993, for example, before all three 1990 physics laureates were inducted.

Newly elected members and their affiliations at the time of election* are as follows:

George A. Akerlof, University of California (UC), Berkeley; Jeanne Altmann, Princeton University; George E. Andrews, Pennsylvania State University; Cornelia I. Bargmann, Howard Hughes Medical Institute (HHMI) and UC San Francisco; Linda M. Bartoshuk, Yale University School of Medicine; John D. Baxter, UC San Francisco; Peter Beak, University of Illinois, Urbana-Champaign; James O. Berger, Duke University; Linda B. Buck, HHMI and Fred Hutchinson Cancer Research Center, Seattle; Dennis A. Carson, UC San Diego.

Anthony R. Cashmore, University of Pennsylvania; Praveen Chaudhari, Brookhaven National Laboratory; Sallie W. Chisholm, Massachusetts Institute of Technology (MIT); Barry S. Coller, Rockefeller University; Jody W. Deming, University of Washington; David J. Derosier, Brandeis University; James H. Dieterich, U.S. Geological Survey, Menlo Park, California; William E. Dietrich, UC Berkeley; Yakov Eliashberg, Stanford University; Stephen J. Elledge, HHMI and Baylor College of Medicine.

John B. Fenn, Virginia Commonwealth University; Lennard A. Fisk, University of Michigan; David G. Forney Jr., MIT; Joanna S. Fowler, Brookhaven National Laboratory; Wendy L. Freedman, Carnegie Institution of Washington, Pasadena, California; Fred H. Gage, Salk Institute for Biological Studies; Solomon W. Golomb, University of Southern California; Carol W. Greider, Johns Hopkins University; Jeffrey C. Hall, Brandeis University; J. Woodland Hastings, Harvard University.

Isaac M. Held, National Oceanic and Atmospheric Administration, Princeton, New Jersey; Karl Hess, University of Illinois, Urbana-Champaign; Arthur Horwich, HHMI and Yale University; Michael Hout, UC Berkeley; Rudolf Jaenisch, MIT; Rodger E. Kasperson, Stockholm Environment Institute, Sweden; Cynthia J. Kenyon, UC San Francisco; Richard G. Klein, Stanford University; Shrinivas R. Kulkarni, California Institute of Technology; Robert A. Lamb, HHMI and Northwestern University.

Judith L. Lean, Naval Research Laboratory, Washington, D.C.; Wen-Hsiung Li, University of Chicago; David J. Lipman, National Institutes of Health; Martha L. Ludwig, University of Michigan; Diane J. Mathis, Harvard Medical School; Henry J. Melosh, University of Arizona; Edward L. Miles, University of Washington; Sidney R. Nagel, University of Chicago; June B. Nasrallah, Cornell University; William D. Nix, Stanford University.

Helen R. A. Quinn, Stanford Linear Accelerator Center; Michael Rosbash, HHMI and Brandeis University; A. Catharine Ross, Pennsylvania State University; Linda J. Saif, Ohio State University, Wooster; Paul L. Schechter, MIT; William H. Schlesinger, Duke University; Robert J. Silbey, MIT; Bruce D. Smith, Smithsonian Institution, Washington, D.C.; Claude M. Steele, Stanford University; Arthur L. Stinchcombe, Northwestern University.

Robert M. Stroud, UC San Francisco; Joseph S. Takahashi, HHMI and Northwestern University; Saul A. Teukolsky, Cornell University; Michael F. Thomashow, Michigan State University; James M. Tiedje, Michigan State University; James L. Van Etten, University of Nebraska; Dale J. Van Harlingen, University of Illinois, Urbana-Champaign; Brian A. Wandell, Stanford University; Arthur Weiss, HHMI and UC San Francisco; Paul A. Wender, Stanford University; Eli Yablonovitch, UC Los Angeles; Masashi Yanagisawa, HHMI and University of Texas Southwestern Medical Center.

Newly elected foreign associates, their affiliations at the time of election, and their country of citizenship (in parentheses) are as follows:

Edouard Brezin, École Normale Supérieure, Paris (France); Haim Brezis, Université Pierre et Marie Curie, Paris (France); Juan Carlos Castilla, Pontificia Universidad Católica de Chile, Santiago (Chile); Zhu Chen, Shanghai Second Medical University (People's Republic of China); Luis Herrera-Estrella, National Polytechnic Institute, Guanajuato (Mexico); Avram Hershko, Technion-Israel Institute of Technology, Haifa (Israel); Herbert Kroemer, UC Santa Barbara (Germany); Rosine Lallement, Centre National de la Recherche Scientifique, Verrières-le-Buisson (France); Linda Manzanilla, National Autonomous University of Mexico (Mexico).

Ryoji Noyori, Nagoya University (Japan); Giorgio Parisi, University of Rome (Italy); Martin C. Raff, University College London, U.K. (Canada); Obaid Siddiqi, Tata Institute for Fundamental Research, Bangalore (India); Tadatsugu Taniguchi, University of Tokyo (Japan); Andrzej K. Tarkowski, Warsaw University (Poland); Janet Thornton, European Bioinformatics Institute, Cambridge (United Kingdom); Alan C. Walker, Pennsylvania State University (United Kingdom); Ada Yonath, Weizmann Institute of Sciences, Rehovot (Israel).

9. QUANTUM PHYSICS

In Clone Wars, Quantum Computers Need Not Apply

1. Charles Seife

If bloodthirsty legions of identical self-replicating robots bent on the destruction of humanity haunt your dreams, rest easy. Science has proven that they can't exist—at least not if they have quantum brains. In a paper submitted to Physical Review Letters, two physicists have shown that it is impossible to build a quantum “universal constructor”—a quantum computer that has the ability to spawn perfect copies of itself.

The idea of a universal constructor goes back more than 60 years to the dawn of the computing age, when John von Neumann, one of the architects of computing theory, started pondering whether self-replicating machines could exist. “It was a step toward trying to understand a living system,” says Arun Pati, a physicist at the Institute for Physics in Bhubaneswar, Orissa, India. After all, most living creatures spend an excessive amount of time and effort trying to make copies of themselves, so if machines could be “alive” in some manner, they would have to be able to reproduce.

Indeed, they can. Von Neumann designed a complex computer program that outputs an exact duplicate of itself—first making a copy of its structure and then breathing life into the copy by giving it a set of instructions that tell it how to replicate. When the duplication process is complete, there are two identical programs capable of making even more identical copies. Case closed.

Now, however, many questions of the early days of computer science—including von Neumann's universal-constructor project—have become interesting again. Many computer scientists and physicists are turning their attention toward quantum computers—logical entities that are at once more powerful and more restricted than their classical counterparts. For example, a quantum computer can theoretically crack public-key encryption codes that are far beyond the abilities of classical computers. On the other hand, quantum computers are hobbled by the “no-cloning” rule, which states that a quantum computer can't make an exact copy of a piece of data without destroying the original—something that ordinary computers do with aplomb, much to the music industry's chagrin. So all the old questions of classical computing, such as whether there can be a universal constructor, are being asked again in the quantum domain.

Now Pati and Samuel Braunstein of the University of Wales, Bangor, have answered that question with a resounding no. By closing loopholes in the no-cloning rule, they showed that in a universe with finite resources, a quantum robot would be unable to make a perfect copy of itself. So, in a sense, argues Pati, it could never be “alive.” That could be bad news for those who speculate that life might have some sort of quantum-mechanical nature.

Not quite, says Seth Lloyd, a physicist at Massachusetts Institute of Technology in Cambridge. Lloyd says that Pati and Braunstein are almost certainly correct, but he adds that a “living” machine wouldn't have to replicate itself exactly—an almost-perfect copy would do just fine. “You can reproduce it to an arbitrary degree of precision,” he notes. “That's good enough for me.”

Braunstein agrees and downplays the proof's implications for the nature of life. “Life as something able to reproduce itself is all nice and good, but it's very simplistic,” he says. To Braunstein, the real value of figuring out what quantum computers can and can't do is that it goes to the heart of what makes quantum mechanics so weird. “It's a very interesting question—looking at machines that are impossible,” he says. “It gives us a language and a powerful way of thinking of the difference between the classical and the quantum—and about what makes quantum mechanics really tick.”

10. PALEOBIOLOGY

Megafauna Died From Big Kill, Not Big Chill

1. Richard A. Kerr

More than 10,000 years ago, when the last ice age was stumbling through its final years, both humans and viciously sharp climate change converged on North America just as three-quarters of the continent's biggest beasts—mammoths, mastodons, giant ground sloths, and saber-toothed tigers among them—disappeared forever. Both human hunters and wrenching climate shocks seemed to have the opportunity to cause extinction. But researchers have never been able to disentangle the lingering traces of humans, climate, and megafauna in enough detail to say who or what did in the great ice age beasts of North America. Now a group of paleoecologists has followed all three players through time, clearing one suspect of megafaunal mayhem and indicting another.

At a recent geoscience meeting,* paleoecologists Guy Robinson, David Burney, and Lida Pigott Burney of Fordham University in New York City, reported evidence that humans arrived on the scene damningly close to the time of the megafauna collapse, whereas climate change was such a latecomer that it could not have played a major role. The key to sorting out this extinction story was following a microscopic marker for each of the three players up through a single geologic record. A key marker was the spores of a fungus partial to dung. The work is a reminder that “it's the small things that are really important,” says paleontologist Richard Laub of the Buffalo Museum of Science. “The approach is a very good one; I suspect they are on the right track.”

Whether humans were behind the dramatic extinctions at the end of the ice age has been long debated. In 1967, geoscientist Paul Martin proposed the “blitzkrieg” hypothesis, in which humans pouring across the Bering land bridge into North America hunted down the great beasts. Pushed to the brink, the megafauna quickly slipped into extinction. As geographer Jared Diamond of the University of California, Los Angeles, has noted, studies in Australia, the Bismarck Archipelago, Cyprus, the West Indies, Fiji, Madagascar, and New Zealand have since shown that the indigenous megafauna in each case succumbed soon after humans first arrived. But those extinctions came anywhere between mid-ice age 50,000 years ago (Science, 8 June 2001, p. 1819) and just 700 years ago, so they were not closely correlated with severe climate change. To Diamond and many others, the consistent coincidence between first arrival of humans and megafaunal demise strongly implies causation.

But North America has proved to be a particularly difficult case. Both humans and an abrupt shift from relative warmth back to full glacial cold arrived about 11,000 years ago as measured by radiocarbon dating, as close as researchers could tell, which was indistinguishable from the timing of the extinctions.

The Fordham researchers sharpened the fuzzy North American extinction picture by using smaller and therefore far more numerous tracers than usually applied there. For climate, they did make traditional counts of tree pollen. These trace a sudden warming followed by an abrupt, millennium-long cold that punctuated the transition from the depths of the last ice age 20,000 years ago to the continuing warmth of the interglacial period beginning 10,000 years ago.

But instead of distinctive fluted projectile points scattered across the continent by the first humans, the Fordham group used microscopic bits of charcoal blown from large fires as a marker for humans. A sharp increase in such charcoal has marked the arrival of humans on islands around the world. And instead of megafauna bones, the researchers used microscopic fungal spores. Palynologist Owen Davis of the University of Arizona in Tucson pioneered the use of spores of the fungus Sporormiella that wash into ponds, lakes, and bogs from the dung left by watering large animals. Rather than crudely tying together macroscopic markers from different sites through radiocarbon dating, the Fordham researchers counted up their microscopic markers through mud layers at four sites in southeastern New York: three megafaunal sites and a cored lake-bottom mud.

Analysis of the four sites revealed a clear progression of events. First, the megafauna population collapsed, as indicated by an abrupt 10-fold decrease in Sporormiella spores to trace amounts. Soon after, microscopic charcoal abundance jumped 10-fold. And only later, something like a thousand years later, did the pollen of boreal forest trees such as alder, birch, and spruce reappear, marking a sharp cooling, the beginning of the last gasp of the latest ice age.

To the Fordham group, humans seem clearly implicated, but climate change looks to have been secondary. “There's an initial overkill” as in the blitzkrieg hypothesis, says Robinson. “The system is knocked out of balance, by human hunting probably.” The human-induced collapse of the plant-eating megafauna led to an overabundance of fuel for fires, natural and human induced. Only much later, in the renewed cold, do the researchers find the last known megafaunal bones. “It makes this process look like it's spread out for a thousand years,” says Robinson. Knocked down, the megafauna finally went out under the weight of further hunting, the cold, the altered environment, or some other stress or stresses that would not otherwise have caused extinction, says Robinson.

The Fordham group has found the same sequence of fungal spore decline, charcoal increase, and megafaunal collapse in Madagascar. But it came during the last 2 millennia without a climate shift to warmth or cold, suggesting that climatic stress isn't even essential for the knockout punch. “That strengthens our case” against humans rather than climate, says Robinson.

New evidence in this contentious field takes time to sink in. “Their approach is a novel one that deserves some additional attention,” says paleobotanist Norton Miller of the New York State Biological Survey in Albany. “My own bias is more toward climate than anything, [but] the fungal story provides some good information that would argue against climate.” Perhaps more of these little things will one day settle the fate of the big things.

• *Joint meeting of the Geological Society of America's Northeastern Section and the Atlantic Geoscience Society, 27 to 29 March, Halifax, Nova Scotia.

11. INFECTIOUS DISEASES

Up Close and Personal With SARS

1. Dennis Normile*
1. With reporting by Gretchen Vogel in Berlin and Martin Enserink in Washington, D.C.

Working at the epicenter of the SARS epidemic, a small group at the University of Hong Kong is at the forefront of the investigation into this mysterious disease

HONG KONG—For a virus hunter, Hong Kong in the spring of 2003 was the right place and the right time. And virologist Malik Peiris, colleagues around the world are saying, proved to be the right person. Peiris and his team at the University of Hong Kong (HKU) were the first to isolate the agent causing severe acute respiratory syndrome, or SARS, early in the week of 17 March—although at first they didn't know exactly what they had. And the Hong Kong lab was one of three groups that several days later—and within hours of each other—identified the culprit as a new coronavirus. Peiris and his team were amused and a little irritated when one of the groups issued a press release on 24 March touting its detective prowess without crediting the other two groups. But having to share some credit doesn't detract from the pride Peiris feels “in the group and the job we did.”

Regardless of bragging rights, fellow disease detectives say the contributions of the HKU group highlight the importance of having a first-rate research team on the ground near the source of an outbreak. “Without Malik, we would know much less about SARS,” says Christian Drosten, a virologist at the Bernhard Nocht Institute for Tropical Medicine in Hamburg, Germany, whose lab is part of a global network seeking the cause of SARS under the sponsorship of the World Health Organization (WHO). Virologist Klaus Stöhr, the network coordinator, simply says that Peiris “is one who produces and delivers.”

Peiris landed in that place and time through a circuitous route. Born and raised in Sri Lanka, he earned his Ph.D. at Oxford University's Sir William Dunn School of Pathology in the U.K., where he impressed the faculty both scientifically and personally. Siamon Gordon, a cell biologist who was a mentor and collaborator during Peiris's student days at Dunn in the 1970s, says, “He had a broad interest in a biological understanding of infectious diseases, not just a narrow interest in viruses.” And Gordon adds, “He was always a gentleman, in the original sense of the word,” remaining unruffled and gracious even under pressure. Colleagues say he is also a man of few words. “He doesn't talk a lot, but whenever he speaks, people listen, and whatever he says is waterproof,” says Stöhr. Both traits are serving him well in the friendly but competitive race to understand SARS.

After academic stints in Sri Lanka and the U.K., Peiris landed in the microbiology department at HKU in 1995, just in time to see firsthand the frightening potential of the 1997 avian flu outbreak. The virus killed six of the 18 people it infectedmore than three times the mortality rate of typical flu epidemics. Peiris set aside his research and pitched in, helping develop a diagnostic test for the causative H5N1 virus. It was later determined that infection spread from chickens to humans but not between humans. The outbreak was contained by slaughtering every chicken in Hong Kong.

The incident hooked Peiris, who wanted to understand how the disease jumped from an animal reservoir and why it proved so lethal. He refocused his research on influenza, the disease interface between animals and humans, and the interaction of viruses and the human immune system.

The high mortality rate and fears that the H5N1 virusor the next onemight develop the ability to spread from human to human also alarmed health authorities around the world. Flu expert Robert Webster, who had been tracking emerging flu viruses from his lab at St. Jude Children's Research Hospital in Memphis, Tennessee, won a grant from the U.S. National Institutes of Health to regularly screen healthy animals in Asia for viruses posing a pandemic threat. The surveillance work in Hong Kong was subcontracted to the Influenza Research Group within the microbiology department at HKU. The group was originally headed by virologist Kennedy Shortridge, who retired last year, leaving Peiris in charge.

The hunt for viruses and Peiris's interest in the animal-human interface fit in with a decision made at about this time by the department to concentrate “our limited resources” on emerging diseases to maximize the group's scientific impact, says department chair Yuen Kwok-Yung.

In January, Peiris's group was ready. The researchers heard rumors of an unusual outbreak of pneumonia in Guangdong Province, which borders Hong Kong. “The first thing going through our minds was that the H5N1 virus had possibly acquired the ability to transmit from human to human,” Peiris says. The preceding December, several geese in Hong Kong parks had died from the H5N1 virus. The influenza team was already working overtime screening samples from flu patients for evidence of H5N1 infection (Science, 7 March, p. 1504).

By early February, the Hong Kong Department of Health and the Hospital Authority had started an intensive surveillance effort to spot unusual cases of severe pneumonia. Peiris's lab was charged with identifying the cause. The H5N1 hypothesis got a boost in mid-February when that virus was confirmed as having killed one member of a family that had visited Fujian Province and having sickened another. It was the suspected cause of death of yet a third family member who died in China.

But H5N1 proved a “red herring,” Peiris says. By early March, epidemiologically linked clusters of cases of what was later called SARS began appearing. WHO announced its global SARS alert on 12 March, and by 17 March, Stöhr's network labs were sharing data in daily conference calls. One of the first things the groups heard from Peiris was that “none of the other SARS patients had any evidence of H5N1, nor did they have any evidence of influenza, nor did they have any evidence of any other respiratory pathogens.” At that point, Peiris says, “We knew we were dealing with something completely out of the blue.”

To track it down, the team took three parallel approaches. Virologist Guan Yi tried to isolate and identify a causative agent by exposing cell lines normally not used for viruses to blood and tissue samples from patients. Molecular virologist Leo Poon started random genetic screening of infected tissues to identify some scrap of DNA that might provide clues to the nature of the bug. And pathologist John Nicholls started studying tissue samples with an electron microscope.

Similar efforts were under way in labs around the world. But the heat was particularly intense in Hong Kong. The government was under fire for its handling of the crisis and was facing decisions on whether to close schools and quarantine individuals who had been in contact with patients. In addition to his research, Peiris was a key governmental adviser who regularly appeared at press briefings. Poon says that during this period he was working 17-hour days. “I just had time to go home to take a shower, get a brief nap, and then come back to work,” he says. “But Peiris had it worse.”

Early in the week of 17 March, the researchers got a break. Tissue cultures isolated from two patients were killing cells in a line typically used to grow hepatitis A. To link the agent to the disease, the team tested blood serum taken from patients during the acute phase of the disease and during recovery. When placed on the tissue cultures, the acute phase samples showed no antibody activity, whereas the convalescent phase samples did, strongly suggesting that whatever was in the cultures was related to the disease. At that point, Nicholls had what he calls “a ‘Eureka!’ moment.” Electron microscope images of the tissue samples showed virus particles surrounded by little spikesthe halo suggestive of a coronavirus.

By the time the researchers had the images, it was late Friday afternoon, 21 March. Accounts of what happened next vary. Peiris says he had to attend an evening meeting of governmental advisers and missed the daily WHO SARS network phone conference. But he later e-mailed his colleagues telling them he strongly suspected a coronavirus. Larry Anderson, chief of the CDC's Respiratory and Enteric Viruses Branch, says the Atlanta group mentioned during the conference call that it had identified coronavirus-like particles by electron microscopy, not knowing that the HKU group had also done so.

Over the weekend, the HKU group sent samples to a Hong Kong government lab equipped to stain tissue for electron microscope imaging. These images showed even more clearly that it was a coronavirus. The CDC researchers, meanwhile, sequenced fragments of genetic material from their sample and could find no matches in searches of known viruses. A collaboration of European groups was making similar progress. By the time of the 24 March conference call, the three groups confirmed they were closing in on what seemed to be a novel coronavirus. Later that day, when it was nighttime in Hong Kong, CDC issued a press release headlined “CDC Lab Analysis Suggests New Coronavirus May Cause SARS.”

“The Centers for Disease Control and Prevention (CDC) announced today that a previously unrecognized virus from the coronavirus family is the leading hypothesis for the cause of severe acute respiratory syndrome (SARS),” it read. The WHO network was mentioned further down, but its role in fingering the virus was not explained. The HKU and European groups were not mentioned at all.

“I don't want to take credit away from the CDC, but our group here deserves some credit as well,” Peiris says, betraying an uncharacteristic trace of annoyance.

CDC's Anderson claims they were unaware the HKU group had isolated and identified a coronavirus until later. “We certainly did not intentionally downplay the work [Peiris] or [his] group did,” he adds.

The Europeans were also slightly miffed by the CDC press release. But Drosten of the Bernhard Nocht Institute says, “We don't care about press releases, we care about publications.” And on this point, the record is clear. The HKU group's paper in The Lancet appeared online on 8 April with reports from the other groups appearing online in The New England Journal of Medicine on 10 April. “That's simultaneously,” Drosten says. The identification of the coronavirus was later clinched by animal experiments carried out at Erasmus Medical Center in Rotterdam, the Netherlands.

Being in the thick of the race boosted the morale of the HKU group. “This is an historic moment for the University of Hong Kong,” says Poon. “With limited people and limited financial support, we're very happy to make this contribution,” he adds.

But Peiris is not celebrating yet. “It's hard to smile when SARS remains such a serious disease,” he says. Scientists need better diagnostics to be able to quickly separate real from suspected cases of SARS and to identify asymptomatic carriers. And Peiris says there are “hundreds of other questions,” starting with whether the coronavirus acts on its own or opens the door to other diseases and where the virus came from in the first place. But having helped identify the virus, HKU researchers are allowing themselves some luxury; Poon reports that he is now working only 12 hours a day.

12. MILITARY RESEARCH

Mach 12 by 2012?

1. David Malakoff

An ambitious new Pentagon effort aims to boost research into high-speed aircraft, but technical barriers remain daunting

Next year, if all goes as planned, a U.S. jet fighter cruising off the California coast will drop a slender, 4-meter-long missile into the sky. A rocket booster will push the missile to Mach 3, or three times the speed of sound. Then an experimental air-breathing engine will kick in, boosting the missile to hypersonic speeds capable of carrying it from New York to London in less than an hour.

Hypersonic flight—anything over Mach 5—has been an elusive target for aerospace engineers, its history littered with promises unfulfilled. But Ron Sega, head of research at the Department of Defense (DOD), vows that things will be different next time. The Pentagon has requested $150 million in new hypersonics funding for the fiscal year that starts on 1 October—some of which will go to academic researchers for basic studies—and Sega believes that the field is ready to soar. “The technology has progressed to the point that we should be able to increase performance by a Mach number per year, reaching Mach 12 by 2012,” he recently told Congress. Sega won't know if lawmakers will approve his request until later this year. But his ambitious timetable—part of a decade-long plan that could pump several billion dollars into hypersonics R&D—has been embraced by a Pentagon leadership eager to transform the military into a force able to strike halfway around the globe at a moment's notice. In the recent Iraqi war, for example, a Mach-12 missile launched from a ship stationed nearby could have reached key targets—such as Saddam Hussein's bunker—a few minutes after intelligence reports pinpointed his whereabouts. NASA has also signed on to the initiative, seeing hypersonic craft as a potentially reusable way to loft payloads into space. But Sega's quest for speed induces a troubling sense of déjà vu among some aerospace veterans still bruised from the cancellation of past hypersonics programs, including the X-30 National Aerospace Plane, which fell victim to technical and budgetary problems in the early 1990s. And although engineers decades ago mastered the basics of hypersonic flight, the technical challenges remain daunting. “Accepting hypersonics as the wave of the future is somewhat like belief in the Second Coming of Christ,” concludes a 2000 Air Force study.* “One might accept its inevitability, but with little idea when it might actually occur.” Pentagon planners say that faith isn't part of their equation. “This isn't Mach 25 or bust—we're taking an incremental approach,” says Sega. An array of recent developments—from real-world tests of new engines to improvements in materials and computer simulations—boosts the chances of success, say outside researchers. “The plan looks pretty sane, with more practical, short-term goals,” says aeronautics researcher Mark Lewis, a science adviser to the Air Force and head of the Center for Hypersonic Education and Research at the University of Maryland, College Park. The U.S. government's interest in hypersonic flight dates from 1949, when Army researchers used a supercharged German V-2 rocket to achieve the first Mach-5 flight. A decade later, the Pentagon and NASA built the X-15 rocket plane, which still holds the world speed record for a piloted aircraft: Mach 6.72. But in recent years, the military's pursuit of hypersonics fell behind other technologies, such as radar-evading stealth designs. As a result, hypersonic weapons are limited to ballistic missiles and short-range, tank-killing projectiles, and more flexible piloted hypersonic aircraft and speedy cruise missiles have stayed on the drawing board. The technical challenges of hypersonic flight are immense. As the recent destruction of the Columbia space shuttle showed, hypersonic airframes must be able to withstand temperatures of 800° Celsius or greater created by friction (Science, 28 March, p. 1971). High-pressure shock waves can produce changes in airflow that still puzzle physicists, despite advances in computer models. Then there is the problem of finding fuels that can fully combust in the millisecond it takes for oxygen molecules to pass through the air-breathing “scramjet” engines currently favored for hypersonic flight. The Pentagon proposes tackling such problems in small steps, starting with an engine that could power a craft to Mach 5 by 2005. Several candidate engines already exist, including a liquid-fueled missile power plant that was ground-tested last year by a team led by the Applied Physics Laboratory of Johns Hopkins University in Laurel, Maryland. The Navy and the Defense Advanced Research Projects Agency plan to put the engine—which is based on a 30-year-old design—into a flight-ready missile late next year and to ramp up to Mach-6.5 test flights off California by 2006. One attraction is that it uses conventional fuel, which is easier to handle than the more combustible concoctions envisioned for faster hypersonic craft. Engine researchers have also been buoyed by the work of an Australian team at the University of Queensland. The team, led by aerospace engineer Allan Paul of Queensland's Centre for Hypersonics, used a sounding rocket to catapult its experimental scramjet to Mach 7.6 over the Australian desert, igniting it during the last few seconds of flight. It's said to be the first-ever combustion at hypersonic speeds within an air-breathing engine. Similar experiments could eventually help the Pentagon reach its goals of a Mach-7 piloted craft by 2008 and one that travels at Mach 12 by 2012. The craft would probably use a combination of rocket and scramjet engines and more problematic fuels, such as liquid hydrogen. Toward that end, this summer NASA will resume testing of the X-43, a 4-meter-long unpiloted craft grounded in 2001 after a disastrous inaugural flight in which a booster rocket zoomed out of control. Some analysts believe that testers dropped the craft from its mother ship at such a low altitude that the unexpectedly thick atmosphere ripped control fins off the rocket. Still, researchers say that such real-world mistakes are essential. “There isn't a hypersonic wind tunnel that allows you to simulate all the important parameters—you might get high pressure but not high temperature,” says Robert Korkegi, a retired military hypersonics researcher who now teaches part-time at the University of Maryland, College Park. A millisecond run of a tiny model isn't the same thing, he notes. But exactly how much money will be available for such work isn't clear. Pentagon officials say the bulk of the new funds will go to building and testing prototypes. Still, “the [funding] climate has never been better” for academic scientists interested in hypersonics, says Maryland's Lewis. The DOD initiative, he adds, “has created a sense of optimism that we are actually going to make some progress this time.” • *Why and Whither Hypersonics? U.S. Air Force Science Advisory Board, December 2000. 13. IRAQI ARCHAEOLOGY Antiquity Experts Endorse Plans to Restore Shattered Collection 1. Andrew Lawler The rubble in Baghdad's National Museum and unsecured Iraqi borders pose long-term challenges to any recovery effort LONDON—His office desk is broken in three pieces and his files sit in a heap. But Donny George considers himself lucky because he found his chair intact outside the National Museum of Iraq; most of the 120 other offices in the museum were stripped bare. Last week the research director for the Iraqi State Board of Antiquities left the rubble in Baghdad for a meeting at the British Museum here. In addition to giving Western archaeologists a detailed account of the April looting, George helped hammer out an international blueprint to repair broken artifacts, recover lost items, and provide desperately needed equipment, salaries, and technical expertise to the museum staff. Three weeks after Baghdad fell and the National Museum was pillaged, the international antiquities community is scrambling to gain its footing in the new landscape. The 40 researchers, conservation experts, and museum officials from around the world who gathered here were relieved to hear that key portions of the collection—including a large library of cuneiform tablets, the Nimrud gold grave goods, and hundreds of Islamic manuscripts—are likely safe in their respective storage facilities in the museum attic, a Central Bank vault, and a vast underground bunker. But they cautioned that a detailed inventory will take time. “A survey will take 6 months once it is started,” says John Curtis, a British Museum archaeologist who visited Baghdad for 2 days last week. “So we're probably looking at well into next year.” That timeframe is at odds with what Curtis called “significant pressure” from U.S. officials for a fast audit. A memo last week from John Limbert, a senior U.S. Department of State official in charge of cultural affairs in Iraq, says “museum director Nawala al-Mutawalli and her staff have begun an inventory of lost, damaged, and saved items.” Limbert also characterized the museum as “a haven of relative safety and sanity,” a prerequisite for efforts to assess the losses—and protect what is left from further damage. The rescue work is complicated by the chaotic state of the museum, a combination of crime scene and archaeological site. “I've never seen such a mess as in these rooms,” says Curtis. The list of missing and damaged items presented last week includes a half-dozen Sumerian, Assyrian, and Roman-style statues, a host of statue heads, two famous and intricately carved Assyrian ivories, and Islamic wooden columns. All office and lab equipment was taken or destroyed, showcases were smashed, and a fleet of vehicles stolen. And there currently is no funding for the 400 archaeologists, 600 technicians, and 1600 guards who make up the State Board. “We cannot even function,” says George, adding that “a team of conservators could come maybe in 2 or 3 months, when everything is safe.” Safety is a precious commodity: George and Curtis are thankful they are alive after being robbed at gunpoint on their way out of Iraq last week. And the condition of archaeological sites and museums in cities north and south of the capital is largely unknown. George says that all was intact when he and Jaber Khalil—State Board chair—toured Mosul and key sites in the north during the bombing before the ground war. Small objects had been removed from Mosul and the new Tikrit Museum had not yet been stocked when it was bombed. There are unconfirmed rumors that Kurdish soldiers stole many large statues and sarcophagi that were in the Mosul Museum. Limbert adds that the important site of Hatra is being protected by a local tribe, while two Assyrian slabs may have been stolen from the ancient capital of Nimrud. In Baghdad, daily radio broadcasts and pleas from two local mosques have generated a stream of returned objects. An Iraqi National Congress representative reportedly retrieved and returned nearly 500 objects, including cylinder seals and tablets, from the southern city of Kut. But Curtis says that the 60 objects brought back while he was in Baghdad represent only “the tip of the iceberg of what's missing.” Thieves gained access to one storeroom by bashing a hole in one wall, but how much was stolen from the dark and still-locked room remains uncertain. Iraqi and U.S. officials are convinced that some of the looting was done by professionals. George offers as proof four glass cutters and a large set of keys—the kind a locksmith would have—that were left behind by looters. Thieves also astutely ignored copies of ancient works. Questions about who's in charge hamper the recovery effort. George said that the museum staff was informed that a large number of boxes containing artifacts are stashed in a nearby neighborhood. But U.S. officials declined to intervene, citing a lack of authority to search houses. George says the new chief of Iraq's nascent police force, an acquaintance, has pledged to conduct searches—perhaps with American assistance in blocking off roads—as soon as he has the personnel. Meeting participants called on the U.S. government to secure Iraq's borders to stanch the outflow. “American forces are not controlling anything,” George says. “And we've asked and asked.” Jordanian customs officials, for example, have intercepted 12 cases of documents and other goods being smuggled into that country, he noted. Participants also agreed that UNESCO should oversee an international effort by scholars to create a database that combines all archives, lists, and inventories relating to Iraqi artifacts. They also backed a United Nations plan to impose a temporary embargo on the acquisition of antiquities that could have come from Iraq. UNESCO plans a mission to Iraq, FBI agents are already there, and Interpol will hold a strategy meeting this week in Lyon, France. The London meeting closed with participants endorsing a 12-point plan that included paying staff salaries, restoring the State Board to full strength, providing new equipment and facilities, resuming publication of the scholarly journal Sumer, and, ultimately, reopening research sites throughout the country. Meanwhile, the British government last week announced its support for tougher antiquity legislation. “Now, if an item can't be tracked, no one can be prosecuted, and that's an important loophole,” says Tessa Jowell, British minister for culture, media, and sports. “We'll attempt to strangle the market for tainted Iraqi objects—and we'll do everything we can to hurry this important legislation through.” But Jowell declined to speculate on whether the British government could have curbed the looting. The question of who will coordinate the ambitious and expensive international rescue effort remains “a slightly contentious issue,” Curtis said. George would like to see the British Museum lead the way, given its longstanding ties to Iraq. But U.S. Department of State's Maria Kouroupas, the only official U.S. government representative at the meeting, questioned the idea of the British Museum as liaison because the Department of Defense's Office of Reconstruction and Humanitarian Assistance is technically in charge of Iraq and likely would pay the bulk of the costs. The cash is already beginning to flow. Limbert last week began handing out$20 to each museum employee, and the Department of State is pledging $2 million for the rescue and restoration efforts. But not everything comes with a price tag. George and other Iraqi antiquity officials remain deeply upset that the U.S. military did not act to prevent the tragedy. One U.S. officer declined to intervene just as an angry crowd was gathering. To stop the looting, George says, “moving a tank 50 or 60 yards would have been enough.” 14. ROMANIA Unexpected Riches From a Fabled Gold Mine 1. Gretchen Vogel Scientists are hoping that ecological concerns and new archaeological finds might derail a major mining venture in southeastern Europe High in the Apuseni Mountains of western Romania lies a treasure coveted since prehistoric times: one of Europe's largest gold deposits. Untold tonnage has been hauled from the Rosia Montana mine over the past 2000 years, and now a Canadian company is hoping to finish the job. The firm, Gabriel Resources in Toronto, plans to build an open-pit mine covering 2800 hectares—about half the size of Manhattan—where it will extract the remaining gold and other precious metals by treating pulverized rock with cyanide. The project promises to breathe economic life into an impoverished region. But many Romanian scientists are staunchly opposed to the mine. Some object on ecological grounds: They worry that cyanide-laced wastewater may infiltrate the local water table. But it's Rosia Montana's past that is increasingly haunting Gabriel Resources. Archaeologists argue that the ancient mine shafts and the artifacts they may contain offer a unique window on gold mining in ancient times as well as the community it supported. Ironically, much of the information has come from digs the company has funded. Last month, opponents released a protest letter signed by more than 1000 scholars—mostly archaeologists and historians—and in March the Romanian Academy inveighed against the project and called on the government to stop it. “The mine will destroy some very, very valuable archaeology, and it will destroy the local environment,” asserts academy vice president Ionel Haiduc, a chemist at the University of Babes-Bolyai in Cluj-Napoca. Gilded past In the second century A.D., the Roman emperor Trajan conquered this region, then called Dacia, in part to exploit the rich veins of gold, silver, and iron. Sixteen hundred years later, Austro-Hungarian Empress Maria Theresa claimed the gold mines to enrich her treasury. Small-scale mining continued through World War II; in the early 1900s, the remote valley in Transylvania was prosperous enough to support a cinema and a Parisian tailor, notes Stephanie Roth, a community activist in Rosia Montana. After World War II, the mine was nationalized and for the next 4 decades was subsidized by the government. But the main seams appeared to be tapped out by the early 20th century, and the region grew poorer and poorer. Hoping to revitalize the region, the Romanian government in 1999 awarded a mining concession to Gabriel Resources, a company founded in 1997 expressly to develop mining in Romania. Rosia Montana is its first project; it will take 16 years, the company says, to extract the remaining gold, an estimated cache of 14.8 million ounces. Archaeologists have known about the site since the discovery in 1796 of wooden tablets describing the area's commercial life nearly 2000 years ago. “Rosia Montana has excited our imagination for 200 years,” exclaims Alexandru Diaconescu of the University of Babes-Bolyai. The tablets, which detail contracts, bankruptcies, and other economic arrangements, have provided insights into the workings of a colony on the edge of the Roman Empire at the height of its power, says archaeologist Ian Haynes of the University of London, U.K. They also reveal who worked the mines in Roman times. Although the documents are in Latin, the names listed suggest that the authors were from Dalmatia, says Diaconescu, consistent with evidence that Rome compelled or enticed people from other mining regions to settle in the area. “This is a genuinely exceptional site,” says Haynes. As captivating as Rosia Montana has been, no one had had the funds to launch an excavation there—until Gabriel Resources came along. “It is high in the mountains, difficult to excavate, and doesn't bring quick results,” explains Diaconescu. A 4-year dig funded by the company under its mining concession has begun to yield intriguing finds that have only served to fan opposition. In the last 2 years, the excavations have uncovered several temples and a Roman mausoleum constructed of stone quarried at nearby Alba Iulia. Gabriel is now building a museum to house the finds and whatever else emerges in the next 2 years. But Haynes and others say that moving the finds will destroy their context, decreasing their value to archaeology. They also decry the potential loss of the mines, which may contain undiscovered artifacts of Roman technology. “If the site is to be destroyed, we need as much data as possible before it goes. If the site is to be saved, then good-quality information is going to be our best argument for saving it,” Haynes says. Ecoterror or ecohype? Opponents admit that they have little prospect of persuading the Romanian government to block the mine, which has the support of several cabinet members. Instead, they are pinning their hopes on the European Union. Romania hopes to join the E.U. in 2007, and critics claim that the mine will violate a 1979 E.U. law prohibiting cyanide discharge into groundwater. The mine would create four open pits, each covering 100 hectares. Pulverized rock would pile up on a 1200-hectare plot of land, and the cyanide-laced water used for extracting the gold would be stored in a 500-hectare tailing pond held back by a 180-meter-tall dam built from waste rock generated by the mine. The project is an “ecological bomb,” contends Sergiu Mihut of the Institute of Biology in Cluj-Napoca. Not only will the mine destroy the local ecosystem, he says, but it also threatens the groundwater. According to a December 2002 Greenpeace-funded report by law experts at the University of Vienna, Austria, the rock layers beneath the planned pond site are porous enough to allow wastewater to trickle through to the water table. Compounding the potential threat, a recent analysis by the Center for Science in Public Participation, an environmental group in Bozeman, Montana, warns that the dam for the tailing pond—which would be built with sulfur-laden waste rock from the mine—would likely leach sulfuric acid into the watershed, endangering fish and aquatic life. Gabriel Resources says the critics have got it wrong. Bruce Marsh, vice president for environment and regulatory affairs at Gabriel Resources, says the ecological concerns are based on an initial feasibility study for the project. He says that the company's latest environmental assessment addresses many of those concerns and claims that the mine will improve the area's water quality. To comply with regulations, “we have to clean up 2000 years of environmental impact,” he says. Centuries of low-tech mining have tinged the area's rivers red with iron, and the water is highly acidic, he says: “If there is no mine, that will continue forever.” Gabriel Resource's operation will remove much of the rock causing the acid drainage, he says, and the company plans to install filters that would reduce cyanide in the tailings pond to 1 part per million. That would meet United Nations standards, he says, and is significantly better than that of some mines now operating in the E.U. The Romanian Academy and other opponents are trying to persuade the government to take a second look at the project's economics. Gabriel Resources acknowledges that a substantial number of the 500 jobs at the mine would go to foreign experts. Moreover, the company must resettle approximately 1200 people from the site. The tradeoffs are not worth it, argues Haiduc, who says the region could be better served by developing tourism around the Roman ruins and its scenic appeal. Opponents will have another chance to argue their case next week when the Romanian Parliament dispatches a team to Rosia Montana to assess the project's environmental and social impacts. A similar team from the European Parliament will follow in October. Whatever the outcome, one thing appears certain for the region's inhabitants: Their livelihoods, as they have been for centuries, will be tied to the gold mine. 15. PHYSICAL ANTHROPOLOGY AND PALEOANTHROPOLOGY MEETING A Shrunken Head for African Homo erectus 1. Ann Gibbons TEMPE, ARIZONA—About 1200 researchers gathered here from 21 to 26 April for back-to-back meetings of the Paleoanthropology Society and the American Association of Physical Anthropologists. The long-legged, relatively big-brained hominid called Homo erectus has long been considered the Moses of the human family—the species that led the first exodus out of Africa more than 1.5 million years ago. But that view was challenged recently when a team working in Dmanisi, Georgia, uncovered three small, 1.75-million-year-old skulls that are older and more primitive than any H. erectus in Africa. They raised the startling possibility that an earlier, small-brained species left Africa first (Science, 5 July 2002, pp. 26 and 85). Now another surprisingly small skull has been unearthed—this time in Kenya. Introduced at the meeting, the diminutive fossil bears a surprising resemblance to the smallest skull from Dmanisi, according to paleontologist Meave Leakey, whose team from the National Museums of Kenya dug up the fossil in 2000. The researchers identify the unpublished skull as the smallest H. erectus known from Africa, implying that some members of this peripatetic species had a puny brain case. “It shows the incredible variation in size within H. erectus,” says paleontologist Fred Spoor of University College London, U.K., a member of Leakey's team. He adds that the resemblance between the Kenyan and Georgian skulls, separated by 3000 kilometers and at least 200,000 years, ties the Georgian fossil more closely to H. erectus in Africa. In a spontaneous viewing in the hotel lobby, the Kenyan and Georgian teams compared casts as a gang of H. erectus specialists crowded around to kibitz on the fossils' sizes, shapes, and identities. “This really feels like the skull we found,” said Leakey, cradling the cast brought from Dmanisi by David Lordkipanidze of the Georgian State Museum in Tbilisi. She and other researchers turned the skulls over, comparing the angle of the ear bones and the curvature of the sides and back. Most—although not all—of those assembled agreed: The casts were two of a kind. Back in 2000, when Kenyan paleontologist Frederick Kyalo Manthi spotted an ear bone poking out of the ground in the scrublands at Ileret, east of Lake Turkana, the Kenyan skull was difficult to classify. The skull is 1.55 million years old, reports paleontologist Louise Leakey, who works with her mother Meave at the National Museums of Kenya. That's the same age as another famous H. erectus fossil from the opposite side of the lake—the strapping Turkana boy (sometimes classified as Homo ergaster). The new skull is much smaller, however, and lacks the prominent brow ridge found in the Turkana boy and other H. erectus specimens. It is so small that before it was cleaned, Meave Leakey and Spoor thought it might be a late member of Homo habilis, a problematic species composed of a grab bag of African fossils from 2.4 million to 1.6 million years old. When Lordkipanidze unveiled his smallest skull from Dmanisi last year, Spoor realized that the crania were quite similar. And as he noted in his talk, both have classic H. erectus features, including a raised keel on the top and a characteristically angled ear bone. Spoor also noted that both have an oblong shape in side view, a teardrop shape in top view, and no prominent brows. The skulls' small size might be because both were from young adults or teenagers, or from females, says Susan Antón of Rutgers University in New Brunswick, New Jersey. Despite such similarities, the Dmanisi skulls are not classified as H. erectus at the moment. They are more primitive than the Kenyan hominid, with a profile resembling H. habilis, says Lordkipanidze. So last year he and his colleagues baptized one of their fossils, a robust jawbone, as a new species, Homo georgicus—a proposal rejected for the skulls by most who saw the casts. “I'd argue that this is H. erectus and that it was descended from H. habilis,” says H. erectus expert Philip Rightmire of the State University of New York, Binghamton. Lordkipanidze announced at the meeting that his team has recently found bones from the neck down plus a fourth, more robust skull, which may help to clarify the fossils' identities. “At the moment I prefer to call [the small skull] early Homo,” he says. “For me, this is the best candidate to be an ancestor of H. erectus [in Asia].” Meanwhile, the Ileret skull offered one more surprise: the pronounced keel on its top. This feature is commonly found in H. erectus in Asia but not in Africa, says Spoor. So the Kenyan skull could be an important link to both Georgian and Asian fossils and may help return H. erectus to its venerable status as the first intercontinental traveler. 16. PHYSICAL ANTHROPOLOGY AND PALEOANTHROPOLOGY MEETING A Miss for Moderns And Neandertals 1. Ann Gibbons TEMPE, ARIZONA—About 1200 researchers gathered here from 21 to 26 April for back-to-back meetings of the Paleoanthropology Society and the American Association of Physical Anthropologists. Ever since paleoanthropologists discovered that Neandertals and early modern humans had lived in caves as close as 100 meters apart in Israel, the obvious question has been: Did these two types of humans live there at the same time? The answer is no, judging from a new study of the ancient climate and landscape at three caves where fossils of early humans and their prey were found. In a talk at the Paleoanthropology Society meeting, a team of American and Canadian researchers concluded that early modern humans and Neandertals lived in the caves under different climatic conditions. By analyzing isotopes in the teeth of goats and gazelles eaten by ancient humans, researchers were able to trace the plants the animals ate. They reconstructed climate so precisely that they could detect even seasonal differences in the climate experienced by Neandertals and early modern humans, say graduate student Kris Hallin of the University of Wisconsin, Madison, and her adviser Margaret Schoeninger of the University of California, San Diego. “This is great work,” says Stanley Ambrose of the University of Illinois, Urbana-Champaign. “It shows something very important about variation in climate at the annual scale.” It also suggests how the two species adapted to different habitats and why they thrived at different times in Israel. The first fossils of early modern humans and Neandertals were found in the region in the early 1930s, but for many years anthropologists thought Neandertals were ancestral to modern humans and so assumed that their fossils were older. Then in the 1980s, modern radiometric dating methods revealed that modern humans had occupied the caves of Qafzeh and Skhul as early as 110,000 to 92,000 years ago. The Neandertals inhabited the caves of Amud and Kebara considerably later, from about 70,000 to 50,000 years ago. Harvard paleoanthropologist Ofer Bar-Yosef, noting that a 1980s study found that modern humans coexisted with African mammals and Neandertals with European ones, proposed that modern humans moved north into the region during the interglacial period 128,000 to 71,000 years ago. Then the cold-adapted Neandertals moved south to the same places during the last ice age, 70,000 years to 45,000 years ago. But uncertainties about the dating raised the possibility that the two types of humans could have met, since all the caves are within 100 kilometers of each other and often closer. To explore whether the Neandertals and moderns took shelter in the caves under different climatic conditions, Hallin analyzed isotopes in fossil animal teeth. During the year or two that a tooth develops and erupts, it accumulates isotopes of carbon and oxygen. The ratio of carbon-13 to carbon-12 reflects whether an animal ate grasses in dry, open landscapes or plants in a more forested landscape. The variation of oxygen-18 to oxygen-16 reveals the season in which an animal consumed water, thus reflecting seasonal rainfall. Hallin applied the method to the fossil teeth of goats and gazelles found in the hearths and garbage of the ancient humans. She found that those eaten by the modern humans at Qafzeh and Skhul grazed in dry grasslands and consumed little water except during winter rains—a climate similar to that of Israel today. Conversely, the animals eaten by Neandertals at Amud lived in a cooler climate in which it rained year-round. (The Neandertals ate more gazelles; the moderns, more goats.) “There was a major change in climate in Israel between the time that it was occupied by modern humans and the time when Neandertals were present,” says co-author and geochemist Henry Schwarcz of McMaster University in Hamilton, Ontario. To Bar-Yosef, the isotope work chiefly confirms the evidence from animal fossils. But Hallin's precise climatic reconstructions use animals that were apparently served up as ancient meals rather than simply found in the same layer as the humans. Thus the work adds new evidence to the idea that this region was an important crossroads, with moderns and Neandertals moving in and out as climatic conditions changed. And it shores up the case against coexistence, adds Tel Aviv University paleoanthropologist Yoel Rak. Neandertals and our ancestors, he says, “were not sitting in the caves playing cards together.” 17. PHYSICAL ANTHROPOLOGY AND PALEOANTHROPOLOGY MEETING First Modern Remains in Europe 1. Ann Gibbons TEMPE, ARIZONA—About 1200 researchers gathered here from 21 to 26 April for back-to-back meetings of the Paleoanthropology Society and the American Association of Physical Anthropologists. Three Romanian spelunkers were exploring the Transylvanian Alps last year when they came across a jawbone lying in the middle of a newfound cave. They took one look at the robust bone and knew it was very old, so they quickly contacted Romanian Academy scientist Oana Moldovan, who in turn called paleoanthropologist Erik Trinkaus of Washington University in St. Louis, Missouri. Trinkaus examined the bone last May and sawed off a sliver for radiocarbon dating. At the meetings he announced his results: The jaw is at least 35,000 years old—which makes it “the first modern human found in Europe.” Modern humans are thought to have swept into Europe about 40,000 to 35,000 years ago, swamping or replacing the Neandertals who had evolved there during the previous 400,000 years (Science, 7 March, p. 1525). Archaeologists have detected the moderns' entrance not by fossils but by the art and tools left behind, including blades, beads, and bone tools more sophisticated than those used by Neandertals. But although modern tools begin to appear in eastern Europe 40,000 years ago, only poorly dated scraps of modern human bones older than 32,000 years have been found. “The jawbone is the earliest well-dated and identifiably modern human fossil in Europe so far, and that is important,” says paleoanthropologist Chris Stringer of the British Museum of Natural History in London. The date, which is a minimum age, is unusually reliable because it was done on the human bone itself rather than associated animals, notes Robert Franciscus of the University of Iowa in Iowa City. A second lab is now confirming the results, says Trinkaus. Trinkaus reported at the meeting that the lower jaw has distinctly modern features such as a chin and a wide piece of bone in the back. But it also has some archaic traits, such as “huge” wisdom teeth, which he thinks link it with earlier archaic humans. Thus, although their tools may have been sophisticated, modern humans were still evolving anatomically as late as 35,000 years ago. Or, as Trinkaus says: “Early modern humans were not particularly modern.” 18. CONSERVATION BIOLOGY Rapid Evolution Can Foil Even the Best-Laid Plans 1. Carl Zimmer* 1. Carl Zimmer is the author of Evolution: The Triumph of an Idea. By triggering bouts of natural selection, efforts to protect and manage endangered species can have unintended—and unwelcome—consequences Natural selection, once seen as a stately and imperceptible process, can be speeded up to resemble a case of hyperactive jiggles. Over the past 20 years, as evolutionary biologists have begun to study natural selection in the wild, they have documented record-breaking changes in some populations of animals and plants that occur in years—not centuries or millennia. Now conservation biologists are beginning to take note. “The last year or two have been the first time that people have really been hammering on this issue,” says Andrew Hendry of McGill University in Montreal, Canada. Hendry is the co-author of a recent paper in Trends in Ecology and Evolution that exhorts his colleagues to think about the effects of rapid evolution when they draw up plans to protect and manage species. Conservation biologists “have actually been studying species that change right under their noses,” adds Joel Brown of the University of Illinois, Chicago. They ignore it at their peril, he wrote in a recent paper in Biological Conservation, because conservation efforts can drive evolution in unexpected ways, sometimes making a protected species maladapted to its environment in just a few generations. But there's a plus as well: A better understanding of rapid evolution may let conservation biologists harness its powers to save species from extinction. The clearest cases of rapid evolution are triggered by sudden changes, either natural or anthropogenic, in a species' environment. On the Galápagos Islands, for example, Darwin's finches evolve larger or smaller beaks as their food supplies fluctuate with the climate. In Trinidad several years ago, scientists triggered a burst of evolution by simply moving guppies from a pond with predators to one without. After 11 years, evolution's mark was apparent: The guppies took 10% longer to reach sexual maturity and as adults weighed 10% more (Science, 28 March 1997, p. 1934). A number of biologists now suspect that fisheries managers have been inadvertently triggering similar bouts of rapid evolution. To keep stocks from collapsing, managers often put a minimum size limit on catch, giving younger fish a chance to breed before they are killed. Despite these efforts, the average size of caught fish has been falling in recent decades in many fisheries. Studies in Europe and the United States strongly suggest that the strategy selects for smaller individuals. The evolutionary advantages are clear: If fish can become sexually mature while still small, they have more chance to reproduce and are likely to pass down more of their genes. As a result, the population on the whole gets smaller. Biologists don't yet know whether this trend threatens the survival of the fish stocks, but fishers already know what it means to their pocketbooks. In Norway, grayling in mountain lakes have long been protected by size limits. Thrond Haugen of the University of Oslo and colleagues have found that after 6 decades, the fish reached adulthood when they were 25% smaller. Researchers at the State University of New York, Stony Brook, have recreated such fishing pressures in the lab. David Conover and colleagues raised thousands of Atlantic silversides and harvested the biggest from each generation. In four generations, the fish became genetically programmed to grow only half as large (Science, 5 July 2002, p. 94). Conover says these results suggest that fisheries will suffer from low yields for a long time even if managers remove catch sizes. Because the small size of the fish is genetically programmed, only an intense evolutionary pressure can reverse the trend. But natural selection in favor of larger sizes is far milder than the intense pressure created by commercial fishing. “That could take thousands of generations,” says Conover. “There's no force that directs evolution in the opposite direction that fishing does.” Some conservation biologists believe that captive breeding programs can also backfire in the face of unanticipated evolution. In studies on wild and captive chinook salmon, Daniel Heath of the University of Windsor in Ontario and colleagues documented that females face an evolutionary tradeoff. On one hand, it pays for a salmon to lay big eggs, because the extra energy she packs into them helps the offspring survive after they hatch. But the bigger the eggs, the fewer a salmon can lay. Captive breeding programs change this tradeoff, because in the less stressful environment of a hatchery, salmon eggs can survive even if they're small, and females that lay a lot of eggs are at an evolutionary advantage. In studies at a British Columbia fish farm, Heath has found that captive salmon have indeed become more prolific egg-layers; over just four generations the eggs have become 25% smaller (Science, 14 March, p. 1738). “You're looking at a phenomenal response,” says Heath—one of the fastest rates of evolution ever recorded outside a lab. If these fish were to be put back in the wild, Heath warns, their small eggs would be less likely to survive to adult fish. He believes the lessons from salmon apply to many other endangered species. “If you grab the last few animals and you put them in a zoo to make sure they don't die, you could potentially drive evolution of some trait that you don't expect,” says Heath. If the animals were eventually released into the wild, “a loss of fitness might mean the difference of survival and extinction. That's the scary part.” Scary, but not hopeless, adds Hendry. He thinks captive breeding programs should try to breed animals and plants in the same way farmers breed crops—selectively, for certain traits. One way to do this, Hendry suggests, is to regularly release a few captive-bred individuals—“selection probes,” as some researchers calls them—and see which survive. The biologists could then breed the relatives of the survivors but not the less fit individuals. “It would be a drastic shift in the way people thought about these things,” says Hendry. But it might save some species in the process. 19. Manganese: A High-Octane Dispute 1. Jocelyn Kaiser A debate over the health effects of airborne manganese is heating up as more and more countries begin adding the metal to gasoline Thirteen years ago, Donna Mergler and her team had good reason to wonder about the health of workers in a manganese alloy plant in a small town called Beauharnois, near Montreal. Ore hauled by barge up the St. Lawrence River was refined at the plant in a giant furnace, poured out in a glowing red stream of iron-manganese alloy, and crushed into pellets for making steel. The factory was in compliance with air quality standards in Quebec. But even the researchers would emerge from the plant “sneezing black particles for the next 24 hours,” says Mergler, a neurophysiologist at the University of Quebec in Montreal. Her team found that the workers' exposure to manganese, an essential dietary element that at high doses causes a debilitating disease similar to Parkinson's, appeared to be linked to lower scores on tests of cognition and motor skills such as finger tapping. Even more intriguing was what appeared to be a subtler sign of manganese toxicity. Some middle-aged men in a control group drawn from the populace around Beauharnois had also scored more poorly than expected in some of the same neurological tests. The study was only suggestive: Mergler's group had limited data on airborne manganese around Beauharnois, leaving open the possibility that other factors were harming the men. But it raised the alarming prospect that even small amounts of inhaled manganese might erode neurological health. The results held up in a 1996 follow-up study funded by the U.S. Environmental Protection Agency (EPA), also led by Mergler, of 270 men and women around Beauharnois: Although the plant by then had been closed for 5 years, men over 50 who lived downwind and had higher manganese blood levels performed worse on motor and memory tests than controls. Disturbingly, the air was well below the threshold—110 nanograms of manganese per cubic meter (ng/m3)—that the Canadian government deems safe. If the shuttered plant had been the only potential manganese headache in Canada, Mergler's findings may have faded into obscurity. But in 1990, the government completed phasing out leaded gasoline, paving the way for widespread use of a manganese-based compound, MMT, in gasoline. The additive increases octane levels, which boosts engine performance and enables fuel to be burned more evenly. Health officials in Canada, which has allowed MMT in gas since 1976, reaffirmed 9 years ago that in their view, MMT is safe. But the U.S. EPA is not so sure and is asking MMT's manufacturer, Ethyl of Richmond, Virginia, for more data. The stakes are high, as MMT and other petroleum additives racked up$648 million in net sales last year for Ethyl. The company notes that MMT, now sold in 25 countries, has been and continues to be extensively tested. “We believe it's a very safe product,” says Donald Lynam, an Ethyl vice president and senior scientist. But opponents claim that manganese could prove as dangerous as the antiknock additive it supplanted: lead, which was phased out after a decades-long debate over the extent to which it impairs child development.

Manganese follows in lead's footsteps in at least one respect: The arguments over its health effects have occasionally turned ugly. MMT is “a very emotional topic within the scientific community,” explains Dave Dorman, a toxicologist at the CIIT Centers for Health Research in Research Triangle Park, North Carolina. Tempers flared at a neurotoxicology conference in 1997 in Little Rock, Arkansas, when the Ferroalloy Association, a meeting co-sponsor, handed out a newsletter each day that downplayed research suggesting that manganese may be neurotoxic at low doses, says neurologist Jay Gorell of the Henry Ford Health System in Detroit. “I had never been to anything like that,” he says.

Temperatures are likely to rise again as EPA and Health Canada complete their latest evaluations of the risk of manganese and MMT in light of fresh studies. Toxicologists have found, for instance, that in rats inhaled manganese can head straight to the brain through the olfactory nerve. On the other hand, measurements in Canada suggest that the MMT levels to which people are generally exposed are too low to cause harm.

Lingering bitterness over lead may make it hard for manganese to get a fair hearing. “A lot of us are very, very suspicious” of claims that MMT is safe, says neurotoxicologist Bernard Weiss of the University of Rochester in New York, who concedes that regulators may well see it differently.

Friend and foe

As a nutrient, manganese is an essential component of several enzymes; a deficiency can lead to heart and bone problems and in children, stunted growth. The liver removes extra dietary manganese from the circulation, so ingested manganese is not a major concern, says EPA risk assessor J. Michael Davis. However, when manganese is inhaled, blood ferries it from the lungs to the brain, where it can readily cross the blood-brain barrier.

It's been known since 1837 that workers in manganese mines can develop manganism, a dreaded illness marked by Parkinson's-like tremors, violent outbursts, and hallucinations. Victims have lesions in the globus pallidus and striatum of the basal ganglia, a part of the brain involved in fine muscle control. But it takes large amounts of manganese to trigger the disease: airborne concentrations as high as 100 or more milligrams per cubic meter. And recently, concerns have grown that welders exposed to manganese in fumes could be at risk for Parkinson's-like disease (see sidebar).

By comparison, manganese exposure from MMT is low: Canada, for example, allows no more than 18 milligrams of manganese from MMT per liter of gasoline, and only a fraction of this amount is thought to reach the air as manganese particles. MMT, or methyl cyclopentadienyl manganese tricarbonyl, was developed by Ethyl in the 1950s as a substitute for tetraethyl lead. MMT isn't the only option: In the United States, the main additive is MTBE, or methyl tertiary butyl ether. But the ease with which this potential human carcinogen can infiltrate groundwater at levels that can be smelled and tasted has alarmed the public. Ethyl markets MMT as an alternative to MTBE. The main selling points, it says, are that MMT is cheaper and reduces tailpipe emissions of nitrogen oxides, which include precursors to smog.

Ethyl won its first approval for MMT in 1976 from Canada, which subsequently conducted a series of safety reviews. Health Canada's latest assessment, in 1994, assumed a safe threshold of 110 ng/m3 for inhaled manganese, extrapolated from worker studies with added safety factors for children and susceptible adults. The agency's review of air quality data from several cities noted that manganese levels were below the threshold and thus too low to worry about.

Although the debate wasn't over—some Canadian legislators still decried MMT's potential health effects and tried to ban it—the additive's future in commerce seemed reasonably ensured, as more countries approved its use. One, Australia, concluded in a draft report last February that MMT does not pose a human health hazard.

A fight was brewing in the United States, however, where EPA had set a lower threshold for inhaled manganese of 50 ng/m3. The agency's concerns began to rise after it reevaluated results from an exposure study in 1990 in Riverside, California, where MMT was permitted in leaded gas used by older vehicles. Extrapolating the data, EPA estimated that if MMT were used in all gas, 5% to 10% of the population could be exposed to airborne manganese at levels exceeding 100 ng/m3. In July 1994, the agency concluded that there was too much uncertainty to say whether MMT is safe and denied Ethyl's request to introduce the compound into unleaded gasoline.

That was not what Ethyl wanted to hear. The company sued EPA, arguing that the agency did not have the authority to bar MMT for health reasons under the Clean Air Act. In 1995, a federal court agreed, but EPA had the authority to require Ethyl to pay for new safety studies even though it was free to sell MMT. In response to the court ruling, a parade of environmental health experts, from lead-effects pioneer Herb Needleman of the University of Pittsburgh to toxicologist Ellen Silbergeld, now at Johns Hopkins University, lined up behind EPA, citing Mergler's data on the control group. The battle peaked in March 1996 when Ethyl published full-page newspaper ads asserting that MMT is safe. EPA's response was to ratchet up the rhetoric: In a statement, Carol Browner, EPA's chief at the time, said that “the American public should not be used as a laboratory to test the safety of MMT,” and called for more testing.

A mixed message

One argument for MMT's safety is manganese's very ubiquity: The air is suffused with low levels of the metal stirred up from soil. People ingest it daily; major sources include leafy vegetables and tea. According to Dorman, MMT doesn't add much to these other sources.

Critics counter that the manganese particles spewed from tailpipes are smaller than those from natural sources and therefore more likely to lodge deep in the lungs. And MMT-derived manganese, Davis says, includes highly soluble forms that more readily cross from lung alveoli into the bloodstream than other forms in crustal dust.

Another reason that EPA says it is cautious is the dearth of studies on the potential effects of low-level, long-term manganese exposure. EPA neurotoxicologist Kenneth Hudnell, a co-author on Mergler's community study, says the agency is considering a proposal for a similar study in a U.S. city. He notes that a recent study by occupational health researcher Roberto Lucchini of the University of Brescia in Italy appears to support Mergler's findings. The as-yet-unpublished research has detected an elevated rate of Parkinson's disturbances in people living near a ferroalloy plant.

Recent work in lab animals has only clouded the picture. Dorman's group at CIIT, with funding from Ethyl, has exposed rats to aerosols of manganese sulfate, the most soluble form from combusting MMT. In their latest study, manganese didn't accumulate in most brain regions at exposures as high as 0.01 milligram per cubic meter, more than 1000 times higher than the levels in Toronto and Montreal air. “There is no change,” Dorman says. “That's encouraging.”

But manganese does accumulate in one brain area—the olfactory bulb—and that gives some researchers pause. Hans Tjalve and Jorgen Henriksson at the Swedish University of Agricultural Sciences in Uppsala have reported that after inhaled manganese enters a rat's brain via the olfactory bulb, it is transported through the brain to the striatum. Other studies have not reproduced the extent of these results, but have found that inhaled manganese penetrates the entire olfactory system, says toxicologist Michael Aschner of Wake Forest University School of Medicine in Winston-Salem, North Carolina.

Researchers dispute what these findings portend for people. Lynam notes that because rat nasal passages are proportionally much larger than people's and the animals breathe only through their noses, they should absorb 40 times more manganese by that route than people do. To get at this question, Ethyl is funding a study by Dorman's group of how inhaled manganese is taken up in primate brains.

Uncertainty also remains over estimates of how much manganese might be inhaled where MMT gas is sold. In the mid-1990s, Ethyl paid the Research Triangle Institute (RTI)to use personal monitors to record individual manganese exposure in 542 people in Toronto. As Health Canada had concluded earlier, the exposures fell well below the threshold. (Lynam thinks EPA's analysis of the Riverside data, which estimated higher levels, made “questionable assumptions and extrapolations.”)

Even though the \$3 million Toronto study was “well conducted,” says Davis, EPA still has questions. For instance, the agency wants to be sure that the results would apply to cities with weather and traffic patterns that are different from Toronto's.

One fundamental concern of some experts is that while the regulations on airborne manganese may protect healthy people, certain vulnerable groups could still be at risk. They worry, for example, that manganese may hasten the onset of Parkinson's in people susceptible to the disease. Providing some support for this idea is a 2000 study in Neurotoxicology and Teratology by toxicologist Don Smith of the University of California, Santa Cruz. He found that rats treated with a chemical that induces a pre-Parkinson's condition developed more severe neurological symptoms, such as loss of motor control, from moderate manganese exposures than did rats without the pre-Parkinson's condition. Other labs are exploring how young and aged animals respond.

One vulnerable group may be people who don't get enough iron in their diet. Aschner, for example, has found that iron-deficient rats are much more likely to accumulate manganese in the brain than are normal rats. The reason, he says, is that manganese and iron ions rely on the same proteins to cross the blood-brain barrier. That's important, because MMT is now being added to gas in some developing nations where many people are malnourished. “I would be concerned with any manganese exposure with any population that's iron deficient,” says Aschner. Lynam doesn't dispute these findings, but he points out that the EPA and Health Canada safe thresholds are designed to protect such sensitive populations. MMT's contribution to air manganese levels is far below those levels, he says. “It's very, very small and is lost in the background.”

Uncertainty reigns

Health Canada is now reviewing the recent findings to keep up to speed on the science—not because it feels its earlier conclusion is wrong, says agency risk assessor Barry Jessiman. By contrast, EPA's review of the Ethyl data to be submitted by the end of 2004 will determine whether the company must conduct more toxicology tests. For now, partly because of health concerns, gas refiners in the United States are buying very little MMT.

Some experts believe that the only way to ascertain manganese's low-level effects on people is to see what happens years after primates inhale the metal, Weiss notes. Ethyl hasn't ruled out such an expensive long-term study, Lynam says, but feels that “if there is future testing, it should take into consideration the results of the ongoing research.”

Whatever the outcome, opposition to MMT is likely to remain entrenched. Critics acknowledge that their concerns are as much philosophical as scientific: It's better to err on the side of caution, MMT opponents say, and to delay the introduction of a substance into the environment until it has been proven safe. “We still have too much uncertainty,” contends toxicologist Joseph Zayed of the University of Montreal.

Weiss compares the debate over manganese to the years of sparring over lead. For both metals, he says, the issue boils down to “incremental risk.” Mergler agrees, asserting that MMT's health effects will be detected not at the individual level, but at “the societal level.” That's an incremental risk that she and others are loath to accept.

20. State Court to Rule on Manganese Fume Claims

1. Jocelyn Kaiser

As scientists spar over the health effects of low levels of manganese (see main text), the steel industry is bracing for a courtroom battle over exposure to the metal at higher doses. A wave of claims arguing that manganese in welding fumes caused Parkinson's-like neurological damage will go to trial beginning next month in a Mississippi state court. The number of claims could rival those for asbestos-related lung disease: There are at least 500,000 welders in the United States, and judging by the rate observed in the general population, 1%—5000—would be expected to develop Parkinson's disease after age 60. If manganese exposure leads to earlier or more cases, “it could be huge,” says neurologist Brad Racette of Washington University in St. Louis. He and others caution, however, that the welders' case is not ironclad.

Welders fix joints together with molten flux from metal bars that sometimes contain manganese. Since the 1930s, doctors have noted neurological disease among welders. But it was several decades before evidence for a link grew stronger, when a 2001 report in Neurology suggested that welders are prone to early-onset Parkinson's. In that study, Racette's group examined 15 welders treated in their Parkinson's clinic. The patients, who had brain scans typical of Parkinson's, had developed the disease around age 45, on average—15 years earlier than controls.

This and other recent studies have inspired a wave of product liability complaints against welding bar manufacturers in states such as Mississippi and Louisiana, where the oil and shipbuilding industries employ thousands of welders. In the last 2 years a law firm in Lake Charles, Louisiana, Ranier, Gayle & Elliot, has filed thousands of claims in state courts against two dozen corporations, including Lincoln Electric and Westinghouse. The lawsuits charge that warning labels of the potential health risk, on welding bar boxes since 1967, were too vague and difficult to see, and the companies should have warned specifically of a risk of neurological damage from manganese. “They conspired together to hide the truth,” contends Brett Powers, a lawyer with the firm. That's not how the companies see it. “The science just doesn't support” a link between welding and Parkinson's-like disease, says Pittsburgh attorney Ralph Davies, outside counsel for Lincoln Electric.

Experts say that in the absence of a large epidemiological study, convincing a jury of a link might be hard. Iron in welding rods competes with manganese for binding sites on proteins that transport it across the blood-brain barrier, so the iron could counteract any toxic effect, points out James Antonini of the National Institute for Occupational Safety and Health. And if welding fumes do lead to Parkinson's, the risk would depend on exposure. Exposure, says Racette, is “probably the biggest wild card.”