News this Week

Science  05 Dec 2003:
Vol. 302, Issue 5651, pp. 766
  1. U.S. SCIENCE FUNDING

    Research Catches a Break in Catch-All Spending Bill

    1. Jeffrey Mervis,
    2. Andrew Lawler,
    3. Jocelyn Kaiser*
    1. With reporting by David Malakoff.

    Lowered expectations. That's why most science lobbyists are expressing quiet satisfaction with a massive 2004 budget bill that Congress stitched together last week. The spending measure (H.R. 2673) allocates 5% and 3.1% boosts to the National Science Foundation (NSF) and the National Institutes of Health (NIH), respectively, in a year when national security rules the roost and the deficit is expected to reach a half-trillion dollars. Other agencies will have to make do with less, however, after legislators played Scrooge or used part of the agencies' budgets to pay for so-called earmarks that benefit the legislators' districts or states.

    “A 5% increase is doing pretty well in this environment,” says Warren Washington, chair of NSF's oversight body, the National Science Board. “But we're certainly going to push for more next year.”

    Congress once again missed its 1 October deadline—the start of the new fiscal year—to complete work on the budget. This year it passed only six of 13 separate appropriations bills that make up the $2.2 trillion U.S. budget. Bogged down by fights over everything from the rules governing overtime pay to the number of electronic and print media outlets a single company can own, Congress decided belatedly to roll the seven remaining spending bills into one. The resulting $820 billion omnibus bill, which was made public on 25 November after being adopted by a House-Senate conference committee, is expected to go before the House next week. The Senate may not vote on the measure until January, however.

    Some highlights for science agencies funded under the omnibus bill:

    NSF: The 5% hike for NSF, to $5.58 billion, is a far cry from the 15% annual rise that legislators had promised last year as part of a 5-year doubling of NSF's budget (Science, 22 November 2002, p. 1537). But it's bigger than the 3.3% increase that President George W. Bush requested back in February.

    View this table:

    The extra $268 million will allow NSF to address several priorities, including an effort to pay graduate students a living wage. Next fall the annual stipend level in selected graduate training programs will jump to $30,000, up from $27,500. Another administration favorite, the 2-year-old math and science partnerships program between universities and local school districts, will get $139 million, $12 million more than this year. And although lawmakers put the brakes on plans to start building the National Ecological Observatory Network and the Rare Symmetry Violating Processes physics experiment at Brookhaven National Laboratory in Upton, New York, they inserted $6 million apiece for the continued planning and design of each project.

    The bill is also filled with legislative preferences. One is a $15 million boost in the $75 million plant genome research program, courtesy of Senator Kit Bond (R-MO). Another Republican-backed measure adds $25 million to a $84 million program for large academic instrumentation, to be spent providing Internet access for colleges that serve large numbers of minority students. At the same time, legislators asked for an analysis of why the 23 “have-not” states funded under a long-running effort to improve their ability to compete for NSF grants never graduate from the program.

    NIH: The $27.82 billion budget exceeds the president's request and matches the Senate's higher figure, thanks to Senator Arlen Specter (R-PA), who pushed for extra education and biomedical research spending. It's the expected “soft landing” from 5 years of increases that doubled NIH's budget. “The appropriators probably did the best they could,” says David Moore, head of governmental relations at the Association of American Medical Colleges.

    A decline in 2004 spending on construction of facilities has freed up funds for a 7% increase for research, although much of the new money will go to biodefense research. And NIH lobbyists are concerned that a tax to finance evaluations of programs at other Public Health Service agencies, now at 2.2%, could grow in future years.

    NASA: Bowing to pressure from Congress, the agency intends to delay its plans to build the multibillion-dollar Orbital Space Plane, for which $550 million was requested this year. The House Science Committee has questioned the purpose of the program, billed as an alternative to the space shuttle, and appropriators heeded the committee's message by suggesting that NASA shelve its plans until the agency adopts a strategic plan. On 1 December NASA officials finally threw in the towel.

    The $15.4 billion budget falls short of even the president's meager request for a 1% increase. Congress also did some significant rearranging of NASA's priorities. It sliced $200 million from the $1.5 billion request for the space station, citing savings from the fleet's grounding due to the Columbia accident, and it cut $70 million from a launch technology package. Legislators also trimmed NASA's requests for several space science missions, lopping $20 million from an effort to build an advanced Jupiter spacecraft, $10 million from proposed astrophysics missions called Beyond Einstein, and $11 million from a proposed global-change spacecraft that would study the poles. The cuts, which will stretch out work on these missions, appear to accommodate tens of millions of dollars in legislative earmarks.

    NOAA: Its key research programs “got funded, but nothing got really well funded,” says Luke Forrest, who tracks the agency's budget for the National Association of State Universities and Land-Grant Colleges in Washington, D.C. Earmarks helped boost the budget of its ocean and atmospheric research office by 7%, to $399 million. But the popular state-based Sea Grant program remains becalmed, at $62 million.

  2. BIOTERROR TRIAL

    Butler Cleared on Most Biosecurity Charges, Convicted of Fraud

    1. David Malakoff,
    2. Martin Enserink*
    1. With reporting by Kerry Drennan in Lubbock, Texas.

    LUBBOCK, TEXAS—In the end, it wasn't the black death that bothered the jury; it was the money. This week microbiologist Thomas Butler was found guilty of 47 of 69 federal charges stemming from his report last January that 30 vials of plague bacteria had gone missing from his laboratory at Texas Tech University Health Sciences Center here. Forty-four of the convictions involved charges that the 62-year-old physician defrauded the university by diverting clinical trial payments to his personal use.

    But Butler was largely cleared of the government's most sensational allegations: that he illegally transported plague bacteria, Yersinia pestis, into and around the United States and then lied to FBI agents when he reported some vials missing. The report sparked a bioterror scare, which ended after Butler wrote a statement in which he admitted to accidentally destroying the vials. Butler has since retracted the confession, and his defense argued that a manipulative FBI agent essentially dictated the statement to the exhausted scientist (Science, 7 November, p. 963).

    Butler looked straight ahead as District Judge Sam Cummings announced the verdicts. As the convictions mounted, Butler closed his eyes, clenched his jaw, and became flushed, apparently near tears. His wife and oldest son sat sober and silent behind him.

    Butler declined comment. Defense attorney Charles Meadows Jr. called the verdict “disappointing” but was pleased that Butler was cleared of “perpetuating a hoax.” The defense team said it will appeal.

    Prosecutor Richard Baker declared victory. “The jury has done what Butler has escaped up to this time; he was held accountable,” he said. Butler faces up to 240 years in prison and $11.7 million in fines, Baker said, although the actual sentence is likely to be far less severe. No sentencing date has been set.

    Observers were divided on the verdict's implications for scientists, some of whom decried the government's prosecution and contributed money to Butler's defense. “This is not a strong verdict one way or the other,” says Larry Cunningham, a Texas Tech law professor who has been following the case. But 2003 Nobel laureate Peter Agre says the message is “chilling. … It still strikes me as an episode from the McCarthy era.”

    Split verdict.

    Thomas Butler, leaving federal court with wife Elisabeth, could face extensive jail time.

    CREDIT: LUBBOCK AVALANCHE-JOURNAL/JIM WATKINS/AP PHOTO

    The 16-day trial gave jurors a crash course in modern biomedical research and campus politics, including extensive testimony on everything from the rules governing human subjects research and dangerous pathogens to the details of clinical trial contracts. (For complete coverage, see www.sciencenow.org/feature/data/butlertrial.shtml.) Some scientists traveled from as far away as Madagascar to testify, and others who live in this tight-knit prairie town sadly noted that they were testifying against a longtime colleague they considered a friend.

    In the end, jurors were convinced that Butler had defrauded Texas Tech by cutting secret “shadow” contracts with two pharmaceutical companies. Under the twin agreements, half of the per-patient fee that the firms paid to run clinical trials was sent to the university as rules required. Unknown to the university, however, the other half went directly to Butler's bank account. The defense team said the shadow contracts were legitimate, private consulting deals. “The government has criminalized a routine administrative disagreement,” says defense attorney Jonathan Turley. Jurors found Butler innocent of a related tax charge of declaring fictitious expenses that offset the income.

    The jury acquitted Butler of all seven charges that he illegally hand-carried plague samples into the United States from Tanzania in early 2002 and then transported cultured bacteria to the Centers for Disease Control and Prevention in Fort Collins, Colorado, and to a U.S. Army research center in Fort Detrick, Maryland. Butler argued that he wasn't aware he was breaking the law. He was also cleared of charges that he covered up having plague bacteria in his laboratory. Butler was convicted, however, on three of four counts of shipping the microbes back to Tanzania in a Federal Express box marked “laboratory materials.”

  3. AIDS RESEARCH

    Earmark Draws Criticism, Creates Confusion

    1. Jon Cohen

    In last-minute negotiations over the 2004 federal budget (see p. 1636), U.S. Representative Bill Young (R-FL) added a curious $10 million earmark for European AIDS vaccine research that has scientists and policymakers scratching their heads. One of many special provisions that politicians stuffed into spending bills as Congress scrambled to end the 2003 session, it has involved an intriguing cast of characters. Among them are a philanthropist and erstwhile motion picture producer, a Republican donor who now serves as the U.S. ambassador to Italy, both the U.S. and Italian top health officials, and the heads of the National Institutes of Health (NIH) in both countries.

    A 25 November conference report from the House and Senate subcommittees that oversee foreign operations instructs the U.S. Department of State to give the New York-based International AIDS Vaccine Initiative (IAVI) $10 million “for cooperative projects coordinated with the European Union's new 5-year program, the AIDS Vaccine Integrated Project.” IAVI is a nonprofit that funds AIDS vaccine collaborations between scientists from developed and developing countries. “It's a large amount that would never be approved through normal channels,” says a staffer for a Senate Democrat who had a front-row seat to the dealmaking. Adds a U.S. public health official who also requested anonymity, “It doesn't smell good.”

    Critics of the appropriation include some U.S. AIDS researchers who think the money would be better spent on domestic NIH grants. “Europe is as wealthy as the U.S. and puts far less money into HIV/AIDS research,” says Robert Gallo, head of the Institute of Human Virology in Baltimore, Maryland. “I have to wonder aloud about this.” Gallo and others who know about the appropriation are also concerned that a likely beneficiary will be an Italian-run AIDS vaccine project that includes a preparation that many researchers think has a weak scientific rationale.

    When in Rome.

    NIH Director Elias Zerhouni (left) and ISS head Enrico Garaci agreed to increase U.S.-Italy collaborations at a ceremony in July.

    CREDIT: PLINIO LEPRI/AP PHOTO

    The political wheels began turning in April, when U.S. Secretary of Health and Human Services Tommy Thompson signed an agreement in Rome with his Italian counterpart, minister of health Girolamo Sirchia, to increase cooperation between the two countries. The U.S. ambassador to Italy, Mel Sembler, recruited Young, chair of the House Appropriations Committee, to help with the effort, says Young spokesperson Harry Glenn. Sembler, a Florida real estate developer, contributed tens of thousands of dollars to Republican candidates and causes, including the reelection of his district's representative, Young.

    Enter American Michael Stern, who describes himself as a “dear friend” of Sembler and “family friend” of Enrico Garaci, head of the Istituto Superiore di Sanità (ISS), the Italian NIH. Stern says he has lived 50 of his 93 years in Italy and has had a colorful career as a World War II reporter, author, motion picture producer, and philanthropist. Stern helped arrange a June meeting at Young's office with ISS's Garaci and Barbara Ensoli, an ISS AIDS researcher. “Everything seemed to fit,” says Stern.

    In July, Stern, Sembler, and Young attended a ceremony in Rome's Chigi Palace at which NIH Director Elias Zerhouni signed a “letter of intent” with Garaci (Science, 1 August, p. 579). News reports at the time said that the agreement—which NIH declined to release to Science last week—involved several diseases and that new collaborative programs would be selected through peer review.

    Over dinner that evening, Glenn says that Young, Sembler, and Sirchia discussed the possibility of focusing on AIDS. “It dovetailed with President [George W.] Bush's efforts on international AIDS,” says Glenn, noting that the U.S. government deeply appreciated Italy's support for the war on terrorism and the Iraq invasion.

    Young's staff subsequently asked IAVI whether it would accept funds to work with the AIDS Vaccine Integrated Project (AVIP), a new venture backed by $12 million from the European Union that Ensoli runs in collaboration with scientists from five other European countries and South Africa. AVIP plans to conduct human tests comparing a controversial vaccine that Ensoli has been working on, based on an HIV regulatory protein called Tat, to three other products. IAVI President Seth Berkley agreed to work with AVIP to “strengthen the European effort,” with no special emphasis on Italian research, he says. “We won't do it otherwise,” says Berkley, adding that “anything we do would be subject to our scientific review methods.”

    Although Ensoli's Tat vaccine is but one part of AVIP, some researchers take strong exception to the appropriation because they have doubts about her preparation, which she has just begun testing in humans both to treat and to prevent HIV infection. Gallo, in whose lab Ensoli once worked, says he was “shocked” by the appropriation. Gallo says NIH had turned down his request to test a different therapeutic Tat vaccine that he believes has a better chance of working. “How do you think we feel when we can't get support, but they can come over, do some politics, and get funding?” asks Gallo. “This is not so nice.” Glenn, Young's spokesperson, insists that Congress has not earmarked funding for the Tat vaccine. “The intent was never to fund a specific project,” he says.

    Even the central players seem confused about just what will eventually be funded, however. Ensoli believes that Congress wants to “cofinance” AVIP. Glenn says the $10 million explicitly aims to foster collaborations with Italian and American researchers. Stern says if the money does not end up helping Italian researchers, “someone in the State Department will have his head cut off.” Adding another twist, Congress specified that the money be spent “in cooperation with” a new NIH global AIDS vaccine program. NIH's Edmund Tramont, who organized the program, says anything it supports “has to pass a scientific review.”

    The $10 million earmark has been folded into the massive omnibus appropriations bill (see p. 1636) that the U.S. Congress is expected to pass in January.

  4. ITER

    E.U. Puts France in Play for Fusion Sweepstakes

    1. Daniel Clery*
    1. With reporting by Xavier Bosch in Barcelona.

    CAMBRIDGE, U.K.—The race to land one of the biggest prizes in experimental physics is coming into the home stretch. Last week, after much delay, the European Union (E.U.) chose Cadarache, France, as its candidate site to host the International Thermonuclear Experimental Reactor (ITER), a $5 billion test bed for harnessing nuclear fusion to generate electricity.

    ITER will be twice the size of any existing fusion reactor if it comes on line, as scheduled, around 2014. It aims to show that such a machine can generate more power than it consumes for extended periods and so pave the way for fusion power stations. The decision has allowed E.U. officials and representatives from the other ITER partners—Canada, China, Japan, Russia, South Korea, and the United States—to begin deliberations on the final choice for siting the giant project. Cadarache and Rokkasho, Japan, are now the main contenders; an agreement is expected before the end of the year.

    The ITER partners had hoped to have the site and financial details sewn up by last summer, but the process got bogged down in part by the war in Iraq and the SARS epidemic. Perhaps the biggest impediment, though, was the E.U.'s impasse over whether to put forward Cadarache or Europe's other contender, Vandellòs in Spain. A technical report by David King, the U.K. government's science adviser, concluded that both would be excellent hosts, but it did not pick a favorite (Science, 12 September, p. 1456). E.U. ministers in September couldn't decide, either. As the pressure mounted, Spain, the underdog because of its comparative lack of fusion experience, offered late last month to double its financial contribution to ITER.

    Then there were two.

    Cadarache (above) is going head-to-head with Rokkasho, Japan, in bid to land ITER.

    CREDIT: © CEA CADARACHE

    Ending the suspense, the E.U.'s Competitiveness Council on 26 November opted for France. Spain, as runner-up, will host the European Fusion Agency, the administrative center of Europe's contribution to ITER, and one of two European ITER directors will be a Spaniard. The consolation prize has failed to console Spanish officials. Andreu Mas-Colell, head of research for the government of Catalonia, where Vandellòs is located, labeled the decision “another demonstration of the power of the French-German axis.” But at a press conference, science minister Juan Costa was more philosophical: “It's not the gold medal, but it's still a medal since our participation will be most relevant.”

    The predominant mood across Europe is one of relief. “We're delighted. At last we have a single European site,” says Alex Bradshaw, head of the Max Planck Institute for Plasma Physics in Garching, Germany's largest fusion research facility. Cadarache is popular because it is already home to France's fusion program. “It is a significant advantage siting next to an existing institution, to have a scientific life and a pool of experts to draw on,” says Christopher Llewellyn-Smith, head of the U.K. fusion program in Oxfordshire. The lack of an E.U. champion, he adds, “was holding things up a bit. Lots of countries are ready to approve ITER. … We have to seize the moment.”

    That moment is at hand, with the ITER partners set to meet in Vienna after Science went to press. But negotiations were not expected to be easy. “I don't know how we are going to reach a decision” on a site, says E.U. delegation leader Achilleas Mitsos, director-general of research at the European Commission. “We must rely on consensus.” The Rokkasho site, in the north of Japan's main island, is next to a newly built nuclear fuel-recycling facility. A third candidate, Clarington in Canada, is likely to be discounted because of a lack of support from Canada's federal government.

    According to Mitsos, the cost-sharing arrangements are nearly set. The host country will foot 20% of the bill to cover construction and infrastructure. The remaining 80% will be shared among the partners. Much of the payment will be in-kind contributions of reactor components.

    A potential stumbling block is that the U.S. delegation does not want to enshrine the ITER agreement in a treaty, which would require the United States to guarantee its funding for the project's duration and would impose liability and arbitration measures in case of a dispute. Other partners “want commitments to be as permanent as possible,” says Mitsos. But he thinks this will not be a showstopper, as long as the partners can reach a long-sought agreement over basics such as where to put the machine and how they'll pay for it.

  5. SPACE-BASED ASTRONOMY

    NASA Draws the Line at Servicing Hubble

    1. Andrew Lawler

    The Hubble Space Telescope has done wonderful science, thanks to occasional shuttle flights that have kept it operating and upgraded its instruments. NASA has one more repair mission on the books for the 13-year-old machine, but astronomers have been pushing hard for a second rendezvous later in the decade. Last month, however, their high hopes were dashed.

    Talk of a second mission is “superfluous” and “absolutely premature,” says NASA space science chief Ed Weiler, citing its high cost, delays in the currently scheduled mission, and an unexpectedly durable Hubble itself. The agency's space science advisory committee, whose members represent all the disciplines involved in space exploration, agrees. “The real issue is the next mission,” says Andrew Christensen, chair of the panel. Those statements are a blow both to Hubble supporters and to a blue-ribbon panel that concluded in August that an extra flight could be scientifically worthwhile—if it could compete successfully with other NASA projects.

    Launched in 1990 and first repaired in 1993, Hubble was slated to be serviced for the last time in 2004 and then returned aboard the space shuttle around 2010. That would coincide with the launch of the James Webb Space Telescope. But the servicing mission will be delayed until at least 2006, and possibly until 2008, because of the problems with the shuttle fleet, says Weiler. And a second flight would not come cheap. NASA now estimates that a second servicing mission would cost from $600 million to $1.2 billion, Weiler adds. The lower-end estimate would pay for doing basic maintenance, and the higher-end one for changing out a host of scientific instruments.

    A seven-member panel led by Princeton University's John Bahcall endorsed a second mission to provide Hubble with the instruments it needs to explore a fresh set of research questions. Such a mission, it added parenthetically, could be competed in the Explorer or Discovery programs, which fund small- and medium-class space missions (Science, 22 August, p. 1029).

    Power walk.

    Astronauts John M. Grunsfeld and Richard M. Linnehan replace a second-generation solar array on the Hubble Space Telescope.

    CREDIT: NASA

    That suggestion struck a nerve among other space scientists, however. NASA's Sun-Earth Connection Advisory Subcommittee, for example, warned Christensen in an 11 November letter that the Bahcall panel's recommendation would subvert the Explorer program and have a “drastic negative impact” on solar research. On 17 November, Jonathan Lunine, an astronomer at the University of Arizona in Tucson, told the space science advisory committee at its meeting at Ames Research Center in Mountain View, California, that funding Hubble from the Discovery program would consume three to five other potential Discovery missions. That would represent a 5- to 7-year delay in the program, he estimated.

    Bahcall panel members cried foul. In a 16 November letter to the same advisory committee, they insisted that their intent was merely to ensure a peer-reviewed competition with similar-sized missions while protecting existing projects. “We didn't have firm cost estimates” for the servicing mission, adds Chris McKee, an astronomer at the University of California, Berkeley, who served on the Bahcall committee. The exact cost of the mission would depend on the extent and complexity of new instrumentation, but McKee acknowledges that a $600 million-plus mission “would have a devastating effect” on other potential Explorer and Discovery missions.

    One astronomer, who requested anonymity, accuses NASA of rallying the space science community against the additional Hubble mission by sending out e-mails last month alerting researchers to the issue. Weiler has long been critical of keeping Hubble operating past the time the James Webb Space Telescope is launched early in the next decade. But he insists that a second servicing mission could still be proposed as part of a competition next year.

    Weiler says that delaying the scheduled repair mission may even have a silver lining: A later flight means a longer life for Hubble. In addition, scientists at the Space Telescope Science Institute in Baltimore, Maryland, believe that Hubble could carry out most tasks with two gyroscopes (four of six are currently operating), although high-resolution data gathering would not be possible without the stability of at least four.

    “We've only lost two [gyroscopes] in the past 4 years,” says Weiler. “There's a damn good chance that we could make it to 2006 doing science.” But the delay in the next mission also increases the chance that Hubble could lose all its gyroscopes in the intervening period, forcing a suspension of all research operations.

    It's not hard to see why Weiler would resist an additional servicing mission. He must devise a plan to keep Hubble from crashing to Earth, because NASA's new rules for operating the shuttles won't permit it to retrieve the heavy payload. Finding an alternative—possibly a space tug that would nudge it into a safe path of destruction in Earth's atmosphere—could cost $300 million. In the meantime, maintaining a Hubble servicing operations center at Goddard Space Flight Center in Greenbelt, Maryland, costs NASA $8 million to $9 million a month.

    But any mission might not even be feasible. Because Hubble flies in a different orbit than the space station does, the shuttle would have no safe haven in case it developed a problem such as the tile damage suffered by Columbia at launch. That's a problem in NASA's post-Columbia world.

    For all those reasons, Weiler believes “there is no rush” for an additional Hubble flight: “My goal is a servicing mission by 2006.” For now, most of the space science community shares that near-term vision.

  6. MANTLE DYNAMICS

    Mantle Plumes Both Tall and Short?

    1. Richard A. Kerr

    For 3 decades, researchers have been debating whether plumes of hot rock rise through Earth's mantle. Geologists and geochemists have inferred deep plumes from traces left at volcanic hot spots such as Iceland and Hawaii. And some seismologists have suggested that they could glimpse a plume or two in their seismic “CT scans” of the mantle. Even so, plumes have stubbornly remained an appealing if unproven concept. Now, as reported online this week by Science (www.sciencemag.org/cgi/content/abstract/1092485), a group of seismologists offers evidence of not one or two plumes but 32. Some of them span the mantle 2900 kilometers from core to crust; others hint of a surprisingly shallow origin less than 1000 kilometers down.

    These seismologists are confident that they've made a breakthrough in plume studies. “This is the first work that really confirms what [plume originator] Jason Morgan said,” says seismologist Raffaella Montelli of Princeton University, first of six authors of the paper. “We are providing visual proof plumes exist.” Other seismologists are more cautious. “I think it is fair to at least suspect that they are overinterpreting their data set,” says seismologist Barbara Romanowicz of the University of California, Berkeley. Until several technical questions are resolved, she says, “I think it is a leap of faith to claim a discovery” of dozens of plumes.

    The Princeton report is getting a circumspect reception not just because of the startling number of plumes it claims. It is also introducing a new way of analyzing the seismic waves that are combined to form an image of Earth's interior. In conventional seismic tomography, seismic waves arcing through the mantle from earthquake to seismometer are considered to follow curved lines called ray paths. Where numerous ray paths traverse hotter than normal rock, the waves are slowed and an anomalously warm spot appears in the image.

    But thin, warm structures—such as the supposed plumes—would be particularly difficult to image in the conventional manner. So Montelli and her colleagues—especially Anthony Dahlen and Guust Nolet of Princeton—developed an analysis that let them take into account how seismic waves actually travel, spread across a wave front rather than along a single line, or ray path (Science, 3 January, p. 35). By taking into account wave-front energy radiating into a ray path and washing out a slow signal, this “finite frequency” technique boosted the strength of signals from plumelike structures by 30% to 60% and more. They also combined the usual short-period waves with long-period waves, which sense temperature variations farther off their ray paths. That increased sensitivity to plumes missed by short-period waves.

    A short one.

    The plume (red-brown) seismically imaged beneath Iceland begins at 660 kilometers.

    CREDIT: R. MONTELLI ET AL.

    The Princeton technique shows plumes beneath most classic volcanic hot spots. In addition to the two broad superplumes that everyone sees, beneath Africa and the South Pacific (Science, 9 July 1999, p. 187), the new method also shows narrow plumes rising off them, sometimes splitting before reaching the surface. Elsewhere, it shows lone plumes stretching from near the core-mantle boundary to the surface. But other plumes appear to rise from about 660 kilometers deep, the traditional boundary between the upper and lower mantle. A few hot spots, including Yellowstone, seem to lack plumes. And in a major surprise, the plumes beneath two of the most classic of hot spots, Iceland and Galápagos, begin at about 660 kilometers rather than at the bottom of the mantle as they had appeared to (Science, 14 May 1999, p. 1095).

    This two-tiered plume population suggests to Montelli and her colleagues that rising plumes recognize some sort of mantle division about 660 kilometers down. A long-standing view of mantle workings had an impenetrable barrier at 660 kilometers, but seismic tomography has lately called that division into question by showing that at least some descending slabs of oceanic plates sink below that depth. If plumes originate at 660 kilometers, there may be enough of a barrier there—perhaps a large, sharp change in the stiffness of mantle rock—to block most mantle material and seriously impede all but the densest slabs.

    Redividing the mantle may be premature, say other seismologists. “I am very skeptical this will be the final answer,” says seismologist Jeannot Trampert of the University of Utrecht, the Netherlands. Seismic data are so patchy—the earthquakes are concentrated in a few belts, and the seismometers are few and far between across oceans—that “telling what is down there using tomography is very hard,” says Trampert. “There are many solutions possible with a given data set.” They've done the best job anyone can do, he says, but plumes depend to some extent on the choice of adjustable parameters; others might get different results with their choices. And the tests used to check on what the method can and cannot see “don't tell you if plumes exist in the real Earth,” says Trampert. “The true Earth may have something the data don't see.” Better data and more analyses, he says, are needed.

  7. NONPROLIFERATION

    Radioactive Sources Move From a Concern to a Crisis

    1. Richard Stone

    CAMBRIDGE, U.K.—First it came to light last month that raiders along northwestern Russia's Arctic coast had broken into two lighthouses and ripped apart thermoelectric generators packed with intensely radioactive strontium-90, a material of choice for would-be dirty bombers. Then, if that didn't make nonproliferation experts jittery enough, in an unrelated incident 2500 kilometers to the south, an unknown but highly radioactive source was apparently melted down by private individuals in Transdniester, a breakaway region of the former Soviet Republic of Moldova. As Science went to press, the International Atomic Energy Agency (IAEA) in Vienna had dispatched an emergency mission to Transdniester to identify the source—and secure it.

    The incidents send a chilling message: Urgent efforts to gather up loose radioactive objects are lagging badly in parts of the former Soviet Union (FSU). Heightening the perceived threat, documents seized in Afghanistan in late 2001 indicate that Al Qaeda has sought such materials with the intention of constructing a radiological dispersal device, or dirty bomb.

    The vandalism of the Arctic lighthouses first came to light on 12 November, when authorities in the Murmansk region reported that the Hydrographic Service of Russia's Northern Fleet discovered damage at a lighthouse north of Murmansk on the Kola Peninsula. It was powered by a radioisotope thermal generator (RTG), which draws power from heat emitted by strontium-90. The unit's steel-and-aluminum casing and its depleted uranium shielding were gone, and its strontium-filled canister lay submerged nearby in shallow water. The next day the team found similar destruction, including a second discarded canister of strontium, at another Kola lighthouse. Late last month the Northern Fleet gathered up the canisters, says Rashid Alimov of the St. Petersburg office of Bellona, a Norwegian environmental foundation. This is only the latest in a string of such incidents chronicled in a 24 November Bellona report.

    Dereliction of duty.

    These RTGs were abandoned on the Kola Peninsula.

    CREDIT: FINNMARK REGION GOVERNMENT

    The Arctic lighthouses have long been a bête noire for antiterrorism experts. When built in the 1970s, each RTG contained between 30,000 and 180,000 curies' worth of strontium, depending on the intended use. (Approximately 40,000 curies of strontium-90 was released during the 1986 Chornobyl explosion and fire.) With a half-life of 29 years, the strontium-90 in Russia's 1000-odd RTGs in operation or at large today remains highly radioactive—and highly vulnerable. “They're just sitting there ripe for the plucking,” says health physicist Joel Lubenau, a senior adviser to the Center for Nonproliferation Studies at the Monterey Institute of International Studies in California.

    IAEA deems the loose RTGs a grave threat. “This source is dangerous and one of the most worrying for us,” says Abel Julio González, director of IAEA's division of radiation and waste safety. In January 2002 the agency launched an operation to hunt down abandoned RTGs in the Republic of Georgia (Science, 1 February 2002, p. 777). Later that year IAEA, Russia, and the United States inked a deal to work together to round up RTGs and other orphaned sources—including truck-mounted seed irradiators filled with cesium-137 powder—throughout the FSU, outside Russia. “My gut feeling is that we have identified most of the major sources,” says González.

    View this table:

    Dealing with derelict RTGs is a high priority, according to a new ranking by a team at Los Alamos National Laboratory in New Mexico (see table). Its September report also reveals that orphaned RTGs are not solely a Soviet legacy: Of 134 strontium-90 RTGs made in the United States, the report states, only 47 have been accounted for. Among other unsung threats, the Los Alamos team highlights new types of truck-mounted irradiators. One model “of particular concern,” the report notes, is a 67-ton irradiator used for treating crops or for research purposes and made by the Beijing Institute of Nuclear Engineering. It contains a staggering 250,000 curies of cesium-137.

    The Los Alamos report weights risk according to how vulnerable a source is to theft. That is what's particularly unnerving about the drama playing out in the rebel republic of Transdniester. The contraband had not been identified as Science went to press. What happened was “probably not malevolent,” says González. Cold comfort, perhaps, considering the radioactive smorgasbord around the world that has yet to be secured.

  8. IRAQ

    Researchers Look West to Model New Academy

    1. Richard Stone

    LONDON—Capping a month of new science initiatives in Iraq, a dozen top Iraqi-born researchers convened here at the U.K.'s Royal Society last week to establish the Iraqi National Academy of Science (INAS). The organization, in the style of Western academies, is intended to be an independent source of funding for Iraqi scientists and of advice to the government. But with autonomy comes poverty: Its leaders say they will have to go cup in hand to sister academies and research institutions.

    INAS seeks to supplant what was, by many accounts, a vile predecessor. The original academy, a Soviet-style network of institutes established in 1947, lost all integrity during the reign of Saddam Hussein, says chemist Ghazi Derwish, science chief of a standing committee that will run INAS until an assembly approves a charter and elects officers in 2004. “The linkage with the presidential palace became so strong as to transform the academy into merely a mouthpiece of the regime,” he asserts.

    INAS—to be headquartered in Baghdad after security improves—will make a clean break with the past, according to Derwish and the other founding fathers. (They are all men.) That has translated into tough ground rules on whom they will support and proffer membership to. The country's nuclear physicists never managed to concoct an atom bomb, so they're in the club. (Jafar Jafar, head of Iraq's nuclear program under Saddam Hussein, who fled to the United Arab Emirates on the eve of the coalition invasion, was invited to the London meeting but had his visa revoked by the U.K. Foreign Office at the last minute.) Chemical and biological weaponeers won't be admitted. Others in the natural sciences, medicine, and engineering: Welcome aboard, your services are vital to rebuilding the country.

    Such a hard moral line is unsurprising considering that the force majeure behind the academy's revival is Hussain Al-Shahristani. Iraq's chief nuclear chemist in the 1970s, Shahristani was jailed for more than a decade before escaping from prison during the first Gulf War in 1991 (Science, 22 November 2002, p. 1543). One of INAS's “main tasks,” says Shahristani, chair of the standing committee, is to reverse the “serious depletion of civil science” after years of being yoked to military objectives. “Some people took a stand against that approach and had to pay dearly,” he says, speaking from experience. But INAS has no plans to investigate war crimes or misdeeds, he says: “That's for others to do.”

    INAS joins two other Iraq science initiatives rolled out last month. The Coalition Provisional Authority set up a science ministry, and the U.S. Department of State leaked plans for a new fund for former weapons scientists (Science, 21 November, p. 1307).

  9. INVERTEBRATE PALEONTOLOGY

    Gutsy Fossil Sets Record for Staying the Course

    1. Erik Stokstad

    Over the past half-billion years, evolution has dished up an almost endless variety of novelties: lungs, legs, eyes, wings, scales, feathers, fur. So when paleontologists find a creature that doesn't change, they take note.

    Witness Colymbosathon ecplecticos. Colymbosathon was an ostracode: a tiny crustacean with a clamlike carapace. Fossil ostracode shells are so common and so varied that geologists use them to date and analyze rocks. On page 1749, however, paleontologists describe a much rarer specimen: one that reveals the oldest soft tissue known for an ostracode. The 425-million-year-old fossil preserves a jaw-dropping amount of detail, including gracile limbs used for swimming and the oldest penis in the fossil record. What's most amazing, ostracode experts say, is how eerily similar the soft-tissue anatomy is to that of modern relatives. “I was flabbergasted,” says Koen Martens, a zoologist at the University of Amsterdam, the Netherlands.

    The 5-centimeter-long specimen comes from a remarkable deposit of Silurian-age fossils in Herefordshire, U.K. The marine animals were buried in volcanic ash, then rapidly mineralized within nodules that preserved their bodies in three dimensions. A few years ago, a team of paleontologists—David Siveter of the University of Leicester, U.K.; Derek Siveter and Mark Sutton of the University of Oxford, U.K.; and Derek Briggs of Yale University—figured out a way to reveal the intricate detail. They grind the rock away, photographing polished cross-sections as they go. Then they assemble the digital images into a three-dimensional reconstruction, a technique that has already uncovered a strange, soft-bodied mollusk (Science, 23 March 2001, p. 2292), a king crab arthropod, and a bristle worm.

    Family resemblance.

    Soft tissue of this fossil (top) closely mirrors that of a modern ostracode.

    CREDIT: D. SIVETER ET AL.

    Colymbosathon is the latest wonder from this trove. “The whole animal is amazing,” David Siveter says. “We've got something we could only dream about.” Features include limbs used for sensing, feeding, and swimming; a “furca,” probably used to grasp prey and carrion; and a stout copulatory organ. (The creature's name is Greek for “amazing swimmer with a large penis.”) Six pairs of gills help peg it as a member of a living family called the Cylindroleberididae, David Siveter says.

    Some ostracode specialists are stunned. “This is a demonstration of unbelievable stability,” says Tom Cronin of the U.S. Geological Survey in Reston, Virginia. Whereas ostracodes diversified into some 33,000 living and extinct species, “these guys have just been plodding along totally unfazed.”

    Finding a modern cylindroleberid in the Silurian clashes with molecular data, which suggest that the group and related families originated relatively recently, says evolutionary biologist Todd Oakley of the University of California, Santa Barbara. There's no conflict for zoologist Anne Cohen, a research associate at the California Academy of Sciences in San Francisco, who thinks Colymbosathon actually belongs to a long-extinct family. In any case, the new fossil indicates that a basic ostracode body plan was already present in the Silurian. It could also help sort out evolutionary relationships of fossil ostracodes.

    The Herefordshire specimens may reveal other long-lost evolutionary blueprints, says David Horne of Queen Mary College in London: “The probability that they will find similarly preserved representatives of other ostracode lineages, and of other arthropods, is both high and extremely exciting.”

  10. SYSTEMS BIOLOGY

    Tracing Life's Circuitry

    1. Elizabeth Pennisi

    A new movement aims to integrate biology, mathematics, and engineering; even if its objective is hard to define, it is all the rage in the academic world

    In September, Harvard University opened its medical school's first new department in 20 years. Its focus: systems biology, one of the hottest—and most elusive—new fields in biology. The nearby Massachusetts Institute of Technology (MIT) had already started a Computational and Systems Biology Initiative with 80 faculty members. And the Weizmann Institute of Science in Rehovot, Israel, is following suit, planning its own systems biology institute. All are forging links between biologists, mathematicians, and engineers. Systems biology is fast becoming the academic topic du jour.

    Fueling this movement is a gush of data. New technologies have inundated researchers with a deluge of information on genes, proteins, cellular dynamics, and organisms' responses to mutations and the environment. But they haven't explained what makes whole organisms tick. Systems biologists are taking on that challenge, relying heavily on mathematics and statistics to integrate data into a more complete picture of how biological networks from cells to whole organisms function. They are building models and making predictions about how biological systems will behave; the ultimate goal is to understand deep mysteries—such as how cells divide, animals develop, plants flower, and humans breathe.

    There's a new world coming, says one of the proponents, David Galas, a molecular biologist at the Keck Graduate Institute in Claremont, California. “It seems to me,” he says, “this is the beginning of real biology.”

    Data deluge

    Indeed, the systems approach may be just what biology needs to keep afloat. The amount of genomic data in the public database at the National Center for Biotechnology Information doubles every 18 months. There are now some 1200 person-years of experimental data on the role of a few genes in the development of the fruit fly alone, says theoretical biologist Garrett Odell of the University of Washington, Seattle. All of this is forcing people to adopt “a new way of doing biology,” says Manoj Samanta, a computer scientist at NASA Ames Research Center in Moffett Field, California.

    Given the sense of urgency, systems biology seems to be on everyone's lips. In early November, the National Science Foundation (NSF) and the National Institutes of Health (NIH) held workshops on the topic. In St. Louis, Missouri, more than 500 researchers swapped ideas and research results at the 4th International Conference on Systems Biology. “There is a real possibility of building knowledge from [the] molecular level to the system level,” says NSF's Mitra Basu, a computer engineer.

    Bewildering beauty.

    This rendering shows the protein actin's various chemical states (green) and the molecules and reactions that alter those states (yellow).

    CREDIT: JOHN CARSON/UCHC

    Challenges lie ahead, however. For one, there needs to be true collaboration. Engineers and computer experts need to remember that “you can't do systems biology without a detailed understanding of the biology,” warns Leslie Loew, a cell biologist at the University of Connecticut Health Center (UCHC) in Farmington. Leaders in this field are struggling to develop common standards, communicate across disciplines, and overcome bewilderment among department heads and grant reviewers. At the same time, Sydney Brenner warns, the movement needs to take care not to get infatuated with data for its own sake. A Nobel laureate at the Salk Institute for Biological Studies in La Jolla, California, Brenner suggests that “if we do not define the problem [first], we won't know what information is important.” He rejects the idea that one can “make a lot of measurements and something will come of it; I think that's rubbish.”

    Nonetheless, the maturing of molecular biology, new data-intensive techniques, increased computer power, and new algorithms “have changed people's attitudes about how they think about [biological] problems,” says Galas. Researchers are increasingly willing to apply engineering concepts to biological systems. Such innovation is essential, says John Hasty of the University of California, San Diego (UCSD), because “uncovering the structure and function of genetic regulatory networks has become one of the central challenges of the postgenomic era.”

    Back to the future

    Although the pioneers may constitute a small circle, “systems biology should not be and will not be an elite club,” says Arcady Mushegian of Stowers Institute for Medical Research in Kansas City, Missouri. Many scientists may already fit under the movement's banner. Biochemists, for example, have spent decades piecing together metabolic pathways. Neurobiologists have traced neural networks in moths, squid, and other organisms. In truth, “systems biology is in the eye of the beholder,” concedes proselytizer Leroy Hood, president of the Institute for Systems Biology in Seattle.

    Physiologists have long tried to understand how life works by collecting detailed quantifiable information on biological stimuli and responses. But modern systems biology is different, say proponents. “It's not just cataloging parts or even interactions, but asking, ‘How do new functions arise? How do you look for stuff that's not evident [from] the details?’” explains Joseph Nadeau of Case Western Reserve University in Cleveland, Ohio. Adds Hiroaki Kitano, a systems scientist at the Japan Science and Technology Corp. in Tokyo and a pioneer of systems biology in his country: “It focuses on the dynamics and properties that arise out of interactions.”

    Couching biology in terms of an information system and analyzing the system mathematically is an essential part of the new approach. Alan Hodgkin and Andrew Huxley pioneered this technique 50 years ago, using a mathematical description and circuit diagram for nerve cells in squid, with some success in predicting how the neurons worked. Models have grown more detailed since then, and researchers have learned that the more data they incorporate, the more accurately they can predict complex biological responses such as changes in gene expression. Eventually, says Sean Athey, a computational biologist at the University of Michigan, Ann Arbor, “these models will allow us to get at fundamental theories.”

    The 1990s saw a steady growth in the sophistication of the systems approach. “What really propelled systems biology was the Human Genome Project,” Hood explains. Essential to that effort was new software that could analyze whole genomes and other large biological data sets. It was the dawn of high-throughput biology, first applied to DNA sequencing and later to studies of gene expression and protein interactions. According to Hood, the genome project demonstrated that biology is really about information systems.

    Although the transition was gradual, systems biology by the mid-1990s had become a mathematics and data-intensive world. In 1995, Harley McAdams and Lucy Shapiro of Stanford University School of Medicine built a model of electrical circuits to examine certain behaviors of a phage, a bacterial virus. It helped them determine why a phage kills the host cell rather than inserting its genetic material into the host's genome. After refining the model, they checked their ideas about how environmental changes affect this behavior by tweaking the model and seeing if their intuition was right.

    Two years later, Stanislas Leibler of Rockefeller University in New York City and his colleagues melded quantitative experimental data with modeling to predict the ability of certain bacteria to orient themselves to specific chemicals; they used quantitative information such as the concentration of the attractant in their analyses. The data-rich analysis revealed that chemotaxis was driven by feedback within the phage-chemical network and not by the concentration of individual molecules. Since then, Leibler and others, particularly Naama Barkai and Uri Alon of the Weizmann Institute, have continued to refine the data and the models. Leibler did more than describe a system; he “really explained the design principle,” says Marc Kirschner, chair of Harvard's new department. “He showed that this system did some things very well—and some things very poorly.”

    In another data-intensive study 3 years ago, Hood and his colleagues tackled gene activity in yeast's sugar metabolism. They changed the yeast's diet from raffinose to galactose, knocked out one gene at a time, and watched to see how gene expression and protein activity changed. Aided by microarrays, mass spectrometry, and computers, they identified 1000 relevant genes and grouped them according to how they and their messenger RNA changed during the experiment. Hood's group merged the results with the protein data to build a model explaining how yeast adapts to a galactose diet, and the model correctly mimicked experimental results. The work illustrated that “it's now possible to really do systems biology seriously,” says Galas.

    Model building is one of the chief objectives of systems biologists, who dream of being able to make verifiable predictions about living things just as physicists make predictions about matter. Eric Davidson, a developmental biologist at the California Institute of Technology (Caltech) in Pasadena, says that the model he created of sea urchin development has made accurate predictions about how regulatory DNA alters its activity in response to genetic mutations.

    Multidimensional biology.

    The systems approach builds models based on data from all levels of biology: gene expression, protein locations in the cell, models of cell function, and computer representations of organs and organisms.

    CREDITS: (CLOCKWISE FROM TOP) SCIENTIFIC COMPUTING AND IMAGING INSTITUTE/UNIVERSITY OF UTAH; C. R. JOHNSON/UNIVERSITY OF UTAH; L. LOEW/UCHC; LLMPP/NIH; R. MURPHY/CARNEGIE MELLON UNIVERSITY

    Davidson's group uses a variety of experimental data: descriptions of developmental pathways, known genes, and regulatory DNA discovered through experiments that disrupted normal gene function. The researchers have pinpointed connections between various genes and regulatory regions. For example, they have detected proteins from the mother that stimulate the formation of the endoderm in offspring. Then they observed repressor proteins setting limits on where endoderm appeared.

    It's a big step to go from modeling gene networks to modeling organs and other large systems, but that's what Case Western's Nadeau is trying to do. He and his colleagues first measured various aspects of heart function in about 20 mouse strains. Using a sophisticated statistical technique, they got results that fit with what was already known about how traits change in concert—such as the correlation between ventricle mass and size during contraction and expansion. “It was a proof of principle,” Nadeau says. “Sooner or later, we are going to have to understand how different organs interact in health and disease.” He is now using this approach to evaluate traits that affect responses to high-fat diets.

    First principles

    Like Nadeau and Davidson, many others are sifting through molecular networks in search of coherent patterns of stimulus and response. C. H. Luo and Yoram Rudy of Case Western, for example, have begun using a model of the heart for clinical studies, helping evaluate congestive heart failure patients for gene therapy. Stanford's Deborah Gordon is using a systems approach on ants to study how individuals “know” when to alter their activity according to the colony's needs. Developmental biologists are modeling how limbs form in embryos; plant researchers are looking at the timing of root development.

    Others are trying to develop explicit rules for these networks. Uri Alon, a physicist-turned-biologist at the Weizmann Institute, is trying to apply circuit theory to biological systems, taking the field a step closer to engineering. His analysis of a transcription network in bacteria, for example, identified specific network components—often called motifs—that were used repeatedly in studies that range from neural networks to whole ecosystems.

    Models make a difference.

    Mice (bottom), sea urchins (top), and other animals that can be genetically altered help researchers make sense of the role of individual genes in life's circuitry.

    CREDITS: (TOP TO BOTTOM) SHERRY BALLARD/COPYRIGHT CALIFORNIA ACADEMY OF SCIENCES; J. NADEAU/CASE WESTERN RESERVE UNIVERSITY

    This work “raises the possibility that complex network behavior can be broken down and understood in terms of individual motifs,” which serve an important purpose, Alon says. They can buffer against misinformation and, in the case of transcription networks, help make sure that genes are expressed in the right order and at the right time.

    “The similarities between evolved circuits and engineered circuits raise the hope that there are deep laws of nature” that unite living and designed systems, Alon adds. But, he cautions, there are differences. Physical systems “just sit there,” whereas “biological systems produce beautiful machines that dance, work perfectly despite cellular noise, and dissolve when they are done.” He thinks the “rules” of biology will remain somewhat elusive.

    All systems go?

    Although systems biology has come a long way since the days of Hodgkin and Huxley, it is still in its childhood. And because the field has been sprouting independently in labs across the globe, it lacks coherent standards for experimental procedures and computer programming. That, say its proponents, could be crippling in the long run.

    Some also worry that researchers have little incentive to share all relevant information and maintain databases. Already, the Internet is full of ghost sites that have languished untended after their creators lost interest or support. “We don't want data to go away when the grant is over,” says UCSD bioengineer Shankar Subramanian. Databases and simulation programs need to be more compatible and convenient, says Eugene Bruce, a biomedical engineer at the University of Kentucky, Lexington. There are so many data on the Web in so many places, “I really get a sense that people are a little overwhelmed,” Bruce adds.

    Help may be on the way. Several groups are maintaining high-quality databases on complex processes, such as cell signaling. The Signal Transduction Knowledge Environment maintained by Science is an expanding database that makes cell signaling easily accessible. Two others are running: the Alliance for Cellular Signaling led by the University of Texas Southwestern Medical Center in Dallas and the Kyoto Encyclopedia of Genes and Genomes in Japan. Meanwhile, the Systems Biology Markup Language (SBML) consortium led by Mike Hucka of Caltech is helping establish common terms. SBML seems to be establishing a “de facto standard,” says Kitano of the Japan Science and Technology Corp. About 30 simulators and analysis tools now follow its guidelines.

    Hearts and minds

    One of the biggest remaining obstacles is also one of the most intractable: integrating disciplines. Even though universities have made some progress building bridges, it's still hard to get mathematicians to “understand what biologists really need” or to get computer scientists and molecular biologists to speak a common language, says Bruce.

    At the NSF and NIH meetings, some researchers argued that only if changes are made in graduate and medical school curricula will the field move forward. They also recommended that peer reviewers be educated about how to evaluate systems biology proposals. The two agencies, they said, should support short courses in systems biology as well.

    Some of these and earlier recommendations have already led to action. This fall NIH established two study sections focused on computational biology. At the same time, NIH and NSF are scrambling to beef up funding. NIH, for example, has set aside $12 million in 2004 for computational biology centers to develop tools for experimental researchers. In 2005, NIH plans to fund both young and seasoned investigators who want to plunge into quantitative work.

    On another front, NSF is pushing computer scientists to take a look at biology. Next year it will award its first grants to researchers to develop computational models driven by biology. The budget has not yet been established. It's an exciting prospect for computer people, NSF's Basu explains. Most software programs are primitive compared to living systems, and insights from biology could greatly improve their quality.

    Major institutions are not waiting. Harvard's new center should grow over the next decade to 25 faculty members, says Kirschner. Training students will be a key focus. MIT has received a gift of equipment from IBM and a $16 million NIH Centers of Excellence grant to jump-start its program. Over the past 2 years, UCSD has hired eight faculty members, all focusing on systems biology and bioinformatics. In November, Stanford licensed a new Web-based computer program to boost its ability to analyze complex genomic data. At Princeton University, David Botstein is pushing his genomics institute to focus more on systems approaches.

    Andreas Wagner of the University of New Mexico in Albuquerque sums it up: “[Systems biology] is in fashion right now,” and everyone “is jumping on the bandwagon.”

  11. THEORETICAL PHYSICS

    At Canada's Perimeter Institute, 'Waterloo' Means 'Shangri-La'

    1. Charles Seife

    Four years ago, a wealthy CEO set out to create a paradise for physicists. Now researchers are starting to live his dream

    WATERLOO, ONTARIO—A mathematician, the saying goes, is a device for turning coffee into theorems. At the Perimeter Institute for Theoretical Physics, beer seems to be the brain food of choice. This is only to be expected. After all, it's built around a bar.

    The institute's building is a converted restaurant, and it's as funky and trendy as a physics research institute can be. Although the common room on the second floor has the requisite chalkboards on every wall, it also has plentiful beer and munchies for the residents. There's usually a postdoc or two plunked down on the floral-print couches, missing a bank shot on the pool table, or bellied up to the always-stocked bar. Much of the time, they're even talking about physics.

    In 3 short years, the Perimeter Institute in Waterloo, Canada—about 100 kilometers west of Toronto—has become a world leader in theoretical quantum physics. It is attracting bright young talent from across the globe, hiring prominent physicists in quantum theory and string theory, and providing fertile ground for the exchange of theoretical ideas. It's also become a paradise on Earth for the postdocs and faculty members lucky enough to get an appointment there. Beer isn't the only lure: There's also sufficient money to bring visitors in, a freewheeling atmosphere of intellectual inquiry, and a chance to play a significant role in shaping an institution as it grows. “We're very spoiled here,” says Ivette Fuentes-Guridi, who is 1 year into her 3-year postdoc position. “I don't know how I'm going to go anywhere else.”

    The Perimeter Institute was born in September 2000, thanks to a C$100 million (US$75 million) grant by Mike Lazaridis, CEO of Research in Motion (RIM)—the company that makes the ubiquitous Blackberry wireless communications device. (Two colleagues also chipped in C$10 million each, and since then, Canada has invested a few tens of millions.) According to Lazaridis, the institute is something that he's been dreaming about since his idealistic student days at the University of Waterloo. “Once a century or so, you get a major scientific breakthrough that drives social change,” says Lazaridis, yet the theoretical research that leads to those breakthroughs often goes begging. “The climate is set up such that results are the name of the game. It's easy to get business to fund research that will pay off in 1 or 2 years; government will fund research that pays off in 10 years. How do you handle the stuff that's generational?”

    Northern lights.

    Young physicists drawn to Perimeter include (left to right) Robert Myers, Olaf Dreyer, Lee Smolin, Simon Ross, Oliver Winkler, and Fotini Markopoulou Kalamara.

    CREDIT: PERIMETER INSTITUTE

    Two decades after leaving the university's electrical engineering program to found RIM, Lazaridis unveiled his answer: an independent Canadian center for undirected research into the foundations of physics. In 1999, he appointed a nine-person board of advisers to frame the institute's research agenda and set about hiring a director. To universal surprise, he picked an unknown: Howard Burton, who had recently earned a Ph.D. in theoretical physics and was in his late 30s. Burton had been planning to abandon academia for a career in mathematical finance. “But I got cold feet,” he says. Instead, he began sending his CV to the CEOs of various technology companies—including RIM, where Lazaridis had just decided to forge ahead with the institute. “I decided that I wanted to do this thing, and serendipitously, within 2 weeks, I had this letter saying, ‘Please save me from my fate in derivative trading,’” Lazaridis recalls. He interviewed Burton and soon established a rapport. “The first step was to try to convince him that I wasn't a madman,” says Lazaridis, who hired Burton in October 1999.

    Burton began recruiting researchers in the three fields the board had chosen for the institute's research program: loop quantum gravity, string theory, and quantum information theory. The fields are related but not tightly linked—yet. For example, string theorists and quantum loop theorists are attacking the same fundamental problem, but their approaches are mathematically and philosophically different (see sidebar). Loop quantum gravity is also less sexy than string theory, which gave Perimeter an opportunity to corner the market on loop theorists, snaring luminaries such as Lee Smolin and Fotini Markopoulou Kalamara of Pennsylvania State University, University Park. “In loop quantum gravity, we're the leading center in the world,” says Perimeter string theorist Rob Myers. “Right away, we're drawing the best postdocs; from that point of view, the Perimeter Institute has made its mark already.”

    Outsiders agree. “I think it's had a really positive influence on quantum gravity,” says Abhay Ashtekar, a gravity theorist at Penn State. “It's really a new influx of resources in the field and a place where young people who are very bright have a new opportunity.”

    In quantum information theory, Burton wooed Raymond Laflamme, a leading theorist with a weakness for experimentation, away from his research group at Los Alamos National Laboratory in New Mexico. “I realized, ‘Oh my god, these guys are serious,’” says Laflamme in a faint Québecois accent. So Laflamme and his family packed up and moved back to his home country. In addition to pursuing theoretical studies at the institute, Laflamme heads the University of Waterloo's Institute for Quantum Computing, an experimental group Lazaridis established in 2002 with a C$6 million (US$4.5 million) grant.

    Perimeter's three-pronged program makes sense, Myers says: “I think they've chosen well. They came up with very good areas to start out in.” There's a good deal of cross-fertilization between the subjects; Myers, for example, is beginning to ponder loop-gravity problems—such as the possible “dispersion relation” of light traveling through a vacuum—from a string-theory background. “This work in modifying the dispersion relation is something I had heard about but never really thought about seriously,” he says. Burton says the institute will almost certainly expand into other areas, such as cosmology, as theorists follow their noses to new subjects—exploration that Perimeter encourages. Laflamme, for instance, is interested in what quantum information theory can reveal about cosmology. “Being here makes me think about this a lot more,” he says.

    The institute now houses eight long-term researchers and about three times that many postdocs and other faculty members. Part of its attraction, the researchers agree, is the freedom. Tangible signs of it are everywhere. In Laflamme's office, for example, the chalkboard is covered with mathematical symbols—a dance of equations that describes the evolution of a quantum wave function—but sheet music for Mozart's fourth violin sonata occupies pride of place on the desk. Sheet music would have been out of place in the staid offices of Los Alamos.

    Pleasure dome.

    The institute's C$20 million building, due to be finished in spring 2004, will house offices, conference rooms, and a squash court.

    CREDIT: PERIMETER INSTITUTE

    Also tilling the intellectual soil is a constant influx of visiting scholars. “There's an unending stream of visitors here,” says Jan Ambjorn, a physicist visiting from the University of Copenhagen who works at the borderline between string theory and quantum gravity. “It's very nice to come here, to talk to good people. [Perimeter] has the economic means to have a very dynamic environment.” Daniel Oi, a visiting postdoc quantum-information theorist from the University of Cambridge, agrees: “There's a lot of cross-pollination. I appreciate this atmosphere: informal, interdisciplinary, relaxed, but still intense.”

    Surprisingly, the postdocs are each authorized to invite visitors to the institute. “All the stuff related to bureaucracy, to travel, is made really easy for us,” says string theorist postdoc David Mateos. They have a say in the governance as well. “The postdocs play quite a significant role,” says Smolin. “Perimeter is not hierarchical.” Postdocs collectively cast a vote in decisions ranging from who should be granted positions to what sort of furniture will adorn the new C$20 million (US$15 million) Perimeter building (which will have its own squash court, as well as the auditorium, common rooms, and offices that theorists traditionally need), now under construction and scheduled to be completed in spring 2004. “One of the founding principles was to have a reasonably flat hierarchy and a reasonably flat decision-making process,” says Burton.

    Burton says his own unconventional background as director—an untried physicist rather than a Nobel laureate—helps set the institute's laissez-faire tone. “I think it's one of the strengths of our model,” he says. “The danger with a place founded by an éminence grise is that he will micromanage research and muddy waters with a preset research agenda. This is a different model.” Instead, Burton says, he functions more like the general manager of a sports team: administering and organizing more than exercising fine control over strategy. “It's been described as being radical or Marxist or idealistic, but I think that's overblown. It's not that dissimilar to a well-functioning department,” he says.

    It's a department without tenure, however. Faculty members have renewable 5-year contracts—although some, such as Laflamme, have tenure at the University of Waterloo (where in May Lazaridis began a 3-year term as chancellor). According to Burton, the lack of tenure “enforces a constant check on performances” and keeps the institute from stagnating. Ashtekar, however, thinks the approach risks scaring away top academic talent. “In business, you can attract good people without offering them [job] security,” but academics are used to tenure, he says. “In the long term, it might be a problem.” Lazaridis disagrees. “If you're good at what you do, you shouldn't have to worry about tenure,” he says. “Perimeter is not about long-term appointments.”

    The very youth of the institute makes it difficult to say whether it will remain as dynamic as it grows to 60 or 70 people, but Burton is confident that within a few years the physics community will be able to judge whether the institute has been a success. “There has to be a sense that the place is happening,” says Burton. “It's like pornography in that we'll know it when we see it.”

  12. THEORETICAL PHYSICS

    Perimeter's Threefold Way

    1. Charles Seife

    Research at the Perimeter Institute for Theoretical Physics focuses on three main fields. String theory—the most familiar and perhaps most baffling to laypeople—seeks to fill a gap in particle physics. The ordinary Standard Model treats fundamental particles, such as electrons or quarks, as points in space, without breadth, depth, or length. Unfortunately, that simplistic assumption gums up the mathematical machinery of the Standard Model and of quantum mechanics. Worse still, current subatomic theories don't account for gravity as they do for the other forces: the strong, the weak, and the electromagnetic force.

    String theory solves these problems by assuming that the fundamental particles are not points but higher-dimensional objects such as strings or membranes. That approach appears to get rid of the nasty mathematics of point particles and creates consistent ideas about how to unify gravity with the other forces. Unfortunately, the strings and membranes must reside in a 10- or 11-dimensional space, so the string-theory universe is much weirder than even the standard quantum one (Science, 23 July 1999, p. 512).

    Loop quantum gravity attempts to solve the same problems as string theory from a slightly different perspective. Instead of proposing a different structure for particles, loop quantum gravity and other discrete gravity theories propose a different structure for space and time itself.

    In place of the smooth, rubbery sheet of Einsteinian relativity, loop quantum gravity posits a complicated, loopy structure for spacetime on the smallest scales. This alteration of spacetime changes the way objects—such as photons of light—move through space. In fact, some of the theories posit that different wavelengths of light move through the vacuum at slightly different speeds, a phenomenon known as a dispersion relation that has recently begun to be tested (Science, 8 November 2002, p. 1166).

    The third area, quantum information theory, takes on the very weirdness of quantum mechanics itself. Indeed, most of the seeming paradoxes of quantum mechanics are paradoxes of information. Heisenberg's Uncertainty Principle says that you can't extract arbitrarily precise information about a particle's position and momentum at the same time. Schrödinger's famous cat is both alive and dead until information about it leaks into the outside world—at which point, it must “choose” to be alive or dead. The spooky action at a distance of “entangled” particles vexed Einstein because it seemed to allow information to be transmitted faster than the speed of light.

    Quantum information theory attempts to divine the laws that underlie the transmission and manipulation of information in the subatomic realm—laws that are radically different from those that govern the classical information that made the computer revolution possible. Indeed, if physicists ever get a large-scale quantum computer working, they would, in theory, be able to crack all the public-key cryptography codes that are so crucial to Internet security. “Quantum information theory is an exciting and interesting new field,” says Perimeter's director, Howard Burton. “It seemed a natural area to go into.”

  13. SULTAN BIN MOHAMMED AL-QASSIMI PROFILE

    Building an Academic Oasis in the Arabian Desert

    1. Richard Stone

    The ruler of a Gulf emirate is spending a fortune—and taking political risks—to persuade his country's best and brightest to stay home

    SHARJAH, UNITED ARAB EMIRATES—The white-robed scholar crouches on the floor of his spacious study and opens a reprint of Claudius Ptolemy's classic treatise on geography. An expert on Arab history and current affairs, Sultan Bin Mohammed Al-Qassimi leafs gently through the atlas, relishing the aroma of the century-old book. “My wife jokes that this is my drug,” he says. He points to a fortified town on the Gulf coast of the Arabian Peninsula that today is the capital of the oil-rich emirate of Sharjah. His emirate. The academic in Shaikh Sultan plans to write an authoritative history of Arabia around the time that Ptolemy, the Egyptian astronomer and mathematician, compiled his maps in the second century C.E. But the leader in him wants to make Sharjah an intellectual powerhouse for the 21st century.

    The ruler of Sharjah for the past 31 years and a member of the Supreme Council of the United Arab Emirates (UAE), Shaikh Sultan, 64, has earned a reputation as one of the Gulf's most enlightened figures. “He is one levelheaded, visionary, and energetic Arab leader,” says Farouk El-Baz, director of Boston University's Center for Remote Sensing. In the past decade Shaikh Sultan has established two universities, six museums, and a science foundation. The bonanza spurred UNESCO to designate Sharjah, home to half a million people, as the “Cultural Capital of the Arab World” in 1998.

    Shaikh Sultan hopes that such attractions will lure home talented émigrés—if conditions are right. By that he means shaking things up politically. Sharjah is the only emirate to have women in its nonelected Assembly, boasting five out of 40 members, as well as two female Cabinet members. And next year's City Council elections will mark the first time that some UAE citizens will have the right to vote. “Any scientist who returns must be able to see that we are developing politically and socially,” he says.

    Dispelling myths

    Shaikh Sultan started out as one of countless educational émigrés from the Gulf. After graduating in 1971 with a bachelor's degree in agriculture from the University of Cairo, he came home intending to devise methods of growing tomatoes in the arid climate. But before he could begin, he was pressed into government service. The United Kingdom, after more than a century as the region's powerbroker, was planning to relinquish control of the Trucial States to a federation that would become the UAE. Although Sultan was the fledgling federation's first education minister, he was soon dispatched on more urgent matters, including negotiations over the status of Abu Mousa, an island in the Gulf claimed by Iran. UAE's educational system was far from his thoughts: “I didn't have time to think of anything else but politics,” he says.

    Visionary revisionist.

    Shaikh Sultan has challenged historical notions of the Gulf while striving to make intellectuals of all stripes feel welcome in Sharjah.

    CREDIT: R. STONE/SCIENCE

    Then tragedy struck. In January 1972, barely a month after the United Kingdom's formal withdrawal from the Gulf, gunmen led by an exiled shaikh burst into the residence of Sultan's elder brother and ruler of Sharjah, Shaikh Khalid, and shot him dead. The following year, after the bereaved Qassimi family had anointed Sultan as the new ruler, their prospects blossomed with the discovery of the first significant oil reserves in the emirate.

    While Sharjah evolved from a dusty village into a modern city, Shaikh Sultan yearned for the life of an academic. He decided to challenge the popular depiction of the shaikhdoms at the turn of the 19th century as little more than a band of pirates preying on innocent Europeans. One book in particular vilified the Qassimi stronghold. Its author “insulted us, calling us killers,” Shaikh Sultan says. Hackles raised, he enrolled as a graduate student in history at the Centre for Arab Gulf Studies at the University of Exeter, U.K. “I was driven into research, to make a deep study of the subject,” he says.

    His doctoral thesis drew upon untapped material from the Bombay Archives, documents detailing the British East India Company's activities in India and its trade routes during the late 18th and early 19th centuries. He argued that the company concocted the piracy threat as a pretext for coaxing the British Navy to stand up for its commercial interests. The navy took the bait, sending ships to the region to defeat the Qawasim (plural of Qassimi). “During the course of my research, I found so much fabrication,” Shaikh Sultan says. In 1986 he published his book, provocatively titled The Myth of Arab Piracy in the Gulf (Croom Helm).

    Although most experts dispute Shaikh Sultan's assertion that Gulf Arabs did not engage in piracy, his work spurred colleagues to take a fresh look at the evidence. “His main argument is sound: that the Arabs and British viewed ‘piracy’ very differently,” says James Onley, a Gulf historian at the American University of Sharjah (AUS). Onley believes that much of the so-called piracy was justifiable retaliation against the nonpayment of a “toll”—protection money—to the Qawasim for sailing through the southern Gulf. Piracy in the usual sense “did occur now and again,” Onley says, but the Qawasim were not the perpetrators: The Gulf's equivalent of Blackbeard, he notes, hailed from Qatar. The book “sparked an important debate that still goes on today about cultural relativism,” he says.

    Sowing seeds

    Along with his scholarly pilgrimage, Shaikh Sultan worked hard to make Sharjah an oasis in a cultural desert, founding museums devoted to archaeology, natural history, science, Islam, and Sharjah's heritage, as well as a hands-on science museum for children. One of his favorite pastimes in his youth, he says, was driving into the desert to stargaze and observe nocturnal creatures. The shaikh turned his love for the outdoors into the Arabian Wildlife Center, a preserve and research facility that houses an array of Gulf fauna and serves as a captive-breeding facility for the endangered Arabian leopard and other rare species.

    The centerpiece of his Arabic renaissance, however, is an academic boulevard lined with palm trees and massive domed buildings on the edge of the capital city. At one end is the 4500-student University of Sharjah, offering separate campuses for men and women in keeping with Islamic tradition. At the other is the co-ed AUS, with 3500 students. “We're a country tied to our religion,” Shaikh Sultan says. “But our religion doesn't say to put boys and girls in different places. There are many things to be corrected.”

    Not just another pretty façade.

    Western-trained scientists are bringing scholarly rigor to the American University of Sharjah.

    CREDIT: AMERICAN UNIVERSITY OF SHARJAH

    A photo of the site of the future academic city, on the eve of construction in November 1996, show a solitary man and a camel in the desert. Less than a year and $135 million from the shaikh's own coffers later, some 3000 workers had finished the main buildings, and in the autumn of 1997 both universities opened to students. The magnificent domes atop the main buildings, Shaikh Sultan says, are meant to echo the architecture of his alma mater, the University of Cairo.

    Underneath the domes is a beehive of activity. AUS's biology and chemistry labs are decked out with the latest ultracentrifuges and atomic absorption mass spectrometers. “Even in North America many undergraduate laboratories would not have this kind of equipment,” says Robert Cook, dean of AUS's College of Arts and Sciences and part of a Western management team provided under an agreement with American University in Washington, D.C.

    AUS and its sister university have landed some Western-trained scientists with adventurous spirits. Daniel Zachary, a nuclear and environmental physicist who earned his Ph.D. from the Massachusetts Institute of Technology, says he came to AUS last year both to pursue his climate-change research and to build scientific bridges between the emirates and Europe and the United States. “There are many tainted preconceptions that the West has about this region,” he says. “We need to overcome them.”

    But building a critical mass of talent takes time as well as money. “Researchers can feel like orphans here. They need attention and nurturing or else they may drift away,” says Andrea Baumann, interim dean of the College of Health Sciences at the University of Sharjah, which counts among its strengths a core of virologists who have international reputations for their work on hepatitis viruses and transfusion-transmitted viruses.

    Transcending tribalism?

    Shaikh Sultan's ambitions extend beyond Sharjah. In 2000, he tried to kick-start scientific cooperation across the Gulf by establishing the Arab Science and Technology Foundation (ASTF) (Science, 26 October 2001, p. 766). He donated $1 million in running costs to the foundation, which gives grants to mostly applied research in areas such as solar power and water desalination and holds an annual conference to spur collaborations.

    But the shaikh's seed money has failed to produce verdant growth. The foundation is nowhere near its goal of a $100 million endowment. “Everyone was hoping that the sky would rain gold,” says ASTF president Abdalla Alnajjar. Adds Farid Ohan, director of the Higher Colleges of Technology in Sharjah: “There's not enough of a realization that science is necessary for the region's development.” And cooperation does not come easily among a group of what were not so very long ago warring tribes. “We're still at a stage of ‘intellectual tribalism,’” says Ohan.

    The roots of that mindset run deep, Ohan says: “When students come out of school, you would not believe how impoverished they are in scientific thinking.” To better nourish young minds, Shaikh Sultan has extended his reform drive into the primary and secondary schools. “Can you imagine that in our schools there are no libraries? Can you imagine? Except in Sharjah,” he says. “If there is no custom of reading, you can't tell someone to read a book. They won't read two pages. You need to plant it in children from the beginning.” The shaikh polishes off 200 to 300 pages a day, he says, a prodigious amount that he admits he's able to digest only because his appetite for politics is running thin.

    That may explain why, after ASTF's sputtering start, Shaikh Sultan is reluctant to crusade for greater scientific cooperation in the Gulf. Instead, he prefers to spend time at home in splendid isolation. Stepping onto his balcony, he can gaze upon a domed atrium, adorned with paintings by Arabian and European masters and the 100 names of Allah scrolling along the rim. Or he can stroll outdoors in the manicured gardens of his new palace, built 3 years ago on land reclaimed from desert on the city's outskirts. “I spend any spare time in my library,” he says. “A man dealing with books should produce books.”

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