# News this Week

Science  23 Jan 2004:
Vol. 303, Issue 5657, pp. 444
1. SPACE EXPLORATION

# Scientists Add Up Gains, Losses in Bush's New Vision for NASA

1. Andrew Lawler*
1. With reporting by Wayne Kondro in Canada, Dennis Normile in Tokyo, Ding Yimin in Beijing, Pallava Bagla in New Delhi, and Daniel Clery and Richard Stone in Cambridge, U.K.

To the relief of many lawmakers, scientists, and space enthusiasts, the United States now has a vision for space exploration with a White House seal of approval. But the remedy for NASA's woes, presented last week by President George W. Bush, includes some unpleasant scientific side effects. It would end the Hubble Space Telescope's brilliant run and could jeopardize the future of any activity that doesn't directly serve the exploration effort.

On 14 January, Bush announced his intention to retire the aging shuttle, redefine the purpose of the half-built space station, and design and build a vehicle to take humans to the moon and then Mars. White House and NASA officials insist that researchers would prosper under the proposal, gaining a new flotilla of lunar robots, increased support for Mars rovers, and advanced technology to benefit outer solar system missions. “This provides more opportunities for science,” says presidential science adviser John Marburger.

But, while applauding the desire to fix NASA's troubled human space flight program—grounded since last February—some scientists worry that a portion of the funding for the new venture will come out of the hide of existing research programs. “It's a serious issue, and people are going to be passionate on all sides,” says Charles Kennel, an earth scientist who heads NASA's Advisory Council and directs the Scripps Institution of Oceanography in La Jolla, California.

Bush's announcement, made at NASA Headquarters in Washington, D.C., follows intensive debate in the White House over how to rebound from the Columbia disaster. It paints a dramatic picture of human exploration over the next 2 decades, but with few details. Bush said the agency would begin testing a new launcher dubbed the Crew Exploration Vehicle in 2008, while a series of lunar robotic missions begins probing the moon. After hauling up the last pieces of the space station in 2010, the shuttle would halt operations. But it would be another 4 years before the new launcher would be ready to transport humans. Work on a lunar base could begin as early as 2015, and the space station would be abandoned the following year. A trip to Mars would follow much later. “The vision I outline today,” Bush said, “is a journey, not a race.” And other nations are welcome to join in, he added.

To pay for it, Bush will ask Congress to add $800 million to NASA's pending$15.4 billion budget for 2004. Its budget would grow by 5% in each of the following 3 years, followed by 1% increases in 2009 and 2010. The bulk of the money for the new initiative, however, would come from reshuffling and cutting existing NASA programs. The biggest savings would not come until the end of the decade, when the shuttle's $4-billion-a-year budget would be available. Administration officials refused last week to say exactly what areas will be cut until the 2005 request is released on 2 February. That reticence tempered early reviews of the proposal. “Everyone is confused,” says one scientist. “I am particularly concerned that NASA's other missions not be cannibalized in an attempt to cover the costs of these proposals,” adds Representative Bart Gordon (D-TN), ranking Democrat on the House Science Committee that oversees NASA. “A couple of billion dollars a year extra for NASA would go a long way to solving this,” says Kennel. Collateral damage. Planetary scientists, flush with the success of the Mars Spirit rover, are ecstatic about the possibility of a new line of lunar robotic missions and an even more robust Mars effort. Astronomers and earth scientists are much less enthusiastic, however. Astronomers were stunned to learn that the president's plan precludes any more servicing missions to the Hubble Space Telescope. “It's a disaster for science and a giant step backward for U.S. astronomy,” says Yale University astronomer Meg Urry. The shuttle was expected to make one trip between 2006 and 2008, and as recently as this fall scientists held out hope for an addtional servicing mission that would have kept Hubble flying until the James Webb Space Telescope is in orbit in 2011. “We're very seriously concerned,” adds Sidney Wolff, director of Kitt Peak National Observatory in Arizona. “It would leave a very long gap.” NASA space science chief Ed Weiler says that killing the mission was a “tough call” but that there was no alternative. Hubble's position in an orbit different from that of the space station raised serious safety issues, he said, and the rush to finish the station by 2010 left no time for a rendezvous with the telescope. Weiler expects Hubble to be able to continue operating normally until around 2007, with the chance of extending its life by adopting power-saving procedures. Wolff proposes that two instruments built for the next Hubble servicing mission instead be placed in orbit by an expendable launch vehicle and operated independently of Hubble. Weiler declined to discuss details of the upcoming 2005 budget request but allowed that “there are not going to be radical, drastic, large cuts to any parts of space science.” Other agency managers said that major observatories—both those on the drawing board and those in orbit—would not suffer either under the president's new plan. An apparent decline from his pending 2004 budget of$4 billion, Weiler added, will reflect the transfer of some programs to the new exploration office NASA created last week.

The long-term fate of earth sciences, on which NASA spends $1.6 billion annually, is less certain. Some Administration sources told Science that large portions of the effort would be shifted to the National Oceanic and Atmospheric Administration (NOAA) to make room in NASA's 2006 budget for the new exploration programs. “It's not true,” replies Ghassem Asrar, NASA's earth sciences chief. He says that satellites deemed operational will be transferred to NOAA, but that there are no major budget decreases planned for the next few years. O'Keefe backs him up, insisting that there will be “no diminution” of the program. “There should be no concerns,” he adds. In his speech, Bush said that the space station, designed to host experimental facilities covering work in materials science, fundamental physics, and molecular biology, would henceforth be devoted to gathering data on the effects of long-term space living. That will force yet another replanning of station research, a topic that a National Research Council panel will tackle in March. “We're excited,” says Mary Kicza, chief of NASA's biological and physical research office. “This gives us a clarity of objective and purpose.” Although Kicza declined to say what research would be halted, or how the budget would be affected, O'Keefe said “it will be a very dramatic adjustment.” The 2016 termination date is several years earlier than NASA had planned to retire the station. In the intervening years, the Russian Soyuz would ferry crews, and an automated European vehicle could transport scientific equipment and samples. Sales pitch. Bush and O'Keefe must now sell their vision to Congress. The president's father failed to do this when, in 1989, he proposed a similar return to the moon and Mars. But many lawmakers appear hopeful that the president's new direction for human space flight will overcome the high costs, low reliability, and lack of focus that has plagued current efforts. “Exactly the jump-start NASA needs to move into the future,” says Senator Sam Brownback (R-KS), who heads the space panel within the Senate Commerce, Science, and Transportation Committee. Representative Sherwood Boehlert (R-NY), who chairs the House Science Committee, called the proposal “a thoughtful, gradual, achievable set of missions.” Brownback's panel will hold a hearing 4 February, with Boehlert's committee to follow the next week. With elections in November, the president's proposal has already sparked a response along partisan lines. Former Vice President Al Gore, a Democrat, dismissed the Bush plan as “an unimaginative and retread effort to make a tiny portion of the moon habitable for a handful of people.” Marburger's predecessor under President Bill Clinton, physicist John Gibbons, called it “a misplaced focus on the future” that caters to “people who like making money building things in space. … It means profits for them.” Bush's plan could create business for the aerospace industry. But companies already benefiting from shuttle contracts would lose out if expensive upgrades were avoided and the vehicle was retired. It's too early to know the impact of the new plan on other spacefaring nations. But space officials in several countries that are partners on the space station generally praised the plan as a way to bolster their field and international cooperation. Russian officials were busy dusting off their own plans for lunar and Mars exploration and were quick to say that they would be able to provide important elements of human expeditions—such as large vehicles—at low cost and with high reliability. “It's a good thing,” says European Space Agency spokesperson Franco Bonacina in Paris: “We're excited; it shows increased interest in space activities.” Canadian Space Agency President Marc Garneau hopes that NASA's emphasis on Mars exploration will help persuade Ottawa to provide the necessary funding for a robotic mission to Mars that he has proposed for early in the next decade. Japanese officials, meanwhile, declined to comment. In contrast, Chinese officials were decidedly cool to Bush's proposal. “China will still depend on its own ability to carry out space plans, including manned flights and deep-space exploration,” says Li Jinduo, spokesperson for Beijing's Commission of Science, Technology, and Industry for National Defense. Li Mingzhu, deputy chief of the Center for Space Science and Applied Research at the Chinese Academy of Sciences, says that “China will not be affected very much” by the U.S. plan. But he speculates that “the shift of U.S. focus will have an impact on the whole world in the long run.” In the meantime, everyone wants more detail. “We will be very happy to work with NASA,” says G. Madhavan Nair, chair of the Indian Space Research Organisation (ISRO) in Bangalore. “But it is difficult for India to make an assessment.” India plans to launch a probe to the moon in 2007, and Nair says that NASA and ISRO are discussing including a U.S. instrument on board the spacecraft. In his speech, Bush named former Air Force Secretary Pete Aldridge to lead a commission and asked for its report by the summer. The new panel is expected to wrestle with issues such as hiring the scientists and engineers needed to do the job and managing such a sprawling initiative. “The president has given us a mandate,” says O'Keefe. “Now all we gotta do is do it.” 2. INFECTIOUS DISEASES # Stopping Asia's Avian Flu: A Worrisome Third Outbreak 1. Dennis Normile TOKYO—Health officials are racing to contain an avian influenza outbreak that surfaced in South Korea in December, then in Japan and Vietnam early this month. It is virulent, they say: After making an unusual leap to humans, it has infected and killed at least five people in Vietnam. Ten more suspect cases in Vietnam are under investigation. Researchers have not yet determined the virus's DNA sequence or its source. But authorities in the region, using the only tool available, have killed more than 3 million potentially exposed chickens to slow its spread. Although the virus appears to be transmitted only by birds and not person-to-person, health authorities are watching it nervously. The more virus in circulation, the greater the chance it could reassort “into something with the lethality of the avian flu and the transmissibility of a human flu,” says Ilaria Capua, a virologist at Italy's National Reference Laboratory for Avian Influenza, a part of the Istituto Zooprofilattico Sperimentale delle Venezie in Padua. The potential for this deadly combination is “frightening,” says Capua, whose lab is also affiliated with the Paris-based World Organization for Animal Health (OIE, from its French name). A more infectious variant could touch off a pandemic. The virus behind these fears is known as influenza A subtype H5N1. Subtypes are categorized by the forms of two surface glycoproteins, hemagglutinin (H) and neuraminidase (N). H5N1 first surfaced in poultry in Hong Kong in 1997, when it jumped the species barrier into humans, killing six of the 18 people it infected. Humans have limited immunity to avian viruses, which means “this virus is bad in humans,” says Robert Webster, a flu expert at St. Jude Children's Research Hospital in Memphis, Tennessee. The reappearance of H5N1 was no surprise. Webster and others have been warning that it could touch off a pandemic ever since it first appeared in Hong Kong. The territory contained the outbreak by slaughtering all of the city's 1.4 million chickens and ducks. But experts have long believed that there are one or more animal reservoirs. “This virus is out there in large amounts somewhere,” Webster says. An evolved variant showed up in wild birds in Hong Kong parks in late 2002. Then in February 2003, a variant nearly identical to the wild bird form was isolated from a Hong Kong man, who died, and his son, who became seriously ill but recovered. The man's daughter had died of an undiagnosed respiratory illness while the family was visiting relatives in China's Fujian Province (Science, 7 March 2003, p. 1504). The source was never pinned down. But Kennedy Shortridge, a virologist and now a professor emeritus at the University of Hong Kong who was involved in the 1997 investigations, says that the evidence all pointed to “the existence of natural reservoirs in southern China.” China has claimed in reports to OIE never to have had any large-scale outbreaks of avian influenza. The appearance of H5N1 in South Korea, Japan, and Vietnam shows that the virus is spreading. But whether it was spread by migratory birds or infected poultry or poultry products is not clear. Webster developed a vaccine for the 1997 variant, but it's not known if it would have any effect on this latest version. Outbreaks of highly pathogenic avian influenza are increasing in frequency and severity, Capua warns. There were only 17 outbreaks in the 40 years from 1959 to 1998, she says. But there have been six in the 6 years from 1997 to 2003—not counting the latest incidents. Capua suspects a combination of factors. The most important may be a phenomenal growth in demand for poultry, leading to denser concentrations of larger poultry farms without appropriate biological safeguards. Once an infection is introduced into this environment, “it spreads very rapidly and is very difficult to get rid of,” she says. Even if the virus is successfully contained this winter, Capua believes it is only a matter of time before it reappears. 3. GENETICALLY MODIFIED ORGANISMS # Europe Takes Tentative Steps Toward Approval of Commercial GM Crops 1. Gretchen Vogel BERLIN—They didn't exactly lay out a welcome mat, but two European countries opened their doors a crack last week to commercial planting of genetically modified (GM) crops. On 13 January, the British Advisory Committee on Releases to the Environment (ACRE) recommended that the Environment Ministry allow herbicide-resistant maize in Great Britain, subject to care-ful controls. Two other herbicide-resistant crops, sugar beets and spring-planted oilseed rape, got a qualified no from the committee, however. In Germany, meanwhile, the agriculture ministry proposed new regulations that would open the way for commercial GM crops. But the law would hold farmers who plant what the press calls “gene foods” liable for any pollen contamination of neighbors' fields, a clause that the German Farmers Association said could discourage most planting of the crops. In 1998, the European Union imposed a moratorium on the approval of new GM varieties. Since then most member countries, facing strong public opposition to the technology, have strictly limited planting of all GM crops. The moratorium expired late last year, however, and several GM varieties are now close to receiving approval. The ACRE recommendations are based on the U.K.'s farm-scale evaluations (Science, 24 October 2003, p. 542). The trials measured the impact of growing conventional and GM crops on weeds and insects, which provide food for birds and other wildlife, in and around farm fields. Herbicide-resistant sugar beet and oilseed rape fields had significantly fewer weeds and insects than their conventional counterparts. In contrast, fields of herbicide-resistant maize had more weeds than conventional maize fields. Based on those results, the committee gave a “yes-but” recommendation on herbicide-resistant maize and said “no-but” to herbicide-resistant beets and rapeseed, says ACRE chair Chris Pollock. Maize should be approved for commercial planting, on the condition that follow-up studies monitor the crops' impact, the committee recommended. It gave a provisional “no” to beets and oilseed rape but noted that their environmental impact was due to the heavy application of herbicides. The crops could be approved if manufacturers come up with a milder herbicide-application scheme. Environment Secretary Margaret Beckett may decide on GM maize by late February. If she gives her approval, the application will be forwarded to the European Commission for review. The ACRE report is positive news for biotechnology in Britain, says Colin Merritt of Monsanto in Cambridge, U.K. “The [approval] process will start to grind on again, instead of being on life support,” he says. It is unlikely that the maize variety will be approved in time for planting this spring, “but next year is looking likely,” he says. In Germany such planting may face higher hurdles. On 12 January, Agriculture Minister Renate Künast, a member of the Green Party and a strong critic of GM crops, outlined her proposal for a new law regulating genetic technologies. Although the proposal would allow farmers to plant E.U.-approved crops, it would also hold them liable for any contamination of the crops of neighboring organic farmers with GM pollen or seeds. Such a rule would not only discourage farmers from planting the crops commercially, says Heinz Saedler of the Max Planck Institute for Plant Breeding Research in Cologne, but would also strongly discourage scientists from conducting field trials of new crops. The proposal may still be modified before it is officially introduced to the Bundestag in February, and Saedler predicts that the current form would face strong opposition in the upper house of parliament, where the opposition Christian Democrats hold a majority 4. DOE NATIONAL LABS # University of California Inches Closer to Preparing Bids 1. David Malakoff The University of California (UC) is recruiting allies for what could be a bruising competition to manage three prominent national laboratories. Last week the UC's governing regents gave President Robert Dynes approval to partner with private firms to shore up its management of the Los Alamos, Livermore, and Lawrence Berkeley national laboratories. UC currently runs all three labs under contract from the Department of Energy (DOE), but the contracts are expected to be put up for competition in the next few years. Although the regents stopped short of giving Dynes the green light to bid to hang onto the contracts, UC officials made it clear that they are girding for battle. “If we compete, we want to sweep the board on all three labs,” said Robert Foley, UC's vice president for laboratory management. UC has been the only manager of the three labs, the oldest of which opened in the 1930s. But last April, after a string of security and financial scandals, DOE announced that it would compete the Los Alamos contract when it expires in late 2005. Congress has since required DOE to compete any lab contract that has been held by the same institution for more than 50 years (Science, 15 August 2003, p. 900). That means UC will also have to fight to keep its Livermore contract, which expires in 2005, and the Berkeley contract, which ends this month. Last November, an advisory panel recommended that DOE not compete the Los Alamos and Livermore contracts at the same time, but the agency won't issue competition rules until later this year. Foley says that UC isn't waiting for a new contract to make improvements. It already has struck preliminary deals with several firms to assist with financial and environmental management at Los Alamos. The partners, which Foley declined to identify, are needed “regardless of whether the university decides to compete,” he said. Such alliances could also improve the university's chances of prevailing in a competition that could include universities in Texas and New Mexico, the nonprofit Battelle Memorial Institute, and private-sector giants Lockheed Martin, Bechtel, and SAIC. Dynes, meanwhile, says he has gotten more than 100 letters asking the university to walk away from Los Alamos and Livermore because of their work on nuclear weapons. And several regents have said they want more discussion before deciding on whether UC should enter any competition. 5. GENETICALLY MODIFIED ORGANISMS # Experts Recommend a Cautious Approach 1. Erik Stokstad To lessen the chance that genetically modified organisms (GMOs) might harm humans or the environment, researchers have come up with ways to isolate engineered species. Transgenic crops' pollen is hobbled so it doesn't spread herbicide-resistance genes to weeds, for example, and growth-enhanced salmon have been sterilized to prevent them from competing with native species if they escape from their ocean pens. Such approaches may not be good enough, according to a report* from the National Academy of Sciences (NAS) released this week. No biological barrier to gene flow—called bioconfinement—is likely to be completely effective, and thus multiple safeguards are needed. But most approaches are untested, the report adds, and it calls for more research into devising and evaluating bioconfinement strategies. A second report out this week, from the Pew Initiative on Food and Biotechnology, points out the need to clarify regulations of GM arthropods. Such bugs have the potential to disrupt transmission of malaria and other diseases, but it's not clear which U.S. government agencies will oversee their development. Not all GMOs will need to be confined, the NAS panel found. Those engineered with benign traits, such as plumper fruit, should be safe. The need for bioconfinement is greater if GMOs contain worrisome traits or are released in droves. Researchers will need to evaluate GMOs individually, defining how much bioconfinement is enough to reduce the chance of gene flow to an acceptable level. “The issue is how unlikely it has to be,” says David Andow of the University of Minnesota, Twin Cities (UMTC). Getting confinement right is important, the panel notes, because in most cases there are few options for detecting escapes or dealing with their consequences. Better markers, sampling strategies, and monitoring methods should be developed. In addition, bioconfinement techniques themselves need greater scrutiny, especially field testing, the report concludes. “There are few cases where people have looked at the long-term reliability of these methods,” says committee member Anne Kapuscinski of UMTC. And because multiple defenses will likely be needed, funding should be boosted to develop and evaluate new methods, say Kapuscinski and others. When it comes to the state of bioconfinement technology today, says Steven Strauss of Oregon State University in Corvallis, “basically we're at square one.” Also at the starting block, according to the Pew Initiative, is the regulatory system for transgenic arthropods. Researchers hope to control plant pests by creating sterile insects or stop the transmission of malaria by introducing disease-resistant mosquitoes. Although the U.S. Department of Agriculture has a regulatory pathway for plant pests, it's not clear who has authority for other kinds of GM arthropods. “It's a quagmire,” says molecular geneticist David O'Brochta of the University of Maryland, College Park. A more glaring problem is the lack of a clearly defined risk-assessment procedure for GM arthropods, says Ravi Durvasula of Yale School of Public Health, who's trying to prevent the kissing bug from transmitting Chagas disease. These issues, the report says, should be worked out before GM arthropods are ready to be released. • * Biological Confinement of Genetically Engineered Organisms, National Research Council, 2004. • Bugs in the System? Pew Initiative on Food and Biotechnology, 2004. 6. BIOMEDICAL POLITICS # Democrats Blast a Sunny-Side Look at U.S. Health Disparities 1. Jocelyn Kaiser When Congress ordered a report on racial and socioeconomic disparities in the health of U.S. citizens, it wasn't expecting a smiley face. But that is what it got, according to Representative Henry Waxman (D-CA), who last week accused the Bush Administration of whitewashing federal researchers' conclusions. Administration officials deny charges by Waxman and other Democrats that they softened the December report; they say editors emphasized “successes” in the summary only because that is the best way to encourage improvements in health care. At issue is the 196-page National Healthcare Disparities Report, authored by three researchers at the Agency for Healthcare Research and Quality (AHRQ). It is packed with data on health care treatment and outcomes for many diseases affecting minority groups and the poor. Waxman's Democratic staff on the Government Reform Committee compared the final version with a June 2003 draft and concluded that Health and Human Services (HHS) officials scrubbed the executive summary. The draft stated, for example, that “racial, ethnic, and socioeconomic disparities are national problems.” The final version simply says that “some socioeconomic, racial, ethnic, and geographic differences exist.” The final summary omits statements that inequalities are “significant” and “pervasive” and also drops some striking examples of inequalities such as higher rates of late-stage cancer and death from AIDS among minorities. New wording, however, notes that “some ‘priority populations’ do as well or better than the general population in some aspects of health care.” AHRQ spokesperson Karen Migdail says that “revisions were done to use successes … as a catalyst for change” in a “glass half-full approach.” She says that “this Administration has made reducing health disparities a major priority.” She adds that “not a number was changed” in the body of the report. Some health policy experts agree with Waxman that the final summary gives a distorted view. “I admire the Administration's ability to look at the positive, but it shouldn't come at the expense of the truth,” says Harvard's Joseph Betancourt, who served on two Institute of Medicine panels on inequities in health care. Another member of one panel, Donald Steinwachs of the Johns Hopkins Bloomberg School of Public Health, says that his group's 2002 report, Unequal Treatment, was “very similar in tone” to the draft HHS report, emphasizing that disparities “have to be a national priority.” Making the report more “upbeat,” he says, “does not accomplish the goal of focusing people on the problems.” The last U.S. Surgeon General during the Clinton Administration agrees: “I'm concerned that the report [has lost] a sense of urgency,” says David Satcher, now at the Morehouse College of Medicine in Atlanta, Georgia. Waxman, who maintains a Web site on this and other allegations of political meddling in science,* has asked HHS to provide details of official correspondence during the report's revisions. 7. BIOMEDICAL FUNDING # NIH Keeps Grants Staff But Braces for Change 1. Jocelyn Kaiser Research chiefs at the National Institutes of Health (NIH) who balked at the Administration's plans last year to shift some assignments to the Department of Health and Human Services (HHS) may breathe easier in 2004. Some of those controversial plans have been put on hold. But one change is going forward: Support staff for extramural grants administration are to be shifted to a central NIH office by April. NIH grants managers are preparing to scramble. Pressure to streamline the$27 billion NIH comes from Tommy Thompson, secretary of HHS. Over the past 2 years, his office has asked all HHS divisions to consider contracting out some types of jobs, such as firefighting, and merging functions such as procurement, budget planning, and grants management across HHS. NIH officials argued that certain directives could have a disastrous effect on scientific hiring and research (Science, 11 July 2003, p. 148). Several months ago, NIH proposed its own alternative plan, and Thompson has accepted this “blueprint,” NIH Deputy Director Raynard Kington told the director's advisory council last week.

Under the blueprint, eight working groups are developing efficiency plans for functions within NIH and will decide if some should be consolidated in NIH-wide service centers, Kington says. The agency has hired the National Academy of Public Administration beginning this week to help develop performance standards.

While the mergers are on hold, other changes under A-76, a government-wide mandate to open federal jobs to private competition, are going ahead. NIH won an A-76 competition last fall enabling it to retain control over clerical and administrative staff who provide grants management support. NIH Director Elias Zerhouni heralded it as a victory, but it came at a price: By 1 April, the grants support staff must be cut 26%, from 909 positions to 677, and it will become part of a new central service pool at NIH. Grants managers will no longer hire and supervise their own staff, and new, lowered pay grades may prompt some experienced workers to leave, according to some NIH officials. These factors, they say, may make it difficult to keep pace with a record number of grant proposals.

“There's a hell of a lot of concern about how it's going to work out,” acknowledges David Whitmer, executive officer of NIH's Center for Scientific Review and a member of the grants support plan team. But he's confident that NIH employees will make it succeed. A computer system will move staff around when there's a lull in their workload, he notes; also, new electronic grants tracking should cut staffing needs.

These management woes may soon be overshadowed by a bigger concern, however: Congress still hasn't approved NIH's budget for 2004, so the agency is working at the 2003 level. And it could be facing an even tighter budget in 2005.

8. NONPROLIFERATION

# North Korea's Nuclear Shell Game

1. Richard Stone

A U.S. team earlier this month was unable to determine whether North Korea has an atomic ace in the hole or is bluffing. Verifying any future freeze of its nuclear programs will require scientific sleuthing—and a leap of faith

Late in the afternoon on Thursday, 8 January, Siegfried Hecker and four other members of an unofficial U.S. delegation were huddled in a chilly conference room at the Nuclear Scientific Research Center in Yongbyon, 100 kilometers north of Pyongyong. They had just finished a tour of the crown jewels of North Korea's nuclear program: a 5-megawatt electric (MWe) reactor and a nearby Radiochemical Laboratory, a massive facility for extracting plutonium from spent uranium fuel rods, said to be the second largest such facility in the world. Hecker, a plutonium expert and former director of the Los Alamos National Laboratory, had confirmed that the reactor was operating normally and, by all appearances, could accumulate in its fuel rods 6 kilograms of plutonium a year—enough for a nuclear bomb. He also confirmed that 8000 spent fuel rods removed from the reactor in 1994 were no longer in a cooling pond. The Radiochemical Laboratory, meanwhile, was “in good repair,” Hecker testified at a 21 January hearing of the U.S. Senate Committee on Foreign Relations.

But the North Koreans were saving their best for last. They claimed to have finished reprocessing all 48 tons of spent fuel last June and brought a metal case into the conference room that afternoon. Nested inside was a wooden box with two glass jars, one of which contained a greenish powder and the second a thin-walled funnel, about 5 centimeters wide at its base and 3.8 cm tall. Inside the first jar, the North Korean scientists claimed, was plutonium oxalate powder. Inside the second: 200 grams of plutonium metal, the raw makings of a bomb.

“I tried to get a feel for the density and heat content of the alleged plutonium metal by holding the glass jar in a gloved hand,” Hecker said. The jar was heavy and slightly warm—“it was definitely not cold as was everything else” in the building. And both the metal and the powder were radioactive. However, he noted, “the bottom line is that with the rather primitive tools at hand, I was not able to definitively identify the purported metal and the powder as plutonium.” And without sophisticated isotopic measurements, they had no way to confirm that it came from the spent fuel rods that the North Koreans claim to have reprocessed last year.

Such ambiguities have kept the world guessing about how far North Korea has traveled on the road to nuclear statehood. Western intelligence agencies have publicly concluded that it possesses one or two fission bombs. But North Korea hasn't yet announced its membership in the nuclear club with a detonation, so there's no guarantee its bombs would work—if it has them. Then there's the question of whether the country has a viable program for enriching uranium, a potential alternative to plutonium as a source of nuclear explosive. According to U.S. officials, North Korean officials admitted pursuing enrichment after Assistant Secretary of State James A. Kelly confronted them with unspecified evidence during talks in October 2002, precipitating the present crisis. North Korea has since denied the existence of an enrichment program, however.

Hecker's group, led by Asia scholar John Lewis of Stanford University, traveled to North Korea to try to resolve some of the ambiguities about North Korea's program as part of an effort to end the current standoff. Earlier this month, North Korea said it would freeze its nuclear program in exchange for security concessions and economic aid from the United States, an offer that U.S. Secretary of State Colin Powell called “a positive step.” This offer is expected to be on the table when the United States, North Korea, South Korea, China, Japan, and Russia reconvene “six-party talks” as early as next month. But the talks could founder on a crucial issue: how a freeze could be verified and facilities monitored—especially centrifuge enrichment plants, which are notoriously difficult to detect. The United States and Japan are taking a hard line. “We will have to assume 100% cooperation from North Korean authorities. Otherwise any inspection and verification would be insufficient,” Mikio Mori, a member of Japan's delegation to the talks, told Science.

## From Russia with know-how

There's little doubt that North Korea has had nuclear ambitions for half a century. North Korean scientists and engineers started training at the Joint Institute for Nuclear Research in Dubna, near Moscow, in 1956. Although the North Koreans could rub shoulders with top talent there, “the Soviet Union treated them like junior partners,” says Tetsuya Endo, vice chair of Japan's Atomic Energy Commission. Science could find no evidence that North Korean scientists had ever visited the Soviet Union's elite, closed nuclear weapons cities. Nevertheless, they “did acquire basic knowledge,” says Endo. “They are very capable and shrewd.” Several South Korean defectors in the 1950s and '60s who had studied nuclear physics in Japan apparently also helped build the program, says Mori, director for multilateral nuclear cooperation in Japan's Ministry of Foreign Affairs.

North Korea established its nuclear research center at Yongbyon in 1962 and in 1965 started running fission experiments on a subcritical assembly purchased from the Soviet Union 2 years earlier. North Korea opted for a “very scaled-down version” of the U.K.'s Calder Hall reactor, says Robert Alvarez, a former senior policy adviser to the U.S. Department of Energy (DOE) now at the Institute for Policy Studies in Washington, D.C. This carbon dioxide-cooled reactor, more effective at generating plutonium than a water-cooled reactor, was central to the United Kingdom's weapons program in the 1950s.

North Korea's effort hit its stride in the mid-1980s. In 1984 it started work on its Radiochemical Laboratory. Two years later the 5-MWe reactor was started up, and construction had begun on a 50-MWe version; in 1989 ground was broken on a 200-MWe reactor in Taechon. If all three reactors were put into operation, North Korea could produce enough plutonium for more than 50 weapons a year (see table).

But North Korea's intellectual link to the Soviet Union was fraying. Soon after the Soviet Union unraveled in 1991, says a former Russian government official, “the North Koreans expressed great interest in high-energy physics and invited our specialists for long-term visits.” They were so persistent, the official says, that “we had to take administrative measures to stop our nuclear physicists from traveling to North Korea.” He insists that the measures worked.

Today “we cannot make a definitive judgment on how much technological expertise they have,” says Mori. “My sense is that they could have obtained sufficient training in Russia—or on their own.” He estimates that Kim Il Sung University and Kim Chaek University of Technology together produce about 300 nuclear science graduates a year.

## The perils of plutonium

In spite of this growing nuclear program, the Democratic People's Republic of Korea (DPRK), as the country is formally known, signed the Nuclear Nonproliferation Treaty (NPT) in 1985 and so had to submit to inspections by the International Atomic Energy Agency (IAEA). The agency conducted six inspections between June 1992 and February 1993. The North Koreans “got increasingly hostile as the inspections became more and more invasive,” says Alvarez. In late 1992, IAEA inspectors found evidence that North Korea had reprocessed more than the roughly 90 grams of plutonium-239 it had disclosed. Their environmental sampling at Yongbyon had revealed varying ratios of americium-241, a decay product of plutonium-241, suggesting that reprocessing had occurred on multiple occasions, an IAEA official told Science. “The IAEA was able to prove the North Koreans were lying, but not by how much,” says Matthew Bunn, a nonproliferation expert at Harvard University.

As the Radiochemical Laboratory was still being outfitted, attention focused on several “hot cells”—lead-lined glove boxes for handling highly radioactive materials—imported from the Soviet Union. “They were probably taking small batches and doing separation in the hot cells,” says Alvarez. How much North Korea might have separated between 1986 and 1992 is unknown; estimates range from 5 to 26 kilograms.

When IAEA officials in 1993 asked to inspect the Radiochemical Laboratory and a nearby waste-storage facility, “the DPRK freaked out,” Alvarez says. North Korean officials refused and announced their intention to withdraw from the NPT. In May 1994 North Korea shut down the 5-MWe reactor to refuel the entire core, spurning an IAEA request to sample the fuel before removal.

Only a diplomatic breakthrough by former President Jimmy Carter in Pyongyang that June averted further escalation of tensions. In the Agreed Framework signed in October 1994, North Korea said it would freeze and eventually dismantle its graphite reactors. In exchange, a U.S.-led consortium, the Korean Peninsula Energy Development Organization (KEDO), pledged to finance a $5 billion deal to supply a pair of light-water reactors and annual shipments of fuel oil. KEDO suspended construction of the reactors last month. Alvarez and a team of U.S. experts arrived in Yongbyon in November 1994 to hash out implementation of the Agreed Framework. They got a surprise. The fuel rods just removed from the reactor lay submerged in a 6-by-15-meter cooling pond that was choked with algae and an opaque suspension of magnesium oxide—rust from magnesium cladding eroding in the warm water. It looked “like a diluted form of Milk of Magnesia,” Alvarez wrote in the July/August 2003 issue of the Bulletin of the Atomic Scientists. Further erosion threatened to lay bare the uranium metal, which can react with water to form hydrogen gas and uranium hydride. Because uranium hydride ignites spontaneously in air, removing such unstable fuel rods from the pool could have sparked an explosion. In a$20 million, 18-month project funded by the U.S. government, each spent fuel rod was laboriously cleaned and bundled into stainless steel canisters filled with argon, an inert gas, to retard the generation of hydrogen. Each canister was placed under IAEA seal and returned to the cooling pond.

Since North Korean officials threw IAEA inspectors out of Yongbyon on 31 December 2002, speculation has focused on the fate of the spent fuel. But North Korea's claims that it has reprocessed the fuel haven't been verified. U.S. spy planes should have been able to detect gases, especially telltale krypton-85, wafting from the Radiochemical Laboratory if reprocessing had indeed occurred there. “You have a good chance of detecting those once they went up the stack,” says Bunn. “We have observed elevated krypton,” acknowledges a senior Bush Adminstration official, “but it doesn't seem to have come from Yongbyon.”

It's more likely, says Alvarez, that the North Koreans “surreptitiously put [the fuel rods] in barrels of water and hauled them off in the middle of the night,” along with the hot cells, for reprocessing outside Yongbyon. Japanese experts have come to a similar conclusion. “If they don't care about radiation exposure, the reprocessing itself is straightforward chemistry,” says Endo. The Admistration official declined to say whether remote detectors are sensitive enough to catch reprocessing in hot cells. The answer, he said, is “classified.”

In the meantime, North Korea has refueled and restarted the 5-MWe reactor, as Hecker's team confirmed.

## Bombs away?

As bad as it sounds, experts say, it's not too late to put North Korea's plutonium genie back in the bottle. “We have frozen and verified the plutonium program very effectively, so we know how to do that,” says Kenneth Luongo, who as director of DOE's Office of Arms Control and Nonproliferation in the mid-1990s managed the process of canning the spent fuel rods.

IAEA inspectors can track nuclear materials entering and leaving a facility if they have access to accurate records and an understanding of a facility's architecture, says Jon Wolfsthal, North Korea nuclear analyst at the Carnegie Endowment for International Peace in Washington, D.C. But Yongbyon would largely be a black box, forcing inspectors to rely on extensive sampling of equipment and the local surroundings for stray particles of nuclear material.

Putting a lid on uranium enrichment—the cause of the recent contretemps—would be even more difficult. Even confirming that North Korea has an enrichment program would be a huge challenge.

As early as 1998, when Alvarez was a senior DOE official, “we were aware that something was going on between North Korea and Pakistan” in gas centrifuges, he says. In such a centrifuge, uranium hexafluoride gas, composed primarily of the isotopes uranium-238 and weapons-grade uranium-235, is spun at twice the speed of sound. Intelligence reports suggested that Pakistan was giving designs for these sophisticated machines to North Korea in exchange for ballistic missiles. Concerns grew in 2000, when the United States discovered that North Korea was attempting to import high-grade aluminum, possibly for the manufacture of centrifuge components.

View this table:

The centrifuges must be linked in a cascade to obtain significant quantities of fissile uranium. To accumulate enough for several bombs, Alvarez says, “they would have to produce thousands of centrifuges.” Just where North Korea might have squirreled away so many centrifuges is an enduring mystery. Sources in the Japanese and U.S. governments have told Science that they have not uncovered any solid information on where North Korea may be enriching uranium. That's not surprising, says Bunn: “Verifying the dismantlement of the facilities you're told about isn't too bad. It's confirming that there aren't any others hidden away somewhere that is the real bear.” The size and power requirement for a centrifuge facility that could produce a bomb's worth of uranium-235 per year, he says, “is about the same as that for a typical Safeway in the United States.” Experts agree that hundreds of centrifuges could stay hidden underground in a relatively small facility.

But one technique might be able to unmask a clandestine laboratory, according to nonproliferation expert Fred McGoldrick of the consulting firm Bengelsdorf, McGoldrick and Associates. Gas centrifuges operate at a higher frequency than power stations provide, requiring frequency converters. These would “reflect a distinct signal back into the line that can be detected,” especially in North Korea's frail electrical grid, McGoldrick argues in a recent working paper from Carnegie and the Nautilus Institute for Security and Sustainability.

In 2000 a trading company in Japan called Meishin attempted to export such converters to North Korea. “At that point we became quite sure that North Korea was pursuing uranium enrichment,” says Osamu Moriya, director of security export control in Japan's Ministry of Economy, Trade, and Industry. Then last April, Japanese officials allege, Meishin tried to send three of the devices by boat to North Korea via Thailand. On a scheduled stop in Hong Kong, customs agents seized the contraband. The incident was a lesson, says Moriya: “North Korea's procurement activities are becoming more cunning.”

Like most analysts, Alvarez believes that the technical hurdles “make uranium enrichment much less of a threat than the DPRK's plutonium production capability.” But negotiators are expected to insist that a freeze on all facets of North Korea's nuclear program be adequately verified. The Bush Administration official told Science that the U.S. will demand measures that are more stringent and intrusive than typical IAEA inspections, including everything from interviewing scientists to installing krypton-85 sensors on North Korean soil. It's not clear, says Bunn, whether North Korea would accept that level of scrutiny. Indeed, the Administration official acknowledges that intrusive verification could delay arrival at any agreement by months—and perhaps even “torpedo any deal.”

The biggest question of all is whether North Korea already possesses a legitimate nuclear arsenal. In its latest unclassified assessment, released last August, the CIA concluded that North Korea has concocted “one or two simple fission-type nuclear weapons and has validated the designs without conducting yield-producing nuclear tests.” Others are not so sure. “A plutonium bomb is easy to make but hard to explode,” says Endo. “They might have a nuclear device, but it might not work as a nuclear weapon.”

As a result, there's considerable uncertainty going into the next round of talks. “We don't have a clear picture of what happens next in the six-party talks,” admits Mori. “We just are not sure of North Korea's final objective: whether they intend to strengthen their ‘nuclear deterrent’ or if they are just bluffing.” If the former, “time is on their side,” notes Endo, as the latest stalemate enters its second year.

9. GENOMICS

# New Sequence Boosts Rats' Research Appeal

1. Elizabeth Pennisi

A concerted effort to unite rat researchers is yielding disease genes, new models, cloning techniques, and a sense of community

COLD SPRING HARBOR, NEW YORK—Mice, watch your tails; the rats are coming. For years mice have reigned as the model animal of choice for biomedical researchers. Small, prolific, and easy to manipulate genetically, mice seem to be the ideal candidate for studying many disease processes. But rats may be better suited for the job, claim their enthusiasts. Rats have long been a favorite of physiologists, who can easily measure and manipulate the rodents' conveniently sized bodies. And now, with new genetic techniques and genomic data coming online, the rat is poised to join the mouse on the lab bench.

Advances are coming from all directions. At a meeting of rat experts here last month,* researchers got their first glimpses of how the ongoing deciphering of the rat genome is leading to new insights into the evolution of this rodent. The sequence has already helped geneticists home in on long-sought genes. Several new rat models were introduced, and other researchers reported progress in making and screening mutants. And for the first time, cloning efforts have yielded adult rats. The increased attendance at this year's annual meeting signaled a reinvigorated rat research community. With all this going for it, “it's likely that the rat will move ahead of the mouse for disease models,” predicts John Critser, a physiologist at the University of Missouri, Columbia.

## Genomic onslaught

When Francis Collins, director of the National Human Genome Research Institute, announced in 1999 his intention to sequence the mouse genome, he was roundly applauded—until a researcher in the back of the room stood up and demanded to know what Collins intended to do about a kindred rodent, the laboratory rat. Collins had no good answer for him. The next few years were a low point for rat research. “Lots of investigators were leaving the rat for mouse because the rat didn't have the genetic and genomic resources,” says Howard Jacob, a systems biologist at the Medical College of Wisconsin in Milwaukee.

Now, thanks to funding from Collins's institute as well as early support from the National Heart, Lung, and Blood Institute (NHLBI), the draft rat genome sequence is online and researchers are taking advantage of the data. Already, “it's been a tremendous resource for the community,” says NHBLI's Susan Old.

A consortium including Baylor College of Medicine in Houston, Texas; Celera Genomics in Rockville, Maryland; Genome Therapeutics Corp. in Waltham, Massachusetts; and several other academic centers started work on sequencing the rat genome in early 2001. They later recruited 70 people from six countries to help with the analysis. By combining the whole-genome shotgun strategy used by Celera to decipher the human genome and the piece-by-piece approach taken by the Human Genome Project, the consortium put together its first assembled sequence in November 2002. Seven months later, the researchers uploaded a second version, which was more accurate and had more of the 2.5 billion bases in order, into the public archive GenBank. A more up-to-date version, including 30 million bases of finished sequence, will be released later this year to coincide with the publishing of the first analyses.

Rat researchers are quite pleased: “They actually got a lot more done than was expected,” says Jacob. The consortium will have sequenced each base an average of seven times. “The quality is very high—almost as good as a finished sequence,” and it rivals that of the mouse, says George Weinstock of Baylor.

As soon as they had an orderly sequence in hand, consortium collaborators rushed to match it up against the human and mouse genomes. “What came out of this was a tremendous amount of information on genome evolution,” Weinstock says. About 39% of the bases are common to all three, and the shared DNA includes about 95% of the regulatory regions and protein-coding DNA for all three species. That's the core mammalian genome, says Ross Hardison of Pennsylvania State University, University Park. Another 700 million bases are specific to the rat and the mouse and may define rodents. Rat-specific DNA comprises the rest, about 750 million bases.

Many of the rat's estimated 26,000 genes—about as many as in mice and humans—are shared with these species. Mice may have up to 1000 more identified genes in common with humans than do rats—perhaps 11,000 in all. Mice and rats appear to have 11,500 that are equivalent, but the genes are often expressed at different times and in different tissues. Further human-rat analyses showed that certain genes in the rat, such as those involved in the immune system, differ from the human versions more than do other genes, such as those involved in the nervous system, suggesting that groups of genes have been subjected to different evolutionary pressures.

Both the mouse and rat genomes resemble the human genome—but shifted into new chromosomal configurations. For example, Guillaume Bourque of the University of Montreal and his colleagues found that there are 19 large-scale arrangements of virtually the same DNA in rat chromosome 10, human chromosome 17, and mouse chromosome 11.

In the rat, duplicated stretches of DNA take up about 3% of its genome, more than the 1.5% or so in the mouse, but less than the 5% to 6% in humans. According to Shaying Zhao of The Institute for Genomic Research in Rockville, Maryland, duplicated pieces of rat DNA have tended to jump from one part of a chromosome to another, whereas those in the mouse often switched to different ones.

Recombination, in which equivalent parts of a chromosome pair swap places, varies among the three species as well. Michael Jensen-Seaman of the Medical College of Wisconsin in Milwaukee and his colleagues calculated that the human genome has recombined up to twice as often as that of either the mouse or the rat. In all three, the rates of recombination vary from one part of the genome to another. With all these insights piling up, “we will soon have answers as to how human chromosomes evolved and how rodent chromosomes evolved,” Weinstock predicts.

For geneticists, the evolutionary insights are just a means to get a better handle on disease genes and aberrant cellular pathways. The genome sequences “have greatly enhanced our ability to conceive and execute experiments in genetic regulation and other key genomic problems,” explains Philip Iannaccone of Northwestern University's Feinberg School of Medicine in Chicago.

Traditionally, it has taken many years and many generations of carefully bred rats to begin to pinpoint a disease gene. Rat researchers celebrate when they narrow the region of interest down to a million bases or so. But then comes the arduous task of testing the genes in that region until they stumble on the right one. “Now we are going to get a better handle on the genes,” says Stanford University's Douglas Vollrath.

At the Mayo Clinic in Rochester, Minnesota, Peter Harris says the new data transformed his search for genes responsible for polycystic kidney disease, which leads to renal failure. He had been tracking down one of these genes in a rat that developed cysts in the kidney and bile duct. At the meeting, he described how scanning genomic information from humans and rats helped him quickly find the responsible gene, PKHD1. It codes for a protein called fibrocystin, which affects the length of cilia, the putative site of the defects in both the kidney and bile duct.

## Genetic maneuvering

Fifteen new rat models of human diseases were introduced at the meeting. One drew the attention of the audience because it may help investigators understand mental illness. Noriko Osumi, a neuroscientist at Tohoku University in Japan, reported that a mutant rat characterized by small eyes improved its social behavior when given a drug used to treat schizophrenia. The mutant, discovered in a laboratory rat colony, was bred for studies of eye development. But Osumi was intrigued because “they are more aggressive and withdrawn.” Tests revealed that they had memory defects and that their brains couldn't filter out irrelevant stimuli—traits also seen in schizophrenic patients. As in humans, the behaviors developed as the rats transitioned into adulthood. The rats have a mutation in the Pax6 gene, and there is some indication that Pax6 expression is abnormal in humans with schizophrenia.

Mutant rodents that occasionally appear in colonies have been a rich source of new rat models. But researchers have not been able to manipulate rats' genetic makeup directly using embryonic stem (ES) cells, as they have done with mice. The standard ES approach is to add or disarm a gene in stem cells, then put the modified DNA into another embryo and monitor the effects in the adult and in subsequent generations. But “ES cells have not been developed [for rats],” says Jacob.

Several groups have turned to cloning as a way to transfer desired genes. A variety of species, from mice to cows, have been cloned by transferring the nucleus from a donor cell to an egg lacking its own genetic material. But with rats, researchers were unable to overcome a fundamental problem: The host cell begins to mature before altered DNA is inserted in it, veering off in the wrong developmental direction.

Last year, Jean Cozzi and Alexandre Fraichard of genOway S.A. in Lyon, France, thought they had the problem licked. They developed a method for pulling out the old DNA and inserting the new in one quick procedure. But they still got no clones. Recently they discovered that adding a protein called M132 delays so-called spontaneous activation long enough to get proper development. In their first try after treating 70 eggs with this chemical, they got three live births, two of which survived, they reported online in Science 25 September 2003 (www.sciencemag.org/cgi/content/abstract/1088313). Those two are thriving, the researchers reported at the meeting.

Iannaccone also had good news about cloning. Like the genOway researchers, he had been stumped for a long time: Even though some embryos implanted into the surrogate female's uterus, they failed to develop. He and his colleagues solved this problem by adding drugs to the oocyte that interfere with the formation of microscopic protein fibers that help with DNA replication. “We are just starting these experiments,” he notes, so they do not yet know how successful they will be in producing adult clones.

Cloning is still a technical challenge, says Jacob. He is more optimistic about new chemical methods that create lots of random mutations. For decades, mouse biologists have used a chemical called ENU to generate mutants, which are then screened one by one for genetic defects. Massive high-throughput efforts are currently producing mouse mutants for every gene.

Several research teams have adapted ENU mutagenesis for rats. One company, Ingenium Pharmaceuticals in Martinsried, Germany, plans ultimately to have two mutants for every gene. Thus far, they have created 140 mutants, Ingenium's Thomas Peters reported.

Michael Gould of the University of Wisconsin, Madison, and his colleagues use a biomarker in yeast to find the right rat for the gene they want to study. After rats have been exposed to ENU and bred, he isolates DNA from the pups' tails to determine which offspring have mutations of the gene of interest—some of which may be functional, others not. He merges copies of the target gene with yeast DNA that contains a gene called ADE2. This chimeric DNA is put into yeast that lack the ADE2 gene. If the rat gene is functional, the newly added ADE2 gene takes over for the yeast's defective ADE2 gene. When that happens, red yeast colonies turn white, and Gould knows he's got a good mutation. “The strategy is very clever,” says Jacob, allowing researchers to screen mutagenized rats quickly.

Scientific and technological advances aside, there are other signs that rat research is up and coming. The first meeting of its kind took place 4 years ago. The goal was to organize the rat research community, then divided among groups that identified with particular disciplines, such as cardiovascular research or neurobiology. It was clear from the successes of nematode, fruit fly, and Arabidopsis researchers that presenting a uniform front helped raise funding, particularly for genome sequencing. The plan seems to be working, says Jacob. The number of meeting abstracts jumped from 88 in 1999 to 120 in 2003, and attendance grew by 50%. The sequence “continues to draw us together and to add new committed scientists to those who already use the rat in the work,” Iannaccone says.

This incipient community is working to improve the sharing of resources. Jacob explains that rat researchers “have not had a Jackson Lab.” This Bar Harbor, Maine, nonprofit develops and keeps mouse models that researchers all over the world can request. In contrast, rat models have been developed one by one, proliferating in small labs, which have been saddled with distributing those animals to other investigators. The rapidly increasing number of strains is making it hard for researchers to keep up this practice. About 500 exist now, and Jacob expects that number to double or triple in the next few years.

In 1993, the National Institutes of Health (NIH) set up a rat repository of frozen embryos that provided some relief, shifting away from a decades' old practice of keeping live animals. According to William Rall, a physiologist at NIH's Veterinary Resources Program, its freezers hold frozen embryos of 157 rat models, including 87 related to autoimmune diseases. Until this year, his group supplied animals derived from these embryos. But the operation recently lost NIH funding. Instead, model rats are coming from the Rat Resource and Research Center at the University of Missouri, Columbia. Already this 2-year-old center is overflowing, says Critser, as the number of researchers contributing models has far exceed expectations.

These resources should make investigators sit up and take notice of the rat's rich experimental history. “The physiology is worked out better than in mice,” says Jacob. In addition, some biologists contend that, biologically, rats are much more like humans than are mice. And that gives Jacob and other rat researchers hope for the future. No longer, he predicts, will they have to “spend a lot of time explaining just why we exist.”

• * Rat Genomics and Models, 11 to 14 December 2003.

10. ARTHUR CARTY PROFILE

1. Wayne Kondro*
1. Wayne Kondro writes from Ottawa.

Canadian Prime Minister Paul Martin created the post of national science adviser—and chose a British-born chemist who has shown that basic research can pay off

OTTAWA—Canadian scientists are about to place their hopes—somewhat nervously—on Arthur Carty, a British-born organometallic chemist-turned-science administrator. On 1 April, Carty takes office as Canada's first national science adviser.

The nervousness stems from the fact that Carty's new boss, Prime Minister Paul Martin, dropped science from its junior cabinet status shortly after taking office in November. That's left some Canadian scientists wondering if Martin's creation of the science adviser's position, and Carty's appointment to the post, is mere window-dressing.

Carty's supporters are confident that he'll make his presence felt. After all, as head of the National Research Council (NRC) for the past decade, Carty turned a moribund government research agency into a lively place of discovery. He's played midwife to 55 spinoff companies, including one whose products include some of the animated figures in the current smash-hit Lord of the Rings movie trilogy. And he's shepherded collaborations with more than three dozen Canadian universities and dozens of European research institutes. Carty ran NRC with the conviction that science must serve economic development more directly—a philosophy that appealed greatly to his new boss.

“He is the hardest-working person at NRC, without doubt,” says Peter Hackett, NRC's vice president for research, who marvels at Carty's “driven” personality and his 6 a.m. arrivals at the office. University of Ottawa chemist Howard Alper speaks for many when he talks optimistically of Carty's opportunity “to carve out a role as the country's inaugural science adviser.”

Some observers worry that Carty will be the one to be carved up and spat out. “You need sharp elbows to be around these guys,” says one senior Liberal Party official about Martin—a shipping tycoon who led a successful 2-year civil war within the party against longtime leader Jean Chrétien—and his team. “And I'm not sure Arthur has them.”

There will be no shortage of early tests. Carty is hoping to elbow his way into top-level discussions of issues such as promoting greater commercialization of university research, more industrial innovation, and more collaboration with government labs. Many scientists wish the list were longer and included more attention to boosting academic research and restoring core support to universities. “We're worried that the Martin government does not fully appreciate the importance of basic research. The emphasis on commercialization of research suggests a narrow view that you can tell ahead of time what research is going to be relevant,” says Jim Turk, executive director of the Canadian Association of University Teachers.

The new science adviser also hopes to help Canada find the best way to support “big science,” both domestic projects such as a proposed research reactor in Chalk River and proposed international programs such as a Mars mission or the International Thermonuclear Experimental Reactor. Proponents were forced to withdraw their offer to host the reactor after the federal cabinet was unable to decide whether the government would support the bid.

## Cooking up new ideas

Carty's journey to the dark-paneled rooms of Langevin Block on Parliament Hill in this capital city began in postwar England. A miner's son, Carty fell in love with science doing late-night chemistry experiments as a schoolboy in the tiny village of Hookergate. He received a state scholarship to the nearby University of Nottingham, where he earned a chemistry Ph.D., and then crossed the Atlantic to follow his mentor, Eric Bullock, to Memorial University of Newfoundland. Two years later he moved to the University of Waterloo, where he spent 27 years as a professor and later dean of research. “He did really outstanding work on metal clusters,” says Alper. During his scientific career, Carty garnered international honors, including the Order of Canada and France's National Order of Merit.

In 1994, at the age of 53, Carty was named president of NRC—and was told almost immediately to pare $69 million from its$455 million budget. The cuts, part of a government-wide retrenchment to erase a deficit, gave Carty an opportunity to invite the 1200 science professionals working at 23 themed institutes across the country to help set priorities for the 88-year-old institution. From those meetings flowed a resurrected postdoctoral program, a spate of international collaborations, and rewards for scientists who commercialized their discoveries. “We've got a much more democratic [institute],” says Hackett. “There are more fresh ideas.”

One of Carty's proudest achievements is the entrepreneurial spirit that now pervades the organization. One shining example is the work of NRC physics engineer Marc Rioux, who developed a laser that captures the geometry and color of objects in three-dimensional images with exquisite precision. Although the technology was originally aimed at museums that wanted to reproduce images of their collections, industrial designer-turned-entrepreneur Helmut Kungl had a notion that it might also apply to the entertainment industry. Working for a firm licensed to develop cameras using Rioux's technology, Kungl went to a ToysUs store, bought a cave troll figurine, scanned it with the laser camera, and sent both the figurine and the image to Peter Jackson, director of the movie version of J.R.R. Tolkien's Lord of the Rings trilogy.

The rest, as they say, is history. Kungl founded a company, XYZ RGB, that created the images of Shelob, the spider, and other wondrous creatures seen in The Return of the King, the final part of the trilogy, which is now breaking box-office records. “The NRC have done a lot of the grunt work for us,” says Kungl, referring to the $11.5 million that NRC invested over the years in Rioux's work. “As a new company, we definitely couldn't have done it without them.” Two years later, Kungl and his team of six are looking to turn an annual profit of$1 million from work on films like the recently released Peter Pan and Jackson's forthcoming remake of King Kong.

Along with promoting spinoffs, NRC labs are also now involved in 111 collaborative agreements with 38 universities, while generating $96 million annually through licensing agreements and contract research. It leads in promoting so-called technology clusters in which NRC, typically in conjunction with a local university and a provincial lab, conducts research to spur the growth of an indigenous industry. Areas of activity include a new fuel-cell industry in Vancouver, value-added aluminum products in Ville Saguenay, photonics in Ottawa, and nanotechnology in Edmonton. In service of those clusters, NRC has sprouted several new institutes, such as the$92 million Institute of Nanotechnology being jointly built by NRC and the provincial government at the University of Alberta campus in Edmonton. “We've turned from being an inward-looking organization to an outward-looking organization,” Carty says.

Carty initially took considerable heat for ostensibly turning the agency into a toolbox for industry. But those concerns dissipated when it became apparent that Carty was simultaneously demanding that the agency live up to higher standards of scientific excellence. It was a straightforward quid pro quo: If Canadians wanted science to serve economic needs, the government should be willing to simultaneously provide funds for top-notch research.

The government has kept up its end of the bargain. NRC's budget rebounded, to $610 million this year. That includes a$460 million core federal component—roughly what Carty inherited a decade ago before the cutbacks—as well as a special allocation of \$54 million a year for contributions to instruments such as the Tri-University Meson Facility in British Columbia.

Thomas Brzustowski, president of Canada's major funding council for the natural sciences and engineering and a close friend since both were at Waterloo, says Carty has done a remarkable job of balancing NRC's need for high-quality basic research with industrially relevant work. “He's managed to stand on two logs and drift downstream and maybe even go over a few rapids. And the logs haven't spread apart.”

Doubtless, the rapids will get whiter when Carty becomes Canada's scientist-in-chief. He hopes that his stature as an active scientist—he's maintained a productive lab at NRC and plans to do the same in his new job—will buy him some political cachet. “It counts for something,” says Carty, who's also an avid cyclist, cross-country skier, and collector of Inuit sculpture.

Not surprisingly, Carty doesn't buy the argument that his new boss is indifferent to the cause of Canadian research: “I have a firm belief that Martin's interest in science goes beyond the periphery.” He also expects that his office will receive adequate financing and staff to do the job properly. “I'm not going to get into this with just a secretary,” he warns. “There has to be enough resources to hire bright people and to provide the appropriate advice.”

Asked why he accepted the post, Carty says that “it's not easy to refuse” an offer from the prime minister to influence science policy at the highest level. And he likens his new post to the NRC job in the sense that both offer him the opportunity “to do something much bigger than I'd tried before.”

11. AMERICAN ASTRONOMICAL SOCIETY MEETING

# Early Galaxies Baffle Observers, But Theorists Shrug

1. Robert Irion

ATLANTA, GEORGIA—Just after NASA's Spirit rover bounced onto Mars, about 2000 astronomers roved here 4 to 8 January to discuss more distant objects at the 203rd meeting of the American Astronomical Society.

“It's not quite time for theorists to panic, but we're getting there,” said astronomer Roberto Abraham of the University of Toronto, Canada, after announcing his group's discovery of a startling number of mature galaxies in the young universe. But although the finding seemed to undermine the standard view of how matter assembled, theorists have respectfully declined to sound the alarm.

Abraham and several colleagues described the newly finished Gemini Deep Deep Survey, an ambitious program with the 8- meter Gemini North telescope at Mauna Kea, Hawaii. The survey is among many efforts worldwide to examine large numbers of galaxies that existed when the cosmos was a fraction of its current age. Such galaxies, astronomers have assumed, trace the way that gravity segregated matter through space as the universe aged. And according to reigning theoretical models, clumps and webs of matter grew until galaxies arose inside massive halos of invisible dark matter. In that “hierarchical” picture, shards of protogalaxies took billions of years to merge and assemble the grand spirals and giant elliptical blobs we see today.

The new results seem to contradict that neat idea. Using a clever technique to subtract the sky's brightness from images of faint galactic targets, Gemini astronomers found about 300 full-size elliptical galaxies populating a small swath of space when the universe was just 3 billion to 6 billion years old. That's roughly 100 times more than expected in some theories, the team claims. “The prediction from hierarchical models is that galaxies should be incredibly little lumps at this time,” says team co-leader Karl Glazebrook of Johns Hopkins University in Baltimore, Maryland.

But the gulf isn't as wide as it appears, says cosmologist Joel Primack of the University of California, Santa Cruz. Theories actually succeed quite well in reproducing the correct sizes and masses of the dominant constituents of galaxies, their dark-matter halos. But they fail to explain why the bright lights within the lumps—great waves of star formation that spawned visible galaxies—turned on when and where they did. “We understand that least of all, and it's the hardest problem in astrophysics,” Primack says.

In particular, today's models can illuminate the web of dark matter with young “starburst” galaxies—which other surveys have detected—but not quiescent elliptical galaxies during the epoch covered by the Gemini survey, says cosmologist Rachel Somerville of the Space Telescope Science Institute in Baltimore. “These results are a long way from ruling out the paradigm of hierarchical structure formation, but they do teach us important lessons about the physics that regulates star formation in early galaxies,” she says. Count on theorists to tune their star-formation dials as more results stream in from ongoing scans of the deep sky.

12. AMERICAN ASTRONOMICAL SOCIETY MEETING

# Star Formation--An Extreme Sport?

1. Robert Irion

ATLANTA, GEORGIA—Just after NASA's Spirit rover bounced onto Mars, about 2000 astronomers roved here 4 to 8 January to discuss more distant objects at the 203rd meeting of the American Astronomical Society.

Astronomers aren't immune to the “fastest, brightest, biggest” headlines that pervade our Guinness Book of World Records society. Taken separately, three reports at the meeting fit the superlative mold. But as a group, the results go beyond superficiality to suggest that theories of star birth haven't properly considered the roles of violent, impulsive events.

In the “brightest” category lies a gigantic star called LBV 1806–20, on the far side of our galaxy's center. New infrared images from the 5-meter telescope at Palomar Observatory near San Diego, California, pierced dust clouds between Earth and the star. A group led by astronomer Stephen Eikenberry of the University of Florida, Gainesville, estimates that the star is 150 times more massive than the sun and up to 40 million times brighter—several times more luminous than the previous king.

Current models of star formation predict that the energy output from such massive objects should blow them apart when fusion ignites at their cores. The star's weird neighbors suggest a solution, Eikenberry says. LBV 1806–20 inhabits a cluster with other giant stars and a rare “magnetar”: a neutron star with an ultrastrong magnetic field. Eikenberry thinks that shock waves from a powerful supernova—which created the magnetar—compressed nearby gas enough to overcome the outward pressure of the new star's fierce furnace. Other astronomers are intrigued, but they want more proof that the star isn't a tight multiple system mimicking a single object.

The galaxy's “biggest” star-forming shocks might come from entire globular clusters of stars, according to another team. Astronomer Richard Rees of Westfield State College in Massachusetts and colleagues used sky photos spanning more than a century to trace the 3D motions of globular cluster NGC 6397, which contains a few hundred thousand stars. During its looping orbit around the Milky Way, the cluster dived through the galaxy's gas-filled disk about 5 million years ago. The spot of that passing impact, Rees says, matches the probable birth site of NGC 6231, a nest of dozens of extremely hot young stars.

Gravitational upheaval from the globular cluster's swift passage through the disk may have compressed the other cluster's parent cloud, an idea first proposed in 1996 by computational astrophysicist John Wallin of George Mason University in Fairfax, Virginia. If true, globular transits could set off major bouts of star formation; Wallin notes that they happen every million years or so.

Tracking down the “fastest” prizewinner also took nifty detective work. Astronomer Alyssa Goodman of the Harvard-Smithsonian Center for Astrophysics in Cambridge, Massachusetts, and a co-worker noticed an oddity in jets of material ejected in opposite directions from a young star called PV Ceph. The launching points of three pairs of jets appeared to trace backward toward a young cluster about 30 light-years away, a long way for a newly fledged star to travel.

When the researchers reconstructed the star's path, they deduced that it has zipped through space for 500,000 years at 22 kilometers per second, a rate Goodman calls “bizarrely fast.” She thinks a gravitational slingshot interaction with another star rifled PV Ceph out of its gas cloud before it finished forming, blasting a visible dark gap in the nebula as it exited.

Goodman's evidence is compelling, says astronomer Ray Jayawardhana of the University of Michigan, Ann Arbor. “We need to pay more attention to the dynamics of star formation,” he notes—an assessment that might well apply to all three extreme scenarios.

13. AMERICAN ASTRONOMICAL SOCIETY MEETING

# A Hot Jupiter Sears Its Parent Star

1. Robert Irion

ATLANTA, GEORGIA—Just after NASA's Spirit rover bounced onto Mars, about 2000 astronomers roved here 4 to 8 January to discuss more distant objects at the 203rd meeting of the American Astronomical Society.

Stars are typically thousands of times more massive than the planets they spawn, even if the offspring are Jupiter-sized behemoths. But one planet has overcome its size disadvantage to create a visible mark on its parent star, astronomers reported. The hot scar, probably sparked by a magnetic interaction, should allow theorists to gauge the strength of the planet's magnetic field. “This opens a completely new realm of extrasolar planetary physics,” says theorist Manfred Cuntz of the University of Texas, Arlington.

Cuntz and two co-authors predicted 4 years ago that tightly orbiting giant planets—so-called hot Jupiters—could create a noticeable reaction in their stars' atmospheres via magnetic forces or tidal attraction. Cuntz recalls that some researchers dismissed the notion, objecting that random fluctuations from stars would mask such signals. Even so, one team started to search for the effects, led by graduate student Evgenya Shkolnik of the University of British Columbia in Vancouver, Canada.

Shkolnik and her colleagues used the 3.6-meter Canada-France-Hawaii Telescope at Mauna Kea in Hawaii to study five sunlike stars with large, close-in planets. The planets race around their stars every 3 to 5 days in sweltering orbits just 10% of Mercury's distance from the sun. The team examined ultraviolet emissions from the stars for extra light from excited calcium atoms, ionized by disturbances in a layer of hot gas just above the visible surface. Most of the stars varied, but the light from a star called HD 179949 waxed and waned in a regular pattern.

When the team scrutinized the signals, collected during three different observing runs, they realized that the emissions tracked the 3.1-day orbital period of the star's planet. “The hot spot kept pace with the planet in precise phase for more than a year,” Shkolnik says. At 400°C hotter than the gas around it, the bright patch emits extra light revolving at a faster rate than the star's 9-day rotation speed.

Cuntz believes that the inverse sunspot arises from constant entanglement between lines of magnetic force from the star and the planet, which should have a Jupiter-style magnetic field. This connection may resemble the impulsive magnetic events on our sun that launch flares, Cuntz says, but the details require new physics to grasp. His group is trying to calculate the strength of the planet's field, based on the spot's brightness.

Although Shkolnik's team is now hunting for a stronger infrared signal from HD 179949 as confirmation, the initial data convinced astronomer Gibor Basri of the University of California, Berkeley. “There is an example of this in our solar system,” he notes. Charged particles from the volcanic moon Io, the innermost of Jupiter's large satellites, trigger radio emissions from Jupiter's magnetic field and even auroras in the planet's atmosphere.

14. AMERICAN ASTRONOMICAL SOCIETY MEETING

# Snapshots From the Meeting

1. Robert Irion

Solar sibling. A faint star in the constellation Scorpio is a dead ringer for our sun, a team of astronomers from Villanova University in Pennsylvania reported. The star 18 Scorpii, about 47 light-years away and barely visible to the eye, shares the sun's mass, temperature, chemical composition, rotation speed, and age. The star's level of activity from sunspots, as gauged by ultraviolet and x-ray emissions, also looks similar to the sun's. Astronomers will keep monitoring this “solar twin” for unusual outbursts or variations in brightness that could foretell active episodes in the sun's future.

Metal factory. Astronomers have found the richest lode of heavy elements yet seen beyond our solar system. The Chandra X-ray Observatory spied brilliant multimillion-degree knots of iron, magnesium, and silicon within the violently colliding Antennae galaxies. The ongoing crash triggers countless supernova explosions, which forge the hot lodes of metal. In some spots, concentrations of magnesium and silicon are about 20 times higher than in our sun, says astronomer Giuseppina Fabbiano of the Harvard-Smithsonian Center for Astrophysics. Such collisions could build billions of rocky planets in a wave of galactic “rejuvenation,” she says.

Galactic loners. Just one of every 10,000 galaxies is truly “isolated” in space. The surprisingly low statistic comes from an analysis of 20 million galaxies in the Sloan Digital Sky Survey. All but 2980 galaxies have a bright neighbor within about 2 million light-years—roughly the distance between our Milky Way and the Andromeda galaxy. The research illustrates that gravity continues to draw most galaxies together, says astronomer Douglas Tucker of the Fermi National Accelerator Laboratory in Batavia, Illinois. Indeed, galaxy mergers are at least four times more common than isolated galaxies in the survey.