News this Week

Science  28 May 2004:
Vol. 304, Issue 5675, pp. 180
1. TECHNOLOGY TRANSFER

U.S. Scientists Faulted on Biotech Consulting

1. Jocelyn Kaiser

Until last week, two federal scientists with a hot new idea for using proteins in blood to detect cancer were on a roll. They had teamed up with a bioinformatics company in Bethesda, Maryland, called Correlogic Systems, published a high-profile proof of principle in The Lancet, and launched a clinical research program that attracted hundreds of outsiders. They worked out an unusual collaboration between their agencies, the National Cancer Institute (NCI) and the Food and Drug Administration (FDA). And they had signed up as consultants with a second firm, Biospect Inc. in South San Francisco.

Then the roll came to a halt. The co-inventors—NCI's Lance Liotta and FDA's Emanuel Petricoin—got caught up in an ongoing investigation of federal scientists' interactions with industry. A Capitol Hill committee summoned them on 18 May to respond to allegations of improper conduct. Their supposed misdeed: They had become paid consultants for Biospect (now called Predicant Biosciences) without informing Correlogic, which claims that the deal risked helping a competitor.

House Oversight and Investigations Subcommittee chair James Greenwood (R-PA) and other panel members said this “secret” consulting may have slowed a public-private partnership on a lifesaving cancer test. “This is an outrage,” Greenwood said, calling it an example of poor oversight by the National Institutes of Health (NIH) (Science, 21 May, p. 1091). Liotta and Petricoin respond that they fully complied with their agencies' ethics rules, and their consulting agreements were officially approved.

The issue dates back to April 2002, when NCI and FDA signed a Cooperative Research and Development Agreement (CRADA) with Correlogic. According to a summary, the partners were to “utilize Correlogic's proprietary software technology” to identify protein patterns indicating disease states. Correlogic also signed an exclusive licensing agreement with NCI to commercialize the technology.

A few months later, Liotta and Petricoin were approached by Biospect, a new company with close ties to NCI: Former NCI Director Richard Klausner was a board member, and two former NCI tech-transfer officials were employees. Liotta and Petricoin received approval from their NCI and FDA ethics officers to consult at a rate eventually set at $3250 for 1 day a month. In testimony last week, Petricoin said they were paid to “survey the public domain for applications” for Biospect's technology, which Liotta described as instrumentation for separating and analyzing biological fluids. Explicitly excluded from their agreements was “pattern analysis,” Correlogic's specialty. A year ago, Correlogic CEO Peter Levine told Science, he heard from “people in the industry” about Liotta and Petricoin's Biospect activities. He also bumped into them in a Bethesda building where the two companies both rented office space. “I was shocked,” Levine says. “These are the same two gentlemen we were sharing all our thinking and planning with.” Levine complained in July 2003 to NCI, which rereviewed Liotta's consulting agreement. NCI officials Anna Barker and Carl Barrett testified that they found no conflict with Liotta's official duties. But by that time, Levine says, “we became very guarded in what we would say” to Liotta and Petricoin. Until a few weeks ago, NIH appears to have continued to support Liotta's Biospect deal, from which he has earned$49,375. A 4 May printout from NCI's ethics database deemed the arrangement “recommended,” even though the companies “do business in the same area,” because Barrett concluded that the work differed from Liotta's official duties on the CRADA with Correlogic. But an NCI ethics official added the note that “this is a very technical distinction” and flagged the case for higher review. The debate soon became moot: Liotta ended the agreement after learning that Biospect had downloaded NCI's publicly available protein- spectrum data. He could not be “absolutely sure” Biospect's research would not “overlap with my government work,” he testified. Petricoin also ended his consultancy after FDA concluded that the agency regulates Biospect's activities. FDA is now launching a review of all staff consulting agreements.

Today, an NIH official says that the agency would not approve Liotta's request because of the “appearance” of a conflict. Levine argues that the scientists could not have kept the two companies' work separate: “If you're being paid $3250 a day by a client, you're going to forget where you learned something.” What would have been the right thing to do? Greenwood suggested that NIH should have told Correlogic of the proposed Biospect deal and asked for prior approval. Petricoin questioned that, however. Taken to an extreme, “they could claim that the field of technology is their domain” and “there would be only one CRADA: the very first one,” he said. Some tech-transfer officials agree that more than one CRADA for a given technology can be desirable. The Correlogic situation “is a tradeoff,” says John Raubitschek, patent counsel for the Department of Commerce. The only good news for NIH was that the committee praised NIH Director Elias Zerhouni for taking steps to disclose more information. Last week, for example, he ordered NIH staff to report past consulting agreements. “We are starting to achieve positive changes,” said Commerce Committee chair Joe Barton (R-TX). Greenwood expects to hold at least one more hearing on conflicts at NIH. 2. SEVERE ACUTE RESPIRATORY SYNDROME Lab Accidents Prompt Calls for New Containment Program 1. Dennis Normile* 1. With reporting by Ding Yimin in Beijing. While breathing a sign of relief that the latest outbreak of severe acute respiratory syndrome (SARS) in China is over, health officials are still deeply troubled that they have not pinpointed the original source of the infection. They are also questioning whether research on the virus should be restricted to prevent further lab accidents. Investigators are convinced that the infections in April involved two separate biosafety lapses within the Institute of Virology at China's Center for Disease Control and Prevention in Beijing. But they have been unable to pin down what went wrong. With four separate infections within the last year at three different institutions in Beijing, Singapore, and Taipei, health experts fear that the next SARS epidemic may be more likely to emerge from a research lab than from the presumed animal reservoir. “We need a global containment program for SARS,” says Julie Hall, the World Health Organization (WHO) coordinator for communicable disease surveillance and response in Beijing. Such a program would involve reducing the number of labs working with the SARS virus and ensuring that the research is done by “fully trained people in proper facilities with the right supervision,” she says. It would be modeled on existing programs for smallpox and polio. She adds that discussions are just getting started and any program will take time to set up. For the moment, experts from WHO and China's Ministry of Health are trying to clarify the source of the initial infections, which eventually resulted in nine confirmed cases and one death. “We feel reasonably confident that they were infected in the Institute of Virology,” Hall says. “But we have not been able to identify a particular spill, or a single needle stick injury, or any one particular event” that led to infection. It is clear that the two researchers became infected in separate incidents. One was working with fragments of the SARS viral genome, which should not be able to cause disease. The other's research did not involve SARS at all. Hall says that the institute's biosafety level 3 lab, which WHO recommends for work involving viral cell cultures and manipulations involving growth or concentration of the SARS virus, is new, well-equipped, and capable of properly containing the virus. But the infections are believed to have occurred outside the biosafety level 3 area, where some research involving the inactivated or killed virus was apparently conducted. Hall says investigators are looking for contamination or evidence that researchers may have been unknowingly working with live, instead of properly inactivated, virus. But they are dubious about finding a definitive answer. “I don't think we're ever going to get to ‘Aha! It was this day and this time,’” she says. In the meantime, she says, problems uncovered during the investigation “raise questions about the management structure and the training of staff.” Bi Shengli, deputy director of the Institute of Virology, says that conclusions about any management or training problems should await the findings of the expert teams. But the institute has suspended all SARS-related research projects. “We are working together with experts from the Ministry of Health to establish biosafety principles before we restart our lab work,” Bi says. The Ministry of Health has also been sending teams of biosafety experts to check on containment facilities and practices at labs throughout China. Hall says a global control program is “somewhere between just thoughts and steps being taken.” But it seems to be gathering support within the research community. “This virus has been distributed to too many labs” in the United States and Europe as well as Asia, says Ronald Atlas, a biosafety expert at the University of Louisville, Kentucky. At the least, he says, a network is needed to track who is working with which samples of the virus. 3. CONSERVATION BIOLOGY Rebels Seize Research Team in Colombia 1. David Malakoff Biologists have launched an international campaign to win the release of two scientists and their guide who were kidnapped last month by Colombian guerrillas. The three men were seized as they conducted an ecological survey in northern Colombia. The Revolutionary Armed Forces of Colombia (FARC), a violent insurgency group known for ransoming abductees, has claimed responsibility. The team—ornithologist Diego Calderón of the University of Antioquia in Medellín, botanist Hermes Cuadros of the University of the Atlantic in Barranquilla, and guide José Saurith from Manaure—arrived in the mountains along the Venezuelan border early last month to prepare a biological survey of a potential national park. The researchers had heard rumors of nearby guerrilla activity, says biologist Andrés Cuervo, a graduate student at the University of Puerto Rico in San Juan. FARC abducted the men on 17 April, and word of the kidnappings soon spread worldwide. Calderón is a founding member of Colombia's new Ornithological Association and, although still a graduate student, is a rising star in the international bird science community. He is also a diabetic who needs twice-daily shots of insulin. Cuadros is an expert on Colombian flora and a former director of Cartagena's botanical garden. Institutions and individuals have flooded a FARC Web site with messages condemning the kidnappings (see www.rnoa.org/indexnuevo.html), and last weekend several dozen groups in Colombia and other nations staged “Birding for Freedom” walks and demonstrations. The events “let FARC know what the heck an ornithologist does in the field,” says Cuervo. Supporters hope that publicizing the abductions will put pressure on FARC to free the men—and dramatize the threat facing all field researchers in Colombia. “Many biologists simply don't go further than city boundaries or a few safe places,” says Cuervo. 4. CLIMATE CHANGE Russia Prepares to Ratify Kyoto 1. Vladimir Pokrovsky, 2. Andrey Allakhverdov* 1. Vladimir Pokrovsky and Andrey Allakhverdov are writers in Moscow. MOSCOW—Snubbing a new report from the Russian Academy of Sciences (RAS), President Vladimir Putin has promised that Russia will move to ratify the Kyoto Protocol to curb greenhouse gas emissions. Russia's ratification would bring the treaty into force. Putin has been coy on commitment, even joking last fall at a conference about the economic benefits of melting permafrost. But on 21 May, after Russia and the European Union had agreed on Russia joining the World Trade Organization, Putin pledged to “hasten Russia's steps towards ratification of the Kyoto Protocol.” That statement marked a sharp turnabout from 3 days earlier, when the Putin Administration announced that it had received the RAS report and “would make a decision that meets Russia's interests.” The RAS panel included academy president Yuri Osipov and ardent treaty critic Andrey Illarionov, an economic adviser to Putin. Illarionov has sought to rebut the view that Russia stands to reap a windfall by selling carbon credits, arguing instead that a vibrant economy would soon bring Russia back above 1990 emissions levels, the Kyoto cap. That view held sway within the panel, says chair Yuri Israel, director of the Global Climate Institute in Moscow. To hew to Soviet-era levels, “we will have to develop or buy new technologies very soon,” he says. At its final meeting on 14 May, he says, the panel concluded that the protocol “does not have a scientific basis and is ineffective at stabilizing greenhouse gases.” Observers suspect that Putin was using Kyoto as a bargaining chip all along. “I bear no grudge,” says Israel, who notes that the RAS report—released early this week—did not explicitly advise Putin on ratification. That, he says, “is a political decision.” 5. MARS EXPLORATION ESA Licks Wounds, But Beagle's Loss Remains a Mystery 1. Daniel Clery* 1. With reporting by Richard Kerr. LONDON—No one may ever know what happened to Beagle 2, the diminutive British spacecraft that was due to land on Mars last Christmas Day but has remained stubbornly silent ever since. But the consequences of its loss, detailed at a press conference here earlier this week, will profoundly change how Europe manages future space missions. At the briefing the British government and the European Space Agency (ESA) released a set of 19 recommendations from a postmortem, sans body, of Beagle 2. But they withheld the bulk of the report, citing commercial aerospace secrets. Although the inquiry found no single technical reason to explain the failure, it noted a number of institutional failings that raised the mission's risk level, said David Southwood, ESA's director of science. “No one was to blame, but everyone was to blame,” said Southwood, who criticized the “entrepreneurial” style in which Beagle 2 was run. Beagle 2 and its “mother ship” Mars Express were born of another failure: Russia's Mars 96 mission, lost after an unsuccessful launch. Many European teams had contributed to that spacecraft, and in 1997, ESA opted to use backup instruments and expertise to launch its own mission. The plan included space for a small lander, and Beagle 2, led by Colin Pillinger of the Open University in Milton Keynes, won the slot. Pillinger embarked on a media campaign to persuade companies to pony up. Although he secured artistic contributions from the rock band Blur and artist Damien Hirst, commercial sponsors proved elusive. In the end, Beagle 2's$76 million cost was met by the Open University, contractor EADS Astrium, various U.K. ministries and agencies, and ESA.

On 19 December 2003, only a few days from Mars, Beagle 2 separated from Mars Express, apparently faultlessly. Because of the probe's tiny size, roughly that of a car tire, the team had opted to forgo a telemetry link to relay how the descent was going. With no hard data to go on, Southwood listed a number of possible scenarios for Beagle 2's loss. The martian atmosphere could have been more dense—or less dense—than expected that day, causing the craft to bounce off the atmosphere, burn up, or descend too fast. Once in the atmosphere, the craft was designed to jettison its covers, deploy a parachute, and inflate its air bags before impact. Anticipated shortcomings in air-bag performance had forced the Beagle 2 team to redesign the parachute on the eve of the mission. The covers might have become entangled with the parachute, or the chute might have wrapped around the lander, trapping it in a cocoon, Southwood said.

The inquiry saved its toughest talk for management. “The lander was treated as an instrument, not as part of the spacecraft,” said U.K. science minister David Sainsbury. ESA had limited control over Beagle 2, noted Southwood, essentially ensuring that it was safe to launch and would not compromise Mars Express or contaminate the surface. As a result, the recommendations specify that a national agency or ESA oversee future landers, full funding be agreed before approval, more resources be spent on testing, and communications be adequate to monitor landings.

At the press conference, Pillinger made light of the recommendations, calling them “motherhood statements.” “We gave Beagle the best shot we could within the constraints imposed on us,” he said. “If you want to add some spice to people's lives, you have to take some risks.” Others see a more serious take-home message. “It's a pretty thorough indictment of the way the project was managed,” says space policy analyst John Logsdon of George Washington University in Washington, D.C.

Pillinger said he would be pushing ESA to launch a new Beagle at the earliest opportunity. Southwood said ESA will consult with the scientific community first, but he foresees a simple lander, to be launched in 2009, again focusing on astrobiology. He hoped to have a plan in place for a meeting of European ministers this fall.

6. NUCLEAR ASTROPHYSICS

New Measurement of Stellar Fusion Makes Old Stars Even Older

1. Kim Krieger

A key nuclear reaction inside stars takes significantly longer than standard models assume, European researchers have discovered. The result, which nuclear physicists at the Laboratory for Underground Nuclear Astrophysics (LUNA) in Gran Sasso, Italy, report in a pair of online papers, implies that the most ancient star clusters are at least 700 million years older than previously believed.

“The LUNA experiment is beautiful,” says John Bahcall, an astrophysicist at the Institute for Advanced Study in Princeton, New Jersey, praising the group as “magically gifted experimentalists.”

The LUNA team used an underground particle accelerator at Gran Sasso to measure the speed of the carbon-nitrogen-oxygen (CNO) cycle, one of the pathways by which stars fuse hydrogen into helium, releasing energy (see diagram). The cycle determines how long it takes a youthful hydrogen-burning star to turn into a giant helium burner. Astrophysicists can estimate the age of a star on the cusp of that transition by measuring its mass and then calculating how long it took to reach its current state.

The CNO cycle, however, is only as fast as its slowest step: a nuclear reaction in which the isotope nitrogen-14 absorbs a proton from hydrogen and turns into oxygen-15. Researchers had estimated the rate of the reaction by shooting protons at nitrogen-14 in particle accelerators. But the measurements were marred by noise from cosmic rays, and astrophysicists suspected they erred on the speedy side.

In papers scheduled to be published in Physics Letters B and Astronomy and Astrophysics, the LUNA researchers report that the limiting step is indeed only half as rapid as previously assumed. Working 1400 meters underground to shield their detectors from cosmic radiation, they smashed protons into a nitrogen-14 target and then measured the gamma rays the nitrogen released as it became oxygen-15. The results push the age of the oldest stars to almost 14 billion years. That's close to the figure of 13.7 billion years for the age of the universe that physicists derived from measurements by the Wilkinson Microwave Anisotropy Probe (Science, 14 February 2003, p. 991), although both still have significant uncertainties, Bahcall says.

The team plans to repeat the experiment at more realistic collision energies, says Carlo Broggini, spokesperson for the LUNA project. The first set of experiments was run at energies above 140 kilo-electron volts (KeV), Broggini says. A new gamma ray detector should allow researchers to study collisions at close to 25 KeV, the peak energy level at which the reaction occurs in stars.

7. MAMMALIAN BIOLOGY

More Genomes, But Shallower Coverage

1. Elizabeth Pennisi

For the human genome, nothing less than perfection was acceptable: Each DNA base was supposed to be correctly identified and in its proper position. But for a host of other mammals now in sequencers' sights, perfection may be too slow and expensive.

The National Human Genome Research Institute (NHGRI) is considering a proposal from a new advisory committee to turn its sequencing centers loose on decoding the DNA of a dozen or so mammals. Elephants and bats are among the top candidates, all of which will be based on how distant they are from humans and one another on the mammalian family tree. But in a policy shift that is being hotly debated—and could be approved as early as next month—the centers would make only a quick pass at the sequence of each species. For the human and mouse genomes, repeated passes identified each base seven times or more. Now the plan is to drop this 7x coverage to 2x. As a result, the new data would consist of thousands of small pieces of DNA too disjointed to put back together in a whole genome sequence.

An important reason for taking this approach is money: Less coverage means lower cost, and that means researchers will get four genomes for the price of one. “You have the possibility of sequencing lots of organisms quickly,” says Edward Rubin, director of the Department of Energy (DOE) Joint Genome Institute in Walnut Creek, California.

But others worry that there just won't be enough data to work with. Michael Lynch, an evolutionary genomicist at Indiana University in Bloomington, says, “You are just going to be left with a hodgepodge of data.” Adds Maja Bucan, a geneticist at the University of Pennsylvania in Philadelphia, “I don't think that 2x is good enough for the kind of biology that we want to do.” Without extensive data, researchers will have trouble trying to understand a genome's overall structure.

Although the new approach could produce a hodgepodge, at least it will be extensive enough to compare with the more fully detailed human, mouse, and rat genomes, says developmental geneticist William Gelbart of Harvard University. And researchers will be able to find new genes and regulatory regions that they can't find when they compare just a few sequences. Already, the analysis of the poodle genome, which had just 1.5x coverage, demonstrated that skimming a genome can yield useful information (Science, 26 September 2003, p. 1898). Some researchers even argue that they could get away with sketchier coverage. “The idea is to find the sweet spot where there's enough information but [the genome] is not too expensive,” Gelbart explains.

Having multiple genomes to compare will pay big dividends, says NHGRI Director Francis Collins. For example, researchers should be able to find hidden regulatory elements common to most species. Besides, Collins argues, 2x is just “a starting point.” Lynch and others wonder, however, whether sequencers will ever complete these genomes, once the quick-and-dirty approach has yielded its initial trove of data.

Monsanto Wins Split Decision in Patent Fight Over GM Crop

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

OTTAWA—A 6-year patent battle between a Canadian farmer and U.S. biotech giant Monsanto has come to a confusing end. Canada's Supreme Court last week ruled 5 to 4 that the farmer had violated Monsanto's patent rights by planting the company's genetically modified (GM) canola seed without paying a licensing fee. But it overturned lower court awards against the farmer, leaving both sides declaring victory. And its decision laid out guidelines for patenting GM organisms that have left many experts puzzled.

“On the surface, [the decision] looks good for the biotech industry,” says patent law expert E. Richard Gold of McGill University in Montreal. “But once you read further, you have no idea what the implications are.”

The case* pitted Percy Schmeiser, a 73-year-old farmer from Saskatchewan, against one of the world's biggest GM crop breeders. It began after Schmeiser harvested a 1997 crop of canola that contained an herbicide-resistance gene patented by Monsanto. The farmer said that the canola had grown from seed that had blown off passing trucks or had gained the gene from pollen that drifted in from adjacent GM fields. The next year, he used his saved seed to sow his own fields—without paying Monsanto an estimated $11,000 licensing fee. The company successfully sued, and Schmeiser appealed to the Supreme Court, claiming that the company couldn't control how he used the seed. The case became a rallying point for farmers' rights groups and was seen as a test of Canada's approach to patenting GM organisms. In a 38-page opinion, the court's majority reaffirmed an earlier landmark decision banning the patenting of “higher life forms,” such as whole plants or GM mice (Science, 13 December 2002, p. 2112). But it rejected arguments against allowing patents on specific DNA sequences or cells to be enforced outside the laboratory, comparing them to patented Lego blocks that can be included in larger products. As a result, Schmeiser infringed Monsanto's gene patent when he planted his seed, even if he obtained it inadvertently or accidentally, wrote Chief Justice Beverley McLachlin and Justice Morris Fish. Infringers must act “quickly to arrange for removal [of the patented material]” if they want to avoid breaking the law, they added. Although Schmeiser didn't follow that guidance, the court declined to order him to turn over profits from the sale of the canola, or pay Monsanto's legal fees, because he earned no additional profit from using the pirated seed. He didn't even spray his canola plants with the herbicide —called Roundup—that they were engineered to resist, the justices noted. Monsanto officials were elated by the split decision. “This ruling maintains Canada as an attractive investment opportunity,” said executive vice president Carl Casale in a statement. Schmeiser was also upbeat, noting that he wouldn't have to sell his farm to pay court awards. “It's a personal victory,” he said. But Terry Boehm of the National Farmers Union in Saskatoon feared that the ruling “allows seeds to become a tool of oppression” by seed companies. Gold says the “bizarre outcome” may reflect the fact that two new judges have joined the court since its 2002 ruling against patenting whole GM organisms. “From a practical point of view, they have gutted” that decision, he says. Other experts say the decision may give a company that produces an organism with a single patented gene enough legal standing in Canada to claim infringement even if it can't patent the whole organism. The decision has “changed the meaning of ‘use’ in such a way that nobody knows what it means,” says Gold. “Patent lawyers across the country are scratching their heads.” 9. PUBLIC HEALTH Asthma Linked to Indoor Dampness 1. Erik Stokstad Indoor mold can cause or exacerbate respiratory problems, says a new report by the U.S. Institute of Medicine. But its impact on a host of other health problems is much less clear. The study, released this week, was requested by the U.S. Centers for Disease Control and Prevention in response to growing concerns about the health effects of indoor mold. Damp conditions are common in about 10% of U.S. housing. “It's a considerable public health issue,” says panel chair Noreen Clark of the University of Michigan School of Public Health in Ann Arbor. Although the panel found that indoor mold can aggravate asthma and cause coughing and wheezing in healthy people, it failed to support arguments about its role in other health problems. The evidence was only suggestive that dampness or visible mold causes lower respiratory illness, such as bronchitis, and asthma in healthy children, the report says. And due to a dearth of well-done studies, the panel couldn't tell whether there is any link to other conditions, including acute pulmonary hemorrhage in infants, forgetfulness, chronic fatigue, or cancer. Part of the challenge is the complexity of damp conditions. In addition to mold, dampness fosters bacteria and mites and causes chemicals to be released from decaying furniture and building materials. Most studies have not teased apart these variables, the panel found. All these unknowns mean that it's hard to quantify the problem and rank it on a list of public health priorities, says epidemiologist Jonathan Samet of the Johns Hopkins University School of Public Health in Baltimore, Maryland. The committee calls for more research on health effects, including better ways to gauge exposure, as well as studies of interventions to fight mold. It urges national guidelines to prevent or correct the problem. Those fixes are unlikely to be technical challenges but can be a financial hurdle for cash-strapped schools or low-income homeowners. 10. PLANETARY SCIENCE Saturn: The Unfinished Symphony 1. Richard A. Kerr The 4-year Cassini-Huygens mission to Saturn will probe the lingering mysteries of a “mini solar system,” much of whose evolution seems to have been arrested in its earliest days Move over, Mars, Saturn is up next. And what it reveals promises to be on a much grander scale than the eons-old remains of a salty martian sea and blocks of blasted lava being captured this year by the twin rovers. The$3.3 billion Cassini orbiter and attached Huygens probe, which will arrive next month after a 7-year trip, will be taking the pulse of the entire Saturn system, replete with grand rings and a bevy of satellites. It's “the most complex interplanetary spacecraft ever built,” according to NASA's press information, and is NASA's largest. And scientists are particularly keen to apply Cassini's powerful instrument complement to a surprisingly young and dynamic ring system. “We're going to get a close-up, time-evolving picture” of the rings, says Larry Esposito of the University of Colorado, Boulder. “It will knock your socks off.”

Beyond the rings, debris from the earliest days still litters the landscape. Tiny satellites have yet to settle into fixed orbits, and some still share orbits with larger companions. Modest-sized Enceladus shows signs of rejuvenation even though it should have long ago run out of the energy to redo its surface. And little Phoebe, Cassini's target in an 11 June close flyby, may be a planetary building block left behind after the rest got swept up or simply flung away. Saturn and company resemble a miniature solar system with the litter of construction lingering and the finishing touches still under way, says Cassini imaging team member Torrence Johnson of NASA's Jet Propulsion Laboratory in Pasadena, California.

Flagship of planetary probes

Ironically enough, Cassini-Huygens arose from—“survived” might be more accurate—an early NASA exercise in cost containment. A Saturn orbiter-plus-probe concept came out of a joint NASA and European Space Agency (ESA) study in 1982. In the mid-1980s NASA studied designs for a standardized spacecraft for the outer planets that, with ESA participation, became the separate Cassini mission and the Comet Rendezvous/Asteroid Flyby (CRAF) mission. But after Congress mandated a cost cap in 1992, CRAF was cancelled and the Cassini- Huygens design was made much simpler.

Still, it ended up at a total mass of 5636 kilograms, nearly double the weight of the Galileo orbiter-probe that ended its 8-year tour of Jupiter in 2003. Launched in 1997 on a circuitous, fuel-efficient route to Saturn, Cassini-Huygens will fire its rocket to settle into orbit on 1 July. Total mission costs come to about $3.3 billion, with ESA chipping in$500 million for the Huygens probe.

The budget cuts did little to shrink the science that Cassini will attempt at Saturn. The 12 instruments on the orbiter total 262 kilograms, compared to the 142-kilogram, 11-instrument payloads of the two Voyager spacecraft that flew through the Saturn system in 1980 and 1981. Galileo's orbiter instrument total was 103 kilograms. Cassini's added instrument mass, incorporating vastly more capable electronics and computing capacity, makes for a powerful science package. For example, the five instruments measuring charged and neutral particles and electromagnetic fields are “far more capable than anything flown before,” says the Cassini team's particles and fields interdisciplinary scientist Tamas Gombosi of the University of Michigan, Ann Arbor, “including around Earth.” Four remote-sensing instruments image and chemically map everything from wispy rings to satellites and Saturn itself at wavelengths from the extreme ultraviolet to the far infrared. The radio used for data transmission doubles as a probe of rings and atmospheres. And Cassini carries two instruments the Voyagers lacked: a radar, for penetrating Titan's clouds, and a dust analyzer.

Earlier visitors Pioneer 11 and Voyagers 1 and 2 blew through the Saturn system in a matter of days, but Cassini will orbit Saturn 74 times over 4 years while dropping the Huygens probe into Titan's atmosphere next January and getting a bead on a still-evolving planetary system. “It'll be like 74 Voyager encounters with instruments an order of magnitude better than Voyager's,” says rings interdisciplinary scientist Jeffrey Cuzzi of NASA's Ames Research Center in Mountain View, California. The Voyagers provided their share of surprises, says Johnson, but “I wouldn't be surprised to be surprised again.”

Rings within rings

All Cassini's instruments, even the particles-and-fields instruments and perhaps the radar, will probe the crown jewels of Saturn, its rings of innumerable icy bits, blocks, and boulders. Researchers will need all the data they can get. “There's so much to explain,” says imaging team member Carl Murray of Queen Mary, University of London.

The Saturn ring system has the look of a work in progress. Four and a half billion years after the planet's formation, the main rings don't seem to be more than a few hundred million years old, and some of the more bizarre features, such as braided rings, are still changing from year to year. The Voyagers revealed thousands of “rings” embedded within the broad A, B, and C rings, like grooves on a 270,000-kilometer-wide phonograph record. They also found impossibly narrow rings, broad, imperceptibly faint rings, and a fuzzy outer ring with a heart of rock. In Saturn, “you've got examples of all the types of ring systems you see in the rest of the solar system,” says Murray, who was a postdoc studying planetary rings when the Voyagers passed Saturn in 1980 and 1981.

More than 2 decades of theoretical work since the Voyagers passed Saturn have taken some of the mystery out of its rings. Gravity, it turns out, can make ring particles behave as weirdly as any subatomic particle. Most of the “rings” within the A ring, for example, are triggered by the periodic gravitational tug of moons orbiting just outside the main rings. A moon such as Mimas can set off a wave that spirals inward like the groove of a phonograph record.

In rings, gravity can also repel. The 700-kilometer-wide F ring just outside the A ring should have long ago spread out, but two satellites orbiting just inside and outside the F ring shepherd its particles back into a tight bunch. As a moon and ring particles pass in adjacent orbits, the moon raises a bulge in the ring that allows an exchange of orbital energy, driving the particles into the ring. But before the bulge comes around again, when the orbital energy exchange would be in the opposite direction, jostling among the ring particles destroys the bulge. The net effect can therefore be a push into the ring.

Plenty of ring mysteries remain, however. “I don't think we have any idea what is causing the structure of the B ring,” says theoretician Scott Tremaine of Princeton University. Moons beyond the main rings or even moonlets embedded in the B ring aren't responsible for most of the finely detailed grooves there. Researchers aren't even sure why the faint, diffuse E ring is there at all; its micrometer-sized particles should have been swept up by Enceladus and other moons long ago. Perhaps E renews itself as its particles collide with Enceladus and splash off fresh particles, or maybe Enceladus is spewing particles from icy volcanoes.

The biggest remaining mystery is the age of the rings. Voyager observations strongly suggest that they do not date from the formation of the planet. If they did, the rain of dark interplanetary debris that pelts them would have blackened them over the eons. Also, if they were primordial, they would have pushed the tiny satellites fringing them farther outward. Some of the finer ring features are clearly of recent origin. The Voyagers found year-to-year changes as the F ring broke into strands that braided and unbraided themselves. “Most likely we're looking at the latest version of rings” as they continue to evolve and age, says Murray.

A dynamic ring system makes a particularly inviting target for Cassini. The processes aging and reshaping the rings of Saturn are likely to be the same ones that operated in the disk of gas and growing particles that gave rise to the planets. “This is the only disk we're going to see close up,” says Murray. “It will be a great test” of ideas about how particles in a preplanetary disk interact. Cassini has an advantage over the Voyagers because it will spend such a long time in the Saturn system, notes Cuzzi: “We'll actually have the chance to see the rings evolve.”

Cassini will bring all the Voyager-type instruments to bear on the rings: imagers, spectrographs for composition, particles and field instruments for ring effects on the magnetosphere, and radio propagation experiments for probing the rings—but at a whole new level. The Ultraviolet Imaging Spectrograph (UVS), for example, is “immensely superior” to Voyager's UV instrument, says UVS principal investigator Esposito. It has 50 times the sensitivity of Voyager's. When it records the light of a star twinkling through the rings, it will reveal 10 times more structural detail than did Voyager. Unlike Voyager, which recorded just one stellar occultation, UVS will observe more than 60 of them, resolving ring structure down to a scale of 10 to 20 meters.

Fuzzy satellites

At Saturn, “we're going in with a lot less background information [on the satellites] to guide us than when Galileo entered the jovian system,” says Johnson, a former Voyager and Galileo team member. The eight sizable icy moons of Saturn appear fuzzy to varying degrees in Voyager images, thanks to their small size (110 to 764 kilometers) and considerable distances from the passing Voyagers. Still, planetary geologists have seen enough of them to suspect that they all had “interesting histories,” says Johnson.

In approaching the icy satellites, Cassini will not have the freedom to roam the Saturn system the way Galileo jumped among the four big Galilean satellites of Jupiter; of Saturn's moons, only Titan is massive enough to gravitationally sling the spacecraft into an entirely new orbit. Even so, Cassini and its more powerful instrument set will make a half-dozen close passes of four of the eight icy satellites and at least two dozen passes at the range of typical Voyager encounters.

The first of several weird objects on Cas-sini's itinerary is 110-kilometer Phoebe, which the spacecraft will pass on its way toward Saturn for the first time. Phoebe's highly inclined and “backward” orbit mark it as a captured object, one slowed into orbit by the drag of the gas that enveloped the still-forming Saturn 4.5 billion years ago. That would make it a surviving building block of the outer planets, a sort of object never seen up close before.

Perhaps weirdest of all the icy satellites is 718-kilometer Iapetus. Even astronomer Giovanni Domenico Cassini, who discovered it in 1672, recognized that one side is bright and the other dark. Post-Voyager opinion is pretty evenly split on how to explain the pitch-black stuff, says Johnson. Some planetary scientists say the dark material oozed from the interior as some sort of volcanic outpouring, whereas others say it fell as dust from some external source, such as dark Phoebe or even Titan's atmosphere.

Most intriguing to geologists is 250-kilometer Enceladus. Voyager got close enough to reveal both ancient, heavily cratered terrain and much younger, ridged plains with practically no impact craters. Apparently Enceladus summoned enough heat in the geologically recent past to melt some of its ice and resurface itself. Many of the other icy satellites show some signs of resurfacing, but how Enceladus did it so recently and extensively remains a mystery. “The common view is that [melting] is hard to do if you only have water ice,” says planetary physicist David Stevenson of the California Institute of Technology (Caltech) in Pasadena. A dollop of another, more volatile compound, such as ammonia, would lower water's melting point and ease the creation of water-ammonia lavas. Erupting water-ammonia geysers on Enceladus might solve the mystery of the E ring's origin as well.

Saturnian wind and rain

Gas giant Saturn certainly wasn't too small or distant for the Voyagers to study, but “we in fact know very little about Saturn,” says atmospheres interdisciplinary scientist Tobias Owen of the University of Hawaii, Manoa. The second largest planet hides many of its secrets far below its cloud tops, which even Cassini will not penetrate. The coming mission may yet pick up some clues, however.

For one, scientists hope to learn why Saturn radiates so much more heat than was generated from the planet's formation. Far out of reach in Saturn's interior, theoreticians say, helium should be separating from the planet's dominant constituent hydrogen and forming droplets that fall like so much rain, giving off heat as they go. The Voyagers misread the extent of helium separation by incorrectly measuring the ratio of hydrogen to helium, says Owen. Cassini's Composite Infrared Spectrometer should do the trick.

The heat welling up from Saturn's interior helps drive the visible eastward circulation of the atmosphere, but it doesn't explain another saturnian mystery. “Why is Saturn the windiest planet in the solar system?” asks imaging team member Andrew Ingersoll of Caltech. Saturn's broad equatorial jet stream blows at more than 1400 kilometers per hour, almost 10 times faster than on Earth.

Ingersoll suspects the answer is that Saturn has no rough surfaces and little turbulence to slow down the winds. “We're going to get up close with a high-resolution camera and measure the small-scale turbulence,” says Ingersoll, who hopes to see whether an especially placid planetary visage can explain the record winds.

The saturnian milieu

The entire Saturn system—planet, rings, and satellites—is immersed in an electrically neutral sea of charged particles, called a plasma, that's confined in the magnetic bubble of Saturn's magnetosphere. And Saturn's “is the perfect intermediate example between the extreme of Jupiter and the home planet,” says Michigan's Gombosi. Comparing the three magnetospheres should help clear up some questions about the jovian magnetosphere, he says. For example, at Earth, plasma normally drags magnetic field lines along wherever it goes. Not at Jupiter. Somewhere, somehow, plasma and magnetic field lines have become decoupled and the plasma is lost from the magnetosphere. Having Cassini follow the plasma for 4 years will make an “unbelievable difference” addressing such problems, says Gombosi.

For all its observational power and its protracted tour of the Saturn system, Cassini will leave much still shrouded in mystery. Some Cassini team members hope against hope for a return visit. In the meantime, however, Gombosi says he's “absolutely determined to have fun” exploring a still-ragged solar system in miniature.

What's to Come …

11 June

Phoebe flyby at 2000 kilometers

26 October

Titan flyby at 1200 kilometers

13 December

Titan flyby at 2300 kilometers

15 December

Dione flyby at 81,000 kilometers

24 December PDT

(25 December UTC)

Release of the Huygens probe

1 January 2005

Iapetus flyby at 63,000 kilometers

14 January 2005 PDT

(15 January UTC)

Descent of the Huygens probe

15 February 2005

Titan flyby at 950 kilometers

17 February 2005

9 March 2005

11. FRANÇOIS D'AUBERT INTERVIEW

Bold Promises, But How to Deliver?

1. Barbara Casassus*
1. Barbara Casassus is a writer in Paris.

Within days of his appointment as France's science minister, François d'Aubert soothed riled researchers with promises of cash and jobs. Now he must show it is not a mirage

PARIS—When François d'Aubert took over as junior French research minister from former astronaut Claudie Haigneré last month, his first task was to quell the biggest revolt by the French research community in living memory. He and his boss, Education and Research Minister François Fillon, acted fast to stave off a lab walkout by bowing to scientists' demands for job protection and releasing millions of euros that the government had owed to research agencies (Science, 16 April, p. 368).

But many researchers are pushing d'Aubert not to rest on those laurels. Scientists such as Henri-Edouard Audier, a chemist on the board of directors of the country's main basic research agency, CNRS, are urging the government to seize a “unique opportunity” to overhaul research and boost spending to bring R&D up to the European Union target of 3% of gross domestic product in 2010. “Funding has a lot of catching up to do,” he says. Audier claims that CNRS would need a 40% budget boost next year “just to stand still.” There will be growth, d'Aubert assures—although he declines to be drawn on how much, because the budget is currently subject to intense negotiations within the government.

D'Aubert's political experience will undoubtedly come in handy. He has been a member of the National Assembly since 1978 and, in addition to a previous stint as junior research minister from 1995 to 1997, has held a number of parliamentary committee budget posts. In an interview with Science last week, the convivial career politician pledged a fatter research budget, secure jobs, and better pay for scientists. Also, he insists that France will not come away empty-handed in its rivalry with Japan to host the $5 billion International Thermonuclear Experimental Reactor (ITER) (Science, 2 April, p. 26). Q: France has a reputation for resisting change. Why should research reform happen now? A: At least the word “reform” is seen in a positive light within the scientific community, which is more than can be said in certain others. There really is a dynamism for change and for rolling back conservatism. Up until now, there has been widespread mistrust of governments, both right and left. We have a unique opportunity to reform the French system for research and innovation: After a wide-ranging debate, the government will propose a law by the end of this year that will lay the foundation for the future. Q: How do you envision the structure of French research, particularly the relationship between agencies and universities? A: Agencies and universities are two pillars of the system. It is out of the question to get rid of either of them, but we must strengthen the links. As for financing, I am pragmatic. We must experiment with more projects financed by foundations and integrate research and innovation. Funding for projects should be provided for up to 5 years, as is the case in the United States. Q: Your predecessor, Mme. Haigneré, called for the creation of a national science foundation for France based on the U.S. model, but you seem opposed to the idea. Why? A: We are looking at the question, but it is impossible to make a carbon copy of another country's institutions, and anyway I am not sure that merging agencies would improve efficiency. Q: The government has reversed the cuts of 550 tenured scientific posts that were at the heart of the protests. What is your policy on these posts for the future, especially in view of the large numbers of researchers who will retire by the end of the decade? Will you increase researcher pay? A: We will maintain the number of tenured posts in 2004: Every retiree leaving a tenured post will be replaced under the same conditions. For subsequent years, there will be an open debate about scientific employment; no decision has been made at this stage. The government's announcement last year of more contract posts did not represent an about-turn in policy; it was to give greater flexibility for guest researchers. We intend to offer higher pay for these posts in the future so that we meet international standards for topflight scientists. Q: What are the prospects for the 2005 R&D budget? A: The 2005 budget is still being worked out, but we promise that it will be bigger than in 2004 and that by 2007 we will have allocated at least an extra €3 billion. We will not freeze or cancel any spending this year and will focus on ensuring that laboratories have enough cash to pay their operating expenses. Q: What should the government's role in research be? A: It should establish the foundation for competitive research. Therefore it should continue to finance most basic research and support applied research by industry. But the private sector must increase its contribution, especially to applied research. The French telecommunications industry, for example, should step up its spending; mobile phone companies are profiting from research without paying a single euro. I hope it will become part of their culture to offer something in return. Q: Are you confident that Cadarache [in the south of France] will be awarded at least part of the ITER project? A: Yes, I am confident that the proposal for an enlarged project to be shared between France and Japan will be approved. It will require an extra €900 million over 10 years, which France and a number of other countries are prepared to finance. We must find an agreement rapidly on this issue. 12. GEORGE C. WILLIAMS PROFILE Stretching the Limits of Evolutionary Biology 1. Carl Zimmer* 1. Carl Zimmer is the author of Soul Made Flesh: The Discovery of the Brain—and How it Changed the World. In shaping current thinking about natural selection and adaptation, Williams's influence has spread beyond his field to encompass economics and medicine as well STONY BROOK, NEW YORK—On a recent sunny Saturday, scientists from the United States, Canada, and Europe gathered at the State University of New York (SUNY), Stony Brook, to talk about their research. A geneticist from Harvard University spoke about preeclampsia, a potentially fatal condition during pregnancy. An ichthyologist described the loyalty—or lack thereof—that male fish show to the mothers of their offspring. Psychologists discussed economic decisionmaking. A psychiatrist reviewed some of the genes associated with clinical depression. This lineup might seem like a random trawl through the sciences. But the researchers who assembled in the auditorium were there for a common purpose: to honor the lanky, white-bearded man who sat quietly in the fourth row, George C. Williams. He may not be as familiar as his peers Richard Dawkins or the late Stephen Jay Gould. But Williams, who spent 25 years at Stony Brook, is generally considered one of the major architects of the study of evolutionary biology, and the meeting's far-ranging talks reflected the scope of his influence. “George Williams was instrumental in making natural selection an intellectually rigorous theory,” says Stephen Pinker of Harvard University, one admirer who wasn't at the meeting. “He forced people to think about how selection actually works and how we can see its fingerprints in the natural world.” In the 1950s, when Williams was doing his graduate work at the University of California, Los Angeles, the science of evolutionary biology had just gone through two decades of spectacular advances. Ronald Fisher and Theodosius Dobzhansky, among others, had used the new science of genetics to work out some of the molecular underpinnings of evolution. Natural selection was now recognized as a change in the frequency of genes in a population. Yet one important part still hadn't been nailed down: the nature of adaptations. It was clear that adaptations evolved, but few biologists had given serious thought to the rules that govern the process. Williams was struck by the ad hoc way that even prominent biologists would explain an adaptation. They'd claim that it had evolved because it provided some benefit; often, an entire population or species supposedly benefited. Williams recalls a lecture he heard by Alfred Emerson, a zoologist at the University of Chicago, about why people age and die. “He said growing old and dying is a good thing,” Williams says. “We've evolved to do it so we get out of the way, so the young people can go on maintaining the species.” “I thought it was absolute nonsense,” says Williams. Whenever people like Emerson claimed that an adaptation was for the good of a species, they never offered an explanation of how, from one generation to another, that potential benefit produced real evolutionary change. Williams suspected that in most cases, no such explanation existed. For him, the primary engine of evolutionary change was the one Darwin had written about in the Origin of Species: competition among individuals of the same species. Most biologists in the 1950s simply failed to think seriously enough about how natural selection could produce adaptations, he says. Williams wrote a series of papers critiquing the notion that adaptations were generally good for a group or a species, rather than an individual. Ultimately, his work led to his classic 1966 book Adaptation and Natural Selection. In it, Williams explained that almost every aspect of biology, no matter how puzzling, was the result of strict natural selection working on individuals. Take a school of fish, for example. It seems as if every individual cooperates for the good of the group, working with others to avoid predators, even if it means that individual gets devoured in the process. Williams argued that the schooling behavior could instead be the product of individual fish trying to boost their personal chances of survival—by trying to get in the middle of the school and by watching other fish for signs of approaching predators. Williams's book had an immediate, profound effect. “It fundamentally changed how biologists think about how natural selection works,” says Randall Nesse, a psychiatrist at the University of Michigan, Ann Arbor, whose own studies of depression and other disorders are influenced by Williams. One reason that the book was so effective was that Williams demonstrated how natural selection could influence the full course of a species' life history. It wasn't necessary to think of growing old as being for the good of the species, for example. Instead, Williams argued that the decline of old age could be caused by pleiotropy—in other words, the harmful side effects of genes selected for advantages they offered during youth. Just as long as the advantages of these genes outweighed the disadvantages, they would become widespread. Ironically, cancer, declining stamina, deteriorating vision, and various diseases of old age could all be the result of natural selection, says Williams: “Pleiotropy is the ultimate reason for all these things.” Williams argued that an organism faces these sorts of evolutionary tradeoffs throughout its lifetime: how much energy to invest in maturing before starting to reproduce, for example, or how much to invest in raising offspring before searching for another mate. Natural selection should find a balance between an animal's current investment in itself and its offspring and in potential future benefits. Williams speculated that animals could also keep track of how these factors change and adjust their behavior accordingly—like an investor deciding which stocks to keep or sell. Researchers have now amassed a wealth of evidence showing that animals do alter their strategies in the face of changing conditions, as Williams proposed, investing more or less care in raising their young. Williams also suggested that his argument could apply to humans as well as animals, helping lay the groundwork for a Darwinian approach to human behavior (frequently referred to as evolutionary psychology). “George was a supportive figure from the get-go,” said Martin Daly of McMaster University in Ontario, a leading evolutionary psychologist. At the meeting, Daly and his wife, psychologist Margo Wilson, illustrated Williams's influence by describing an experiment they published in the 7 May issue of Biology Letters. The experiments grew out of a well-known economic phenomenon called “future discounting.” People typically choose a small amount of money they can get today over a larger amount they will get in the distant future. Daly and Wilson proposed that the value people put on resources in the present and the future is influenced by natural selection: The better one's prospects for reproductive success look in the near term, the more one will discount the future. “We wanted to see if we could do an experiment that would manipulate people's discount rate,” said Wilson. First, they ran a simple discounting experiment on a group of male subjects who, as expected, tended to choose small money now over bigger sums far in the future. Then they ran the experiment again, but after showing the men a picture of an attractive woman. (They gave their subjects no explanation about the picture.) Daly and Wilson found that seeing that picture made the men even more likely to choose money in the short term. (Pictures of cars, by comparison, didn't affect future discounting.) Although Williams has convinced many people of the value of his ideas, the notion that human behavior can be broken down into such finely tuned reproduction-boosting adaptations is, to say the least, controversial. The late Stephen Jay Gould liked to call this approach “Darwinian fundamentalism,” and he credited Williams's Adaptation and Natural Selection as “the founding document for this ultimate version of Darwinian reductionism.” Likewise, Gould and others—such as Elliot Sober of the University of Wisconsin, Madison, and David Sloan Wilson of SUNY Stony Brook—have accused Williams's followers of focusing obsessively on individuals and reflexively dismissing the possibility of group selection or species selection. Sober and Wilson, for example, argue that cooperative behavior may have evolved in our own species because cooperative groups outcompeted uncooperative ones. It's a testament to Williams's stature that Sober is careful to distinguish between Williams and Williams's followers. “Williams is less hostile to group selection than his followers are. It's ironic that he's become the icon for the anti-group selectionists.” Although speakers at the meeting didn't directly address these controversies, they did confront a major disappointment: the failure of Williams's adaptationism to influence medicine. Since the early 1990s, Williams has argued that because medicine compensates for the shortcomings of our adaptations, doctors should get a sound grounding in evolutionary biology. Exploring the evolutionary forces that have shaped our bodies could produce new hypotheses about the causes of diseases, he maintains, and point the way to more effective treatments. At the meeting, evolutionary biologist David Haig of Harvard University offered an example of the insights that the Williams approach can offer to pregnancy. Haig pointed out that during a pregnancy, the evolutionary interests of mother and child overlap in some ways but conflict in others. The investment a mother puts into the child can potentially reduce the amount of energy she could put into future children. The child, on the other hand, benefits if its mother focuses all her attention on it. Haig showed how this perspective on pregnancy can shed light on preeclampsia, a mysterious condition that causes dangerously high blood pressure in pregnant women. Haig suggested that preeclampsia might be the result of a fetus trying to draw nutrients to the placenta. He proposed that, when in need, a fetus might release factors into the maternal bloodstream that damage the walls of the mother's blood vessels, thereby raising the resistance of her circulatory system. Because the resistance in the vessels feeding the placenta would be lower, more blood would flow to the fetus. At the Stony Brook meeting, Haig reported on recent research by Ananth Karumanchi of Harvard Medical School in Boston and his colleagues, who studied a curious protein released by the fetal placenta that blocks the repair of damaged blood vessels. Karumanchi and his co-workers found that levels of this substance—known as placental soluble Fms-like tyrosine kinase 1 (sFlt1)—rose significantly in women with preeclampsia just before the symptoms emerged, a finding that Haig cites as “evidence of the antagonistic relationship of fetal and maternal factors.” “It's an outstanding hypothesis,” Karumanchi says of Haig's research. “It makes a lot of sense in my mind.” He points out that even in normal woman who do not experience preeclampsia, levels of sFlt1 rise toward the end of pregnancy. “As the fetus is growing, it needs to get more blood to itself, and so it secretes more of the protein,” he speculates. Yet at the meeting, Haig readily admitted that this evolutionary approach has not yet penetrated the medical community. “Darwinian ideas are not making a big impact” on the way doctors think, said Haig, pointing out that at his own Harvard Medical School, students still get no training in evolutionary biology. Karumanchi admits that he learned about Darwinian medicine only when Haig approached him recently. “I'd never thought that evolutionary biology was important before now,” he says. “There's a big barrier between people like me who are physicians and people who are in biology departments. Those barriers need to be broken.” Mart Gross, a biologist at the University of Toronto, agreed that Williams's ideas have yet to produce as much impact outside of evolutionary biology as he and other followers believe they deserve. He, for one, puts an optimistic stamp on the situation. “It's still very early on,” says Gross. “After all, think how long it took for Darwin's ideas about natural selection to really take hold. I think Williams is at the same stage.” It is clear that just as Darwin remained controversial long after his death, the legacy of George Williams's work will stimulate research for decades to come. 13. SOUTH KOREA Suddenly, Science Moves to the Top of the Government's Agenda 1. Mark Russell* 1. Mark Russell is a freelance writer in Seoul. South Korea isn't happy with its scientific enterprise. But several small steps could make a big difference in how students are trained and science is conducted SEOUL—Criticizing Korean science is a cottage industry here. Complaints range from the mediocrity of universities and industry to micromanagement by government bureaucrats. But scientists' biggest complaint—that vested interests are blocking needed reform and that nobody is listening—no longer seems valid. This month, in his first public speech since beating back an attempt to impeach him and winning the voters' endorsement of his Uri Party in parliamentary elections, President Roh Moo-hyun asserted the importance of innovation to the Korean economy and named science as one of the sectors most in need of improvement. Roh's 15 May speech came on the heels of nationwide school reform, a major boost in research spending, and new budget authority for the Ministry of Science and Technology (MOST). “Market mechanisms are not working properly, so the government is focusing more on science and industry, especially high-tech sectors such as biotech and nanotechnology,” says Koo Bon-jae, head of the basic science and labor bureau at MOST. The goal, says Chung Kun-mo, president of the Korean Academy of Science and Technology, is to create a modern scientific culture “that is not about following others but about venturing into new areas.” Carving out that new path won't be easy, say critics, as the problems in each sector defy easy solutions. Although Korea awards a higher percentage of degrees in science and engineering than any other country, for example, it ranks 15th in the amount of money spent per student. The result, says Park Chan-mo, president of Pohang University of Science and Technology, one of Korea's top science schools, is that most programs tend to focus on theory and book-learning rather than more costly hands-on training. “We are not short of students, but we are short of quality,” says Park. Out of some 200 universities, he notes, “only about seven focus on research.” To address that problem, the government plans to more than double spending on science scholarships this year, to$46 million. Other changes would give students greater academic flexibility by having them apply to the university rather than to a particular school or program within the institution and would make medical school more like its U.S. counterpart by requiring entering students to hold a bachelor's degree.

Similarly, research spending is the fastest growing item in the national budget, up 8.5% this year to $5.3 billion. Part of that is a 7-year,$1.2 billion plan launched in 1999 to bolster research, foster academic reforms, and increase Korea's share of papers in top-flight journals. Although the so-called Brain Korea 21 program has helped, Korean scientists say that it has not been enough to change old habits.

The government is also hoping to counter the perception that careers in science are low-paying and low-prestige by offering more opportunities for scientists in government service, which ranks high on the employment pecking order. This year it announced plans to reserve at least 30% of its new jobs for science and engineering graduates, with the goal of making technical training mandatory for half of all higher-level government slots by 2013.

Other changes should give science greater political clout. Last month MOST's National Science and Technology Committee won the right to review all research proposals before the budget office makes final spending decisions. In the past, the budget office was free to reshuffle those proposals to accommodate the priorities of other government agencies. The government also announced that the science minister, Oh Myung, will become one of three vice prime ministers, giving him a bigger role in making policy. “The new system should be in place by the end of the year,” says Koo of MOST.

The government is also leaning on Korea's largest companies, the chaebols, to hire more scientists and build a better career ladder for them. To make their science graduates more attractive, universities in turn have recently added management training to the list of required courses and expanded ties to the chaebols. “This enables students to get more hands-on experience and allows us access to talented science students,” says Kim Heung-shik, senior manager of recruiting at LGE, the multibillion-dollar maker of electronics and household appliances.

In his presidential address, Roh recognizes that progress on all fronts will be needed to move his country ahead: “Government administration and the market will have to be innovative. Technology and the market will need to be innovative. And the talent pool must be nurtured.” The formula, if it is followed, could eventually force a lot of scientists to find other things to complain about.

14. Is the U.S. Brain Gain Faltering?

1. Jeffrey Mervis*
1. *With reporting by Ding Yimin in Beijing and Pallava Bagla in New Delhi.

Fears that U.S. graduate programs in the sciences are no longer attracting their share of the world's brightest students don't square with the facts

Plant geneticist Ralph Dean remembers the first time he met Heng Zhu, who was to become his first foreign-born Ph.D. student. It was at a 1993 conference in Madison, Wisconsin, and Zhu's mentor at the Chinese Academy of Sciences' (CAS's) Institute of Genetics had thought highly enough of his student to fly him all the way from Beijing to match him with a good U.S. lab.

Dean was immediately impressed. “He was dynamic, outgoing, and spoke good English,” says the 46-year-old professor and director of integrated fungal research at North Carolina State University in Raleigh. Dean may also have seen a little of himself in the budding Chinese scientist: He had followed a similar path, having come to the United States in 1980 as a graduate student from his native England “because this was where I could do the best science.” Best of all, says Dean, then at Clemson University, “I had a great project for him to work on. So I took the risk.”

Dean's instinct was right. This month, 11 years after that fateful encounter, Zhu, 36, moved into a spanking new lab at Johns Hopkins University's School of Medicine as a tenure-track assistant professor of pharmacology and molecular sciences. After completing his Ph.D. in 1999, Zhu snared a postdoctoral position at Yale University, where he earned a reputation as a wizard with protein microarrays. By last fall, Zhu was considered such a catch that the head of the new center he has joined went to the trouble of assembling a recruitment package touting the glories of Baltimore—including a souvenir Orioles baseball jersey—and shipping it to Zhu's fiancée (now wife) back in China.

Zhu's scientific journey from Beijing to Baltimore typifies the upward mobility that U.S. graduate education offers to hundreds of thousands of students every year from around the world. It's a familiar story, and it comes with a clear and upbeat moral: Open borders provide spectacular benefits to both the immigrant scientist and the host country.

At least, it's been that way for the working lives of most U.S. scientists. But some university administrators and department chairs are worried that a post-9/11 United States has become a less attractive destination for many foreign students. Most can relate unhappy tales of a brilliant student who couldn't get through immigration to enroll, or a foreign-born colleague detained on the way home from an international meeting. Any interruption in this stream of foreign talent to U.S. shores, they say, could threaten the country's status as the world's leading scientific power.

In March came news that seemed to confirm the worst fears: Two university-based surveys reported a downturn in the number of graduate applications from foreign students for the 2004–05 academic year (Science, 5 March, p. 1453). Research dean Lenore Kola of Case Western Reserve University in Cleveland, Ohio, remembers her reaction when the data started to show up in her computer. “It was like we hit a wall in February,” she says. Her office projects a 41% drop in the number of international grad school applicants for the 2004–05 academic year.

To many administrators, the survey seemed to offer proof that the federal government's new immigration policies were undermining their institutions' abilities to attract the world's best students. “Sadly, the unpredictability and delays that characterize the new system have resulted in a growing number of the world's brightest young people deciding to remain at home or go to other countries for their graduate education,” wrote Robert Gates, a former CIA director and current president of Texas A&M University in College Station, on the 31 March opinion page of The New York Times.

But are these fears well founded? Is the next Heng Zhu less likely to come to the United States because of the country's post-9/11 attempts to combat global terrorism? More broadly, what factors shape the flow of young international scientific talent into U.S. universities? For answers, Science talked with dozens of U.S. academics and examined admissions data from their institutions. We probed attitudes in China and India, the two biggest sources of overseas talent. We looked at what's happening in Australia, widely held to be an increasingly popular destination for young scientists.

The picture that emerges is different in many respects from the one Gates and many of his academic colleagues have been painting. One important reason is that the number of applications to U.S. graduate schools from foreign students has soared in recent years. Another is that the chances of a foreign applicant becoming a member of the next entering class are extremely low: As few as one in 50 receive an offer of admission, and fewer than half of those admitted actually enroll. In fact, policies affecting the “demand” side of the equation—the number of foreign students U.S. graduate programs want, or can afford, to admit—are likely to have a greater impact on quality than fluctuations in the supply side. The data also raise doubts about the pervasive fear that the top students are going elsewhere: The number of Chinese graduate students in science and engineering entering Australian universities, for example, is actually declining. The biggest—and so far unanswerable— question, however, is whether the best students are being scared off. So far, at least, there's little indication that that's the case.

What follows is an attempt to put the concern over visa restrictions into the context of other key factors that influence the number and quality of foreign students in U.S. graduate education.

1. Is there an irresistible lure from Down Under?

In his op-ed piece, Gates echoed the popular wisdom that many of the best Asian and European students are flocking to Australia to pursue graduate science and engineering degrees that they would otherwise have earned in the United States. A recent report by the Australian government of a 16% rise in foreign student enrollment has reinforced that perception. But a closer look at the numbers shows that assumption to be incorrect.

Let's start with higher education as a whole. Yes, the number of overseas students at Australian universities rose by 16% in 2003, to 136,000. But the rise comes after a 10% drop in 2002, which was preceded by a 20% jump the year before. Enrollment—overwhelmingly of undergraduates—is cyclical. An epidemic such as severe acute respiratory syndrome or an Asian economic crisis can constrict the annual flow one year just as a declining Australian dollar or the Olympic games can pump it up the next, explains Jennie Lang, director of international students at the University of New South Wales (UNSW), one of the country's biggest universities. (In fact, one-third of those overseas students don't even leave their country but attend branch campuses in their native land.)

There are also good reasons to believe that enrollments won't continue to rise. “We've reached our maximum on international students, and we are in a holding pattern,” Lang notes. The university has capped the number of international students at 25% (she calls it a guideline) “to ensure that students continue to have an Australian experience—to study with Australians—and to be sure that Australians have a chance to pursue their educational opportunities.” Although the guideline now applies only to UNSW, other educators say it is likely to spread because other campuses are feeling the same pressures.

With regard to advanced training in the sciences and engineering, the data fail to support the giant sucking sound that U.S. academics claim to be hearing. For starters, the Australian postgraduate education system is tiny compared with the U.S. system. Last year, Australia's universities enrolled a total of 539 international students in doctoral degree programs in the natural sciences, engineering, and information technology. By comparison, there are 2.5 times that number of first-year foreign students enrolled in U.S. doctoral programs in physics alone—and physics represents only about 3% of the overall U.S. science and engineering doctoral pool.

In addition, Australian educators say the system is already near or at capacity. “We can't add students unless we get more buildings and more lab space,” says Michael Archer, UNSW's vice president for research. More to the point, there's little money to attract international graduate students. “They either bring their own money or pay their own way,” says Lang. “We offer them about 80 to 90 scholarships a year,” she notes, out of a total doctoral pool of 1500 to 2000 students.

Finally, country-by-country enrollment trends within Australia belie the notion that Asia's best graduate students are heading south and east rather than west. For example, the number of Chinese doctoral students studying science and information technology in Australia is half what it was a decade ago, falling from an average of 230 in the 1990s to 108 in 2002. Engineering enrollment has also tumbled, from about 175 for most of the previous decade to 115 in 2002. The trends are scarcely better for the much smaller Indian contingent: There's been a slight rise in the number of science Ph.D. students starting in the latter half of the 1990s, from 27 in 1998 to 45 in 2002, while the number of engineering students has hovered at around 30.

2. Do fewer applicants mean fewer foreign students on campus?

It might seem logical to assume that a decline in the number of applications from abroad would lead directly to a drop in the number of international students on U.S. campuses. Wrong. Most U.S. universities receive so many applications from overseas—in particular China and India—that the number of applications often has no affect on the number admitted, much less on enrollment. Indeed, many universities have experienced such a surge in international applications in recent years that any drop-off this year leaves them still comfortably ahead of historical levels.

At Case Western, for example, the number of applications from Chinese students—who represent 80% of the school's foreign applicants—has more than tripled in the past 4 years. So this year's haul, even after a 41% decline, will still match 2002 levels and be twice the number that applied in 1999. Yet, despite the surge in applications, the number of international students admitted by Case Western has held steady for the past 5 years.

This experience is not unusual, because the number of foreign students enrolled in any particular U.S. graduate school depends on many factors in addition to the number and quality of overseas applicants. For public universities, a big one is money. International students cost more to educate, and that can be a limiting factor in how many foreign students a department can enroll. James Allen, chair of the physics department at the University of California (UC), Santa Barbara, explains how it works at his university.

Foreign students typically represent from 20% to 25% of the graduate students in Allen's department, a figure that places it below a nationwide average of 50%. It's not for lack of student interest: “We get 400 to 500 applications [each year] for 20 to 25 slots,” explains Allen, “so there's plenty to choose from.” Instead, Allen says, the demographics are influenced by reimbursements to the department for what he calls “excess tuition and fees” for out-of-state students. “It's never enough,” he says. “So as the number of foreign students grows, we can either beg [the dean] for more money or get it out of department funds.”

This winter, Allen says the department decided to “bite the bullet” and spend $100,000 from its budget to pay for four or five more international students. “There was a lot of gnashing of teeth,” he recalls. “But we all agreed that they were great students. So instead of accepting 60, we accepted 80.” (The department's one-in-four yield rate—one student shows up in the fall for every four admitted—is fairly typical and adds some guesswork to the financial equations.) In return, he says, the department is tightening its belt by dropping one lecturer and adopting a series of one-time savings. Some departments make the de facto cap explicit: The physics department at UC Berkeley, says chair Christopher McKee, aims for no more than 25% international students so that it can afford to pay their nonresident tuition rates. However, most adopt a more informal process. “Yes, there are financial constraints,” says Richard Attiyeh, graduate dean at UC San Diego. “But our goal is to get the best students.” Some university administrators say that domestic students are simply a better fit for their programs. Vanderbilt University School of Medicine in Nashville, Tennessee, for example, currently has 34 different research training grants from the National Institutes of Health, which require participants to be U.S. citizens or permanent residents. Vanderbilt takes pride in its relatively small population—10% to 15%—of international students. “We don't have too much trouble recruiting good students, so we haven't needed foreign students as a source of labor,” says senior associate dean Roger Chalkley, who oversees graduate biomedical research education and training at the medical school. “We also very much prefer them because their English skills are so much better than the Asian kids'.” Still, the high bar doesn't seem to deter applicants: Last year, for example, the school received 710 applications from foreign students and enrolled 14. The good news for departments seeking to maximize the number of U.S. citizens in their graduate programs is that the drop in foreign applications has been offset at many universities by rising demand from domestic students. At Duke, for example, the number of domestic applications for graduate programs hit a 10-year high this year. It also exceeded the number of foreign applications for the first time since 2000. The University of Texas saw a similar flip-flop in the nationality of its graduate school applicants. “From my view, this is a very good thing,” says Lew Siegel, dean of Duke's grad school. “It means that more U.S. students are interested in STEM [science, technology, engineering, and mathematics] careers, and that's a trend we desperately need.” Bei-Tseng (Bill) Chu, chair of the software and information systems department at the University of North Carolina, Charlotte, has watched those opposing trend lines shape the school's new graduate program in information technology. “Our program has grown by 27% since 2002,” he says, “and the enrollment has gone from a majority foreign to a majority domestic.” He says that foreign students were scared away from the field after the dot-com bust but that domestic students “have an easier time” understanding the larger role that information technology plays in society. 3. Are visa barriers the reason for the drop? There is no doubt that many international students have a harder time entering the United States now than a decade ago and that non-U.S. citizens working here face more obstacles getting back into the country after personal or professional travel abroad. Zhu himself received an unexpected 11-month “vacation” after returning home on an expired H-1B visa in 2002, and his new bride is still back in China, hoping to join him soon in the United States. Such incidents have raised real concerns that have echoed throughout U.S. campuses in the past couple of years, and few would disagree with Gates's observation that “we simply cannot tolerate a visa process that fails to differentiate quickly and accurately between legitimate scholars and [those] who may pose genuine security risks.” Viewed from India, however, a downturn in U.S. employment opportunities, as Asia's economy remains strong, appears to be a bigger disincentive for Indians thinking of studying in the United States. Vijaya Khandavilli, a microbiologist and educational adviser in the New Delhi office of the U.S. Educational Foundation in India, says students visiting her office complained of neither arbitrary visa decisions nor unduly long wait times. Instead, she says, fewer students see the point of spending a long period abroad when their job prospects after graduation are so uncertain. Academic officials in China, the largest source of foreign applicants for many U.S. programs, say that anticipated visa problems are only one of several reasons Chinese students may be thinking twice about coming to the United States. A growth in postgraduate education in China is giving domestic students a better chance to complete their educations at home, says Yan Xuehong, deputy director of student affairs for the postgraduate school at CAS. And she says there is also a rising demand for these graduates. Wang Geng, who's finishing his master's degree in electrical engineering at the top- rated Qinghua University, says he made a “halfhearted” effort 2 years ago to gain a slot in a top U.S. graduate program and that his friends who succeeded “are worried that they will not be able to find an ideal job after graduation.” He Yifeng, a graduate student in chemistry at Beijing University, is confident that he can get a good education in China—and a good job afterward. Even so, He says that he plans to apply for a Ph.D. or postdoc position in the United States “once the opportunities improve, [because] studying in the States is still the best place to broaden your mind and gain more insights.” Another factor that may be affecting applications from China is a change last year in the qualifying test for graduate admissions. The Educational Testing Service (ETS) noticed that scores on its Graduate Record Examination from China, Taiwan, and South Korea would rise by as much as 100 points throughout the month, then dip at the start of the next month before resuming their climb. “This scalloping pattern was so obvious,” says David Payne of ETS in Princeton, New Jersey, that there was “no doubt” students were obtaining answers to the test, which changes every month, from those who took it early in the month. By changing to a paper-and-pencil test and reducing the frequency and number of sites where the test is administered, ETS says it has rooted out the problem. But it wasn't good for business: The number of students taking the test fell by 50% this year in China and by 43% in Taiwan. To be sure, the drop could simply reflect a reduction in the number of students who want to pursue graduate work in the United States. Indeed, Payne says the volume also dropped by 37% in India, where the exam procedures were not changed. But several university graduate deans believe that the more rigorous security might have scared off students less confident of their academic abilities. If so, that drop in applications may have come disproportionately from the lower end of the spectrum. 4. Is quality declining? Even as U.S. department chairs and administrators worry about the ones that might have been turned away, they are quick to add that they don't think the quality of the current applicant pool has suffered. And they say it's much too early to speculate on whether declining numbers of applicants will affect the quality of future classes. Given the high ratio of applicants to available slots, however, most chairs expect to continue to have plenty of excellent candidates to choose from. “I'm not ready to say that the sky is falling,” says Alice Gast, vice president for research and assistant provost at the Massachusetts Institute of Technology, where the number of international applications to its six graduate programs has returned to 2000 levels after a 16% drop in the past 2 years. “I've been looking at MIT figures historically, and you can see how political events over the years have impacted the numbers.” Alan Goldman, chair of the physics department at the University of Minnesota, says that “we were bracing for a tremendous attrition rate last year [in the number of applications], but it's been less of a problem than we thought. I'm not saying that it's not a problem—there are perceived and real barriers to entry. But we're managing.” As Zhu settles in at Johns Hopkins, he can still remember the bumpy road he traveled to get there. “First my Chinese adviser wanted me to apply to graduate school at CAS,” he says. Then Zhu got rejected by all but one U.S. graduate program—“and they didn't offer any money, so I didn't go.” Finally came the opportunity to travel to America and “find someone who would sponsor me.” A tighter immigration policy is probably no match for someone with such perseverance. But for U.S. academics, the question remains: Are there still enough people like Zhu out there? 15. Profile: Xavier Delannay 1. David Malakoff Twenty years ago, soybean geneticist Xavier Delannay got a memorable taste of the uncertain life of an industry scientist: The California biotech start-up that he had joined right after a postdoctoral fellowship lasted less than a year. But the Belgian native decided that the opportunities in America were too good to pass up. So he joined Monsanto Co. in St. Louis, Missouri, and by the time his alma mater, the University of Louvain, offered the relative security and prestige of a plum academic job a few years later, “it was too late.” “I'd planned to return home to a university, but the science and interactions I was experiencing here [at Monsanto] seemed much more interesting and exciting,” he says. He's now a senior scientist overseeing much of the company's soybean biotech research. Delannay, age 52, arrived in 1979 to pursue graduate work at Iowa State University in Ames because “my professors said the U.S. experience would help me.” Soon, he was swept up by the commercial wave created by the biotechnology revolution. At Monsanto, he ran the first full field test of transgenic tomatoes and helped develop the first widely used transgenic crop variety: a soybean engineered to resist herbicides. “If I had stayed in Belgium, I'd certainly be a university professor,” says Delannay, who became a U.S. citizen in 1993. “But I wouldn't have been able to achieve what I have done scientifically. It wouldn't have been possible; there weren't the resources or the capability.” 16. Are U.S. Students a Bellwether of Quality? 1. Jeffrey Mervis At the same time university administrators raise concerns that the inflow of foreign talent is drying up, the notion persists that the quality of a graduate program can be measured by the number of foreign students enrolled. In particular, the higher the percentage, the lower the quality of the program. Although most academics admit that it's based at best on anecdotal evidence from site visits and casual conversation, they seem to be convinced of its validity. The biggest assessment of U.S. graduate departments—the National Research Council's decennial ratings—says otherwise. The NRC assessment asks scientists to rate the quality of programs in their field, based on the reputation of their faculty members. The 1995 assessment correlated that rating with various demographic information, including the percentage of Ph.D.s awarded to U.S. citizens. The higher the score, the stronger the connection between program quality and domestic enrollment. The NRC's analysis found a negative correlation for programs in 10 of the 26 scientific areas represented, meaning that the quality of the program is positively linked to the number of foreign graduates. The negative correlation is highest for psychology, with a rating of −0.35, and aerospace engineering, with −0.17. Even on the plus side, only two fields topped 0.30 (chemical engineering, at 0.39, and biomedical engineering, at 0.31). As NRC's James Voytuk notes, “that's a pretty weak correlation. I'd tend to disregard anything smaller than 0.30.” 17. Profile: Rajan Gupta 1. David Malakoff When theoretical physicist Rajan Gupta left India nearly 30 years ago to start a career in the United States studying high-energy physics, he never expected to make regular trips home to help tackle public health issues ranging from AIDS to alcoholism. But 5 years ago, the scientist's life took an unexpected turn after he and his family traveled through his homeland. “My 6-year-old son came to me and said: ‘We have so much. We must do something for those who don't.’” Soon, Gupta—who had done some computer-modeling work on the HIV pandemic —was educating himself about the AIDS crisis and forging links with groups in India. He now takes 6 weeks of leave a year from Los Alamos National Laboratory in New Mexico to spend time in some of India's poorest communities. “I've had the privilege of studying an exciting area of fundamental science; it's time to give back to society,” he says. Gupta, 50, who has been a U.S. citizen since 1999, came to the United States to do graduate work at the California Institute of Technology in Pasadena, where he earned a doctorate before joining Los Alamos in 1985. There he uses supercomputers to model the interactions between elementary particles such as quarks and gluons. His efforts to improve public health, which include counseling Americans, have “probably made me a less competitive scientist,” he admits. And his visits to India—where he works with villagers, women's groups, and students (t8web.lanl.gov/people/rajan)—can be exhausting, he says: “Each time I go with tremendous enthusiasm and come back depressed by the magnitude of the need—but also more aware of the responsibility that comes with privilege.” 18. Settling In on Campus 1. Yudhijit Bhattacharjee Immigrant scientists say that it can take a while to warm up to the U.S. academic climate—but there are big benefits for both sides Zhong Lin Wang is a materials scientist, not an actor. But as he sat in his Atlanta hotel room in June 1994, rehearsing the graduate lecture he was to give the next day at Georgia Institute of Technology, he knew that his chances of getting a faculty position rested on his performance in the classroom. “The department was already impressed with my research credentials,” says Wang, who at the time was working at the National Institute of Standards and Technology in Gaithersburg, Maryland. “What they wanted to know was: ‘Can this guy speak English? Will he be able to teach?’” Growing up in Pucheng, China, Wang had always wanted to be a professor. But after earning his Ph.D. in 1987 from Arizona State University in Tempe, Wang had been turned down for numerous academic posts. Although he couldn't prove it, he was convinced that his ethnicity had played a significant role in those rejections. “The perception of a language barrier was a bigger obstacle than language itself,” he says. A decade later, as a tenured full professor at Georgia Tech, Wang has long since shattered that barrier. And the 10 students he has helped earn graduate degrees are testimony to his ability to function in a U.S. academic setting. But like thousands of other immigrant scientists, Wang has had to walk the extra mile to gain the acceptance of his U.S. colleagues. In return, U.S.-born scientists have benefited from the cultural influences of their immigrant colleagues and expanded their research horizons. Immigrant scientists often gravitate to scientific problems of pressing interest back home, and links they forge with researchers in the United States and their country of origin have paved the way for increased global collaboration (see sidebar). At the same time, the strength of ethnic ties can sometimes create what are known as “nationality labs,” in which the majority of students and scientists are from the same country as the principal investigator. Such labs can stifle the free flow of ideas and information and create an environment in which lab members feel undue pressure to conform to traditional norms, including hierarchical structures and long hours. Learning the ropes As Wang discovered, language can be a significant barrier to landing an academic job. But the problem doesn't end when an immigrant scientist is hired. Although Wang believes he showed from day one that “teaching is not about language but about delivering ideas,” no native-born graduate students joined his lab in his first 3 years at Georgia Tech. “They just didn't know how well they'd be able to communicate with me in a work environment where we'd be interacting frequently,” he says. Only after Wang had taught a few graduate classes and interacted with several nonimmigrant students did the barriers begin to fall. And even though language wasn't a problem, it took a special effort by Wang and his native-born lab members to establish a comfortable working relationship. One of his graduate students, Daniel Moore, recalls a difficult moment 2 years ago when he asked for a week off during Passover to be with his family in New York. Wang wanted him to stick around to present a poster at a local conference. “I explained to him that I was Jewish, and that this was a very important holiday for me,” Moore says, adding that Wang was willing to listen and finally granted the leave. Limited language skills and unfamiliarity with American culture can be a significant disadvantage for immigrant researchers at scientific meetings. Beyond the challenge of simply being understood, many Asian-born scientists play down the importance of communicating what they have discovered, says Da-Lin Zhang, a Chinese-born meteorologist at the University of Maryland, College Park. “We apply ourselves entirely to the research and don't think about how to present it,” he says. As a result, exciting work presented by an Asian-born researcher can sometimes generate a lot less interest than it deserves. In turn, says Zhang, Chinese- and Korean-born scientists are less likely to be asked to be keynote speakers at scientific meetings. Cultural and language differences can also hinder networking, says Mei-Yin Chou, a Taiwanese-born physicist at Georgia Tech. Chou, who came to the University of California, Berkeley, in 1980 to get her Ph.D., says it took her a few years to learn the importance of marketing her work. “You can't be shy about going up to people at conferences,” she advises her doctoral students—of whom three are Chinese, one is Indian, and one is African. “And then you can't start telling them about your research right away. You must find the right moment.” Although the barriers of culture and language can make assimilation a challenge, they ultimately have little impact on the research activities of immigrant scientists, says Maryland's Sergei Sukharev, a Russian-born biophysicist who came to the United States in 1987 as a postdoc. The diversity of U.S. academia, he says, fosters an environment in which national origin is almost irrelevant to scientific discourse. “The spirit is ‘I don't care about your writing style, I don't care if you are a cocktail boy or a recluse. All I care about is what you are saying in your paper.’” Nationality labs Although foreign-born faculty members can facilitate the flow of international graduate students and postdoctoral researchers into the United States, the result can be ethnic enclaves within university departments—groups that consist predominantly of graduate students and postdoctoral fellows from the principal investigator's native country. It's not unusual to walk into one of these labs and find members having scientific exchanges in Chinese or Russian or one of India's regional languages, says Raymond Clark, a molecular biologist who witnessed such teams in action while a postdoc at the University of California, San Diego (UCSD). “Not only does this prevent the speakers from improving their language skills—damaging their career prospects,” says Clark, now a consultant at UCSD's Office of Government and Community Relations, “it also excludes other group members from the discussion.” Such labs can also reduce the quality of the research experience. If the PI happens to be from a culture that puts a premium on seniority and age, for example—as in India and China—a lab member from the same country may feel uncomfortable questioning the PI's research decisions and scientific judgment. “If I were working with a Chinese-born PI, I'd probably be more tactful about voicing criticism in the lab,” says economist Chunling Lu, a Chinese-born research fellow at Harvard Medical School in Boston, Massachusetts, whose supervisor is a native-born American. Ashwini Dhume, an Indian-born biomedical scientist at the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Maryland, also has reservations about working for a PI from the same country. “Before I came to graduate school here, my Indian friends warned me: ‘If you work for an Indian or Chinese boss, you'll have to work 24 hours a day,’” says Dhume. She disregarded the advice and joined an Indian-born researcher's lab because “there was a higher comfort level in interacting with him.” Soon, however, she discovered that her mentor expected her to work longer hours than native-born members of the group. “His message was: ‘How can you be like these American kids? You should be working through your weekends and vacations,’” she says. “It wasn't that I didn't want to work hard. But I didn't like being treated differently.” At the same time, some immigrant scientists have imported a culture that is even more freewheeling than the U.S. variety. Leonid Glazman of the Theoretical Physics Institute at the University of Minnesota, St. Paul, is one of six Russian-born scientists on the institute's current seven-member faculty who helped popularize a “Russian-style seminar” throughout the school of physics and astronomy. It encourages listeners to aggressively ask questions right from the start of a talk. At times the main speaker is pushed aside, and things can get downright abrasive. “When the Russians started doing this kind of questioning at our departmental seminars, it was frowned upon,” says Glazman. “But now I see many native-born Americans doing the same thing.” Although immigrant faculty members agree that importing the discipline and rigor of the educational culture in their native countries can be positive, many limit the number of individuals from any one country in their labs in order to encourage cross- cultural interaction. “I've made a deliberate decision to keep no more than two students from any one [foreign] nation in my lab,” says Farokh Mistree, an Indian-born mechanical engineer at Georgia Tech, whose 11-member group includes two Indians, one Chinese, one Korean, and seven U.S.-born graduate students. Wang is particularly sensitive about the tendency of lab members from the same country to stick together. He also wants to reduce the chances that his foreign-born students are subjected to the same doubts about their language skills that he faced. In his own lab of 10 graduate students—half U.S.-born and half from Asia—hangs a notice banning students from speaking to each other in Chinese or surfing Chinese sites during lab hours. “I don't want any of my students to graduate with the feeling that being from a different culture is a disadvantage,” he says. 19. A Clearer Look at Asian Pollution 1. Yudhijit Bhattacharjee Veerabhadran Ramanathan, an Indian-born atmospheric scientist at the Scripps Institution of Oceanography in La Jolla, California, has helped bring to the fore a research area that wasn't on the U.S. radar screen. Literally. Last year Ramanathan launched a project to study the composition, regional patterns, and impact of aerosol clouds over southern and southeastern Asia. The idea grew out of a 1999 experiment that revealed a thick, brownish haze of air pollution covering an area from the Himalayas to the northern Indian Ocean. “I could have studied brown clouds anywhere in the world, but I chose a region that includes India,” he says. “That's probably not accidental.” Seeing the cloud over the Bay of Bengal and imagining how the aerosols might disrupt monsoonal rainfall patterns for India and other south Asian countries so haunted Ramanathan, now a U.S. citizen, that he drew up a proposal to set up more than a dozen climate- monitoring stations across Asia. The Atmospheric Brown Clouds project, funded by the U.S. National Oceanic and Atmospheric Administration and five Asian nations, is already spawning collaborations between U.S. scientists and researchers in India, China, Japan, and South Korea. Russell Dickerson, an American-born meteorologist at the University of Maryland, College Park, says his participation in the 1999 experiment led him to shift his research focus from the developed to the developing world. “It made me realize that studying air pollution in south and east Asia was critical to understanding global climate change,” he says. Dickerson is now participating in a NASA-funded project being led by his Chinese-born departmental colleague, Zhanqing Li, that aims to investigate the effect of aerosol clouds above the China region. 20. Profile: Marina Protopopova 1. David Malakoff Fourteen years ago, organic chemist Marina Protopopova left her Moscow laboratory for a brief sabbatical in the United States—and never returned. “I was having such a good experience, and I kept saying: ‘I'll stay just a little bit longer.’” Three years into her extended absence, the Russian Academy of Sciences’ Zelinskii Institute cut her loose. “My mom was more upset that I was fired than I was,” she says. “I've had an awesome experience here.” Born in Siberia and trained at Moscow State University, 44-year-old Protopopova now lives in suburban Maryland. Her journey began with an invitation from an American collaborator in San Antonio, Texas. “I came with$30 in my pocket, but everyone was incredibly supportive,” she says. Still, “the first 3 months were exhausting” due to language barriers. “I didn't even get a telephone because it was too tiring to understand [callers].”

What sold her was the scientific culture. “In Russia, we had these brilliant academicians, but they never gave open lectures like they do here,” she says. That openness outweighed the provincialism of some of the students. “They didn't even know there was an ocean between [the U.S.] and Russia,” she says in amazement.

After teaching and corporate chemistry stints in Illinois, Protopopova followed her husband—an American academic—to Maryland. In 1999 she joined Sequella, a Rockville, Maryland-based biotech company that is developing tuberculosis drugs. Now the firm's director of chemistry, she heads a multinational team that includes several Russians. There's “absolutely no way” she could do similar work at home, she says.

The mother of two young children, Protopopova has applied for U.S. citizenship. Her only regret is the distance from her parents and relatives. “Siberia really is on the other side of the world.”

21. Profile: Alberto Saal

1. David Malakoff

As a young academic in his native Argentina, geochemist Alberto Saal had trouble finding current issues of journals. Often, it was because his university library couldn't afford them. But sometimes colleagues hoarded the most recent issue to get a leg up on competitors. “After 50 years of mostly military rule, the academic system was virtually bankrupt,” he says. “I realized I had no future there.”

So despite holding a Ph.D. from the National University of Córdoba, Saal enrolled in a master's degree program at the Massachusetts Institute of Technology (MIT). Four years ago, at the age of 39, he earned his second Ph.D. (in oceanography) from a joint program run by MIT and the nearby Woods Hole Oceanographic Institution. Last year, Brown University in Providence, Rhode Island, hired him as an assistant professor in a tenure-track job.

Coming to the United States “was like being a kid thrown into a candy store,” says Saal. In particular, he reveled in the freedom to pursue his boundless curiosity and the sometimes edgy give-and-take between students and mentors. “Here, if you challenge a professor, they say: ‘Hey, what's your name and would you like to work for me?’ At home, the professor was always right,” he says.

Now, with students of his own, Saal is trying to create a similarly freewheeling intellectual climate as he pursues his studies of the composition of volcanic islands and the continental crust. And he admits that he “tries not to go completely bananas” when he encounters the same petty academic bickering that drove him from Argentina. Still, his decision to restart his professional life has paid off, he says, with “some of the happiest moments of my life.”

22. Perceptions and Realities of the Workplace

1. Jeffrey Mervis

Foreign-born scientists are a growing segment of the U.S. scientific workforce. But what does the trend really mean?

The status of foreign scientists is a sure-fire conversation starter for academics and science policy makers these days. But most discussions of the topic tend to be based on anecdotes, and a little bit of data goes a long way.

There are, however, a few well-documented trends. The most obvious is that foreign-born scientists are a rising presence in the U.S. workforce (see graph at lower left). Figures from the 2000 census show that foreign-born Ph.D.s make up 38% of the U.S. doctoral-level scientific workforce, up from 23% in 1990. And their share is even larger if those with degrees in the social sciences are excluded (see graph at lower right).

A second trend is that a growing number of foreign scientists working in the United States earned their doctoral degrees in another country. Traditionally, foreign scientists first came to the United States to pursue graduate studies, but now more than one-quarter of the foreign-born Ph.D. scientists in the U.S. workforce immigrated after earning a Ph.D. elsewhere. That shift may reflect both the improved quality of advanced scientific training in Asia and, at the same time, the region's limited ability to provide the postdoctoral training that many disciplines now demand.

A third trend is the increased likelihood that foreign-born scientists will remain in the country after earning their doctoral degrees. Michael Finn, an economist at the Oak Ridge Institute for Science and Education in Tennessee, reported recently that 71% of foreigners who earned their degrees in the United States in 1999 were still there in 2001, up from 69% of a 1997 cohort surveyed in 1999 and only 49% for a 1989 cohort tracked 2 years later. For Chinese students who earned U.S. Ph.D.s in 1999, the rate was an astounding 96%. Stay rates were almost as high when Finn tracked degree-holders for 10 years instead of 2, and they did not vary much across cohorts.

Those trends are supported by data, much of it published by the National Science Foundation, whose mission includes charting the health of the U.S. scientific workforce. But they say little about the questions that policymakers most want answered, including whether there are “too many” foreign scientists or what the U.S. government should be doing to train more domestic students. Although it's risky to venture into territory not supported by data, many have been unable to resist such excursions.

For example, 1996 chemistry Nobelist Richard Smalley believes that “citizenship matters” in trying to project whether the U.S. will retain its leadership in global science. And he's troubled that “there are a hell of a lot more Chinese and Asians going into science and engineering than Americans.”

The Rice University professor likes to provoke audiences with extrapolations of the future scientific workforce based on current levels of Ph.D. production in the United States and Asia (see graph at left). His take-home message: “By 2010, 90% of all Ph.D. physical scientists and engineers in the world will be Asian, and half of them will be living in Asia.” In interviews, however, Smalley is quick to point out that these projections rest on the improbable assumption that all the factors affecting the U.S. scientific workforce over the past 15 years—from the end of the Cold War and the Tiananmen Square massacre to a high-tech economic boom-bust cycle and heightened concerns about terrorism—will continue their effects for the next decade.

Even with those caveats, Smalley's message so impressed a chair of a task force of the President's Council of Advisors on Science and Technology that the same forecast popped up this spring in PCAST's draft report on the U.S. scientific workforce. Robert Herbolt, former chief operating officer at Microsoft, stretched Smalley's speculative calculation even further by referring to a world of Ph.D. scientists that would soon be “90% … Asian, living in Asia.” Then he turned the prediction into a rallying cry for his domestic audience: “What can we do about this shift of talent to other countries? What can we do to stem the tide?”

That rhetoric was a bit much for other PCAST members, however. “People don't respond to stemming tides,” counseled Charles Vest, president of the Massachusetts Institute of Technology. “I think we need to send a more positive message about strengthening the domestic workforce and training better teachers.” After a long discussion, PCAST asked the task force to take a second crack at the topic.

For all his concern about the nationality of future U.S. scientists, Smalley believes that most research universities will continue to recruit and welcome large numbers of international students and foreign-born faculty members, because such openness is one of the factors that makes the U.S. scientific enterprise so potent. Recalling how his lab went from one or two foreign students in the 1980s to more than a dozen today, Smalley says, “I want the best students, and I've gotten pretty relaxed about where they come from. The world is changing, but we'll cope with it somehow.”

23. A Foot in Each Country

Many foreign-born scientists who succeed in the United States are helping those they left behind—without leaving their new home

Geneticist Bruce Lahn has studied and worked in the United States for more than a decade, but a piece of his heart remains in his native China. He wants to help it compete in science at the highest levels, and he's decided that the best way to do that is to stay in the United States.

At 35, Lahn is an assistant professor at the University of Chicago and a Howard Hughes Medical Institute (HMMI) investigator. But he's also serving as chief scientific adviser to a new primate research facility in Guangzhou. The $1 million Center for Stem Cell Biology and Tissue Engineering comprises a laboratory at Sun Yat-sen University and a primate-breeding facility an hour's drive away. Directed by Lahn's former postdoc Peng Xiang, the center aims to develop transgenic primates and isolate hundreds of lines of monkey and human stem cells. Chinese scientists have tremendous potential, says Lahn, who came to the United States in 1988 as an undergraduate. But “they lack vision. I thought that the way to change that was not to go in as the director of some institute, but to demonstrate a new approach by being a role model.” The new center, he says, will “serve as a cultural messenger of how to do science.” Lahn is part of an apparently burgeoning international phenomenon. Although the numbers remain small, foreign-born researchers are reaching out to colleagues back home while remaining anchored in the United States, says Paula Stephan, an economist at Georgia State University in Atlanta. “I can't put my finger on any hard piece of data,” she says, “but there are all kinds of indications that more of this is happening.” Science has talked with more than a dozen scientists who have a foot on another continent to find out what works, what motivates them, and what advice they might offer others. Although they differ greatly by field, geography, and age, the researchers are united by a desire to repay the countries that gave them their starts by transferring some of the methods, standards, and culture of science found in the United States. The key is the connection: Researchers say they can contribute more by retaining their positions and influence in the United States than by going back home. Anecdotal evidence suggests that such down-home collaborations are also growing more formal and ambitious. Decades ago, well-established researchers might simply invite others from their countries to work in their labs for a couple of years. Now, even junior faculty members fly back and forth several times a year to help start institutes and businesses in their homelands. Such efforts have undoubtedly improved the quality of science in up-and-coming nations. Obstacles abound, but most researchers say such bridge-building is well worth the hassles. Bridges old and new Arriving in the United States shocked Tong Hyub Joh, a neuroscientist at Cornell University's Weill Medical College in New York City. “I thought I had very high standards for myself,” says Joh, who immigrated from South Korea in 1959 to start graduate school at the University of Illinois, Urbana-Champaign. “But I didn't know how to tackle a research problem. I had no experience. I remember how I suffered.” After receiving his doctorate from New York University in 1971 and joining Cornell the next year, Joh decided to help other Koreans gain the research skills he had lacked. He began hosting Korean researchers for 2- to 3-year stays in his lab. Three decades later, he has trained more than 50 of them, and many hold prominent academic positions in South Korea. At first, Joh says, his guests were mainly professors who had little research experience and weak backgrounds despite their lofty job titles. But his charges have grown both younger and better trained over the years; now, he says, they're mostly postdocs. In fact, Joh says, the quality of South Korean science has risen so much that many Koreans no longer see the advantage of coming to the United States. “In 10 years,” he predicts, “it will be very hard to recruit Korean scientists.” Joh's simple but effective assistance typifies the efforts of older researchers. But younger scientists such as Yale University geneticist and HHMI investigator Tian Xu often have grander plans for their compatriots. Like Joh, Xu struggled after graduating from Fudan University in Shanghai and coming to the United States in 1983. For a while, he even lived in an abandoned house in Harlem. But a Yale doctorate, followed by a 3-year postdoctoral position at the University of California, Berkeley, led to a faculty appointment at Yale. In gratitude to Fudan and Yale, Xu is helping build a bridge between the two universities. Together with Min Han of the University of Colorado, Boulder, and Yuan Zhuang of Duke University in Durham, North Carolina, Xu co-directs the Institute of Developmental Biology and Molecular Medicine at Fudan University. Funded primarily by China's National Natural Science Foundation and its Ministry of Education, the 2-year-old institute boasts five full-time faculty members and focuses on using fruit fly and mouse genetics to decipher the functions of mammalian genes. Yale beams its weekly genetics seminar to the institute by video teleconferencing, and Xu has taught a course each year at Fudan on genetic analysis. To prepare students to compete on the world stage, the institute conducts all business in English. The institute plans to tackle large-scale mouse experiments that are “way too expensive to do in the U.S. or any other developed nation,” says Xu, who spends about one-fourth of his time in China. “We're determined to do absolutely first-rate work.” The benefits of beneficence The advantages of setting up shop overseas also appealed to physical chemist Bartosz Grzybowski of Northwestern University in Evanston, Illinois, who grew up in Gdansk, Poland. Grzybowski received his doctorate from Harvard in 2000 and last year came to Northwestern. In 2002, he and childhood friend Piotr Barski founded ProChimia Poland, a high-tech company in Gdansk that specializes in surface chemistry. “When you're 29 and you're just out of graduate school, no serious investor in the U.S. will talk to you,” he says. But in Poland, expenses were so low the two entrepreneurs didn't need any backers. “We had$500 and we started a company with it,” says Grzybowski, who spends 6 to 8 weeks a year in Gdansk. “In the States, it would be impossible, but in Poland somehow it worked.” Last year ProChimia sold $200,000 worth of reagents for making bioassay chips and other supplies to scientists at dozens of American and European universities, and it recently attracted its first American investors. Grzybowski hopes it will seed a biotech boom in Gdansk. Although ProChimia is now profitable, many researchers with new ventures in their native land say that they give more than they get back in return. That's OK with Wayne Getz, a biomathematician at the University of California, Berkeley, who sees himself as a conduit funneling U.S. intellectual resources to colleagues in his native South Africa. After apartheid ended in 1994, Getz launched several collaborative projects, including a$1.8 million, 5-year study of bovine tuberculosis in Kruger National Park funded by the U.S. National Science Foundation. Last year he helped found the South African Center for Epidemiological Modeling and Analysis in Stellenbosch, which will track the nation's AIDS epidemic.

Getz, who received his doctorate in 1976 from the University of the Witwatersrand in Johannesburg, says that being in Berkeley gives him the opportunity to tap into intellectual resources, particularly the knowledge of AIDS researchers in the University of California system and the San Francisco area, that are in short supply in South Africa. “What's important is the access I have to this expertise.”

To forge such connections, many researchers are willing to make significant sacrifices professionally. Alash'le Abimiku, a virologist and immunologist at the University of Maryland's Institute of Human Virology in Baltimore, says that fighting the spread of AIDS in her native Nigeria at times means placing her academic ambitions on the back burner. “If I'd been in my lab full-time, I could have published much more,” she says. “But I don't regret it at all.”

Abimiku received her doctorate in 1988 from the London School of Hygiene & Tropical Medicine and came to the United States in 1991 to work with AIDS pioneer Robert Gallo, then at the National Cancer Institute in Bethesda, Maryland. That year the two founded the International Center for Scientific Culture—World Laboratory AIDS Research Center in Jos, which is funded primarily by the Plateau state government. Abimiku, who is director of the center, intended to focus on isolating the particular strain of HIV then emerging in Nigeria. But she soon found herself concentrating on basic screening and education to combat the epidemic. In the beginning, Abimiku spent nearly half her time in Nigeria.

Over the years, Abimiku's focus has turned back toward science—her group isolated the strain of HIV prevalent in western Africa. Funding from the Bill and Melinda Gates Foundation has helped her expand her efforts in Nigeria. “The academic contacts over here have catalyzed a lot of the things we've been able to do there,” she says.

The discomforts of home

All agree that reaching back to one's homeland requires time, commitment, and sacrifice. And the locals may resent expatriates who barge in assuming they'll be the big fish in a small pond. “There are already fish swimming around trying to protect their territory,” says Getz.

The indigenous scientific culture may resist change. Theoretical physicist George Sudarshan of the University of Texas, Austin, juggled dual positions in the United States and India for more than 15 years, including heading an interdisciplinary center at the Indian Institute of Sciences in Bangalore and the Institute of Mathematical Sciences (IMS) in Chennai. Although the Bangalore center eventually foundered in interdepartmental politics and closed in 2003, in its time it catalyzed the exchange of ideas across disciplines, Sudarshan says. The IMS continues to flourish.

But Sudarshan was also hoping to inspire Indian researchers to greater productivity, which didn't happen. “I was under the misapprehension that if only they had someone to guide them, they would suddenly become very productive,” he says. “But they continued in their sleepy ways. … You're fooling yourself if you think you can single-handedly change the system.”

Even so, most researchers who build bridges to their homelands are willing to endure the hassles for the personal satisfaction they gain. “Even if I won the Nobel Prize,” Abimiku says, “if my work doesn't help my country, then I don't think it would be very satisfying.” That attitude drives foreign-born researchers to use their success in the United States to attempt bold new projects that will improve science throughout the world.

24. Profile: Lai-Sheng Wang

1. David Malakoff

A bloody massacre will forever be a defining moment in the career of physical chemist Lai-Sheng Wang. Like thousands of other Chinese-born researchers who came to study in the United States in the late 1980s, Wang took advantage of relaxed immigration rules following the Chinese Army's 1989 crackdown on democracy protests in Beijing's Tiananmen Square in order to stay. He became a U.S. citizen in 1998.

“I think I might have tried to stay anyway, but without Tiananmen I probably would have had to go back home,” says Wang, who holds a joint appointment at Washington State University in Richland and the nearby Pacific Northwest National Laboratory.

Wang, 42, came in 1983 for graduate work at the University of California, Berkeley, and joined Washington State a decade ago after a postdoctoral stint with Nobel laureate Richard Smalley at Rice University in Houston, Texas. Since then, he has published regularly in top-tier journals and won accolades for his work probing the structure of nanomaterials. He doubts he could have done as well at home, although he says China and other nations are beginning to catch up to the United States. “The facilities and cooperation here are very advanced,” he says.

Despite his accomplishments, Wang says it has “taken years, years, and years” to adapt to the more aggressive and outspoken culture of American science. “In the beginning I just wanted to study,” he says. But as his English improved, “I came to realize that I was expected to ask questions and be skeptical. I had to become less passive and more confident to keep up.”

Now, Wang recognizes some of the same passivity in his own graduate students, among them seven from China and one from India. “They tend to speak out only when they are absolutely sure of themselves,” he says. But his efforts to encourage more debate, he adds, “sometimes succeed.”

25. Profile: Roxanne Duan

1. David Malakoff

When biomedical researcher Roxanne Duan left Taiwan 20 years ago to pursue a doctoral degree at the University of California, San Francisco, she resisted socializing with students from similar cultural backgrounds. “I was trying hard to fit into American society and didn't want to be isolated in a little Chinese group,” she recalls.

But after graduating and building a career in the biotechnology industry, Duan began reconnecting with her Asian roots. And this year, at age 43, she's set to become president of the 500-member Chinese Biopharmaceutical Association, USA, a Maryland-based networking group. “I was feeling the need to look for my Chinese identity, I guess,” says Duan, who works on antiviral drugs at Functional Genetics, a biotech company in Rockville, Maryland. Not only has the association given her an opportunity to help younger Chinese scientists, especially women, she says, “but now I have a place where I can talk [Taiwanese] politics.”

Duan came to the United States planning to pursue an academic career. But she was soon attracted to industry: In 1996, she joined Human Genome Sciences, also in Rockville, and 2 years ago she set out on her own. But after failing to raise sufficient capital to fully develop her company, which aimed to fine-tune technologies for teasing out protein functions, she threw in her lot with Functional Genetics.

“I'm the typical American in some ways,” she says, ruefully noting that she's “one of those suburban, single moms driving around with two kids.” But she's Taiwanese, too. “I was taught to have a tremendous sense of responsibility for my parents, but I only see them once a year at most,” she says. “It can be heartbreaking.”