# News this Week

Science  09 Mar 2001:
Vol. 291, Issue 5510, pp. 1872
1. GENOMES

# Rat Genome Spurs an Unusual Partnership

1. Eliot Marshall

Even as sequencing groups are struggling to finish the human genome—two-thirds of it remains in rough form—they're taking on a big new assignment. Last week, the U.S. government plunked down about $60 million in new money to have three labs—one academic center and two private companies—race ahead on the rat genome. A public-private effort to sequence the mouse genome is already under way, promising a rough draft this year and a finished, or gap-free, sequence by 2005. The rat is needed, researchers say, because it has been used more than the mouse for studies of physiology, and it offers an independent view of how genes work in a rodent. Nailing down this new genome will be almost as daunting as sequencing the human genome in draft form, however, because rodents also have 3 billion base pairs of DNA. The plan calls for fast work, with delivery of a draft sequence of the Norway brown rat containing 90% or more of the functional genetic information by 2003. Francis Collins, director of the National Human Genome Research Institute (NHGRI) —which is funding this initiative jointly with the National Heart, Lung, and Blood Institute—says that having the genomes of three of the most important mammals in biomedical research in hand “will greatly speed the unraveling of the genetics and physiology” of human disease. The rat project is remarkable for the new public-private coalition it creates and the efficiencies it aims to achieve. It brings together scientists who until a few weeks ago were competitors, melding their techniques. Richard Gibbs and colleagues at the genome center at Baylor College of Medicine in Houston, Texas, will lead the effort, and a group at Celera Genomics in Rockville, Maryland, will add brute-force sequencing power. Gibbs's team was one of 16 in the nonprofit consortium that raced Celera to the finish line on the draft human genome (Science, 16 February, p. 1177). Celera's principal investigator is sequencing expert Robert Holt, a pharmacologist who joined the company at its founding in 1998. View this table: Genome Therapeutics Corp. in Waltham, Massachusetts, will provide more sequencing muscle, using funds reprogrammed from the mouse project after several companies pitched in with private support (Science, 13 October 2000, p. 242). Smaller grants for clone preparation are also going to Pieter de Jong of Children's Hospital Oakland in California, Marco Marra of the University of British Columbia in Vancouver, and Shaying Zhao of The Institute for Genomic Research in Rockville, Maryland. Baylor will take on the difficult task of assembling the raw data into a coherent genome. Celera's assignment is more limited, says president J. Craig Venter: It will generate raw sequence data and offer advice. Gibbs says his group will rely less than Celera did on high-powered computer analysis to assemble the genome and more on a strategy that uses mapping and tight management of data. “It's fair to say the human genome was sort of kludged together heroically” with disparate techniques, Gibbs says. He hopes this project will set a new standard for efficiency, sequencing the rat genome just 4.5 times over, about half the level of redundancy used for the human genome. This will leave significant gaps, but human and mouse data should make genome assembly manageable. Celera is “happy to be collaborating with Baylor” on this project, says Venter, although he thinks there was “some resistance” within the academic community to including his company in the effort. But he notes that he has always worked well with the Baylor group and that Celera was included for a simple reason: NHGRI reviewers concluded that its sequencing proposal was one of the best. Venter is doubtful, however, that the rat sequence can be assembled into the correct order with so little redundancy in the raw data. Gibbs is confident. “We're going to break the$100 million barrier for a mammalian genome,” he predicts. That may not sound cheap to a traditional small-lab biologist, but it's a fraction of the human genome's price.

Both teams will abide by a new set of mandatory data-release rules established last December. These require grantees to make public on a weekly basis raw information taken directly from sequencing machines—more detailed data than were required from human genome sequencers. The groups have agreed not to patent or use the data for research before making them public through the National Center for Biotechnology Information (http://www.nhgri.nih.gov/Grant_info/Funding/Statements/RFA/data_release.htm).

Researchers are delighted by the pace of the project, not only because of the insights it promises to shed on human disease but also because rat DNA will provide a critical third point (with mouse and human data) for triangulating in on the function of human genes. “I have been a banner waver for the rat genome” for nearly a decade, says Howard Jacob, a molecular biologist at the Medical College of Wisconsin in Milwaukee. “I'm ecstatic about the speed with which the public sector is investing in this project.”

2. MALARIA RESEARCH

# Sequencing Set for Dreaded Mosquito

1. Michael Balter

PARIS—Scientists have agreed to terms on a long-awaited effort to sequence the genome of the mosquito Anopheles gambiae, the main vector for the malaria parasite in sub-Saharan Africa. Meeting at the Pasteur Institute here on 3 March, representatives from 20 research centers in 12 countries started laying plans for the project. Like the rat sequencing project (see previous story), it will include Celera Genomics of Rockville, Maryland, and feature unrestricted public access to data.

View this table:

Sequencing of the Anopheles genome is expected to begin in the next 6 months. Because some of the partners—including the Pasteur and the French gene-sequencing center Genoscope—have already begun preliminary gene mapping and sequencing, a “rough draft” of the full sequence could be completed by year's end. Revealing the mosquito's 260 million DNA base pair sequence—together with those of the human genome and the malaria parasite Plasmodium falciparum now nearing completion—should open up new strategies for controlling the deadly disease, which kills some 1.5 million people each year, mostly African children. This genetic treasure trove will allow researchers “to get to the parasite at every possible level,” says Fotis Kafatos, director of the European Molecular Biology Laboratory in Heidelberg, Germany.

The initial sequencing and genome assembly should run “significantly less than 10 million,” says Kafatos, who initiated the project with Anopheles expert Frank Collins of the University of Notre Dame in Indiana (Science, 23 July 1999, p. 508). Additional funds will be needed to fine-tune the sequence and begin detailed analyses of the genes and their functions. Together with Genoscope, Celera will perform the initial sequencing using the “whole-genome shotgun” approach it unleashed on the human genome. Although not all the financing is in place, the French government has pledged to cover Genoscope's participation in the initial sequencing. Celera has submitted a grant proposal to the U.S. National Institutes of Health to cover at least part of its costs. Researchers who have campaigned for years to have the mosquito's genome sequenced are delighted that the big guns of modern gene technology will at last be brought to bear on Anopheles. “We are really excited,” says Kafatos. “A unique global collaboration has finally crystallized.” 3. ARCHAEOLOGY # Heavy Damage Feared After Taliban Decree 1. Andrew Lawler Two ancient Buddhas captured the world's attention last week, as Afghanistan's Taliban leaders began to carry out a decree to demolish all carvings and statues of animals and humans. The government-sponsored destruction extends even to artifacts from its own, Islamic tradition, as well as thousands of lesser known items that experts say combine Western and Eastern traditions in unique and irreplaceable ways. The Taliban, which few governments recognize as legitimate rulers, believes animal and human representations are antithetical to Islamic teaching. Archaeologists are stunned by the decree's breadth. “It is a most enormous tragedy,” says Norman Hammond, a Boston University archaeologist who worked in Afghanistan in the 1970s and has written about its treasures. Afghanistan's special archaeological heritage derives from its position as the ancient crossroads of Asia. Alexander the Great left behind artisans who built Greek-styled statues at cities such as Alexandria Oxiana, now Ai Khanum, on the Oxus River. Chinese caravans crossed Afghanistan's rugged terrain heading west. Buddhist influence seeped in from India to the southeast, and Islam swept the region from the west. The result was often a rich blending of styles. A Kabul Museum collection of panels from the first century, for example, show clear Mediterranean, Chinese, and Indian influences. The two giant Buddhas, which stand 37 and 54 meters high in the sandstone cliffs of Bamiyan and date from the third and fifth centuries, have become symbols of the new policy. But the decree apparently also would cover objects in the Kabul Museum, such as a 1000-year-old copper dish bedecked with mythical animals and a Koran quotation. Hammond also fears the worst for frescoes in Islamic-era palaces at Lashkair Bazar and at Ghazni, which includes a building decorated with a stone frieze. How much of the Kabul collection was intact even before last week's decree is unclear, however. The museum, closed to Westerners for years, already has been severely damaged and at least partly looted. The Taliban leaders so far have rejected pleas by the United Nations to rescind the decree and have mocked offers by museums such as New York's Metropolitan Museum of Art to rescue smaller objects in danger. “I ask Afghans and the world's Muslims to use their sound wisdom,” Taliban chief Mullah Mohammed Omar was quoted as saying on 4 March on official radio. “Do you prefer to be a breaker of idols or a seller of idols? Is it appropriate to be influenced by the propaganda of the infidels?” As Science went to press, the destruction of the Buddhas had begun. Government officials also boasted that two-thirds of the thousands of offending objects had been smashed. Nevertheless, a special envoy from the United Nations was trying to broker a solution, and other Islamic nations expressed outrage over the decree. 4. ASTROBIOLOGY # Are Martian 'Pearl Chains' Signs of Life? 1. Richard A. Kerr Life on Mars jumped back into the headlines last week with the publication of two papers claiming that nanoscale mineral grains in the famous martian meteorite ALH84001 were left by ancient martian bacteria. One paper was old news to researchers (Science, 22 December 2000, p. 2242). The other got a generally cautious reception when it was reported in the media, but now many experts are turning downright incredulous as they get a chance to inspect the published images. One of the two papers “defines a new low in the great ALH84001 debate,” says microscopist John Bradley of MVA Inc. in Norcross, Georgia, a longtime critic of martian microbe claims. Even the fence sitters are unimpressed: “There's a lot of subjectivity” in the analysis, says geologist Allan Treiman of the Lunar and Planetary Institute in Houston. “They've gone too far in interpreting the images” as signs of life. Meteorite ALH84001 first made headlines in 1996, when a group of researchers claimed that the chemical, mineralogical, and isotopic makeup of the meteorite—and some buggy-looking microscopic features—spoke of ancient life back on Mars. All but one of those lines of evidence have been withdrawn or discounted as not definitive, singly or collectively. The remaining evidence is grains of the iron-oxide mineral magnetite a few tens of nanometers in size, the same sort of particles that some earthly bacteria form, stringing them into long chains to make magnetic compasses. In one of the 27 February Proceedings of the National Academy of Sciences (PNAS) papers, microscopist Kathie L. Thomas-Keprta of Lockheed Martin in Houston and colleagues argue that about one-quarter of ALH84001's magnetite is indistinguishable from the magnetite of a particular terrestrial magnetotactic bacterium, and therefore the martian magnetite probably has a bacterial origin, too. Thomas-Keprta made the same argument in another paper late last year. Other researchers agreed about the resemblance but concluded that the evidence was not extraordinary enough to prove such an extraordinary claim. Now comes the claim that some of ALH84001's magnetite is arranged in chains like pearls on a string, just the way some bacteria form magnetite on Earth. In the second PNAS paper, Imre Friedmann of NASA's Ames Research Center at Moffett Field, California, and colleagues present scanning electron microscopy (SEM) images of what they believe are chains of magnetite grains produced by bacteria. In a mode of SEM operation that highlights heavy elements such as iron, images show bright blobs of presumably iron-rich material lined up across the surface. “The chains we discovered are of biological origin,” says Friedmann, because the fuzzy blobs have a uniform size and shape within a chain, have consistent gaps between them, are aligned end to end when elongated, and can bend in curved chains, just like magnetite chains of earthly bacteria. Initial news reports quoted vague reactions from experts who had yet to see the images or had seen them in faxed versions only, but the real McCoys are getting a decidedly cool reception. Microscopist Peter Buseck of Arizona State University in Tempe is among the most receptive. “It's an interesting paper,” he says. “I have no problem dismissing some of the [chains]. There are others that seem to come close to a real [bacterial magnetite chain]. It's a matter of taste.” Buseck can't recall anyone finding anything like these chains preserved for so long on Earth. Here they seem to fall apart on the death of the bacterium, not be preserved for billions of years as required for any martian examples. Meteoriticist Ralph Harvey of Case Western Reserve University in Cleveland is less understanding. “We've seen this before” with ALH84001, he says. “Someone says, ‘Let's take a novel technique and turn it on a very complex rock.' Who knows what the inorganic magnetite in rock may look like with this technique? They're just interpreting things in a narrow way.” Some nonbiological process might just as well produce magnetite in such arrangements, he says, given that magnetite very much like Thomas-Keprta's has been made in the laboratory (Science, 31 March 2000, p. 2402). An equally intensive search of other rocks—both extraterrestrial and earthly —is in order, says Harvey. If these “chains” are going to change anyone's mind, adds Buseck, “we're going to need better chemistry and images [of the chains], perhaps better than is available now.” 5. GERMAN SCIENCE # New Money to Lure Talent From Abroad 1. Robert Koenig BERN—When she visited Silicon Valley and Stanford University in January, Edelgard Bulmahn, Germany's research minister, quizzed German scientists about why they had left their homeland. She got an earful: Complaints ranged from a dearth of jobs to distaste for rigid university hierarchies. Bulmahn appears to have taken such complaints to heart. Last week, she announced that her ministry will channel82 million into various initiatives aimed in part at winning back expatriate scientists and preventing talented young researchers from leaving. “We want to stop the brain drain,” says Bulmahn, “and instead start up a brain gain.”

Bulmahn and others in Germany's science establishment have plenty of reason for angst. Several German scientists have won Nobel Prizes for research done in U.S. labs, including physicist Horst Störmer in 1998 and cell biologist Günter Blobel in 1999. Compounding the problem, a recent study found that about 14% of German science students land graduate or postdoc positions in the United States, and up to a third of them don't return.

To try to begin countering this trend—as well as inject foreign blood into German universities—the research ministry has tapped government revenues raised last year from licensing use of communications frequencies to help launch new programs at the Alexander von Humboldt Foundation and the Academic Exchange Service (DAAD). “We want to attract some of the world's best scientists to Germany,” says Humboldt president Wolfgang Frühwald, who calls the new government funding “an important initiative.”

Humboldt is using its share of the extra funding—$46 million over the next 3 years—to launch new programs such as the Wolfgang Paul awards. This program aims to attract between 15 and 20 top-notch scientists to Germany by offering grant support of as much as$2 million over 3 years. While the Paul awards are aimed mainly at non-German scientists, native Germans who have worked abroad for more than 5 years are eligible to apply. “We're interested in the high quality of the researchers, not the countries on their passports,” says Humboldt's Thomas Hesse. In another program, Kosmos, Humboldt will give 3-year grants of up to $1.1 million to younger scientists. The other beneficiary of the new funds, the DAAD, will get about$34 million over 3 years to jump-start three new programs. One, Innovatec, will sponsor about 50 guest scientists annually—open to any professors at all levels outside Germany—to work at German universities. Another program will help fund exchanges of between 500 and 1000 graduate students and advanced undergrads a year. The new programs will complement ongoing efforts to give young researchers more independence and to help transform German universities (Science, 5 January, p. 23, and 2 February, p. 821).

Bulmahn thinks these initiatives, along with a wave of retirements at universities expected over the next 5 years, will open up new opportunities for scientists. As she told the California expatriates, “it would be great to see you again in Germany.”

6. SCIENTIFIC MISCONDUCT

# Fallout From German Fraud Case Continues

1. Robert Koenig

BERN—An expert panel has criticized Roland Mertelsmann, one of Germany's best known cancer researchers, for failing to detect data falsification and manipulation that allegedly occurred in his department and in some papers on which he was listed as a co-author. Responding to the findings, the rector of the University of Freiburg last week asked the state government to launch disciplinary proceedings. Mertelsmann, chief of the university medical center's oncology and hematology department, immediately called the inquiry “unfair” and vowed to mount a vigorous defense.

Last June, a task force found that 94 papers co-authored by former cancer researcher Friedhelm Herrmann between 1988 and 1992 contained likely falsifications or instances of suspected data manipulation (Science, 23 June 2000, p. 2106). Herrmann, who quit his post at the University of Ulm in the wake of the allegations, had worked in Mertelsmann's department at Freiburg.

Investigating Mertelsmann's role in the questionable work, the Freiburg panel, headed by Albin Eser—director of the Max Planck Institute for Foreign and International Criminal Law in Freiburg—found no evidence of falsifications by Mertelsmann, who was listed as a co-author on 58 of the Herrmann papers the task force called into question. But the panel faulted Mertelsmann for failing to monitor his department's research closely enough to detect the alleged misdeeds.

The Freiburg panel also cited “serious irregularities” related to two articles co-authored by Mertelsmann that did not involve Herrmann: a September 1994 paper in Blood and an August 1995 paper in The New England Journal of Medicine. The panel found that some data in these papers, describing clinical trials of cancer treatments, were presented in such a way that they gave the impression of being “more complete and consistent than was actually the case.” The panel also found inadequate records of whether some patients had given written informed consent to participate in the trials.

According to the panel, these shortcomings—which also involved other researchers who have since left the university—showed “reckless violation of the rules of good scientific conduct.” The panel's report credits Mertelsmann, however, for deleting nearly all the suspect papers from his publication list and taking an active role in correcting or retracting some papers.

In a statement last week, Mertelsmann complained that he had been denied adequate access to key documents related to the allegations and had not been given the opportunity to respond before the report was made public. He stated that he had not yet read the report but would defend himself “against any allegations.” Mertelsmann could not be reached for further comment.

At a 1 March press conference, university rector Wolfgang Jäger said he has asked the state of Baden-Württemberg's Research Ministry to initiate a disciplinary proceeding “to clarify the extent of [Mertelsmann's] personal responsibility” for the questioned research. A spokesperson for the ministry, which is not obliged to launch such a proceeding, says a decision is expected in the next few weeks.

Meanwhile, the Freiburg medical center's supervisory board has asked Mertelsmann to withdraw voluntarily from clinical research for the duration of any disciplinary hearing. Jäger said no further actions are necessary, because the center and its faculty have taken steps—such as adopting stricter rules of conduct—to safeguard research integrity.

7. QUANTUM CHROMODYNAMICS

# Quark Quirk Triggers Nuclear Shrinkage

1. Charles Seife

If atoms had egos, a few lithium nuclei would be nursing bruises right now. By sticking an exotic type of quark where it doesn't belong, physicists have cut the nuclei down to four-fifths normal size. In the process, the scientists are edging toward a theory that can explain nuclear interactions of all varieties.

“Shrinkage of about 20% is very surprising,” says Hirokazu Tamura, a physicist at Tohoku University in Sendai, Japan. “Nuclear physicists know that compressing the nucleus is very, very difficult.”

So instead of trying to squeeze an atomic nucleus, Tamura and colleagues from Japan, China, Korea, and the United States set out to shrink it from within. In the 5 March Physical Review Letters, the physicists describe how they injected a little dose of strangeness into a lithium-7 nucleus. Through a handful of particle interactions, they substituted a strange quark for a down quark, turning one of the atom's neutrons into a particle called lambda, or Λ. “It's quite similar to the neutron, but somewhat heavier,” says John Millener, a physicist at Brookhaven National Laboratory in Upton, New York. “A proton is two ups and a down, a neutron is two downs and an up, and a Λ is an up, a down, and a strange.” The quark substitution turned lithium-7 into lithium-6-Λ, a so-called “hypernucleus” with subtly different properties from a garden-variety lithium nucleus.

The difference stems from the Pauli exclusion principle, the quantum-mechanical rule that forbids certain particles from having the same quantum state. Given the chance, a neutron in a nucleus will occupy the lowest possible energy level, or ground state. Two neutrons can inhabit that level, but only if they have different quantum states. For that to be true, one neutron must have spin +½, and the other must have spin −½. A third neutron, however, must take a higher energy position farther away from the center of the atom. The same exclusion rules apply, independently, to protons.

Lithium-6 has three protons and three neutrons; one proton and one neutron are in the higher energy state, loosely bound to the core. Enter the Λ. Because a Λ particle is distinct from both protons and neutrons, it is exempt from the Pauli exclusion principle that governs those particles. As a result, it sinks directly into its ground state, joining the low-energy protons and neutrons at the center of the nucleus. “You put the Λ in the system, and it makes everything more stable by interacting with the [protons and neutrons],” Tamura says. The extra Λ binds the particles more tightly together but, unlike an added proton or neutron, takes up no additional space. The stabilized nucleus shrinks.

Tamura's team observed the shrinkage by precisely measuring gamma rays that emanate from lithium-6-Λ hypernuclei. The gamma rays reflect the shifting of particles' spins within hypernuclei—information that can help scientists determine not only a hypernucleus's size, but also how its components interact with one another. “Nobody's been able to measure this with such high precision,” says Millener, who hopes that understanding those interactions will shed light on so-far-obscure aspects of nuclear physics. “We don't really have a theory for these interactions.”

8. PHILANTHROPY

# Russian Billionaires Launch Science Fund

1. Vladimir Pokrovsky,
2. Andrey Allakhverdov,
3. Marina Astvatsaturyan*
1. Vladimir Pokrovsky, Andrey Allakhverdov, and Marina Astvatsaturyan are writers in Moscow.

MOSCOW—Two unlikely saviors have come to the rescue of Russia's impoverished scientists. Last month, a new foundation endowed with $1 million from a pair of young tycoons announced that more than 200 researchers will receive salary supplements of up to$10,000 this year—as much as 10 times their annual salary. While commending the so-called oligarchs for their generosity, some observers have complained about the secrecy of the selection process.

This is not the first time that a billionaire has bailed out Russian science. In the early 1990s, U.S. financier George Soros spent $120 million of his own fortune to endow the International Science Foundation (ISF), which doled out peer-reviewed grants to more than 30,000 scientists in the former Soviet Union. Then in 1995, one of the most notorious of Russia's oligarchs, Boris Berezovsky, gave$1.5 million to support travel grants for Russian scientists.

Now comes the Public Charity Foundation for the Support of National Science, funded entirely by Oleg Deripaska, the 32-year-old head of the megacompany Russian Aluminum, and Roman Abramovich, a 34-year-old oil industry executive and governor of the Chukotka region across the Bering Strait from Alaska. In setting up the foundation without fanfare last year, the two billionaires “did exactly the same as Soros had done: They gave money and kept themselves in the background,” says Pavel Arsenyev, former executive director of ISF's Moscow office.

The new foundation's executive director, Maxim Kagan, says candidates for grants were chosen from among past winners of three academic competitions run by the Russian Academy of Sciences (RAS) and the office of Russian President Vladimir Putin. From this list of names, Kagan says that experts selected winners based on factors such as the number of citations their papers had received. The 2001 grants went to 10 prominent academicians—including Yuri Kagan, Maxim's father—who each will receive $10,000 this year; 200 young Ph.D.s and doctors (the highest academic degree in Russia) each get$3000 and $5000 respectively. The RAS will administer the awards for the charity, which reserved$100,000 for overhead.

The selection process was conducted in secrecy—the foundation has even refused to name the experts that helped select winners—and this has prompted some grumbling. “The atmosphere of secrecy may cause suspicion,” says Arsenyev, who wonders if there even were any expert advisers. He also complains that only RAS scientists appear to have been eligible for the prizes. “If Soros were to do this,” he says, “he would have begun with the scientific community en masse.” The former head of the ISF's scientific council, Vladimir Skulachev, argues that it would have been more transparent had the prize money been distributed by the Russian Foundation for Basic Research, the country's main natural sciences granting agency.

According to Kagan, even if the new foundation can raise money to continue beyond 2001, the selection procedure is unlikely to become more transparent. He says that RAS president Yuri Osipov views the foundation as a Russian version of the Nobel Committee, which also keeps its deliberations secret.

In unveiling the foundation, Abramovich and Deripaska said they were moved to act by the parlous state of Russian science. It's also great PR in the power struggles between the oligarchs and Putin over taxes and privatization of state assets, notes Skulachev. A few years ago, Skulachev says, Berezovsky tried a similar tactic when he persuaded six other businessmen to help him create a $150 million science fund modeled after ISF. But the scheme fell apart before it got off the ground, says Skulachev. “If they had created the foundation,” he says, “it would have been more difficult for Putin to struggle with them.” Whatever the political benefits, Abramovich and Deripaska certainly have won the hearts of at least 210 scientists. 9. CHINA # Academician to Lead Science Ministry 1. Yimin Ding* 1. Ding Yimin writes for China Features in Beijing. BEIJING—A remote-sensing expert who has been in charge of promoting high-tech enterprises has been chosen to head China's Ministry of Science and Technology (MOST). Xu Guanhua succeeds Zhu Lilan, who assumes a top legislative post within the National People's Congress. Xu, who has been Zhu's deputy, will direct a rapidly growing science and technology budget that reached$6.5 billion in 1999. He oversees state-run scientific institutes, including the Chinese Academy of Sciences (CAS), as well as funding for key basic research projects, high-technology development, scientific infrastructure, and international collaborations.

A native of Shanghai, the 60-year-old Xu was trained as a forestry scientist and spent 30 years working for the Chinese Academy of Agricultural and Forestry Sciences before moving to CAS. Named an academician in 1992, Xu is credited with helping to develop the country's remote-sensing industry using domestically made global information system instruments, as well as improving the research environment within CAS and nurturing young talent. “He was quite strict,” says Niu Zheng, Xu's first doctoral student, who is now a research professor within the Institute of Remote Sensing Application. “But no matter how busy he was, he would always find time to discuss a scientific issue.”

As executive vice minister of science and technology in charge of high-tech industries in the mid-1990s, Xu argued in a speech for “active measures to promote the venture capital market,” including listing more high-tech enterprises on the country's stock exchange. He also lobbied for the application of information technology in a variety of fields, from medicine to transportation. At MOST, he built up a loyal following among scientists. “He is a man of action and principle who [has] an easygoing style,” says Sun Chenbei, a former MOST staffer who is now China representative for a Canadian consulting company.

Zhu, a polymer chemist, has been named vice chair of the Education, Science, Culture, and Health Committee in the national legislature.

10. BEHAVIORAL GENETICS

# Study Suggests Pitch Perception Is Inherited

1. Constance Holden

Can't carry a tune? Chances are you can lay a lot of the blame for that on your genes, according to a report on page 1969. By studying twins' ability to perceive sour notes in familiar tunes, a U.S.-British team has concluded that the perception of relative pitch is highly heritable and is dependent on higher brain functions. And that, say geneticist Dennis Drayna of the National Institute on Deafness and Other Communication Disorders and colleagues, means that pitch perception may offer a window into brain processes that are also used in language.

The researchers administered a test, called the Distorted Tunes Test (DTT), to 284 pairs of female twins, about half of them identical and ranging in age from 18 to 74, from the St. Thomas' U.K. Adult Twin Registry. The DTT plays short snatches of 26 familiar melodies, from “Turkey in the Straw” to “Silent Night,” most of them with one or more notes altered. Subjects indicate whether the tune sounds right. The distortions in the DTT are all obvious, with no pitch altered by less than a halftone. Some tunes are drastically altered (see sample from “America the Beautiful”). So anyone who gets more than three wrong is judged to be somewhat tune-deaf.

Because the identical twins' responses correlated far better than those of the fraternal twins—0.67 versus 0.44—Drayna's team believes that the trait is strongly influenced by genes. Indeed, the team estimated the heritability for tune deafness at 0.80. That's about as high as it ever gets for genetically complex traits, rivaling features such as height. “These results demonstrate for the first time the powerful influence of genes on the ability of humans to recognize correct pitch and melodies,” says co-author Tim Spector, who heads the twin research unit at St. Thomas' Hospital in London.

Brain researchers are fascinated by pitch perception, because it taps into cognitive functions, Drayna says. A person can do well on an audiological test and still flunk the DTT—and vice versa—showing that the “musical pitch perception is largely independent of peripheral hearing,” the researchers conclude. And although absolute pitch (the ability to recognize an isolated note) is to some degree trainable, scores on tests of relative pitch perception “don't change appreciably over an individual's lifetime,” says Drayna—a finding suggesting that, as with language, there's hard wiring involved.

Evan Balaban of The Neurosciences Institute in San Diego agrees that the study is an “important” one that “is looking at something very likely to be a central [brain] function.” The study clearly demonstrates a biological basis for pitch discrimination, Balaban says. But he's reluctant to buy the heritability estimate, in part because twins are somewhat more prone than nontwins to developmental disabilities. As evidence, he points out that almost 40% of the twins showed some evidence of deficits in pitch recognition compared with 27% in the control population. The authors argue that their twins are no different from the general population, in which 5% have severe deficits in pitch recognition. They say cultural unfamiliarity with some of the tunes might have lowered the scores a bit.

Scientists hope the study of pitch will provide a lever for studying communication disorders. “The pitch contour of the voice communicates a lot of information about emotions, [so] to tell the difference between different pitch contours would use some of the same abilities” as are used in talking, notes Balaban. Severe defects in pitch perception therefore “could be a subtle indicator” of imperfections in wiring in language-related cortical areas. Drayna agrees, citing as “tantalizing evidence” anecdotal reports of severe tune deafness in people with certain speech and language disorders, such as a problem with processing spoken words known as “cluttering.”

Other researchers are also in hot pursuit of brain clues offered by pitch perception. In a paper published in the January issue of Developmental Psychology, psychologist Jenny R. Saffran of the University of Wisconsin, Madison, reported that 8-month-old infants, “like many songbirds,” may come equipped with absolute pitch—further evidence of the importance of pitch recognition for language learning, she says. Saffran speculates that this knack, which is rare in adults but can be enhanced by early training, is superseded by relative pitch perception as the brain develops. And that talent, which is both more useful and more cerebrally sophisticated, now appears to be primarily determined by the genes.

11. AIDS VACCINES

# Long-Lasting Immunity Conferred in Monkeys

1. Jon Cohen

Faced with the lack of a critical reagent, Harriet Robinson of Emory University in Atlanta was forced to redesign an AIDS vaccine experiment. From that minor setback has emerged an impressive finding about the lasting power of her vaccine approach.

In a paper published online today by Science (http://www.sciencexpress.org/), Robinson, Emory colleague Rama Rao Amara, the paper's first author, and others describe a two-step AIDS vaccine strategy they developed in collaboration with Bernard Moss of the National Institute of Allergy and Infectious Diseases (NIAID). In a large monkey experiment, this vaccine appears to have stimulated long-lasting immunity. “It's among the most exciting concepts that we've seen in this [monkey] model,” says Peggy Johnston, head of NIAID's AIDS vaccine program.

Robinson, Amara, Moss, and co-workers built their experiment around a laboratory-made, hybrid virus called SHIV, which is part HIV and part SIV, a simian AIDS virus. They first injected 24 monkeys with a vaccine that contained several SHIV genes stitched into a circular piece of bacterial DNA. Following vaccination with this relatively easy-to-make “naked DNA,” the researchers gave the animals a booster shot consisting of a variety pack of SHIV genes carried by recombinant modified vaccinia Ankara (MVA), a version of the virus used as the smallpox vaccine. Rather than raising antibodies that can derail the AIDS virus before it causes an infection, both the naked DNA and MVA vaccines primarily stimulate the immune system to target and eliminate already infected cells.

Robinson and colleagues planned to test this approach by “challenging” the vaccinated monkeys with an inoculum of SHIV placed in the animals' rectums. This is a more real-world test than injecting the virus under the skin or into a muscle. To do the experiment, the researchers needed a “challenge stock,” a batch of SHIV that had been tested on monkeys to determine the minimum amount of virus needed to establish an infection rectally. After she had started vaccinating monkeys, Robinson realized that she would have to make the challenge stock herself, which took three tries.

By the time they challenged the 24 vaccinated monkeys, 7 months had elapsed since the animals had received a booster shot. “Originally we had planned to challenge at 3 months,” laughs Robinson. The vaccinated animals became infected with the SHIV, but 20 weeks later, 23 of 24 monkeys had controlled the infection and had suffered no immune damage, the researchers report. All four of the unvaccinated control animals, in contrast, had consistently high levels of SHIV in their blood, and their immune systems steadily declined; all the control monkeys subsequently died from AIDS. “This is the closest thing to a real-life challenge that we've seen yet,” says James Bradac, who heads the NIAID division that oversees monkey trials of AIDS vaccines.

An HIV version of this DNA/MVA vaccine—which has no company behind it but is being manufactured under contract—is slated to begin human trials in the United States by early next year.

12. PRION RESEARCH

# Getting Yeast Prions to Bridge the Species Gap

1. R. John Davenport

The sheep disease scrapie has been around for centuries without infecting humans. But the strikingly similar “mad cow disease,” a progressive and ultimately fatal neurodegenerative condition, has apparently slipped from infected cattle into the human population. Both scrapie and mad cow disease are almost certainly transmitted by an abnormally folded form of a protein, known as a prion. That has left researchers with the problem of trying to figure out what determines whether a particular prion disease can spread from one species to another. New results with yeast prions may now provide a clue.

Although yeast prions are not infective, their behavior resembles that of mammalian prions in some ways. Both form when a normal prion protein adopts an abnormal shape or conformation. This abnormally folded protein can then induce the same shape change in other normal copies of the same protein, causing them all to clump together in insoluble aggregates. In the case of mammalian prions, these may damage the brain, while the aggregated yeast prion proteins lose their normal activity.

Ordinarily, a yeast prion from one species of yeast cannot induce the shape change in the corresponding prion protein from another species. But work reported in the 8 March issue of Nature by Jonathan Weissman and Peter Chien of the University of California, San Francisco, indicates that this species barrier can be overcome if the prion protein can adopt multiple structures and can thus interact with prion proteins from more than one species. If something similar happens with the prion that causes mad cow disease, it might explain how it is able to cause disease in humans as well as cattle.

Weissman and Chien performed their experiments on the yeast prion protein Sup35. Previous work had shown that the Sup35 proteins from the yeast species Saccharomyces cerevisiae and Candida albicans can't induce one another to change shape and form insoluble prion aggregates. To figure out the structural basis for this species barrier, the researchers replaced the normal SUP35 gene of S. cerevisiae with a three-part hybrid gene consisting of the DNAs encoding 40 amino acids from the Saccharomyces protein, 100 amino acids from the Candida protein, and the portion of Sup35 responsible for its normal biological function, which is turning off protein synthesis at certain sequences. They also added to these cells a separate piece of DNA encoding the prion-forming part of either the Candida Sup35 or of the Saccharomyces Sup35. The researchers wanted to see if either of the proteins made by these DNAs could push the hybrid protein into a prion state.

The Candida protein and the Saccharomyces protein turned out to be equally effective in switching the hybrid protein into the prion form in cells. But the phenotype of those cells, a result of the biologically active domain of the hybrid being turned off, was more severe in the cells induced with the Candida protein.

To determine whether these differences, reminiscent of prion strains previously seen in both yeast and rodent models, were due to different conformations of the hybrid prion, Weissman and Chien turned to the test tube, where prion proteins form long, organized fibers. Consistent with their results in yeast cells, the researchers found that fragments of prion fibers, made up of either the Saccharomyces protein or the Candida protein, could accelerate the hybrid protein's incorporation into prion fibers.

The real surprise came when the researchers let these test tube polymerization reactions run until essentially no remnants of the original Saccharomyces or Candida fibers remained. Chimeric fibers that had been seeded by Saccharomyces fibers would in turn trigger prion formation only by the Saccharomyces protein. Likewise, chimeric fibers seeded by the Candida protein would seed soluble Candida protein but not soluble Saccharomyces protein. The chimeric fibers, apparently, could “remember” the shape of the protein that had originally seeded them even though that protein was gone.

How the hybrid protein is able to structurally adapt to prions from both species is unclear. “We have to start looking at this experimentally,” Weissman says. He hopes to get structural information about the chimeric fibers by examining them using atomic force microscopy or cryo-electron microscopy.

Researchers are already intrigued, however, by what the results suggest about the source of the species barrier. “It's not just the differences in amino acid sequences, but also the differences in conformation that the prion takes” that may establish that barrier, says yeast prion researcher Susan Liebman of the University of Illinois, Chicago.

The big question now is whether something similar can explain why the mad cow disease prion, but not the one that causes scrapie, can cause disease in humans. “Yeast is a simple way to carve out one step, and that's conversion of normal protein into another, oligomeric [prion] form,” says physical biochemist Peter Lansbury of Harvard Medical School in Boston. “Beyond that, people really need to think about the huge differences [between yeast and mammalian prions].”

13. POLICY

# Science Lobbyists Aim for Better Balanced Budget

1. David Malakoff
1. With reporting by Jeffrey Mervis and Jocelyn Kaiser.

Scientists are happy about another huge proposed boost for NIH, but they say there's more to science than biomedical research

Don't get mad, get moving. That seems to be the scientific community's reaction to President George W. Bush's lopsided budget request to Congress, which showers biomedical science with cash and largely snubs the physical sciences. Despite the disparity, few science lobbyists are openly complaining. Instead, they are stepping up efforts to convince Congress to rewrite the budgets of the National Science Foundation (NSF) and other losers in the opening round of the 2002 budget contest. “There is no point in antagonizing the new Administration,” says one science society operative in a comment echoed by many of her peers. “We're looking ahead.”

The Bush plan, released on 28 February, is just a skeletal outline; full details won't come until early April. But the 175-page document, “A Blueprint for New Beginnings,” makes clear the new Administration's R&D priorities for the 2002 fiscal year that begins on 1 October. Leading the list is a 13.8% increase, to $23.1 billion, for the National Institutes of Health (NIH). That boost, which Bush announced last week (Science, 2 March, p. 1677), would keep the agency roughly on track to double its budget by 2003. The plan also favors Pentagon research programs, proposing a 6% hike to about$45 billion, and corporate research, promising to make permanent a tax credit for industrial R&D spending that would otherwise expire in 2005.

But the list of winners among government science agencies is short. High-profile interagency initiatives on nanotechnology and information technology have disappeared, leaving those disciplines to compete with every other field for scarce resources. NSF and NASA are slated for increases of 2% or less—below the expected rate of inflation. The $19.7 billion Department of Energy (DOE) faces an overall 3% cut, with an unknown portion coming out of its$3.4 billion Office of Science. The U.S. Geological Survey (USGS) could lose 11% or more of its $883 million budget, while the Department of Commerce's$145 million Advanced Technology Program, which funds precompetitive industrial research, would be abolished. The plan also calls for canceling several space science missions and a study of whether NSF's ground-based astronomy program should be transferred to NASA (see sidebar).

Health and Human Services Secretary Tommy Thompson was the most visible Administration official on budget day, conveying the good news in person after visiting NIH's clinical and research facilities. But most other high-level science officials had little to say. Citing increases for graduate student stipends and mathematics research that total less than $30 million, NSF Director Rita Colwell issued a brief statement saying that “the president's priorities clearly mirror our own in these areas.” She pointedly ignored any mention of the agency's meager increase of 1.3%. The numbers also got a lackluster reaction from researchers and lawmakers. Biomedical groups plan to push for an even larger raise for NIH, to$23.7 billion. And even some Republican lawmakers are worried that skimping on basic research at NSF will hamper the quest for economically valuable technologies in many fields. “NSF's number is a concern,” says Senator Wayne Allard (R-CO), a member of the Senate's Republican High-Tech Task Force.

Seizing on such doubts, science lobbyists are targeting a congressional budget resolution, due out next month, that will set overall levels for broad budget categories. The heads of dozens of major research universities, for instance, wrote on 1 March to Senate Budget Committee chief Pete Domenici (R-NM), requesting that he “pay special attention to the NSF in this year's resolution.” Domenici has already said that he wants to boost Bush's request for $661 billion in discretionary spending—the one-third of the federal budget not dedicated to social welfare programs. Other prominent Republicans have hinted that the Administration's proposed$1.6 trillion tax cut over 10 years may be scaled back to free up more cash. White House officials, meanwhile, have threatened to veto any final appropriations bills that raise spending beyond the requested 4% increase. That sets the stage for a confrontation over R&D funding likely to continue into the fall.

The president's budget contains these highlights for selected science agencies:

NSF: A record $530 million increase last year lifted its budget to$4.4 billion, the first step in what agency officials hoped would become a 5-year doubling path. But this year's increase would be barely one-tenth that size, a meager $56 million. Within an essentially flat budget, a$200 million state-based math and science education program receives top billing. And although details of the program, initially based at the Department of Education, remain sketchy, NSF officials already know that they must squeeze $110 million from existing education programs to pay for it. Highly touted Clinton initiatives in information technology and nanotechnology—which together received a$190 million boost last year—lose their place of honor in the new budget, leaving NSF officials scrambling to continue research in those areas without an infusion of new money.

The budget outline also questions one of NSF's top priorities: increasing the size and duration of grants. “There is little documentation that this is having a positive impact on research output,” the president's budget declares about recent efforts to do so. “There is no question that researchers will be more effective if grant sizes and duration are increased,” counters computer scientist Anita Jones of the University of Virginia, Charlottesville, vice chair of the National Science Board, which oversees NSF. NSF-funded biologists, she notes by way of example, receive grants less than half the size of NIH awards. To clear up the confusion, the Administration wants NSF to enclose supporting data when submitting its 2003 budget request in the fall.

The Bush budget would also delay any new facilities. That includes the $400 million Atacama Large Millimeter Array, a joint project with the European Southern Observatory in the Chilean high desert that NSF had hoped to start next year, and two large networked facilities, for seismic monitoring and biodiversity assessment, that Congress deferred this year. NSF's dark cloud has two silver linings. The first is a boost, from$18,000 to $20,500, in annual stipends for graduate students in a variety of discipline-based and agencywide programs. The second is an additional$20 million for mathematics research. But Colwell had also hoped to raise postdocs' stipends, and the math figure is a far cry from an NSF proposal to quadruple the division's current $122 million budget in 4 years. DOE: Early indications are that most science programs will emerge relatively unscathed by the proposed 3% cut to DOE's$19.7 billion budget. But agency science officials are forecasting flat budgets for physics and other fields—meaning reduced buying power and no facility improvements. The outline also promises careful scrutiny of unnamed “major” science projects, raising fears of delays at the Spallation Neutron Source, under construction at Oak Ridge National Laboratory in Tennessee.

USGS: Intensive lobbying from agency officials and outside interest groups has prompted the White House to cut in half a proposed 22% drop in USGS's $883 million budget. But even an 11% cut, says USGS director Chip Groat, means “we're going to have to [lay off] people.” Groat is also worried about language calling on the agency to “better target” its contribution to managing national parks and lands. The words suggest that programs not specifically tied to federal lands—from stream-gauge networks to seismic monitoring—”would be out the door,” Groat says. The one morsel of good news is that a rumored effort to shift scientists in USGS's Biological Resources Division to other Interior agencies appears to have lost steam after objections from Congress. EPA: A roughly flat overall budget (after removing pet projects added by Congress) is likely to mean level funding for its$696 million science and technology account. The outline is silent on the fate of the Clinton Administration's Climate Change Technology Initiative.

USDA: Bush expressed support for agricultural research in the final presidential debate in St. Louis, and his budget calls for investing in biotech and new products. The agency's main extramural grants program, the $106 million National Research Initiative, is hoping for a small raise. 14. POLICY # Budget Could Send Space Science Off in New Directions at NASA 1. Andrew Lawler 1. With reporting by Jeffrey Mervis. The budget outline the White House unveiled on 28 February caps a week of startling news for NASA. On orders from the White House, NASA managers last week told Congress they intend to cancel plans for a Pluto flyby and a mission to study the solar wind. The agency is also following orders to make major cuts to the international space station after acknowledging huge cost overruns in the orbiting lab. Meanwhile, the president has called for a blue-ribbon panel of scientists to decide whether the space agency should swallow up the ground-based astronomy program run by the National Science Foundation (NSF). Congress may not go along with all the directives in the president's budget, which would boost NASA's$14.3 billion budget by a modest 2%. But observers see the flurry of activity as a sign that the new Administration intends to grapple with difficult issues sidestepped by President Bill Clinton's team. “They seem interested in solving problems that have been left in the closet,” says Bill Smith, a former Democratic House staffer who runs the Washington, D.C.-based Association of Universities for Research in Astronomy.

For example, the president's 2002 budget would kill off the Pluto and $350 million Solar Probe missions in favor of Mars exploration and high-energy astrophysics missions, setting clear priorities within a limited budget. But Congress may have other ideas: The current competition to build a cheaper and faster Pluto mission for a 2004 launch remains on track after a Senate spending panel told NASA space science chief Ed Weiler late last week not to pull the plug. Weiler has agreed to let bidders go ahead with their proposals, due this summer. Support for some type of mission to Pluto also remains strong in the scientific community. “Stay tuned. Pluto isn't dead yet,” says planetary scientist Michael Drake of the University of Arizona, Tucson, who chairs a NASA advisory panel on solar system exploration. “Pluto has not been targeted; it's just that it is seen as a new start, and there's not enough money.” Indeed, the Bush budget contains money for new propulsion technologies that, if feasible, could allow a “future sprint” to Pluto before 2020, according to the budget plan. Also controversial is the White House decision to create a blue-ribbon panel to examine the government's astronomy programs, which traditionally have been split between ground-based telescopes funded by NSF and space-based observatories funded by NASA. The panel, the budget plan says, should consider “the pros and cons of transferring NSF's astronomy responsibilities to NASA,” which currently funds about two-thirds of the federal astronomy grant pie. The group, expected to consist of eight to 10 eminent outside scientists, is due to report its findings by 1 September. The directive came as “a real shocker,” says Weiler, adding that “NASA did not initiate this request.” A recently released National Research Council report on the next decade of astronomy makes no mention of the need for such a transfer. But Smith and Administration officials say that there is dissatisfaction at the White House Office of Management and Budget over the lack of cooperation between the two agencies, institutional expertise, and concern about whether NSF's budget will have room for major facilities. Although such a review is reasonable, says Robert Eisenstein, head of NSF's math and physical sciences directorate, “we can make a dramatically good case” for keeping the two agency efforts separate. “You need both players,” he adds, pointing to NSF's track record on such recent large projects as the twin Gemini telescopes and the Laser Interferometer Gravitational-Wave Observatory. Weiler has his own concerns. Any transfer that takes place without an accompanying shift of staff and money, he warns, “would be a disaster for astronomy.” In human space flight, the Administration took NASA to task for allowing space station costs to balloon over the next 5 years by an estimated$4 billion. To pare back, agency officials say they will cancel a module devoted to crew quarters and a large rescue vehicle, shrink the crew size from seven to three, and put off decisions about future facilities. While the budget warns NASA to set aside enough money for “research equipment and associated support,” fewer facilities and a smaller crew mean science may suffer in the long run.

15. BOTANY

# Patience Yields Secrets of Seed Longevity

1. Kathryn Brown

After more than a century, the world's longest seed viability experiment keeps on sprouting—and inspiring scientists worldwide

On a brisk fall day almost 122 years ago, Michigan botanist William Beal stirred handfuls of ordinary plant seeds into damp sand and sorted the sand into 20 clear glass bottles. When Beal finished, each bottle was identical, containing 50 seeds from each of 20 plant species. He had a single question: How long can a seed survive in the dark, cold ground, yet still burst into life when blessed by sun or rain? To find out, Beal buried his 20 uncorked bottles mouth down, east to west, on a secret, sandy knoll at Michigan Agricultural College. Every fifth year, he decided, he would dig up one bottle, plant the contents in a greenhouse with light and water, and see which seeds sprouted.

Today, Beal's study—stretched into 10-year, then 20-year increments—has become a tradition at the school, now Michigan State University (MSU) in East Lansing. It is the world's oldest seed viability experiment. Generations of stubbornly sprouting seeds—particularly moth mullein, a European weed crowned with a showy yellow flower—have inspired far-flung researchers, from plant biologists to crop scientists to restoration ecologists. “This is nature's Rip Van Winkle story,” says Frank Telewski, an MSU botanist and curator of the W. J. Beal Botanical Garden.

While Beal's seeds sleep, a growing number of scientists have moved beyond his original question to explore the mystery of seed longevity. Why do some plant seeds hang on for decades—even centuries—while others barely survive winter? And how? “Think of this tiny sliver of a seed, just a remnant of a weed,” remarks Paul Cavers of the University of Western Ontario in Canada. “How on Earth can it live for so long?”

## Dark secrets

The secrets of seed longevity lie below ground, in natural seed banks. Being parsimonious, most plant species do not allow their seeds to germinate all at once. Instead, the seeds take turns—some sprout in a given spring or fall, while others sit out for one or many seasons to come. Drab and brown, the seeds attract little attention from predators and subsist on internal sugar stores. Through such tricks, plant populations boost their chance of surviving in a fickle world.

This meager underground existence can last for months—or decades, depending on the seed. Finally, if the soil is turned over at just the right time, meeting a particular seed's unique demands for temperature, light, and water, the plant will burst above ground, announcing its presence. In Holland during World War I, bloody battles and freshly dug graves at Flanders Field uprooted so much dirt that long-dormant poppies suddenly burst into red bloom. It was bitter beauty.

Every so often, a botanist reports finding viable ancient plant seeds in a canoe, say, or inside a tomb, but the estimates of plant age are often hard to confirm. So far, the oldest seed reliably recorded came from a sacred lotus in a withered lakebed in Liaoning, China. The Paozhi Basin lake, whose sediments date back to the Holocene era, had once blossomed with lotus plants cultivated by Buddhist monks. In 1994, scientists at the Beijing Institute of Botany gave Jane Shen-Miller of the University of California, Los Angeles, a handful of sacred lotus seeds. Shen-Miller and her colleagues germinated and radiocarbon-dated the seeds. They estimated one of the seeds to be roughly 1450 years old.

“The secret of the sacred lotus may be its seed coat,” says Shen-Miller. “The coat is very hard, built to prevent water and air from entering and degrading the seed.” The sacred lotus is also blessed with a hardy collection of repair enzymes, such as L-isoaspartyl methyltransferase and other proteins that minimize seed damage, resist attacks by fungi, and help the seed survive harsh temperatures. “The lotus is a scientific treasure,” remarks Shen-Miller, adding that the flower could reveal biochemical traits that boost quality of life by repairing the molecular damage of aging.

Although not as lovely as a lotus, Beal's subjects—midwestern weeds—have received their own share of attention. Since the earliest row crops, farmers have been hacking down and spraying pesticides at pigweed, lamb's quarters, and other unwelcome visitors in their fields—only to find the weeds return the next growing season. And the next. It was this dilemma that reportedly inspired Beal to study seed longevity.

Raised as a Quaker in rural Michigan, Beal was serious and watchful. His students were often expected to study plant specimens for hours at a time. When someone glanced up from a microscope, Beal was known to respond, “Keep on squinting.” In his own work, that perseverance paid off, Shen-Miller says. “There is no experiment like Beal's in the world,” she remarks. “Nobody can go back a century and start a study like this.”

One Saturday morning last April, Telewski and fellow MSU botanist Jan Zeevart retraced Beal's steps once more, shoveling away decades of soil to uncover the 15th of Beal's 20 bottles. They sprinkled the bottle's contents onto a tray of sterilized soil, covered it with cellophane, and put it under the bright light of a growth chamber. As the two researchers ventured off for breakfast, Telewski couldn't help but hope that the seeds would sprout. “These seeds are like Halley's Comet,” Telewski says. “You expect it to keep coming back, but you just don't know until you see it.”

Days passed. Then a week. Finally, two dozen seedlings inched into the air. All but two were moth mullein (Verbascum blattaria), whose yellow flowers feed fly-by-night moths. The remaining plants were other Verbascum species. Moving the ungerminated seeds into a cold chamber, Telewski and Zeevart also persuaded one small mallow weed (probably Malva neglecta) to spring up. During the last dig of the Beal experiment, in 1980, Verbascum and Malva species were also the sole survivors, notes Zeevart: “The experiment has been perfectly reproduced, 20 years later.” Why have these two species held on? No one knows.

Beal simply wondered how long seeds could linger underground and remain viable. But his experiments have taken on a life of their own, energizing plant biologists and restoration ecologists alike. In the 1970s, botanists Carol and Jerry Baskin, a husband-and-wife team at the University of Kentucky, Lexington, first took notice of the Beal project. Sifting through papers published at each study interval, they observed that ragweed seeds buried by Beal did not germinate until 40 years into the study. Why?

Eventually, the Baskins figured out that the ragweed might never have germinated were it not for a fluke of nature. The MSU teams always dug up the bottles in fall—but it turns out that ragweed germinates only in spring. By chance, the fall of 1919 was so cold that the ground at the MSU garden froze, preventing the unearthing of the ragweed seeds until spring—and giving them their chance to shine. “At the time, researchers didn't realize how tightly seed germination can be linked with the changing of the seasons,” recalls Carol Baskin.

Indeed, at the dawn of the Beal study, scientists knew little about the life of seeds underground. In recent years, the Baskins and other researchers have shown that seeds actually slip into and out of dormancy, keeping rhythm with the changing temperatures of the seasons. Yank a fistful of summer annual seeds from the ground in fall, and no amount of light, water, or sweet murmuring will coax them to germinate. Wait until spring, however, and the right mix of warmth and wetness—sometimes even in a dark closet—will send the seedlings skyward. Some particularly ambitious plants, including moth mullein, will germinate any time a seed is unearthed and set under light.

## Recreating nature

Nature has no hard-and-fast rules for which kinds of plants—weedy, cultivated, gorgeous, or gross—can survive as seeds for many seasons. In the forest, some woody plant seeds sit below ground indefinitely, emerging only after intense fire sears the soil. In the desert, a wildflower seed might wait years for the right amount of rain before sprouting. The reward of life often goes to plants whose seeds evolve ways to survive in the torrid, frozen, soaked, or parched crevices of Earth. “Nature, in her divine wisdom, devised these extraordinary keys to life that let plants survive in extreme conditions,” says Robert Bandurski, a retired MSU botanist who participated in the Beal study's 1970 and 1980 intervals.

Beal's study gives hope to restoration ecologists who want to recreate landscapes that have been trampled by grazing cattle, overrun by invasive weeds, or ripped up for suburban development. “This study suggests that if plants have dormant seeds in the soil, those seeds might eventually still sprout and essentially restore the plants that were there,” explains Cavers at Western Ontario. Natural seed banks, however, vary tremendously in size and viability. To restore lost ecosystems, conservationists often help nature along by scattering native plant seeds themselves.

Back in Michigan, the Beal study continues. Every dig, about half the moth mullein seeds in a given bottle reliably pop up. “We'd like to see this continued until there's just one bottle left,” says Zeevart, who's preparing a paper about the most recent study results. “The way this one Verbascum species is going, it might survive for a very long time.” When the last bottle is opened—at this rate, in the year 2100—researchers should know more about what keeps these seeds alive. No matter what they discover, Beal has already succeeded. Early in the study, he wrote about seed survival: “In the fall of 1879, five years ago, I began some experiments, hoping to add something to the information we now possess on this subject.” Add something, he has.

16. ENGINEERING EDUCATION

# Olin Puts Up $500 Million for 'No-Excuses' College 1. Jeffrey Mervis A small college under construction outside Boston aims to fix what's wrong with U.S. engineering education—and cost is no obstacle NEEDHAM, MASSACHUSETTS—Diana Dabby wants to create Renaissance engineers. A concert pianist and composer as well as a Massachusetts Institute of Technology (MIT)-trained electrical engineer, Dabby has developed a course on Leonardo da Vinci's scientific and artistic achievements that she thinks is just right for students at the not-yet-ready-for-prime-time Olin College of Engineering. “I want them to be fluent in several languages—science, mathematics, the creative arts, and entrepreneurship,” says Dabby, a member of the initial group of 10 faculty hires, adding that her technical expertise informs her music and vice versa. “And I think I can do that at Olin.” Such a course would be music to the ears of Olin's president, Richard Miller. As head of the first freestanding undergraduate engineering college in the United States in nearly a century, Miller hopes to shake up an educational system that he and many others believe is not keeping up with today's fast-paced, high-tech economy. It's a system crammed with traditional courses and little room for burgeoning areas such as computer and bioengineering—or the communications and business skills that most students will need to succeed outside academia. It also has a poor record of attracting women and minorities, even though these groups comprise a rising share of the college-age population. “Most engineers end up being trained rather than educated,” says John Slaughter, the former president of Occidental College in Los Angeles who now heads the National Action Council for Minorities in Engineering. Adds William Wulf, president of the National Academy of Engineering (NAE), “When we deprive students of a liberal arts education, we make them poorer engineers.” Olin College intends to provide an alternative. Miller doesn't seem fazed by the challenge, nor by the target opening date of September 2002: “Our goal is to produce graduates [about 150 a year] with the ability to predict, create, and manage the technology that will shape the future.” That education may include courses on da Vinci and starting a dot-com, as well as bread-and-butter subjects such as fluid mechanics and thermodynamics. There will be no academic departments and no tenure for faculty members, who instead will be given 5-year renewable contracts. Olin wouldn't be able to test these ideas—indeed, it wouldn't exist at all—without a benefactor. Fortunately, it's got a very generous one: the Franklin W. Olin Foundation, formed in 1938 by a New England entrepreneur who made a fortune manufacturing ammunition and small arms. It has made available its entire endowment of more than$500 million to get the college up and running. Olin will also benefit from a close relationship with its next-door neighbor, Babson College in Wellesley, which has a top-rated entrepreneurship program for business majors. With these resources, Olin aims to have a big impact. “We will be disappointed if we create something that is not applicable to other engineering schools,” Miller says.

Although the college's self-funding and small scale so far have kept it off the radar screens of the mainstream engineering community, some university administrators are starting to take notice—and to raise concerns. Last fall, participants at a National Science Foundation-sponsored workshop for women academic engineers expressed fears that Olin's emphasis on precollege achievements would simply replicate the “white, bright, and male-dominated” culture at most engineering schools. And some educators have questioned whether its approach is really all that new, or is capable of being scaled up if successful.

“A lot of people are doing these things—more electives, an emphasis on entrepreneurship, and so on, although Olin is doing this formally, and all at once,” says Al Soyster, dean of engineering at Northeastern University in Boston. Still, there's a touch of envy in his voice when he thinks about the possibilities. “My hat's off to them,” Soyster adds. “And if they are successful, I think that others will follow.”

## No-excuses zone

The new college is taking shape on 28 hectares of land off a two-lane road that winds through the prosperous Boston suburb of Needham. Construction crews are rushing to complete four buildings in time to admit a small, prefreshman class in the fall. This part is old hat for the Olin Foundation, which for 2 decades ran a competitive grants program that built 72 labs at 57 small colleges around the country. However, in 1997, the foundation terminated the program and announced it would instead pour money into its own creation. “We had looked at the buildings program as a way to energize those schools and raise their sights by giving them the necessary facilities,” says Lawrence Milas, a New York lawyer who is president of the foundation. “A new college would be the ultimate development grant, as well as a tremendous memorial to Mr. Olin, who was trained as an engineer.”

## Age of enlightenment

Such a statement would have been ridiculed during the long dictatorship of António de Oliveira Salazar. “For 50 years, we had a government that despised new knowledge,” says Manuel Nunes da Ponte, director of the Institute of Chemical and Biological Technology in Lisbon. Salazar saw intellectuals as a threat to his iron-fisted rule and expelled dozens of professors. “Certain fields, like psychology, could not be taught,” says Gago, who as a student leader was exiled to Paris in 1970. One of the very few notable researchers to work in Portugal during the dictatorship was neuroscientist António Egas Moniz, who won a Nobel Prize in 1949.

Even the April 1974 revolution that toppled the Salazar regime failed to lift science out of the doldrums. That didn't happen until 1990, when the government, tapping E.U. infrastructure funding, launched Ciência. It was a 4-year, $380 million applied science program that provided stipends for young researchers and gave many institutes the means to buy badly needed equipment. “It was a major jump in our history,” says João José dos Santos Sentieiro, director of ISR, which used the money to collaborate on Europe's first civilian AUV. Basic research continued to suffer, however, until Gago was lured back from CERN, the European laboratory for particle physics near Geneva, in 1995 to become the country's first science minister. Gago reversed the tilt toward applied research and won increases that have lifted R&D budgets from$477 million in 1995 to $707 million in 2000. Gago also spread the money across many fields. “It was such a novelty to see money going into the humanities,” says UM English literature researcher Ana Gabriela Macedo. “People were in shock.” To help tackle deeper flaws in the science system, Gago hired Magalhães, a mathematician at Lisbon Technical University, to run the new FCT. The duo put their colleagues on notice: Mediocrity would not be tolerated. The first step was to appoint foreign experts to review grant proposals and entire institutes. The exercise allowed directors to justify dissolving weak labs and reassigning staff. The country's most important privately funded research center, the Gulbenkian Institute of Science, experienced the most radical overhaul. The institute was founded in the 1960s by the Calouste Gulbenkian Foundation, named after an Armenian oilman who lived much of his life in Portugal and who left$2.6 billion to fund the arts, a mission later expanded to cover the natural sciences. In the dark years before Portugal joined the European Union, the institute was considered a lone bastion of strong biological research. But it had slipped badly by the early 1990s.

Rejecting a proposal to transfer the institute to the state, the foundation chose instead to ship out the entire staff, many of whom were hired by universities. “The foundation did not want to have this institution doing research anymore; they wanted to just do teaching,” says António Coutinho, an expatriate immunologist who had set up a graduate studies program at the Gulbenkian while working at the Pasteur Institute in Paris.

Coutinho, however, managed to persuade the foundation to create a new institute from the ashes of the old. Asked to lead the transformation, Coutinho retired from the Pasteur and hired a cadre of young researchers on 3- and 5-year contracts to study everything from viral pathogenesis to mouse genetics. The Gulbenkian reopened in 1998. “Coutinho has a free hand to shape the institute, and he's done a great job,” says Kai Simons, director of the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden.

Such radical restructuring wasn't possible with Portugal's 12 national labs, which consume 15% of the country's R&D budget in areas ranging from mining to tropical research. Although international panels have called for a major overhaul, one prominent scientist is even more critical: The labs “have grown fat and totally useless.” But the political impact of massive layoffs meant that “eliminating a national laboratory was never an option,” says Magalhães. Instead, the government has instituted reforms that impose greater accountability on the labs and demand a minimal return on investment.

## The next step

Blocked from gutting the existing national laboratories, Gago and Magalhães decided to anoint new ones. In 1999, they invited public institutions—apart from the national laboratories—and private nonprofits to compete for 10-year contracts to carry out “research of interest to the state,” says Magalhães. Last November, four centers were selected as “Associated Laboratories,” guaranteeing each millions of dollars to hire scientists and fund their work. The projects range from assessing the risks of genetically modified organisms to preventing gastric cancer (46 of every 100,000 Portuguese develop the disease, by far the highest incidence in Western Europe). The money is helping to lure talent from abroad: Da Ponte's institute, for instance, is poised to bring on a senior scientist from Max Planck among 25 new hires.

This year, the FCT will extend the program to materials science, coastal research, information technologies, and social sciences. In an allied initiative, the science ministry later this year plans to unveil a new biomedical institute, which Gago calls “our own NIH.”

Although many scientists praise the associated lab program for allowing top-notch institutes to hire young scientists on long-term contracts, some academics are nervous. “The structure will compete with universities,” contends UM bioengineer Manuel Mota. He worries that over time the associated labs will accumulate just as much dead wood as the national laboratories. Others hope the government will confer elite status on top universities, too. “My deep wish,” says UM's Leão, “is to adapt the model to the university system,” including making a commitment to full-time researchers.

Many scientists say the most urgent need now is to upgrade equipment bought a decade ago under the Ciência program. “We are working with hardware that will probably break down soon,” says Mota. To address that concern, the government will unveil a National Program for Scientific Equipment, to run through 2006, as part of its billion-dollar S&T programs.

A generation ago, such a fantastic sum for Portuguese science would have been at best a dream. Now, says da Ponte, “the new generation has the freedom to do research in a way that the older generation never had.”

19. MIR SPACE STATION

# Fiery Demise Spells End of Longest Research Run

1. Elena Savelyeva,
2. Andrey Allakhverdov,
3. Andrew Lawler
1. Elena Savelyeva and Andrey Allakhverdov are writers in Moscow.

Although disappointed at losing the opportunity to perform planned experiments, scientists are celebrating Mir's 15 years as a research platform

MOSCOW—This spring, cosmonauts on the Mir space station were to have assembled and launched an innovative solar-powered spacecraft—a prototype for a new generation of Mars explorers. It would have been “a very big and beautiful experiment,” says Alexandr Chernyavsky of Energia Corp., a Moscow-based titan that has produced hardware for spacecraft from the first artificial satellite, Sputnik. But plans for the so-called “M-Module” are now history, along with Mir, which comes to a blazing end next week along with some \$80 million worth of research equipment and the jobs of hundreds if not thousands of engineers, scientists, and technicians.

While Chernyavsky and his Energia colleagues rue a lost opportunity, many others are feting the creaky old station for 15 years of unexpectedly robust research—the longest running space laboratory ever. Although increasingly hobbled by declining budgets and aging equipment, cosmonauts made important findings, from measuring the ratio of heavy helium atoms in the interstellar medium—a key value for evaluating models of how the universe evolved—to learning how to grow food in space for long-duration flights. “It will be a long time before such experiments are repeated,” says Vladimir Sychev of the Institute for Biomedical Problems in Moscow. And Western researchers hail the station for providing vital data and experience on the road to the international space station now under construction, which began, ironically, as the West's Cold War response to Mir.

Denounced by many former cosmonauts, the decision to bring down Mir proved impossible to reverse. “No experts can guarantee that no failures or shortcomings could happen” if the station were kept in orbit, says Yuri Koptev, general director of the Russian Aviation and Space Agency. And Energia's longtime chief Yuri Semyonov blames Mir's fate on “the irreversible processes of aging.” So next week, the 137-ton Mir is scheduled to be guided into a low-angle descent through Earth's atmosphere. Although most of the station will burn up, several truck-sized pieces will survive and—it is hoped—plunge into the Pacific.

Mir was the product of more than a decade of Soviet experience with space stations, which were prized as high-profile examples of socialist technical competence. Its main module was launched in 1986; smaller pressurized labs were added later. The first, an astrophysics facility called Kvant, went up the next year. Kvant 2, mostly for housing equipment, followed in 1989. The next year brought Kristal, which carried furnaces for materials research. After long delays, Spektr and Priroda were added in 1995 and 1996; both contained mainly Earth-observation equipment as well as room for U.S. experiments.

Although Mir primarily served as a test-bed for space hardware, its list of scientific achievements is long. More than 100 cosmonauts and astronauts from a dozen countries conducted some 23,000 experiments. Data from Kvant, for example, allowed Swiss and Russian astrophysicists last November to define the ratio of helium-3 and helium-4 in the interstellar medium—the first solid data that should yield insights into the universe's evolution, says Georgi Zastenker of Moscow's Institute of Space Research.

Of prime research importance were studies of the effects of microgravity on living things, from wheat to people. In humans, the results were “unique data on various medical aspects—from cardiovascular changes to bone tissue losses,” says Valery Polyakov, deputy chief of the Institute for Biomedical Problems and a veteran of the longest space flight, 438 days. These data, he says, “will enable the biomedical support for a human flight to Mars.” Japanese quail hatchlings showed that in space the birds' embryos were not obviously affected by microgravity—but the chicks did not adapt to weightlessness and died, notes Sychev. Adult birds, however, coped just fine. And researchers grew wheat in a small greenhouse, showing that microgravity does not affect photosynthesis. “It was a hugely successful experiment,” says John Uri, a life scientist at NASA's Johnson Space Center in Houston.

But Russian research methods proved to be sloppy compared to Western procedures. Much of the human physiological data, for example, was not presented in reports. “Individuals carried the information, and you went to them, not to libraries,” says Dieter Andresen, a European Space Agency (ESA) manager in Noordwijk, the Netherlands. Data evaluation “was not done in ways that in our judgment [were] efficient or systematic,” says Andresen. But he adds that ESA's own physiological experiments on Mir proved “tremendously successful.”

Likewise, French officials say their 11 years of life sciences and fluid research experiments on Mir were a solid investment and good preparation for the international space station. Frustrations, however, included severe limitations in transmitting data that crimped the ability of scientists on the ground to control experiments, says Lionel Suchet, a French space agency manager who oversaw many of those missions.

Although a relative latecomer to Mir, NASA conducted batteries of experiments in a variety of fields—such as snapping more than 20,000 detailed images of Earth—in exchange for much-needed funds for the ailing Mir and the overall Russian space program.

Mir's lasting legacy may be in the area of neither engineering nor biology, but sociology. Unlike NASA, Russian officials put great emphasis on selecting crew members that could get along, conducting frequent stress tests and giving them substantial flexibility in day-to-day duties. “The cosmonauts had room to improvise and an incredible amount of freedom,” says one NASA scientist. The result, she says, was high productivity over crushingly long missions. And that may prove an invaluable lesson for the multinational crew building Mir's successor.