# News this Week

Science  08 Jan 1999:
Vol. 283, Issue 5399, pp. 150

# Institutes Reinvent Themselves As Part of Well-Funded Reform

1. Hui Li*
1. Li Hui writes for China Features in Beijing.

BEIJING—Deng Maicun seems an unlikely leader of a revolution at the Chinese Academy of Sciences (CAS), which operates the country's premier network of research laboratories. The 39-year-old chemical engineer lacks a doctoral degree and admits he isn't at the cutting edge of research in his field. But as the new director of the Dalian Institute of Chemical Physics in northeastern China, he's a pivotal figure in a massive reorganization that aims to turn CAS into a lean, mean, merit-based research machine and into a model for research across the country.

The Dalian institute is one of 12 projects approved in November by China's governing body, the State Council, as part of a 3-year, $650 million effort known as the Knowledge Innovation Program. The sweeping initiative groups 40 of CAS's more than 120 institutes into nine megafacilities and turns Dalian and two other prominent institutes into test-beds for a slew of management reforms.* In addition to lopping 38,000 positions from the existing CAS staff of 68,000 by 2010 and eliminating lifetime tenure, the reforms are meant to relieve institutes of responsibility for nonresearch activities such as housing and medical care and to give scientists more authority over personnel decisions (see sidebar). The new program is also a vote of confidence in the leadership of CAS president Lu Yongxiang, a mechanical engineer who has promised to revamp operations so that institutes can better contribute to the world's store of knowledge and to the country's economic growth (Science, 30 January 1998, p. 649). In time, the reforms should produce savings. But implementing them requires a large up-front investment. The new program represents a doubling of CAS's annual operating budget, although it falls short of CAS's initial request for$800 million. The funds will buy equipment and raise salaries for existing staff and up to 300 talented young Chinese scientists lured back from positions overseas. In addition, a large chunk will be used to cushion the blow to laid-off workers. The lavish support, CAS officials confess, puts them in the hot seat. “On one hand, we need the money badly to carry out in-depth structural reform,” says CAS vice president Yan Yixun. “On the other hand, we feel a great amount of pressure because we cannot use a lack of money as an excuse if we fail to come up with tangible results.”

The Dalian institute is the first of the CAS projects off the mark. In November, it received a down payment on a $9 million award meant to help it downsize from 800 to 150 fixed positions. Deng says his primary job is “to create a good living and research environment for the institute.” And giving scientists a major voice in personnel decisions, he adds, is the key to cutting through the red tape and cronyism that stand in the way. This fall, a first-ever committee elected by researchers chose 10 laboratory heads to oversee the hiring or rehiring of staff. The laboratory heads, like the institute director, will be elected every 4 years, and those who serve two terms running will receive permanent positions. The rest of the research staff will be put on renewable 2-year contracts. The new lab chiefs also represent the next generation of scientific leadership. The competition was limited to those 56 or younger, and youth ruled: Eight of the 10 heads are under the age of 40. At the same time, however, nearly all the jobs went to in-house candidates. Deng, who came up through the institute's ranks, says that tight deadlines prevented the institute from advertising the lab chief slots. As a result, only one outside scientist—who heard of the competition via word of mouth—even put in a bid. “We will do our best to invite outside applications for the next term,” says Feng Aisheng, office manager at the institute. Although senior scientists recognize the need to make room for fresh talent, some say that a rigid adherence to age restrictions is counterproductive. Yi Baolian, 60, a member of the selection committee, wasn't happy about being removed as head of a key national research project involving scientists at nearly a dozen institutes. “There was only 2 years left, and it was such a big project,” he says. “Why couldn't they let me keep my position? Or they could find me an assistant if they think me too old.” After losing on appeal, Yi says he has offered to help coordinate work among the various partners. The proposed Shanghai Academy of Life Sciences (SALS) appears to be furthest along in figuring out how to create a CAS megainstitute. Tang Zhangcheng, former director of Shanghai's Institute of Plant Biology and deputy head of the academy's preparatory committee, says a key to success is streamlining the duties of the director: “In the past, directors had too much to worry about, from seeking research funds to taking care of a funeral.” Once the reforms are in place, he adds, “institute directors will have no pretext for not doing their job.” The structure of the SALS, still under review by CAS, would bring together eight biology-related CAS institutes—in biological chemistry, cytology, physiology, brain research, medicines, plant biology, insects, and biological engineering. The research portfolios of each institute would remain independent, but SALS would oversee operating budgets and handle such support functions as real estate, libraries and information networks, and the care of laboratory animals. The current director of the brain research institute, Wu Chien-ping, is in line for the top post at SALS. To allow the institutes to focus on their core task—producing good science—some support functions will be spun off. Outside companies are expected to take over such nonresearch services as transportation, and a separate office is planned to handle state issues such as Communist Party affairs, trade union membership, and family planning. Institutes would no longer provide apartments or medical care for their employees, although they would still partially subsidize the cost of housing and health insurance. CAS plans to appoint the directors of all the new megafacilities as well as the heads of individual institutes. But it is treading carefully around a proposal to create an outside board of directors that would set broad policy for the Shanghai academy and serve as a model for other clusters. “The government needs to think it over, and that takes time,” says CAS's Yan, noting that the proposal involves the use of state assets. But time is a precious commodity. The government grant covers only the first of a scheduled three phases of reform through 2010. And funding for the rest of the restructuring depends on a successful transition to a more productive, merit-based system of managing research. Deng knows that the clock is ticking and that his youth and lack of scientific stature are seen as disadvantages. But he believes his 10 years' experience as a manager has prepared him for the task. “Good scientists do not necessarily make good administrators,” he says. “To enliven research, the most important thing is to allow a freer mobility of researchers. And I promise to make that happen in my institute.” • * Other megainstitutes include: in Shanghai, Applied R&D (electronics and materials); in Beijing, Mathematics, Information Science, Materials Science, and Earth Sciences; in Lanzhou, Natural Resources and Environment; in Shenyang, Advanced Manufacturing; and an astronomical observatory using facilities in Nanjing, Shanghai, Xian, and Yunnan. Other model projects include the Theoretical Physics Institute in Beijing and the Nanjing Institute of Geology and Paleontology. 2. CHINESE ACADEMY OF SCIENCES # Neuroscience Institute Breaks New Ground 1. Jeffrey Mervis* 1. With reporting by Li Hui in Beijing. Bai Lu of the U.S. National Institutes of Health (NIH) flew to Shanghai in the spring of 1996 looking for someone to help him and two other Chinese-born, U.S.-trained neurobiologists set up a joint lab there. His success resulted in regular exchanges and a string of papers. But the trip did much more than create a scientific partnership: It planted the seeds for a new institute that aims to become not only a world-class research facility but also a model for how China can manage science more creatively. “It's a rare opportunity for China to forge ahead in neuroscience,” says Mu-ming Poo, a 50-year-old biologist at the University of California, San Diego, who will serve as the institute's part-time director. “But it has to be done right.” The Chinese Institute of Neuroscience (CIN), which won final approval from the government in November, will be unlike any existing institute. Although housed initially at the Shanghai Brain Research Institute, CIN will be independent of its host and enjoy considerable autonomy from its parent, the Chinese Academy of Sciences (CAS). Its budget will allow up to 30 senior scientists to operate their labs to Western standards, including a start-up package approaching$300,000, plus 100,000 a year in running expenses and salaries three or four times the norm in China. The money comes from an unusual mixture of sources: CAS, the Ministry of Science and Technology (MOST), and the Shanghai municipal government. Most striking of all, however, is the government's commitment to a hands-off management policy: The institute can recruit throughout China and can set its own administrative policies on everything from ordering supplies and equipment to letting grad students burn the midnight oil. “The vice premier [Li Lan-qing] promised us that people would have complete freedom to move,” says Lu, 41, who heads the synaptic plasticity unit at NIH's National Institute of Child Health and Human Development. “It's also important that scientists set the rules.” Although the new institute will be run strictly on merit, its origins rest on old ties. The idea for a joint lab came from Yi Rao, a neurobiologist at Washington University in St. Louis, Missouri, and Lu's colleague at Shanghai Medical University. The third partner, Lin Mei of the University of Virginia, Charlottesville, is a former colleague of Linyin Feng of the Shanghai brain institute, who manages the lab. The success of that collaboration led the brain institute's director, neurophysiologist Wu Chien-ping, to ask the trio to think about creating a Western-style research institute. Lu brought in Poo, his mentor in the late 1980s at Columbia University and a leader in studying the mechanisms of synaptic formation and activation, to draw up a proposal. Poo knew what he wanted. “It had to be a new institute, the appointments had to be merit-based, and there had to be steady support,” says Poo. The government's response to the proposal, submitted this summer, came with unprecedented speed. CAS officials liked the idea but didn't have sufficient resources to bankroll it. So government officials created a new administrative entity that allowed them to invite other partners. MOST and Shanghai city quickly joined the team. “In addition to the increased funding, the status gives us a lot more freedom,” says Mei. “The existing rules don't apply.” By November everyone had signed off, and the U.S.-based scientists began spreading the word. The project has also received a boost from the first-ever Gordon Research Conference in China, a 5-day session held last fall in Beijing that was co-chaired by Lu and Wu. Mei credits Wu with shepherding the new institute through the many layers of bureaucracy. Wu, in turn, says that Poo's participation made it an easy sell. “The proposal came from a world-renowned neuroscientist,” he notes, “which greatly increased its chances of success.” Marc Caron, a Howard Hughes Medical Institute investigator at Duke University, calls Poo “a superstar, scientifically,” and Carla Shatz, an HHMI investigator at the University of California, Berkeley, notes that Poo's “talent and energy level will be a real shot in the arm for Chinese neuroscience.” Poo plans to spend 3 months a year in China and to leave day-to-day scientific operations in the hands of a strong deputy. He says the government's pledge of 10 years' support allows plenty of time to build up the institute. He's also confident that its track record—measured in top-flight journal publications and graduate students trained—will warrant continued government support as well as private funding. And he hopes that success will be infectious. “We may be an isolated island [of excellence] now,” he says. “But if we succeed, I hope other institutes will follow in our footsteps.” 3. GENETICS # Which Jefferson Was the Father? 1. Eliot Marshall The claim that Thomas Jefferson fathered at least one child by his slave Sally Hemings got a big boost in credibility last November when scientists published some stunning new data. A U.S. pathologist and a group of prominent European molecular biologists announced in Nature that they had found DNA sequences in the Y chromosome of the Jefferson family that matched DNA from the Hemings family. The finding set off a flood of news reports declaring that the third U.S. president had, as rumored, fathered an illegitimate child by Sally Hemings. But now the authors of the report say the evidence for that is less than conclusive. In responding to letters in this week's issue of Nature, lead author Eugene Foster—a retired pathologist in Charlottesville, Virginia—and co-authors make it clear that the data establish only that Thomas Jefferson was one of several candidates for the paternity of Eston Hemings, Sally's fifth child. However, they argue that, because Jefferson was Hemings's owner and lived with her at the Monticello plantation outside Charlottesville, “the simplest explanation” is that he was indeed the father. Meanwhile, the Jefferson data have taken on a political spin. Reed Irvine, director of the conservative organization Accuracy in Media, based in Washington, D.C. claims that the news media purposefully distorted the results of Foster's study. In his current newsletter, Irvine says the news was released with “impeccable timing” to give comfort to President Bill Clinton on the eve of the U.S. national elections last November. Irvine thinks that journalists used the report to suggest that Jefferson “also had a problem with sex,” thereby minimizing Clinton's affair with Monica Lewinsky. Foster describes the conspiracy theory as “ridiculous,” but he and his colleagues decided, he says, that they needed to respond publicly to several other points made by critics. One of these is Herbert Barger of Fort Washington, Maryland, a genealogist and husband of a Jefferson family descendant. He helped locate living members of the Jefferson family and persuaded them to donate blood to the DNA study. Not only did the authors neglect to mention his help, Barger says, they completely ignored a plausible theory he advanced. Barger argues that the most likely father of Eston Hemings is not Thomas Jefferson, who was 65 at the time Eston was conceived, but Jefferson's brother Randolph, 12 years his junior, who lived 20 miles away. Other candidates, Barger suggests, are Randolph's sons, all of whom lived near Monticello, visited from time to time, and had the same Y chromosome as their father and uncle. Barger notes that one unsubstantiated account mentions that Randolph's son, Isham, spent his adolescence at Monticello, and that one contemporary recalled that Randolph liked to party in the slave quarters at night. Foster agrees that he should have credited Barger, who was “fantastic” and “of immense help to me” in recruiting Jefferson family members to the study. His written comment now sets the record straight. Foster also acknowledges that Barger wrote a memo about a year ago suggesting that Randolph or Isham Jefferson might have been the father of Eston Hemings. Foster says he didn't credit Barger because Nature doesn't permit acknowledgments in the correspondence section, where his report appeared. Asked why he failed to mention Randolph and Isham Jefferson in the initial article, Foster says it was because they weren't suspects. For years, members of the Jefferson family had claimed that sons of Thomas Jefferson's sister—Peter or Samuel Carr, who lived at Monticello—were the most likely to have fathered Hemings's children. The DNA study was intended chiefly to settle that question, Foster says: “The Carr connection was what [our article was] about.” Besides, Y chromosome data cannot be used to identify individual paternity within the Jefferson clan. That's a job for historians, Foster says. But that's not how it sounded in the headlines on the initial Nature report and on an accompanying comment by geneticist Eric Lander of the Massachusetts Institute of Technology and historian Joseph Ellis of Mount Holyoke College in South Hadley, Massachusetts. The Foster article was titled: “Jefferson fathered slave's last child,” and the comment included a heading that said: “Now, DNA analysis confirms that Jefferson was indeed the father of at least one of Hemings' children.” Foster agrees that the headlines were “misleading” because they suggested that the data were conclusive. He attributes this “unfortunate” slipup to the haste with which his article and the Lander-Ellis essay went to press. They were hurried into print, he says, to beat the popular media, which had learned about their results and were poised to publish. “All of [the confusion over headlines] probably would have gotten straightened out if there had not been this frantic rush to beat the leaks,” Foster says. Nature staffer Rosalind Cotter agrees that “the whole thing really was rushed through.” For his part, Ellis says he did not discuss the evidence for or against Randolph and Isham, because “very little is known about them” and “they had never been suggested as candidates.” He adds: “It is scientifically plausible” that Randolph or Isham Jefferson was the father of Eston Hemings, “but it is a very, very remote possibility.” Historians will probably spend years trying to determine just how remote—or how plausible—that connection is. And the increasing emphasis on Thomas Jefferson's sex life rather than his political career, Ellis says, “just drives me nuts.” 4. CELL BIOLOGY # Immortalized Cells Seem Cancer-Free So Far 1. Dan Ferber* 1. Dan Ferber is a writer in Urbana, Illinois. In ancient Greece, immortality was the province of the gods, who spun the length of each lifetime. But last year it was scientists who rendered normal human cells immortal, by adding the gene for a chromosome- capping enzyme called telomerase (Science, 16 January 1998, p. 349). The achievement raised hopes that the telomerase-immortalized cells might be used to replace cells lost to injury or diseases such as diabetes and rheumatoid arthritis. But that promise was tempered by a big concern: Because telomerase prevents normal cell senescence—one of the cell's several safeguards against cancer—the altered cells might turn cancerous once in the body. Now, the same researchers who created the cells show that they can grow—perhaps forever, at least in lab cultures—without displaying the typical signs of cancer. Some researchers caution, however, that the new work hasn't removed all the worries about using the cells in therapy. The researchers doing the work, including Jerry Shay and Woodring Wright of the University of Texas Southwestern Medical Center in Dallas and Choy-Pik Chiu of Geron Corp. in Menlo Park, California, turned to telomerase to try to overcome a natural barrier: Normal cells divide only a limited number of times in culture. That meant that efforts to replace tissue lost to injury, disease, or aging by removing healthy tissue, growing it in the laboratory, and transplanting it back into the body are often impractical. Researchers had traced the difficulty to the shortening of the cells' telomeres, specialized DNA structures that stabilize the ends of chromosomes. The telomeres ebb away with each cell division until the cells become senescent and eventually die. Telomerase, which can rebuild telomeres, is not made by most normal cells. But about a year ago, Shay, Wright, Chiu, and their colleagues found that adding an overactive version of the telomerase gene to foreskin fibroblasts and retinal epithelial cells extended their life-spans by more than 25%. The cells are still going strong after three times their normal lifetimes, Shay says. To allay fears that transplanting such immortalized cells into the body might open a Pandora's box of cancer, the Texas and Geron groups, now working independently, tested the cells for other telltale traits of cancer cells. These include the ability to continue growing when their DNA is damaged, when they are in contact with other cells, or when deprived of calf serum and the growth factors it contains—all conditions that stop normal cells in their tracks. The two groups found none of these abnormalities in the telomerase-immortalized cells, nor did they see any of the chromosomal changes, such as loss of whole or partial chromosomes, that are characteristic of cancer cells. The cells also failed to form tumorlike colonies, as cancer cells do, when suspended in a jellylike medium called soft agar, even after two key growth-suppressing genes, p53 and pRB, were inactivated. And they did not form tumors—or grow at all, for that matter—in susceptible mice. Taken together, the two groups' papers, which appear in the January issue of Nature Genetics, show that key checkpoints on cell growth are still intact in these cells, says cancer biologist John Sedivy of Brown University: “I think it's a very significant piece of work.” Cancer experts caution, however, that these experiments don't eliminate the possibility that the cells will become malignant in humans. “We don't know that and we can't know that from these experiments” because of the differences between mice and humans, says cancer biologist Robert Weinberg of the Massachusetts Institute of Technology. Indeed, cancer biologist Al Klingelhutz of the Fred Hutchinson Cancer Research Center in Seattle points out that while Geron and other companies are pursuing telomerase blockers as potential treatments for tumors, “these same researchers contend that immortalized cells are still normal and could be used for treatment of age-related disease. Is it really possible to have your cake and eat it too?” he asks. Shay and Calvin Harley, chief scientific officer of Geron, respond that it may very well be. To make sure that telomerase-containing cells aren't malignant, they are doing further tests, such as seeing how many additional mutations it takes to make the cells cancerous. And as a further safeguard, Harley says, Geron plans to put telomerase on a tight leash in replacement cells for damaged tissue: Rather than using a perpetually active telomerase, the company plans to add regulatory sequences to the gene that would enable it to be turned on and off at will by drugs. Another obstacle besides possible malignancy may limit the use of the technique, however: Telomerase may not immortalize all cell types, Weinberg and other experts say. But Harley says preliminary results suggest that the enzyme can do the job once researchers figure out how to grow the cells properly in culture. Clearly, much more work will be needed to find out whether telomerase-expressing cells will prove useful in the clinic. But if they do, then using them to overcome tissue damage would result in more than a Pyrrhic victory. 5. ORIGINS OF LIFE # RNA Study Suggests Cool Cradle of Life 1. Gretchen Vogel Debate on the origins of life has lately centered on a simple question: Was the cradle of life hot or cold? Many researchers argue that the first cells arose in the scalding waters of hot springs or geothermal vents, while a small but prominent band of holdouts insists on cool pools or even cold oceans. With no fossils to go by, the argument has circled a variety of indirect clues, with recent evidence favoring hotter environs. But now on page 220 comes good news for the cold camp: Evidence from the genes of living organisms suggests that the cell that gave rise to all of today's life-forms was ill-suited for extremely hot conditions. To probe the temperature preferences of early cells, Nicolas Galtier, now of Edinburgh University in Scotland, Nicolas Tourasse of the University of Texas, Houston, and Manolo Gouy of the University C. Bernard in Lyon, France, analyzed 40 living organisms for two genes that act as a sort of thermometer for an organism's ideal growing temperature. Their work suggests that in the ancestral cell, these genes could not have withstood temperatures above about 70°C—a more moderate temperature than many have proposed. Although the evidence is indirect, other biologists say the work is a clever approach that will reinvigorate the debate about the conditions in which life began. The notion that the last common ancestor of all life lived in very hot conditions has recently gained followers (Science, 2 May 1997, p. 700), in part because some of the organisms that populate the lowest, earliest branches of the tree of life live in extreme environments today—the so-called hyperthermophiles thrive between 80° and 90°C. And most geologists believe the early Earth was racked by volcanoes and asteroid impacts, which create hot environments. Galtier decided to test this theory by tracking the evolution of two temperature-sensitive RNA molecules in the cell's protein-making factory, the ribosome. The ribosome is in part made of RNA—which is itself composed of nucleotide bases—and so depends on the bonds between the bases to work properly. But those bonds are temperature sensitive: Some withstand high temperatures better than others. For example, the bases guanine (G) and cytosine (C) form a strong bond, while adenine (A) and uracil (U) form a weaker bond. Other studies have shown that the ribosomal RNA of heat-loving organisms has more G and C than A and U, presumably because the G-C bond holds up better in the heat. Using the two ribosomal RNA molecules, Galtier's team constructed a phylogenetic tree for 40 living organisms ranging from bacteria to mammals. They then used a computer model to find the most likely proportion of G and C in the RNA molecules of the ancestor of all 40 organisms. To their surprise, the model concluded that the ancestral RNA for both molecules had only a moderate G+C content, well below that of all known hyperthermophiles and consistent with organisms that live at moderate temperatures. To check their work, the team ran the model again with a different phylogenetic tree; the result was unchanged. To show that the model was not simply finding the average G+C content of all the organisms, they ran it again using only organisms with high G+C contents—and still found only a moderate G+C content. Even so, it's difficult to extrapolate back billions of years, warns evolutionary biologist Norman Pace of the University of California, Berkeley, who has favored a hot origin for life. “Things get awfully murky back there,” he says, calling the moderate G+C content “mud in already murky waters.” And the last common ancestor of all living things must have lived some time after the very first stirrings of life. But others welcome the result. “Statistical methods can be much more powerful than many people realize,” says evolutionary biologist Ziheng Yang of University College London, who finds the analysis convincing, although he “would not take it as the last word” on the topic. Even Galtier agrees with that. But if he has his way, the evidence for a cooler ancestor will once again heat up the origins-of-life debate. 6. PLANETARY SCIENCE # Pluto: The Planet That Never Was 1. Govert Schilling* 1. Govert Schilling is an astronomy writer in the Netherlands. Nearly 70 years ago, Pluto became the ninth member of the sun's family of planets, but now it's on the verge of being cast out of that exclusive clan. The International Astronomical Union (IAU) is collecting votes on how to reclassify the icy body: as the first (and largest) of the so-called trans-Neptunian objects, or as the 10,000th entry in the growing list of minor bodies orbiting the sun. In either case, Pluto may officially lose its planetary status, leaving the solar system with only eight planets. Children's books and planetariums may not acknowledge the loss. And Brian Marsden of the Harvard-Smithsonian Center for Astrophysics in Cambridge, Massachusetts, who launched the discussion 6 years ago, says no one is trying to demote Pluto. “If anything, we're going to add to Pluto's status,” he says, “by giving it the honor of a very special designation.” Cold comfort for Pluto, maybe, but its reclassification will at least end a long identity crisis, which began soon after its 1930 discovery at Lowell Observatory in Flagstaff, Arizona, by Clyde Tombaugh, who died in 1997. Pluto turned out to be much smaller than all the other planets (according to recent estimates, its diameter is only 2200 kilometers), and its orbit is strangely elongated. It didn't belong with either the Earth-like rocky planets or the gas giants. A clue to its true nature came in 1992, when David Jewitt of the University of Hawaii, Honolulu, and Jane Luu, then at the University of California, Berkeley, discovered a small, icy object beyond the orbit of Neptune. Provisionally cataloged as 1992 QB1, this ice dwarf measures a mere 200 kilometers in diameter. Since then many more trans-Neptunian objects (TNOs) have been detected, some of which move in very Pluto-like orbits around the sun. These “supercomets” populate the Kuiper Belt, named after Dutch-American astronomer Gerard Kuiper, who predicted its existence in the early 1950s. “Pluto fits the picture [of the solar system] much better if it's viewed as a TNO,” says Luu, who is now at Leiden University in the Netherlands. At present, more than 70 TNOs are known, and apparently, Pluto is just the largest member of this new family, which explains why it was found over 60 years before number two. If astronomers had known about the other TNOs back in the 1930s, Pluto would never have attained the status of a planet, Luu says: “Pluto was lucky.” A couple of months ago, the kinship between Pluto and the TNOs led Richard Binzel of the Massachusetts Institute of Technology to propose that Pluto be made the first entry in a new catalog of TNOs for which precise orbits have been determined. It would then enter the textbooks as something like TN-1 (or TN-0, as some astronomers have suggested). Marsden agrees that Pluto is a TNO, but he doesn't like the idea of establishing a new catalog of solar system objects, arguing that astronomers already have a perfectly serviceable list of numbered minor bodies (mostly asteroids). “The question is: Do we want to recognize [trans-Neptunian objects] with a different designation?” he asks. He points out that the Centaurs—TNOs that have been nudged well inside Neptune's orbit—have been classified as asteroids and says he sees “no reason for introducing a new designation system for objects of which we have representations in the current [catalog of minor bodies].” Instead of making Pluto the founding member of a new catalog, Marsden wants to add it to the existing list. “The current number is 9826,” he says. “With the current detection rate, we should arrive at number 10,000 somewhere in January or February.” He notes that asteroids 1000, 2000, 3000, and so on have all been honored by the IAU with special names, including Leonardo and Isaac Newton. “What better way to honor Pluto than to give it this very special number?” But the prospect of lumping Pluto with the solar system's riffraff outrages supporters of a new TNO category. “It's the most idiotic thing” she's ever heard, says Luu. Pluto is certainly not an asteroid, she says. To try to settle the issue, Mike A'Hearn of the University of Maryland, College Park, is collecting e-mail votes from 500 or so members of IAU divisions on the solar system, comets and asteroids, and other relevant topics. “I wanted to arrive at a consensus before Christmas [1998],” he says, “but it may take a while, since the community as a whole doesn't seem to have a consensus.” Neither proposal has attracted a majority: Although many people opposed Marsden's proposal, a comparable number were unhappy with Binzel's idea, A'Hearn says, because Pluto would still be an anomaly, being much larger than the other trans-Neptunian objects. A'Hearn says that if no consensus can be reached, Pluto will probably not end up in any catalog at all, making it the ultimate outcast of the solar system. However the debate settles out, Pluto's career as a planet seems to be ending, and even astronomers are wistful at the prospect. “No one likes to lose a planet,” says Luu. A'Hearn agrees. “It will probably always be called the ninth planet” by the general public, he says. 7. RUSSIA # Nuclear Strongholds in Peril 1. Richard Stone As Russia's economy deteriorates, the danger grows that the country's once-privileged nuclear cities will hemorrhage the talent and materials that rogue nations crave for making nuclear bombs SAROV AND SNEZHINSK, RUSSIA—Vadim Simonenko has the kind of background and experience that make many nuclear weapons experts nervous. He began his career in the 1960s designing atomic explosives for carving out canals and rose through the ranks to become deputy scientific director at the All-Russia Scientific Research Institute for Theoretical Physics (VNIITF)—an elite nuclear weapons design center in Snezhinsk, a closed city set amid a patchwork of lakes and spruce and birch forests east of the Ural Mountains. Simonenko has always enjoyed his work: “My ideas are like a hobby,” he says. The problem is that his job now pays like a hobby. Today, Simonenko is scrambling to find money for research and, like his colleagues throughout Russia's vast nuclear research enterprise, he's wondering when he will see his next paycheck. Simonenko's plight—and that of thousands of other talented Russian nuclear scientists—makes him a prime target for any country wanting to build a nuclear program. His team “is one whose expertise would no doubt be extremely interesting to proliferators,” says one U.S. expert. Indeed, at scientific meetings—most recently last July in Italy—Indian and Pakistani scientists have invited Simonenko to visit their countries and give seminars. He turned them down, preferring, he says, to seek collaborations with colleagues in the West. But he acknowledges that, if no Russian or Western organization were to support his work, he would consider other offers. Other suitors, surely, are waiting in the wings. “At nearly every nuclear institute they visit, [U.S. officials] find another recently received Iranian business card,” says Matthew Bunn of Harvard's Belfer Center for Science and International Affairs. Reassuringly, nuclear physicists like Simonenko appear to be resisting these overtures, according to several dozen scientists and government officials interviewed by Science during a recent visit behind the barbed wire fences that still surround the country's 10 “nuclear cities.” “These people are the real heroes of the story,” says Bunn. “It is their devotion to their country and their work that has been the key factor preventing a proliferation catastrophe.” But with Russia's economy continuing to erode, lucrative job offers from abroad could become more and more tempting. “There are many countries with a strong proliferation agenda ready and willing to court these nuclear specialists,” said U.S. Department of Energy (DOE) Secretary Bill Richardson at a public forum last month to unveil a Nuclear Cities Initiative (NCI) to counteract this threat. Ominous signs of strain are increasingly evident among the once-elite researchers in these secret cities, the names of which have only recently begun to appear on official maps. Last year, thousands of nuclear workers took to the streets in Snezhinsk and Sarov to protest months of unpaid wages. These nuclear sanctums are bracing for further unrest: Acknowledging that it can no longer maintain its sprawling nuclear weapons complex, Russia's Ministry of Atomic Energy, or Minatom, says that as many as 50,000 of the 130,000 weapons specialists in its nuclear cities may have to find new work in the next several years. And that could be an underestimate. “It could be safely assumed that the nuclear weapons program could be supported by a third of its current staff,” says Oleg Bukharin, an authority on Russia's nuclear cities at the Center for Energy and Environmental Studies at Princeton University. Hoping to prevent a massive nuclear brain drain, Minatom and DOE are teaming up to launch the NCI, a15 million program to create thousands of jobs in Russia's nuclear cities (see sidebar on p. 160). The goal is not just to keep knowledge behind the barbed wire: In facilities scattered across the former Soviet Union lie enough weapons-grade materials to produce 40,000 nuclear bombs, DOE estimates. “The challenges are absolutely incredible,” says NCI director William Desmond, whose daunting task is to convince U.S. companies to invest in cities barely acquainted with the free-market reforms that have transformed Moscow and other major Russian cities.

The stakes are enormous. “Six years of steady improvement in the security of Russia's nuclear stockpile threatens to unravel under the crushing blow of that country's current economic crisis,” says Kenneth Luongo, director of the Russian-American Nuclear Security Advisory Council. “Not since the collapse of the old Soviet Union has the situation been so dire.”

## A tale of two cities

For researchers like Simonenko, today's hardships are a cruel contrast to the Cold War era, when the Soviet government poured vast resources into the nation's efforts to match the United States' nuclear might. Within weeks after the obliteration of Nagasaki and Hiroshima, a team led by Igor Kurchatov, the father of the Soviet nuclear program, began scouting for a location for a supersecret nuclear weapons design center. His group eventually settled on a village called Sarov, revered for its mineral waters and for a monastery established in 1706 and dedicated later to St. Seraphim. The area, just 410 kilometers by rail from Moscow, was sparsely populated.

In winter 1946, Kurchatov ordered 10 physicists working at two Moscow institutes—Laboratory Number Two, a nuclear research center formed in 1939 that now bears Kurchatov's name, and the Institute of Chemical Physics—to relocate to Sarov. They were assigned to KB-11, the designation for the budding nuclear design center, now called the All-Russia Scientific Research Institute for Experimental Physics (VNIIEF). Sarov disappeared from public maps, even as devout Russians were still flocking to the monastery. “Pilgrims would come and gather outside the barbed wire fence” erected around the town, says Dimitrii Sladkov, a towering young man who, although he dresses in black and wears a long black beard like a Russian Orthodox priest, is assistant director in the nuclear center's information office. Sladkov, a student of Sarov's history, says that to deter pilgrims from wasting their time—and prying into its affairs—the center blew up the monastery's two cathedrals in the early 1950s. All that remains today is the monastery's campanile, the symbol of Sarov.

The physicists who came to live in Sarov—renamed Arzamas-16, a so-called mailbox linked to the city of Arzamas 35 kilometers to the north—were soon joined by hundreds of new recruits, as Arzamas-16 officials scoured the universities for the best young minds. One was Yuri Trutnev, a physical chemist who graduated from Leningrad State University in 1950. “When I was chosen to work here, I was told only that I would work in Middle Russia,” he says. “I was told I would have a chance to work with the best scientists.” When Trutnev arrived in February 1951, he reported to a division headed by the great physicist Yakov Zel'dovich. “Only when I opened the first report did I understand where I had got to and what I would do. It was a project related to the development of thermonuclear weapons.” Much decorated for his scientific achievements, Trutnev was part of the team that designed the Soviet Union's first hydrogen bomb, detonated in Kazakhstan in August 1953—just 4 years after the Soviet Union tested its first atomic bomb, modeled on a U.S. device.

Such work called for the utmost secrecy, and Arzamas-16 was like a prison, a city surrounded by a double barbed wire fence and guarded by armed troops, with entry and exit restricted by the KGB. The city experienced nearly total physical isolation. “The only thing we got from outside Sarov was the fissile materials,” says Trutnev, referring to the uranium and plutonium that were purified in other closed cities. “Everything else was produced onsite,” including necessities like food and clothing. For the first 5 years of the center's existence, most staff members were not even permitted to leave the city. “When I tried to go on vacation in 1952, my bosses sent me from one boss to another. They tried to make you spend vacations here at the center,” says Trutnev. The center paid a sizable bonus—50% of one's monthly salary—to those who complied.

As the nuclear arms race gathered steam in the mid-1950s, Soviet officials felt vulnerable having most of their nuclear weapons scientists concentrated in a single locale. In September 1955, they fissioned the nuclear weapons team at Arzamas-16, sending 40 theoretical physicists and mathematicians, followed in 1957 by a second wave of 370 designers and technicians, to a city newly carved from a spruce forest on a lake about 1400 kilometers southeast of Moscow. This was Chelyabinsk-70, now renamed Snezhinsk, or snowflake—so remote that even now, a lonely shishkabob hut is about the only landmark on the road connecting it to Ekaterinburg, 100 kilometers to the north.

Chelyabinsk-70 officials also went on a recruiting drive. Among those they pursued was Vladislav Nikitin, a student in the nuclear physics department at Moscow State University. In 1958, the Ministry of Medium Machine Building, the murky name of the Soviet nuclear weapons bureaucracy, “offered me a job in a Siberian plant or in a premier research institute in the Urals,” says Nikitin, now deputy director for human resources at VNIITF—not much of a choice. “The manager had a ready-made document—they knew my decision,” he says. He did not come to regret it. “We never had a moral problem with what we were doing,” he says. “It was a sacred thing.”

For 4 decades the two centers competed with each other to draft new designs for the Soviet arsenal, with resources unequaled in other research institutes across the country. The insanity may have peaked in 1961, around the time of the Cuban missile crisis. That's when Arzamas-16 tested a 50-megaton bomb, which released 20 times as much energy as all the bombs in World War II combined. Tested at the Novaya Zemlya site above the Arctic Circle, the bomb's mushroom cloud billowed 20 kilometers wide and the flash was seen for thousands of kilometers; the shock wave circled the globe three times. “It was developed for political reasons, not strategic,” says Nikitin.

Both centers also branched out into nonmilitary uses of nuclear explosives, setting off a total of 156 “peaceful” detonations. Trutnev and his colleagues, for instance, developed a charge that would consume most of its radioactive byproducts during the explosion. They placed it 90 meters under a river in Kazakhstan and blew open a huge trench that filled with water. “In a year or two, we could swim and fish there,” says Trutnev, who at 71 seems no worse for the experience.

Not to be outdone, Chelyabinsk-70 devised nuclear charges for extinguishing oil fires, blasting ore deposits, and mapping the Earth. In the 1970s, a team led by scientists from Chelyabinsk-70 divided Siberia into a 500-square grid, intending to explode charges at each grid point to discern the rock types in the crust, a project that was halted after 100 explosions. Russia performed its last nuclear test in 1990; the Comprehensive Nuclear Test Ban Treaty, signed by Russia in 1996 although not yet ratified by the Russian parliament or the U.S. Senate, would outlaw any further explosions. The treaty also marked the end of an era in which Russia held its nuclear scientists in high esteem. “The social environment in the country is changing rapidly,” says Nikitin, who is openly nostalgic for the days when he and his colleagues could conduct peaceful nuclear explosions. “The image of nuclear physics here has gone from very well respected to a kind of monster.”

## Opening up to the world

The weapons scientists' fall from grace began long before the test ban treaty finally brought an end to the ultimate demonstration of their handiwork. The end of the Cold War and the collapse of the Soviet Union suddenly eliminated the nuclear cities' main raison d'être. Like their counterparts in the U.S. weapons labs, Russian nuclear scientists were suddenly faced with a new mission: Instead of the cat-and-mouse game of nuclear deterrence, their main goal became ensuring the reliability and safety of existing weapons. But unlike their U.S. counterparts, they were forced to take on this role with limited resources, in a country in economic turmoil. Says VNIITF scientific director Evgeny Avrorin, “Nuclear weapons are not on the list of priorities in Russia now.”

As the labs were trying to adjust to the new era, Russians everywhere were coping with the harsh realities of life after communism: bread lines and poverty after the ruble's value plummeted in 1991 and 1992. The nuclear cities weathered the crisis reasonably well, at first. “There was no affluence as you would see on Malibu beach, but they were doing OK,” says John Shaner, head of the Center for International Security Affairs at Los Alamos, who has visited Sarov and Snezhinsk several times since 1992.

As conditions in the nuclear cities began to deteriorate, Western analysts began sounding the alarm about a potential nuclear brain drain. The Russian side fueled those fears: In 1992, for example, the Kurchatov Institute acknowledged that Libya had offered two of its scientists $2000 a month to work at its Tajura Nuclear Center, which the Soviet Union had helped Libya build a decade earlier. Minatom added to Western concerns in the early 1990s when it founded Chetek Corp. a company composed of scientists from the nuclear cities that offered to conduct nuclear explosions in other countries for, among other things, incinerating chemical weapons stocks. Although Chetek disappeared about 4 years ago—a Minatom spokesperson claimed to Science that he has never even heard of the firm—its formation underlined fears that a proliferation threat was emerging from the post-Soviet turmoil. The response from the West was a series of initiatives designed to help Russian weapons scientists make the difficult transition into civilian research. First off the mark in the United States was DOE, which runs the United States' own nuclear labs. Even before the collapse of the Soviet Union, U.S. weapons scientists had begun to reach out to their former Cold War adversaries. In 1988, U.S. and Soviet weapons experts performed joint underground nuclear explosions at the Nevada Test Site and at Semipalatinsk, Kazakhstan; the aim was to develop improved techniques for monitoring each country's nuclear tests. These early meetings triggered a delicate pas de deux between the weapons labs that resulted in a groundbreaking event in 1992, just months after the Soviet Union dissolved. That February, the directors of the Los Alamos and Lawrence Livermore national labs visited Arzamas-16 and Chelyabinsk-70—cities off limits even to most Russian citizens (Science, 28 April 1995, p. 488). “The lack of trust quickly evaporated,” recalls Avrorin, who last month stepped down as VNIITF director. “We did not find James Bond among the Americans, and they did not find horned devils among our side.” The visit sparked an ongoing series of experiments between the weapons scientists, called the lab-to-lab program, that began with studies on high-energy magnetic fields—an area pioneered by weapons scientist-turned-dissident Andrei Sakharov—and has since branched off into disciplines as diverse as systems for accounting for nuclear materials and environmental remediation. The collaborations “are an important confidence-building measure that allows U.S. and Russian scientists to get to know one another and understand each other's facilities,” says Scott Parrish, a policy analyst with the Center for Nonproliferation Studies (CNS) at the Monterey Institute of International Studies. Both sides have had to tiptoe around certain projects that straddle the border between open and classified research, however. Particularly touchy is work on ISKRA-5 at VNIIEF, the second most powerful laser in the world after Livermore's NOVA. Both lasers are designed to test the feasibility of using inertial confinement fusion as an energy source, and both are also used to study deuterium-tritium implosions and other phenomena that could yield knowledge useful for modeling nuclear weapons. “We have contacts with Livermore, we exchange experimental results, but we haven't had any joint experiments. The work at these facilities is in a so-called sensitive area,” says project scientist Sergei Garanin. “Both sides have national security issues, secrets that should not be shared,” adds Nikitin. VNIIEF's ambitions for the pricey laser facility suggest that the government, at least on paper, is willing to commit major funding to maintaining stockpile reliability. To keep up with Livermore, which is building its next-generation laser, the National Ignition Facility (NIF), VNIIEF is laying the groundwork for ISKRA-6, a niobium-based laser. VNIIEF hopes to have ISKRA-6's first module, dubbed Luch (Russian for beamlet, named after NIF's Beamlet module), up and running by 2001, says Garanin, “if the financial crisis doesn't postpone it.” Indeed, Western experts are skeptical that Russia will ever come up with the$300 million needed to build the rest of ISKRA-6.

While the informal lab-to-lab collaborations were taking shape, the United States, the European Union, Japan, and Russia banded together in November 1992 to create the most ambitious effort so far to provide a lifeline to weapons scientists: the International Science and Technology Center (ISTC). The center has committed $190 million to projects employing 21,000 weapons experts across the former Soviet Union. About 17% of that sum has gone to Sarov and Snezhinsk. “Nobody has become rich thanks to ISTC,” says theoretical physicist Boris Vodolaga, deputy director for international collaboration and conversion at VNIITF, “but clothing for children and medicines have been purchased with ISTC money.” Some scientists don't like to imagine their lives today if the ISTC hadn't come to the rescue. “The ISTC project changed my life,” says Sergey Shumsky, a senior research fellow at the Lebedev Physics Institute in Moscow. Shumsky, a former plasma physicist, is part of a team led by Serge Terekhov at Snezhinsk that 3 years ago won a$600,000 ISTC grant to design neural nets for doing everything from searching the Internet to discerning explosions from both nuclear devices and natural events such as earthquakes and meteoroid strikes. Their computer program for analyzing seismic data is so precise, he claims, that “one can even locate the mine shaft where an explosion took place.” The team is now negotiating licensing deals with Russian companies. Snezhinsk is also doing environmental studies, including a highly regarded ISTC-sponsored project to reconstruct events surrounding an explosion 40 years ago at a nuclear waste facility, which blanketed a nearby swath of land with radioactive isotopes (see sidebar on p. 164).

But Terekhov and other researchers, particularly in Snezhinsk, express a growing disenchantment with ISTC. The center “just does nothing to promote commercialization of projects and their outcomes,” says Yury Lazarev, who managed a project completed a year ago that laid the theoretical groundwork for a microwave laser capable of delivering short, intense pulses. Instead of funding projects for 2 years or so, Vodolaga argues, ISTC should provide long-term support for worthy projects, shepherding them to the market. ISTC deputy executive director Sergey Zykov says, however, that such an approach would limit the number of people his organization could help.

Indeed, neither of the two heavyweight programs aiding weapons scientists—ISTC and DOE's Initiatives for Proliferation Prevention—“has yet succeeded in fostering the establishment of a single self-sustaining commercial enterprise employing a significant number of people in a nuclear city,” a group led by Princeton nonproliferation guru Frank von Hippel points out in the September/October 1998 issue of The Bulletin of the Atomic Scientists. All of this has heaped a heavier burden on the newly formed NCI, which will focus exclusively on creating jobs in the cities that support the nuclear institutes.

If any one event captured the new, darkening mood in the nuclear cities, it was the tragic death 2 years ago of VNIITF director Vladimir Nechai. In October 1996, as winter was approaching, Nechai had no money to pay salaries for his 10,500 employees. Almost 2 months earlier, he had written to then-Prime Minister Viktor Chernomyrdin and to the head of Minatom, decrying the $20 million debt the government owed VNIITF. His letter produced a response: In late October, Minatom transferred enough money to VNIITF's bank account to pay pensions and salaries. But, according to a Minatom spokesperson, the institute's account had been frozen temporarily because it had not paid its utility bills, and it could not withdraw the money right away. On 31 October Nechai shot and killed himself. “It was quite a shock,” says Shumsky. “Most people respected him; he was young and energetic.” The funeral the next day drew thousands of mourners, but the Kremlin appeared to pay little attention: No government officials showed up for the event. Prominent Russian politician Grigory Yavlinsky, leader of the opposition Yabloko Party, noted that fact in an editorial in The New York Times. “Nechai sacrificed his life to call attention to the plight of Russian science,” Yavlinsky wrote. “And he was not heard.” View this table: A different kind of tragedy shook Sarov 8 months later. Alexander Zakharov, a 45-year-old senior scientist at VNIIEF, was working alone on a secret experiment with what institute officials refer to only as a bench-top “critical assembly.” Zakharov was holding the assembly in his hands when it suddenly “began to work,” says VNIIEF's Sladkov, drenching Zakharov in an estimated 600 rems of radiation—thousands of times the dose most people receive in an entire year. “He immediately understood what happened,” says Sladkov. “He knew he was severely damaged and was becoming very sick.” Zakharov was flown to Moscow for treatment but died 2 days later. A Minatom investigation, which included interviews with Zakharov on his deathbed, concluded that the researcher had turned off safety features that would have prevented the accident. VNIIEF staff accept the finding that Zakharov was to blame, but they say the incident added to the malaise in Sarov. “It caused a lot of heartache in the town and at the institute,” says Sladkov. Since those twin tragedies, researchers in both nuclear cities have become increasingly outspoken in demanding better conditions. Last July, 3500 VNIIEF staff members went on an unprecedented daylong strike; in November, 3000 of their colleagues in Snezhinsk followed suit. “Life has become more full with hardships and an absence of confidence in the future,” says Avrorin, who resumed his previous post as VNIITF's scientific director last month when theoretical physicist Georgy Rykovanov became the institute's new director. Western experts say they know little about the ongoing classified research in the nuclear cities and how it fits with Russia's emerging stockpile stewardship program. “We do know that people are still computing and explosive shots get fired; experiments are going on at Novaya Zemlya, even if we do not know exactly what they are doing,” says Los Alamos's Shaner. “We can guess that their computations are not going on anything like the teraflop machines coming online at the U.S. labs. They are certainly trying to develop some kind of stockpile stewardship program, but we do not know a lot of details about it.” But even for those scientists still working on weapons research, life has changed. One major handicap is a lack of current journals; VNIITF now can only manage subscriptions to a few major ones. “We have a constant feeling of information hunger,” says Vladimir Ananiychuk, head of VNIITF's information department. And like their colleagues throughout the rest of Russia, many scientists in the nuclear cities—particularly those not on Western grants—have less time for research because they supplement their income by working second and third jobs. One scientist in Snezhinsk manages the local department store; another in Sarov has started a company that makes margarine. If many nuclear scientists were to lose their jobs and find themselves in dire straits, says Vodolaga, “nobody can guarantee that won't be used as a lever by terrorists, who would be willing to avail themselves of the experts here.” He points out, however, that the institute has locked up the foreign passports of scientists privy to state secrets and “will never authorize a trip” to Libya or other countries deemed a proliferation threat. Another sobering restraint that may be keeping nuclear scientists in Russia is fear for their own lives. The CNS's Parrish says that weapons scientists have told him that colleagues are unwilling to take jobs in such countries “because they fear that they would be killed after finishing whatever work they contracted to carry out in order to keep the program in question a secret.” CNS, which keeps a database on nuclear trafficking, has not heard of any cases of Russian nuclear scientists going to rogue nations to work on weapons programs. However, “there is now increasing concern that some Russian scientists could be serving as consultants” via e-mail and other forms of communication, says Parrish. “A large degree of assistance could be rendered in this sort of way without anyone traveling to Iran or Libya.” An even higher security risk may be the young, poorly paid guards who patrol the fences surrounding Snezhinsk and the other nuclear cities, says CNS director William Potter. “They are largely ignorant about proliferation concerns and are exceptionally vulnerable to recruitment by organized crime,” he says. Some observers say there is only one foolproof way to bottle up the makings of a bomb. “To ensure that no one in the former Soviet Union could, in any way, provide Iran or Iraq with scientific knowledge would require the reinstitution of many of the hated features of a police state,” argues Susan Eisenhower, chair of the Center for Political and Strategic Studies. Few people want to return to that kind of rule, but one reminder of it—the fences that separate the nuclear cities from the outside world—is likely to persist. About 10 years ago, says Avrorin, Minatom officials began debating whether to take down the perimeter fences but leave up the electrified ones surrounding the fissile materials. At the time, he says, inhabitants had a mixed opinion about whether the fences should stay. They remain in place, and “if a referendum were held today to take them down, I'd predict it would be defeated almost unanimously,” says Avrorin. The fences, he says, have shielded the cities from the organized crime that pervades the rest of Russia and have deterred petty thugs: “Nobody is afraid to go outside after dark.” Thus fenced off from the outside world are the ingredients for making nuclear bombs and the chefs that know the recipes. “These people are endearing,” says Tom Owens of the U.S. Civilian Research and Development Foundation, a fund that supports R&D collaborations between U.S. scientists and former Soviet weapons scientists. “You have to pinch yourself to remember what they were doing 10 years ago.” But what will they be doing 10 years from now? 8. RUSSIA # U.S. and Russia Join Forces in High-Stakes Job Hunt 1. Richard Stone Russia's nuclear cities, which flourished during the Cold War as secretive, privileged wards of the Soviet state, might seem an unlikely place for private enterprise. But the cities are rich lodes of high technology, and they have tens of thousands of nuclear weapons experts who might be lured away by would-be nuclear powers as jobs there dwindle. So this year, the U.S.-Russian Nuclear Cities Initiative (NCI) is taking on the task of persuading U.S. companies and others to invest in new ventures in Russia's once-secret nuclear weapons centers. Russia's Ministry of Atomic Energy (Minatom) says that as many as 50,000 nuclear weapons experts will need new jobs over the next several years—a formidable task in the wake of Russia's sharp economic downturn since last August. The crisis has raised new proliferation concerns (see main text), instilling a sense of urgency in the fledgling program. “Quick successes are important,” says NCI director William Desmond. “But we have to be careful in our hurried pace” to create lasting jobs. The U.S. Department of Energy (DOE) and Minatom had been kicking around the idea for such an initiative “at very high levels” for months, says a DOE official, before Vice President Al Gore and former Russian Prime Minister Sergei Kiriyenko announced NCI last July. The venture will spend$15 million this year to try to stimulate job creation in Snezhinsk, Sarov, and Zheleznogorsk, a center for processing weapons-grade plutonium. It will complement another DOE effort, the Initiatives for Proliferation Prevention (IPP), which will also spend $15 million in the nuclear cities this year, part of its broader portfolio for supporting former Soviet nuclear, chemical, and biological weapons scientists. Whereas IPP essentially serves as a matchmaker, hooking up Russian ventures with U.S. national labs and companies, NCI also hopes to nurture telecommunications and other infrastructure in the nuclear cities needed for businesses to grow, leveraging its resources with those of industry and other players. “We would like to create one major business activity” by the end of this year that provides at least 200 jobs in each city, says Desmond, who also oversees IPP. Officials plan to expand the NCI, expected to last up to 7 years, to as many as seven more cities in 2000 and beyond (see map, p. 158). One of the biggest challenges for NCI managers will be to infuse a market-driven culture in the nuclear cities. “As a rule, scientists are poor businessmen,” says Snezhinsk's Vladimir Lykov, who leads a picosecond laser project with much commercial promise but who is struggling to devise a business plan. One hurdle that he and others say they face is the security in the cities, which limit visits and communication. “We have a hard time making business contacts,” says Dmitrii Sladkov of the nuclear center in Sarov, in which visitors must be escorted constantly by security personnel. “It's a major problem.” The initiative hopes to build on some small steps the cities have already taken on their own. For instance, Sarov managers and nuclear center officials a couple of years ago set up a development fund strictly for civilian enterprises; it has provided seed money for about 30 businesses so far. The fund has raised$10 million toward an ambitious goal of $300 million, and it has asked NCI to chip in, a request DOE is considering. The first NCI efforts, which could get off the ground as early as next month, would establish business centers in each city—places where Russian and Western firms could hold meetings and have free access to e-mail and telephone lines, commodities that are now tightly controlled by the nuclear centers. “In terms of real job creation—that's going to take some time,” says a DOE official. One promising venture is an IPP-funded silicon wafer production plant in Zheleznogorsk. That's a “showcase model we hope to extend,” says Desmond. To sweeten the deal for industry, Russia has pledged to “take all necessary measures” to exempt from customs duties and taxes any equipment, supplies, and services provided under the initiative, according to an agreement signed by the two governments last September. Still, Desmond acknowledges, “this will always be a risky activity for U.S. businesses.” Industry officials agree, saying they are intrigued but not yet sold. “We know very little about these cities,” says a scientist with Westinghouse Energy Systems. “We need to know more for industry to support this.” Russia has also said it will invest money of its own in the program, says Rose Gottemoeller, director of DOE's Office of Nonproliferation and National Security. But because of the economic crisis, she says, “we have to take that with a bit of a grain of salt.” More than just the future of the nuclear cities is at stake in the effort, says Desmond. “This is not an American solution to a Russian problem.” NCI's main measure of success, he says, will be how it benefits the United States: “We believe we will be successful if we have contributed to our national security.” 9. RUSSIA # Keeping a Wary Eye on Chornobyl's Unsettled Remains 1. Richard Stone CHORNOBYL, UKRAINE—The downpour on 27 June 1990 came as a welcome gift for Ukrainian farmers toiling in their last summer under Soviet rule, but it triggered alarm bells here at the infamous Chornobyl* Nuclear Power Plant, the scene 4 years earlier of the world's worst nuclear accident. Deep in the bowels of the burned-out reactor number 4 building, in a room filled with a jumble of uranium fuel and building materials, detectors vigilant for signs of fissioning atoms started screaming. Within hours, neutron counts in room 304/3 had soared from 2.5 to 156 counts per second. Chornobyl scientists feared that rainwater leaking into the ruined reactor was slowing neutrons emitted by the fuel, leading to a self-sustained fission reaction marked by a telltale surge in neutrons. A physicist dashed into 304/3, risking his life to dump neutron-quenching gadolinium nitrate on the seething mass. That brave deed ended the immediate crisis, for neutron counts ebbed over the next few days. But the drama that June and several later flare-ups following rainstorms have left an enduring mystery for nuclear physicists: How big is the threat posed by the tons of uranium fuel scattered through the damaged reactor building? Among those trying to answer this question have been researchers from Russia's closed nuclear cities, aided by Western funds (see main text). New data presented at a recent conference suggest the odds of a second explosion are small. But researchers are continuing to monitor the situation: Western experts recently installed new devices for watching the scary chemistry. A crack team of Soviet nuclear physicists, many of whom were drawn from the nuclear cities, was dispatched to Chornobyl immediately after the explosion and subsequent fire on 26 April 1986. Their first task was to advise a military effort to gather radioactive debris into several hundred dumps near the plant and to build a massive concrete sarcophagus over the destroyed reactor hall. The scientists took some unusual precautions. “When we worked in very high radiation areas, we were told to take 50 grams of spirits beforehand” to supposedly fortify the body against radiation damage, says Lev Belovodsky of the All-Russia Scientific Research Institute for Experimental Physics (VNIIEF) in Sarov, who was in charge of measuring the radiation doses of people who built the sarcophagus. “But in the spirit of our country, we added a half-liter.” VNIIEF scientists have since played a prominent role in tracing the steps that led to the explosion. “We have always been involved with the risks of transient nuclear processes,” explains Vyatcheslav Solovyev, deputy head of the theoretical division at VNIIEF. The weaponeers soon spotted a glaring deficiency: “We found that there was a lack of computer codes in our country and abroad to predict this kind of accident.” Over the past decade Solovyev and his colleagues have developed computer programs for analyzing conditions inside RBMK-class reactors like the one that blew up at Chornobyl, which are still operating at several other power stations across the former Soviet Union. Researchers from the nuclear weapons complex have also helped gauge the threat lurking in the sarcophagus. Recent estimates suggest that about 170 tons, or 90% of the original uranium dioxide, flowed as lava into the warren of rooms beneath the reactor hall. Along the way it mixed with tons of building metal and concrete as well as sand, boron, and other materials dumped from helicopters after the explosion in an effort to quench the smoldering fuel. The lava solidified into a unique mineral, in its crude form called fuel containing masses (FCMs). “Its structure is very complicated,” says Solovyev. At the conference, researchers downplayed the risk that the fuel will go critical. After analyzing sketchy data on the distribution of FCMs and neutron moderators such as water and graphite, Leo LeSage and Ronald Turski of Argonne National Laboratory concluded that the FCMs can barely sustain a fission reaction, even under the most favorable conditions. “You can't rule out [an explosion], but it's very remote,” says LeSage. However, longtime Chornobyl researcher Alexander Borovoi of Moscow's Kurchatov Institute points to a new threat: The gadolinium nitrate dumped in the sarcophagus has begun to disassociate. Free gadolinium slows neutrons and could foster a chain reaction. “Thus, instead of a nuclear safety provision as an absorber it becomes a nuclear hazard,” he says. Some experts contend that high neutron counts like the June 1990 surge were red herrings that may have resulted from moisture-sensitive detectors. “I don't believe there are any oscillations in neutrons, simply false signals,” says Belovodsky. Technicians at the sarcophagus last month installed a series of new boron trifluoride-based neutron and gamma ray detectors, designed by a team at the Pacific Northwest National Laboratory (PNNL). The arrays should eliminate spurious neutron counts if the detectors are more sensitive when wet, says George Vargo of PNNL's International Nuclear Safety Program. Everyone agrees that finding a way to prevent water from accumulating in the sarcophagus would remove any criticality threat; Chornobyl management has plugged holes in the leaky sarcophagus, but an estimated 1000 cubic meters of water still finds its way inside each year, much of it during the spring melt. As fears of a second explosion ease, the debate is heating up over the long-term fate of the sarcophagus. Ukrainian officials want to remove the FCMs and bury them elsewhere, but for now such a strategy is too dangerous, says PNNL's Roger Anderson: “It could expose workers to lots of radiation.” In Belovodsky's view, “The best and cheapest solution is to fill the sarcophagus with concrete and make it a grave forever.” • * New spelling adapted from Ukrainian. • International Cooperation for Chornobyl, 13–16 October 1998, Slavutych, Ukraine. 10. RUSSIA # Retracing Mayak's Radioactive Cloud 1. Richard Stone The yellow smoke pouring out the doors of the radioactive waste storage building at the Mayak Production Association that cloudy fall day was an ominous sign. Two workers were dispatched to investigate what had gone awry inside a concrete bunker used to store radioactively contaminated liquids, byproducts of processing plutonium for weapons. The duo donned gas masks and descended into the crypt, where they were met by a blast of heat. Unable to see anything in the smoky corridor, they switched on a fan and left. Lucky for them. A few minutes later, at 4:20 p.m. on Sunday, 29 September 1957, a gigantic explosion ripped through the radwaste pit, the report reverberating all the way to Chelyabinsk-40, a closed nuclear city some 10 kilometers away. At the storage facility, the workers—amazingly, all of them escaped injury—watched as billowing dust clouds blotted out the fading daylight. That night the clouds glimmered crimson; residents of an open city 70 km to the south thought they were watching the northern lights. Little did they know that radioactive fallout was settling over a 400-km-long swath of land. That chilling account was pieced together from public sources and Mayak archives by Mikhail Avramenko, a nuclear physicist at the All-Russia Scientific Research Institute for Theoretical Physics in Snezhinsk, some 40 km north of the accident scene. Avramenko compiled this picture—parts of which he has submitted to the journal Atmospheric Environment—in an effort, sponsored by the International Science and Technology Center, to devise computer programs for modeling the fate of radionuclides released into the atmosphere. The simulations, which model how weather conditions, air currents, and other factors might disperse radioactive particles, are meant to help forecast the consequences of another explosion at any of the several nuclear sites in the Chelyabinsk region (see map on p. 158). “Accidents at these facilities could affect many towns,” says Avramenko, who has established a center at Snezhinsk dedicated to such modeling. The explosion in 1957 dispersed 2 million curies over some 20,000 square km, prompting the evacuation of more than 10,000 people from contaminated villages. Based on Mayak records, Avramenko calculated that the ill-fated 250-cubic-meter storage tank contained about 20 million curies of radioactivity, including such long-lived isotopes as strontium-90, cesium-137, and plutonium. More horrific releases occurred on purpose: From 1949 to 1956, Mayak dumped an estimated 76 million cubic meters of liquid radioactive waste directly into the Techa River. Some 64,000 people who lived downstream are the subjects of a Russian-U.S. effort to reconstruct the doses they absorbed and to study their health effects (Science, 24 February 1995, p. 1084). Avramenko found no evidence to dispute the official explanation for the accident: that a water cooling system had failed, drying out the waste and cooking the precipitated salts until they ignited in a chemical inferno. He estimates that the blast was equivalent to the detonation of 25 tons of TNT, about a third of original estimates. “This study was excellent, with a very sound approach to determining the chemistry, the energy release, and doing some interesting modeling,” says Steve Gittomer of Los Alamos National Laboratory. Avramenko hopes his data won't have to be put to a real-life test. “Now we know much more about the process of storage of radioactive waste,” he says. But with Russia hard-pressed these days to fund its stockpile stewardship program and maintain its radwaste facilities, observers fear that residents of the Chelyabinsk region may be sitting on a nuclear tinderbox. -R.S. 11. MATERIALS RESEARCH SOCIETY MEETING # Finding Speed on the Smallest Scales 1. Robert F. Service BOSTON—The speedy and the slight were on display at the semiannual Materials Research Society meeting held here from 30 November to 4 December. Among the highlights were tiny catalysts trapped in porous polymer spheres, a high-speed combinatorial study of corrosion, and a chemically triggered nanotransistor. ## Starburst Cages for Catalysts Like master chefs, catalyst makers are always refining their recipes. One of the surest ways they've found to get winning results from a metal catalyst is to divide it into smaller and smaller particles, which increases the overall surface area on which chemical transformations can occur. Yet this isn't as simple as it sounds. Like unsifted flour, tiny catalyst particles can clump together, reducing the surface area. At the meeting, a team of researchers led by chemist Richard Crooks of Texas A&M University in College Station described a new ingredient that can get the lumps out of this recipe: small porous polymer spheres called dendrimers that can encapsulate metal particles and keep them from sticking together while allowing reactants and products to diffuse in and out. Already, Crooks and his team have grown dendrimer-encapsulated nanoparticles of several metals, including copper, silver, platinum, ruthenium, palladium, nickel, and even composites of platinum and ruthenium. The new work is “a nice approach,” says Richard Finke, a nanoparticle expert at Colorado State University in Fort Collins. Besides protecting the metal particles, he notes, the dendrimers can also serve as molds for growing them in a precise size. If the work pans out, it could lead to better catalysts for the fuel cells that burn methanol or hydrogen gas. But Finke cautions, “It's still early on.” Among other things, researchers have to prove that the polymer shields are stable and don't reduce the catalytic efficiency of the particles. That's been a problem for earlier strategies that envelop catalysts in detergent-like molecules called surfactants or in layers of conventional linear polymers: Reactants can't easily make their way past these barriers to the metal surface. But Crooks and his colleagues suspected that dendrimers might work better. These molecules branch repeatedly, forming a spherical starburst of branches that can trap nanoparticles while allowing reactants and products to diffuse freely. Moreover, because the branching is easy to control, all the dendrimers in a batch are virtually identical, allowing them to act as templates for nanoparticles with a consistent size and makeup. To create encapsulated copper particles, Crooks's team combined dendrimers made from polyamidoamine, which contain numerous amine groups that bind positively charged metal ions, with a solution of copper sulfate. When the researchers added sodium borohydride, a strong reducing agent, the copper ions precipitated out into metallic copper particles, which grew within the dendrimer. Depending on the size of the dendrimers, the particles contained from just four to 64 atoms—small enough to be an efficient catalyst. “That's it,” says Crooks. “It's really easy. It only takes about 1 minute to do this.” By simply changing the initial metal salt, the researchers were able to create other encapsulated metal particles. Already Crooks and his colleagues Mingqi Zhao and Li Sun have shown that their new dendrimer-bound catalysts are effective at adding hydrogens to small hydrocarbons such as alkenes, a chemical transformation that's done by the trainload in industry as a step toward making everything from drugs and dyes to rubber products. What's more, dendrimer-based catalysts might be better than existing versions at selecting the right feedstocks from a mixture, says Crooks. The team found that whereas linear alkenes—simple, spaghetti-like molecules—easily diffuse into the dendrimers, more complex branched versions have a harder time wriggling their way inside. What's not yet known is whether the new dendrimer-bound catalysts are actually more efficient than their brethren. But Crooks says his team is looking into that now. If so, dendrimers could be in for a big future as tiny reaction chambers. ## Single Electrons With a Chemical Sense Single-electron transistors, which coax electrons to flow one at a time through nanometer-sized specks of material, could take electronic devices to extremes of tininess. Now, new work suggests that these devices could also find their way into ultrasmall, ultrasensitive chemical sensors. At the meeting, a team led by chemist Dan Feldheim from North Carolina State University in Raleigh reported a new scheme in which the electrical current flowing through what amounts to a single-electron transistor (SET) varies depending on the chemical makeup in a solution surrounding the device, a phenomenon analogous to a nerve cell firing in response to specific neurotransmitters. By harnessing this ability to convert a tiny chemical signal into an electronic response, the new scheme could lead to a bevy of simple and sensitive chemical sensors, useful for detecting everything from chemical toxins to trace components in cells. “It's a very clever approach” to making chemical sensors, says Northwestern University chemist Chad Mirkin. To make their sensors, the NC State team started with two electrodes, one a simple gold pad and the other the electrically conductive tip of a scanning tunneling microscope (STM). An STM maps the contours of conductive surfaces by nudging its tip up close and allowing electrons to leap across to the surface, in a flow that's proportional to the separation. Other researchers have shown that placing a metal or semiconductor nanocrystal between two electrodes can turn this setup into an SET. Because electrons repel one another, only a limited number can reside on the tiny nanocrystal. As a result, additional electrons can hop from one electrode, the STM in this case, to the nanocrystal only as other electrons leave by jumping to the other electrode. As in a conventional transistor, a third “gate” electrode controls the tempo of the electron movements. Placed near the nanocrystal, the gate raises the electrical conductivity of the tiny island when it is charged, getting the electrons to hopscotch faster. Feldheim and his colleagues wanted to see, he says, “if we could get that same [gating] effect chemically.” Their idea was to coat gold nanocrystals with organic compounds that can alter their charge and thereby act like a gate electrode. In this case, the researchers coated gold nanocrystals with small ring-shaped molecules of an organic substance called galvinol. After attaching the coated nanocrystals to a gold electrode with the help of Velcro-like molecules called hexanethiols, they then dunked the assemblage in a water-based solution, maneuvered an STM tip close to the surface, and raised the solution's pH by adding a buffer. As the solution grew more basic, it pulled protons away from the galvinols, leaving the molecules negatively charged. This added charge makes it more difficult for an electron to hop onto the island and find its way to the gold electrode, creating a drop in the electrical current. The result, in short, was a SET-based pH sensor. The NC State team's approach is still tied to a tabletop-sized STM, which restricts its possible applications. But the researchers are at work on a scheme to make arrays of tiny electrodes in pairs separated by just 5 nanometers or so, with a single nanocrystal perched between the paired electrodes. Because it's relatively easy to coat nanocrystals with a variety of compounds that are themselves sensitive to the presence of other chemicals, a single array could signal the presence of a range of molecules. Cells, which manage this type of sensitive chemical detection day in and day out, may be in for a little competition. ## Combinatorial Test of Corrosion On a copper plate, J. Charles Barbour and his colleagues at Sandia National Laboratories in Albuquerque, New Mexico, are turning combinatorial chemistry on its head. The technique is typically used to create all possible combinations of a handful of chemical building blocks, thereby synthesizing in one fell swoop thousands of compounds to test, say, as possible drugs. But at the meeting, Barbour and his colleagues showed how the same approach can also be used to study a destructive chemical reaction: corrosion. The researchers created a grid of differing conditions in the thin copper film. First they increased the thickness of a protective copper oxide coating in half-centimeter horizontal strips from bottom to top; then they boosted the number of defects, created by bombarding the metal with copper ions, in vertical strips from right to left. The researchers exposed the foil to air spiked with hydrogen sulfide to see where the sulfur reacted with the copper to create copper sulfide, a hallmark of corrosion. A lower number of defects turned out to be far more important in limiting corrosion than a thick copper oxide overcoat. Such studies, says Barbour, could help researchers prevent the corrosion of copper in advanced electronics circuitry and aluminum in aircraft. 12. AMERICAN SOCIETY FOR CELL BIOLOGY MEETING # Bacteria Pull Cell Skeletons Out of the Closet 1. Evelyn Strauss SAN FRANCISCO—An air of optimism pervaded the annual meeting of the American Society for Cell Biology, held here last month. The$2 billion boost the National Institutes of Health budget got this year explained some of the good cheer. But the 8000 participants also found much excitement in the science, which ranged from new roles for the giant protein titin to the subtle tricks of the salmonella pathogen.

The ability of disease-causing bacteria to manipulate the cells they infect can make cell biologists drool with envy. Take the food-poisoning bacterium Salmonella typhimurium: When this pathogen encounters target cells, it stimulates a dramatic ruffling in the cellular membrane at the point of contact. The ruffled membrane then grabs the bacteria and pulls them inside. Biologists are now learning just how S. typhimurium tricks cells into aiding it.

At the meeting, Daoguo Zhou, a postdoc in microbiologist Jorge Galán's lab at Yale University School of Medicine, reported that a bacterial protein called SipA appears to play a key role in this uptake. Injected into cells by the bacteria, it apparently binds to one of the main components of the cell's internal skeleton, a protein called actin. By modifying the properties of actin, SipA helps stabilize the fibers supporting the ruffles.

In addition to providing insight into how S. typhimurium coopts host cell molecules and causes disease, the result may lead to a better understanding of normal mammalian cell behavior. Actin rearrangements similar to those triggered by SipA also occur during the cell migrations needed for embryonic development and in cells responding to growth factors or becoming cancerous. The pathway that results in membrane ruffling “touches on almost every aspect of cell life,” says Dafna Bar-Sagi, a cell biologist at the State University of New York, Stony Brook. Studies of bacterial mutants unable to stimulate events critical to ruffling could help scientists dissect the separate steps of the pathway and thus those of normal events.

The current finding is an outgrowth of a discovery made several years ago when researchers learned that many bacterial pathogens, including S. typhimurium, have a kind of molecular syringe that injects substances into target cells, stimulating them to take in the bacteria. To study this molecular subversion, the Galán group identified proteins that are delivered by the syringe. They then constructed S. typhimurium strains that lacked the genes for these proteins and probed how the mutations hamper the ability of the bacteria to infect cells.

One protein turned up by this screen, called SopE, is necessary for ruffling to occur. By forcing host cells to produce SopE or by injecting them with the protein, the Galán group showed that by itself SopE induces a rather weak and generalized ruffling of the whole cell membrane, rather than the strong ruffling seen at the sites of bacterial contact. Something else was apparently needed to localize the host cell reaction.

At the meeting, Zhou reported that SipA seems to fit the bill. Host cells in contact with bacterial mutants lacking SipA ruffled only loosely, even when all the other invasion genes were present. To find out how SipA works, the Yale team used genetic and biochemical techniques to look for proteins that SipA might team up with in the cell. The clues they gathered ultimately pointed to actin. Direct evidence that the two proteins interact came when the researchers mixed purified preparations of actin and SipA. When they centrifuged actin filaments, SipA ended up in the pellet too, indicating that the actin and SipA directly contact each other.

The team went on to probe exactly how SipA modifies actin behavior. Electron micrograph studies pointed to one difference. Actin filaments containing SipA appeared very straight instead of having the small kinks seen in actin strands without SipA. The researchers also found that SipA decreased the amount of actin required to form filaments and made the filaments more prone to form bundles with the help of another cell protein called T-fimbrin. Together, these findings suggest that SipA strengthens the actin filaments and that this fortifies the membrane protrusions, enabling them to stick out farther and envelop more bacteria.

As Julie Theriot, a cell biologist at Stanford University School of Medicine, describes the emerging picture, “SopE slaps the cell in the face and says, ‘Wake up.’ Then SipA takes the global response and physically focuses it, causing the cell to reach up to where the Salmonella are.”

No one has yet found a eukaryotic counterpart of SipA, but experts say it's likely that at some point during evolution, a Salmonella predecessor captured a host protein and adopted it for its own purposes. “In the best case scenario, we'll find out that the same mechanisms Salmonella use to induce these activities will end up explaining what we see in other circumstances,” says Bar-Sagi. If so, biologists' envy of bacteria will no doubt turn to gratitude.

13. AMERICAN SOCIETY FOR CELL BIOLOGY MEETING

# An All-Purpose Protein Shock Absorber

1. Elizabeth Pennisi

SAN FRANCISCO—An air of optimism pervaded the annual meeting of the American Society for Cell Biology, held here last month. The $2 billion boost the National Institutes of Health budget got this year explained some of the good cheer. But the 8000 participants also found much excitement in the science, which ranged from new roles for the giant protein titin to the subtle tricks of the salmonella pathogen. These days, stretchy fabrics once fashionable only for runners, gymnasts, and speed skaters can be found in all kinds of clothing, even formal attire. A few threads of Lycra spandex fibers can help even the soberest outfits keep their shape. Now cell biologists are finding to their surprise that a giant stretchy protein called titin, which helps support the force-generating fibers in skeletal muscle, isn't limited to athletic duty either. At the meeting, Tom Keller of Florida State University in Tallahassee reported that his team found this accordion-like molecule in the structural fibers that help give human platelets their flexibility and in the smooth muscle of chicken gizzards. And in a much more surprising development, molecular biologist Cristina Machado from Johns Hopkins University in Baltimore described how she found titin in cell nuclei, where it may help the chromosomes shrink into compact structures prior to cell division. “People have assumed that [titin] is just a muscle protein,” says Ilia Ouspenski, a cell biologist at Baylor College of Medicine in Houston. Finding it in the nucleus, he adds, is “entirely unusual and new.” Early inklings of titin's versatility came in 1992 from Keller. While using electron microscopy to study another protein, myosin, in the smooth muscle cells of chick intestines, his team noticed that the cells contained micrometer-long threads, which looked like the giant protein. They later found the same protein in platelets and in the smooth muscle of chicken gizzard, and they have since been studying its function by labeling it with specific antibodies. It's perhaps not surprising that titin is in smooth muscle cells and platelets, because all these cells undergo mechanical stresses that an elastic protein could help counteract. But Machado's findings were unexpected—even to her. Patients with the autoimmune disease scleroderma sometimes make antibodies that react to nuclear proteins, and to learn more about those proteins, Machado, a postdoc working with Deborah Andrew at Johns Hopkins, screened fruit fly embryonic tissue for proteins that react to those antibodies. Once the team had a hit, they identified the protein by using the same antibody to search a “library” of bacteria expressing fruit fly genes. To their astonishment, the antibody picked up a protein whose gene proved to be the fruit fly equivalent of the titin gene. “I was looking for a chromosomal protein, and here I found a muscle gene,” Machado recalls. (The results appeared in the 20 April Journal of Cell Biology.) Since then, Machado has been studying fruit fly strains with mutations in the titin gene to get a better fix on what the protein does. As expected, the muscles of embryos with no titin at all “were all screwed up,” and the embryos did not survive, Machado reported at the meeting. Fruit flies with milder mutations fared slightly better, but they had an unexpected handicap: Their DNA seemed to replicate poorly. When Machado looked at larval brain cells that were preparing to divide, she saw that the chromosomes had not condensed, nor had they begun to pair off and line up properly. The few chromosomes that did pair up were three times more likely to separate prematurely than those in fruit flies with normal titin, she told the meeting participants. The researchers also saw chromosome breakage, an observation suggesting that in chromosomes, as in muscles and platelets, titin acts as a shock absorber that helps keep the structures intact. This may help explain, she says, how chromosomes can condense and expand 10,000-fold over the course of the cell cycle. Because of titin's size—with a molecular weight of 3,000,000 it's the largest protein known—researchers are puzzled about how it gets into the nucleus from the cytoplasm, where it is made. Nevertheless, “the data are absolutely compelling,” Ouspenski says. “There can be no doubt that [the finding] is real.” 14. AMERICAN SOCIETY FOR CELL BIOLOGY MEETING # Homing In on a Sperm Receptor 1. Evelyn Strauss SAN FRANCISCO—An air of optimism pervaded the annual meeting of the American Society for Cell Biology, held here last month. The$2 billion boost the National Institutes of Health budget got this year explained some of the good cheer. But the 8000 participants also found much excitement in the science, which ranged from new roles for the giant protein titin to the subtle tricks of the salmonella pathogen.

From the U.S. president on down, it seems everyone is in a jam over sex. Sex causes problems for scientists, too, especially when it comes to understanding a key event: the union of mammalian eggs and sperm. But at the meeting, Nicole Sampson, a chemist at the State University of New York, Stony Brook, reported new findings that may help.

Although researchers have identified several sperm proteins that appear to bind to mammalian eggs, they have had less success at pinning down the receptors on the egg that grab onto those sperm molecules, mainly because eggs are scarce. Indirect evidence did suggest that an integrin, a type of protein known to be involved in cell-cell interactions, might be an egg receptor for sperm, but no one had detected physical contact between the integrin and any sperm proteins—until now, that is. Sampson and her colleagues have shown that the integrin binds to a small piece of sperm protein called fertilin already known to be critical for fertilization. (The results also appear in the January issue of Chemistry and Biology.) “This is the first evidence of direct binding [to fertilin],” says Paul Primakoff, a cell biologist at the University of California, Davis. The result might eventually lead to novel contraceptives that work by blocking fertilin binding to the integrin and perhaps also to a better understanding of human infertility.

Researchers had suspected that fertilin might attach to an integrin, because the sperm protein's amino acid sequence identified it as a member of a group of known integrin-binding proteins called disintegrins. Several teams had also found that peptides that correspond to fertilin's integrin-binding region bind to the egg membrane and inhibit sperm-egg fusion—presumably by blocking the sperm protein's attachment site. Antibody and other indirect evidence suggested that an integrin called α-6/β-1 might form that site, but Sampson and her colleagues decided to look directly for the receptor, using the putative integrin-binding domain of fertilin as bait. By narrowing their search to integrins, they exploited the limited number of available eggs to good advantage—and got very lucky.

To find possible fertilin-binding partners on the egg, the researchers synthesized a radiolabeled peptide containing 13 amino acids from the putative integrin-binding region of fertilin plus an amino acid that would attach to any nearby proteins in response to a flash of light. When they then incubated this peptide with mouse eggs and zapped the mixture with light, the researchers found that the peptide had attached to just one protein, which proved to be α-6/β-1 integrin. “The most remarkable thing to us was the specificity of labeling,” says Sampson.

Even if further research proves that the egg integrin is a sperm receptor, the finding will not entirely explain the sperm-egg binding process. “While this interaction is important, there are likely to be other sperm and egg molecules that complement it,” says Janice Evans, a reproductive cell biologist at the Johns Hopkins University School of Public Health in Baltimore. Still, the peptide the Sampson group used to fish out the α-6/β-1 integrin does inhibit in vitro fertilization, suggesting that the egg integrin could provide a new target for birth control. That could prove tricky, however, because the integrin is also on other cell types, posing challenges in drug delivery and raising the possibility of side effects.

Nevertheless, the finding is a sign that researchers are making headway in solving the puzzles of mammalian sex—at the molecular level, at least. “We didn't know the molecules on sperm and egg that were involved in [membrane] interactions just a few years ago,” says Richard Schultz, a developmental biologist at the University of Pennsylvania, Philadelphia. “There's been a quantum leap in our understanding since then.”

15. PALEOANTHROPOLOGY

# Ancient Child Burial Uncovered in Portugal

1. Constance Holden

In a rock-shelter in rural Portugal, archaeologists last month made a rare find: the complete skeleton of a young child of our own lineage, whose body was covered in red ochre and buried with ceremony perhaps 28,000 years ago. Researchers say the child may prove to be the oldest well-preserved early modern human on the Iberian peninsula. And in addition to the bones themselves, the burial may provide cultural clues to a pivotal era, when the last of the Neandertals co-existed with modern humans in southern Iberia.

Although the skull was shattered, the lower jawbone, complete with teeth, is almost intact, and the protruding chin clearly marks the child as an anatomically modern human, says Joao Zilhao of the University of Lisbon, Portugal's director of antiquities and leader of the excavation team. The find was made in early December when two of Zilhao's assistants were inspecting rock art in a valley about 140 kilometers north of Lisbon and spotted sediments containing charcoal and stone tools. Further probing yielded human arm bones and eventually a complete skeleton.

The body had apparently been wrapped in a blanket or animal skin drenched in red ochre, a practice thought to be related to ochre's resemblance to dried blood. A pierced marine shell, probably a pendant, lay near the throat, and animal bones were near the head and feet. Such features are typical of early modern human burials in central and eastern Europe, says Zilhao; the child's skeleton shows that early humans maintained common cultural practices over a vast area.

The bones were 2.5 meters below stone tools dated to about 21,000 years ago, suggesting that the bones could be as old as 28,000 years. If so, “it is really one of the first modern humans [in the region]—the ones that caused the extinction of the Neandertals,” says Zilhao. Only two other western European burials are so old.

Other researchers are excited by the news. Paleoanthropologist Erik Trinkaus of Washington University in St. Louis rushed to Portugal this week to examine the bones. If the ages hold up, the find will be highly significant, says anthropologist Chris Stringer of the Natural History Museum in London. “We have very little material [from] this critical period” in Iberia, he says.