News this Week

Science  12 Jan 2001:
Vol. 291, Issue 5502, pp. 222
  1. U.S. SCIENCE POLICY

    New Faces Please and Puzzle Researchers

    1. David Malakoff

    Science advocates are reacting with cheers, groans, and puzzlement to a host of recent picks for key science policy-making jobs in Washington. The choices include a new chair of the House spending panel that controls the budget of the National Institutes of Health (NIH); another that oversees research at NASA, the Environmental Protection Agency (EPA), the Department of Energy (DOE), and the National Science Foundation; and the new heads of DOE and EPA.

    The appointment prompting the warmest reception is the ascension of Representative Sherwood Boehlert (R-NY) to lead the House Science Committee. He replaces Representative James Sensenbrenner (R-WI), who becomes top dog at the higher profile Judiciary panel. Boehlert, a 10-term lawmaker who is one of the House's most liberal Republicans, “will be a breath of fresh air,” predicts physicist Michael Lubell, lead lobbyist for the American Physical Society. Unlike the prickly, highly partisan Sensenbrenner, who relished grilling NASA Administrator Dan Goldin over cost overruns on the international space station and DOE officials on their contribution to CERN's Large Hadron Collider, Boehlert is likely to strike a more measured pose, lobbyists say.

    New staff director David Goldston, a longtime Boehlert aide, says his boss is likely to focus on math and science education, alternative energy sources, and environmental research. And he plans to reverse a rule barring scientists coming to Washington for 1-year congressional fellowships from working on the committee. But like Sensenbrenner, Boehlert may oppose a largely symbolic bill that calls for doubling the federal government's spending on R&D. Boehlert believes there may be more effective strategies for boosting science budgets.

    Science lobbyists are still looking into most of the other choices, who benefit from openings caused by a 6-year limit on House committee chairs. Representative Ralph Regula (R-OH), the new head of the House appropriations subcommittee that oversees NIH's budget, has a tough act to follow: retired Representative John Porter (R-IL), who became a science community favorite for leading efforts to double NIH's budget. Although Regula “is no John Porter,” says one lobbyist, “he'll be under pressure from the Republican leadership to sustain NIH's budget increases.” DOE lobbyists are tracking the moves of Representative Sonny Callahan (R-AL), a relatively unknown quantity who now heads the spending panel that oversees the agency's budget.

    In the Senate, it appears that Senator Arlen Specter (R-PA) will retain his post as chair of the committee that oversees NIH. Late last year Specter said he wanted a respite from the bitter budget wars. But some observers predict that new power- sharing rules—including putting an equal number of Republicans and Democrats on every committee and allowing panels to move controversial bills to the Senate floor on a tie vote—will make Specter's life more pleasant. “He won't be caught in as much crossfire,” predicts one lobbyist.

    DOE supporters are looking to a confirmation hearing next week for clues to the thoughts of Michigan Republican Spencer Abraham, chosen to lead DOE, the government's third largest funder of basic research. Defeated in November after a single Senate term, Abraham had taken little interest in energy issues and was one of four senators to sponsor a 1999 bill that called for dismantling the department. By 2000, however, Abraham was calling for increased funding for DOE's $3 billion Office of Science.

    Meanwhile, climate scientists hope that President-elect George Bush's pick to lead the EPA, New Jersey Governor Christine Todd Whitman, had only a temporary lapse when she confused the cause of climate change and ozone depletion in a recent interview with The New York Times. Global warming science is “still somewhat uncertain,” she said, adding that “clearly there's a hole in the ozone that has been identified. But I saw a study the other day that showed it was closing. It's not as clear, the cause and effect, as we would like it to be.”

  2. SOLAR, PLANETARY STUDIES

    Two Fields Prepare to Take the Long View

    1. Andrew Lawler

    Taking a page from a successful playbook written by U.S. astronomers, researchers who study the sun and its interactions with Earth's atmosphere will begin an intense effort next week to set long-term scientific and mission goals. The idea behind this study, and a similar exercise being considered by planetary researchers, is to present a unified front before federal agencies and Congress. But the tactic is a gamble: The diverse interests of the solar community don't fit easily under one umbrella, and some planetary scientists say the technique is not well suited to a small field with only a handful of missions.

    Decadal surveys carried out by the National Research Council (NRC) have been very effective tools in winning strong political backing for astronomy and astrophysics. All four large projects recommended in the 1991 survey, for example, became reality, prompting envy from those in other fields that traditionally fare less well. In addition, political attacks on a new NASA solar program called Living With a Star (LWS) (Science, 28 July 2000, p. 528) have pointed up the value of having solid backing for any large scientific undertaking. “We need a national perspective,” says Lou Lanzerotti, a physicist with Lucent Technologies in Murray Hill, New Jersey, who will chair the 12-member NRC panel. “A fairly broad spectrum of federal agencies, research communities, and industry are interested in this.”

    In addition to space-based programs like LWS, the panel will also examine ground-based research such as the National Science Foundation's (NSF's) space weather initiative. The committee will establish five subcommittees—each with up to 10 people—to examine theory, modeling, education, and public outreach activities as well as specific missions. The 2-year study, called “Solar and Space Physics: A Community Assessment and Strategy for the Future,” will be funded primarily by NASA and NSF, with support from the National Oceanic and Atmospheric Administration and the Defense Department.

    Sunny view.

    Two active equatorial regions on the sun as seen by the 2-year-old TRACE (Transition Region and Coronal Explorer) satellite.

    CREDIT: TRACE

    A deluge of data from a series of new spacecraft as well as from ground-based experiments studying the sun's current peak of activity have raised the profile of solar researchers. The LWS is supposed to build on that momentum by launching a series of spacecraft around the sun and Earth. But the program drew criticism last year from some members of Congress for being too applied, while some researchers complained about its scientific foundation and about NASA's plan to give substantial control to a Maryland contractor. “LWS popped up overnight, and now we're playing catch-up,” says James Burch, a physicist with the Southwest Research Institute in San Antonio, Texas, who will serve on the NRC panel. “It was a little bit of the cart before the horse.”

    The first LWS mission, to study solar dynamics, is slated for 2006; future missions have yet to be defined. In November, NASA formed a standing committee, led by solar physicist Glenn Mason of the University of Maryland, College Park, to examine the detailed research that LWS should conduct. Mason and Burch say their respective panels will work together on a stronger research plan for LWS, with Mason's panel providing the specifics and the NRC group outlining the broader scientific strategy. Mason acknowledges that LWS has created rifts among scientists. “This is like a family fight over a future inheritance,” he says. “The community will only have itself to blame if the program isn't done well.” The NRC panel will also try to ease tensions between researchers who conduct primarily space-based work and those focused on ground-based efforts. NASA spends much more on the field than does NSF, but most goes to building hardware. “If you look at how much money is actually going to support scientists, the two agencies are much more balanced,” says Robert Rosner, a University of Chicago astrophysicist.

    As the solar and terrestrial physics effort gets under way, NASA is encouraging planetary scientists to adopt a similar broad-brush study. “This approach clearly is liked by members of Congress,” says NASA space science chief Ed Weiler, who spent 20 years as program scientist for the Hubble Space Telescope. “So let's let the [NRC] decide what is best.”

    But the community is not unanimous that a survey makes sense. “I'm more and more concerned that the pace of events leaves the decadal model in the dust,” says David Black of the Lunar and Planetary Institute in Houston, noting how capitalizing on the recent discovery of a possible ocean on Europa would not have been part of any long-range plan. At the same time, other scientists say that their relatively small field is capable of resolving disputes without a time-consuming and expensive study.

    Old hands warn that surveys are no panacea. John Bahcall, the Princeton University astronomer who led the influential 1991 NRC survey, agrees that, “in principle, a survey is a good idea. But ultimately it depends on the strength, will, and leadership in the community to make difficult decisions.” In other words, the conclusions of the new NRC panel may be less important than demonstrating that it can speak with one voice.

  3. HUMAN GENOME

    NIH Considers Paying to Use Private Database

    1. Eliot Marshall

    Officials at the National Institutes of Health are negotiating terms under which NIH scientists can have access to the controversial genome database offered by Celera Genomics of Rockville, Maryland. If the talks are successful, some NIH scientists may soon have their own Celera accounts, at an initial cost of up to $15,000 per user per year.

    Some NIH staffers are flabbergasted that such a deal might be in the works—partly because NIH is funding genome sequencing projects that are releasing data free of charge through GenBank, a public database NIH runs. Several NIH scientists have requested access to the Celera database, however, and NIH officials say they've received complaints that academics using Celera's data have “scooped” intramural researchers on discoveries.

    National Cancer Institute director Richard Klausner confirms that NCI staffers ran an informal evaluation of the Celera database. “A variety of intramural scientists who are expert” in this field “felt that the database that they were looking at was very useful and very powerful, and that it would add value” to public data, he says. The reviewers, according to members of the team, included NCI staffers J. Carl Barrett, Neal Copeland, Michael Dean, Dean Hamer, Nancy Jenkins, David Munroe, Stephen O'Brien, and Louis Staudt. Klausner says he doesn't know how many other institutes might be interested, but “whatever we do will be available across the NIH.”

    Celera spokesperson Heather Kowalski declines to comment on the reported negotiations. But she says the current rate for an academic subscription to the genome database—which includes mouse and human sequences and gene-reading software—is $7000 to $15,000 per user per year, although the term “user” is not well defined. In contrast, pharmaceutical companies pay $5 million to $15 million per year.

    Klausner says he isn't aware of any legal barrier that would prevent NIH scientists from becoming Celera subscribers, nor does he see a problem in spending public money to get access to data that may be freely available through GenBank. “We would [only] do this if it is cost-effective and valuable to enhance the public research,” Klausner says. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, also says his scientists should “have access to all scientific resources that the extramural people” can use. Steven Hyman, director of the National Institute of Mental Health, agrees: “If any of my scientists were to ask, I would sign up without compunction.” Like Klausner, Hyman sees no problem in paying for the data twice: “We do it all the time” with scientific journals, he argues: “We pay for the research, we pay for publication costs, and then we pay for the journal subscription for our scientists. We do it without complaining. …”

    Insiders say it's impossible to guess how or when the negotiations will end. At present, the company is trying to answer 15 detailed questions from NCI scientists about fees and access. The company's responses, according to one NCI scientist, could make or break the deal.

  4. PALEONTOLOGY

    New Fossil Fills Gap in Bird Evolution

    1. Erik Stokstad

    Early birds have never had it so good. Paleontologists who study bird evolution are reveling in new finds from around the world, especially China (see special Focus section beginning on p. 232), that provide ever more evidence of dinosaurian ancestry. Meanwhile, evidence bearing on an equally puzzling question—the origin of modern birds—has been frustratingly scarce. But an 80-million-year-old bird from Mongolia may be about to change all that.

    Described in this week's issue of Nature, the Late Cretaceous fossil is the best preserved close relative of modern birds found in more than a century. “This specimen is paramount for understanding the origin of modern birds,” says Luis Chiappe of the Natural History Museum of Los Angeles County. For starters, he notes, “it's saying that our picture of the early evolution of birds is certainly more complicated than we thought.”

    The most primitive bird known, Archaeopteryx, flapped over Jurassic lagoons some 150 million years ago. By the early Cretaceous a more advanced group of birds had appeared. Called the Enantiornithes, or “opposite” birds, for the way their foot bones grew, they flourished for 70 million years before going extinct. Many have been discovered in the last 2 decades. Unfortunately, the fossil record is much more limited for their successors, the Ornithurae—the group that includes living birds—which are thought to have emerged roughly 65 million years ago. Paleontologists had relatively complete skeletons for only two, Hesperornis and Ichthyornis, both discovered in the 1870s.

    Now Julia Clarke of Yale University and Mark Norell of the American Museum of Natural History (AMNH) in New York City unveil Asparavis, a new fossil bird from the Ukhaa Tolgod region of Mongolia. Not only is the specimen a long-coveted ornithurine, but it is also breathtakingly well preserved. The skeleton is three-dimensional, rather than smashed flat—highly unusual for fragile birds—and so the anatomy stands out in sharp relief.

    Asparavis is already turning up some surprises. For example, it appears to have a mosaic of primitive and advanced traits. Clarke and Norell have found 27 features that make Asparavis an ornithurine and link it with modern birds, such as its 10 fused sacral vertebrae. But they also found 12 traits that were thought to be unique to Enantiornithes. If those traits aren't diagnostic of that group, the dozen or so fragmentary fossils classed as Enantiornithes by those features may not actually belong to the group—and that could upset the standard idea that Cretaceous enantiornithines were much more diverse than ornithurines. “It's not as simple a picture as we thought,” Clarke says.

    No matter how these features shake out, paleontologists are thrilled to have such a complete bird to work with. “You don't see birds that old in that good condition,” notes Jim Kirkland of the Utah Geological Survey in Salt Lake City. “This fossil will be an incredible focal point for what we will know about bird relationships.” And that would be something to crow about.

  5. TRANSGENIC ANIMALS

    Infant Monkey Carries Jellyfish Gene

    1. Gretchen Vogel

    Efforts to make a fluorescent green monkey are not quite a glowing success—yet.

    In an attempt to create the first transgenic primate, scientists at the Oregon Regional Primate Research Center in Beaverton have produced a rhesus monkey that carries the gene coding for green fluorescent protein (GFP). This gene, first isolated from glowing jellyfish, has been inserted into a host of experimental species, including plants, frogs, and mice. Although he is not green, the 3-month-old monkey named ANDi, described on page 309 of this issue, is something of a proof of principle. The achievement could lead to valuable experimental models for certain diseases and a better understanding of primate and human development, say other biologists. But the cumbersome technique is not likely to lead to transgenic humans, green or otherwise.

    Close, but no glow.

    ANDi, the first transgenic rhesus monkey, carries the gene for green fluorescent protein but does not glow green.

    CREDIT: CHAN ET AL.

    To produce ANDi, reproductive biologists Anthony Chan, Gerald Schatten, and colleagues injected a genetically modified virus into the unfertilized eggs of rhesus monkeys. A few hours later, they injected sperm into the oocytes to fertilize them. As with other in vitro fertilization (IVF) procedures in nonhuman primates, this one was relatively inefficient. Half of the fertilized eggs developed into embryos, and five pregnancies resulted from 20 embryo transfers, including one set of twins, which were miscarried.

    Three healthy monkeys were born, but the team has detected the GFP gene only in ANDi. The miscarried twins also carried the GFP gene, but unlike ANDi, their hair follicles and toenails did glow under fluorescent light. Schatten attributes the miscarriage to the fact that rhesus twins are rare, but the team is investigating whether it might be related to the inserted gene. So far, the team doesn't know whether ANDi's cells are expressing the protein. But Schatten says other transgenic animals have delayed producing their transgene for up to a year after birth.

    Although the gene transfer techniques the researchers used are routine in other organisms, reproductive biologist Ted Golos of the Wisconsin Regional Primate Research Center in Madison says the birth of ANDi is the first demonstration that a primate egg can develop normally after such manipulations.

    “We've made an incremental step from one species to another,” Schatten says. And even that small step involved multiple hurdles. Whereas the experiment “is essentially several days' work in transgenic mice,” Golos notes, monkey eggs are difficult to collect, and primatologists do not know how to artificially control a monkey's reproductive cycle. That meant the researchers had to time the experiment precisely so that an embryo was ready when a surrogate mother was at the right stage of her reproductive cycle. In fact, ethics considerations aside, the project might have been easier to achieve in humans, for whom IVF technology is much more advanced.

    Even so, the work will not inspire fertility doctors to try the technique with human embryos anytime soon, Schatten predicts. Scientists can't control where the modified virus enters the genome, so the risk of an inserted gene interrupting an important gene would be relatively high. “I don't see an immediate therapeutic application,” says bioethicist LeRoy Walters of the Kennedy Institute of Ethics at Georgetown University.

    And until researchers find more efficient ways to create specific genetic changes, says Schatten, transgenic monkeys will not be common research tools. Even if those techniques were feasible, expense and ethical considerations would limit the use of transgenic monkeys as medical models, he says: “We don't need a knockout monkey for every disease.”

    But for questions that are difficult to study in rodents, such as those related to aging, neurodegenerative diseases, immunology, and behavior, transgenic primates could prove a plus, Golos says. Schatten predicts that genetically altered monkeys could be a boon to developmental biologists as well. Because monkeys are large enough to fit into magnetic resonance imaging machines, researchers might be able to introduce gene markers and track organ development by noninvasive means. “ANDi and his future cousins and brothers and sisters will help us bridge that gap between what we know in the mouse and what we're keenly interested in in human development,” he says.

  6. CIRCADIAN RHYTHMS

    Mutant Gene Speeds Up the Human Clock

    1. Marina Chicurel*
    1. Marina Chicurel is a science journalist in Santa Cruz, California.

    “Early to bed and early to rise, makes a man healthy, wealthy, and wise,” advised Benjamin Franklin in his Poor Richard's Almanack for the Year 1757. Today, as then, people assume that self-discipline is the key to following such counsel. But in a paper published online today by Science (www.scienceexpress.org), a team led by Ying-Hui Fu and Louis Ptácek at the University of Utah in Salt Lake City shows that a person's genes may be more important. The researchers have identified a mutation that causes people to be extreme early birds, rising, say, at 4:00 a.m. The discovery opens a window into the genetic basis of the human circadian clock, which keeps body activities such as sleeping and eating running on a roughly 24-hour rhythm.

    Researchers have identified genes that drive the circadian clocks in fruit flies, mice, and other species. They have also found what seem to be the human equivalents of some of those genes, but they've had no direct proof that those genes are in fact part of the human clock machinery. The Utah team has now provided that proof for one of the human genes, known as hPer2, by showing that a mutation in the gene speeds up the circadian clock. “It's the first example of a circadian clock gene in a human,” says Joseph Takahashi, a geneticist at Northwestern University in Evanston, Illinois.

    It's also one of the first times that researchers have linked a single gene to a complex human behavior. Ultimately, the work could lead to treatments for patients affected by the mutation, which causes a disease called familial advanced sleep-phase syndrome (FASPS), and perhaps even for people with more common sleep disturbances.

    FASPS is an inherited disorder discovered just last year by Utah's Christopher Jones and colleagues. The internal clocks of these patients appear to run fast, shifting their sleep schedules ahead by about 4 hours. Fu and Ptávcek's team set out to find the genetic cause of this circadian shift by combing through the DNA of members of a large family afflicted by the disorder, searching for genetic variations associated with the disease.

    They ultimately homed in on the end of chromosome 2 as the likely site of the defective gene—an intriguing finding, as that's where the human equivalent of one of the animal circadian clock genes is located. The researchers soon discovered that most of the family members afflicted with FASPS, but none of those unaffected, carry a single base-pair mutation in one copy of this gene, known as hPer2. In addition to fingering hPer2 as the culprit in FASPS, the finding also provided a clue as to how the mutation might be exerting its effects.

    The mutation maps to a region of the hPer2 protein, known as PER2, that looks like it might be a target for phosphate addition by an enzyme called casein kinase Iη. Last year, Takahashi's group discovered that hamsters suffering from a FASPS-like disorder carry a mutation in the gene encoding just that enzyme (Science, 21 April 2000, p. 483). The kinase seems to help maintain the proper 24-hour cycling of the mammalian circadian clock by phosphorylating PER proteins.

    Clock researchers have found that PER and other clock proteins accumulate during the 24-hour circadian cycle until they reach a concentration that acts to shut down genes, including the per genes themselves. The proteins' concentrations then decline until this inhibition is relieved and they start accumulating again in the next day's cycle. The correct timing of the gene down-regulation seems to depend, in part, on phosphate addition to the PER proteins by a kinase enzyme, possibly casein kinase Iη. Takahashi's team found that the mutant kinase does not phosphorylate PER proteins as well as the normal enzyme does. Combined with evidence from PER studies in fruit flies, this led the researchers to propose that, as a result, PER might build up faster than it should, shortening the circadian cycle.

    The new work by the Fu and Ptácek team now provides evidence for a similar scenario in humans. They've shown that mutated fragments of PER2 are not phosphorylated as readily by casein kinase Iη as are fragments from the normal protein. So even though the human mutation differs from the hamster mutation, its similar effects on PER phosphorylation are likely to result in similar consequences: early PER2 buildup and an accelerated cycle. “This paper fits in so beautifully with [the hamster] story,” says Takahashi.

    But the story is far from over. Still uncertain, for example, is whether the hPer2 mutation has other effects that might contribute to the acceleration of the body's circadian clock. In addition, the mutation is probably just one among many that can affect human clocks. Indeed, Fu and Ptávcek have identified two dozen families who suffer from FASPS without carrying the hPer2 mutation.

    Ptácek now wants to search for small molecules that affect the phosphorylation state of PER2 as a first step toward developing drugs that either speed up or slow down the clock—helping not only FASPS patients but perhaps run-of-the-mill early birds or night owls, as well as jet-lagged travelers and night-shift workers. In the future, a pill may be all it takes to fulfill Franklin's sage advice.

  7. FISHERIES SCIENCE

    Ear Bones Reveal Homing Tendencies

    1. David Malakoff

    For centuries, anglers along the marshy Delaware Bay have eagerly awaited the annual return of the weakfish, a blue-gray finned delicacy that crowds into the estuary each spring to spawn. Recently, scientists have joined the expectant throng, hoping to test a hunch: that many of the frisky adults making whoopee beneath the waves were themselves born in the bay's cloudy waters just a few years earlier.

    Now, on page 297, researchers offer intriguing evidence that, contrary to common belief, weakfish do indeed have a strong homing instinct. The finding, based on a study of chemical isotopes bound up in the fishes' tiny ear bones, suggests that many marine fish populations may be more complex than once envisioned. The research could also prompt fisheries managers to rethink how they regulate catches and help conservationists design more effective marine reserves.

    Lend me your ears.

    Weakfish otoliths, or ear bones, provide geochemical clues to the fish's birthplace.

    Biologists have long known from tagging and genetic studies that salmon and some other anadromous fish have a remarkable ability to navigate back to their birth rivers after years at sea. But documenting similar “natal homing” in fish that spend their entire lives in salt water has proved difficult. One problem is that these fish generally don't display telltale genetic differences; they also produce young that are too small, too numerous, or too dispersed for easy tagging or recapture.

    To get around these difficulties, Simon Thorrold, currently of the Woods Hole Oceanographic Institution in Massachusetts, and his team looked to chemical clues contained in otoliths, tiny concretions that form in the ears of many fish. As the otolith grows, each new layer of calcium carbonate captures the chemical signature of the surrounding water. As a result, the bony pebble “acts like a flight recorder, encoding time-specific information about the waters through which the fish passes, from birth to death,” says Robert Warner, a fish biologist at the University of California, Santa Barbara.

    To begin their study, in 1996 Thorrold's team analyzed otoliths from hundreds of juvenile weakfish caught in Delaware Bay and four other major estuaries along the East Coast of the United States. Each estuary, they discovered, has a unique geochemical signature created by different ratios of chemical isotopes, including carbon-13, oxygen-18, and various forms of magnesium, barium, and strontium. The team returned to the same areas in 1998 and captured 2-year-old weakfish fresh from their wintering grounds off Cape Hatteras, North Carolina. The researchers then analyzed the central cores of the adult fishes' otoliths, formed when the half-meter-long spawners were mere minnows, to see where they originated.

    The results were “surprising,” given that most biologists view weakfish as a single coastwide stock, says Thorrold. Most of the 2-year-old fish could be easily matched to their home waters, and subsequent statistical work suggested that up to 81% of the spawners had found their way back home. And even the 19% to 40% of fish that strayed to new spawning grounds didn't miss by much, typically ending up in adjacent estuaries.

    That mixing probably explains why weakfish up and down the coast are genetically similar, Thorrold says. But it may be a mistake, he adds, for state and federal fisheries managers to ignore the geographically distinct spawning populations even if they are not genetically different. “You can't assume that vagrants from one estuary can quickly replenish another estuary's stock that has been overfished,” he says. Similarly, designers of protected reserves—often touted as nurseries that will supply fish to areas where fishing is allowed—may have to reshape plans. “Putting a reserve in one estuary may not do a lot of good” for another area's stocks, Thorrold says.

    Although the study's policy impacts may not be felt for years, researchers say it is another sign of the otolith's growing value to scientists. European researchers, for instance, have recently launched a multimillion-dollar effort to use otolith signatures to track cod and other economically important fish. Steven Campana, a biologist at the Bedford Institute of Oceanography in Dartmouth, Nova Scotia, says otoliths “give you some very precise information not available from other kinds of studies.”

  8. AIDS RESEARCH

    HIV Inhibitor Blocks Virus From Cell

    1. Laura Helmuth

    HIV, the virus that seemed invincible in the early days of the AIDS epidemic, has yielded ground to drugs that block its replication. But some strains of the wily virus have developed resistance to current drugs, and not all patients respond well to today's cocktail treatment. Searching for alternatives, researchers in the past several years have focused on another of the virus's vulnerable spots: the mechanism that snaps the virus into place against a host cell, allowing it to enter. Now, a team of researchers reports a new way to gum up that mechanism and prevent HIV's envelope from melding with a host cell membrane. They've designed a molecule that, in cell culture at least, prevents HIV from infecting cells.

    “One wants to continue to identify new targets to attack HIV and add to the combination regime,” says structural biologist Peter Kim of the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology in Cambridge, whose team designed the molecule.

    In the early 1990s Kim, recently tapped to head research and development at Merck Research Laboratories worldwide, and other research teams figured out how influenza infiltrates host cells. Many other viruses, including HIV, use a similar trick. The attack begins when HIV encounters a CD4 receptor on a T cell. This triggers a protein called gp41 that's anchored to the surface of the virus. The gp41 protein shoots out a harpoonlike projection that pierces the T cell's membrane. Then the two ends of the stretched-out gp41 protein snap together, pulling the virus's envelope and the cell membrane together. They fuse and allow the virus to penetrate the T cell.

    Interference.

    A new compound, 5-Helix, stops HIV from fusing its membrane with a host cell's.

    ILLUSTRATION: CAMERON SLAYDEN

    Once this harpoonlike mechanism was understood, researchers began looking for wrenches to throw in the works. They've found two, and this week, in a paper published online today by Science (www.scienceexpress.org), Kim's group reports designing a third.

    Before gp41 snaps the two membranes together, it's elongated in an intermediate formation. The two arms of the protein, called the C-terminal (anchored to the virus) and the N-terminal (hooked into the T cell) regions, are exposed. Drugs that bind to either end prevent the extended protein's two arms from clicking together into the final structure. Compounds that grab hold of the N-terminal region are currently in clinical trials, where they've been shown to reduce the viral load in people infected with HIV. Now Kim's team has designed a compound that binds to the C-terminal region.

    The new molecule, dubbed 5-Helix, is the product of a “very clever, rational drug design,” says HIV researcher John Moore of Cornell's Weill Medical College in New York City. The compound closely mimics the final structure that gp41 assumes when it fuses the viral and cellular membranes. That conformation contains six interconnected coils that fold together to look like a cluster of three hairpins. 5-Helix has five of the six coils, and it desperately wants another coil to fill in the gap. It does so by binding to the C-terminal end of the stretched-out gp41 much more effectively than the N-terminal end of the protein, thus preventing gp41 from folding together.

    “The issue now,” says Moore, “is not, ‘Does [such a compound] work in vitro·,' but ‘Can you translate it to in vivo·'” If 5-Helix or a related compound does work in humans, it probably won't dominate the market, he says. The protein would be digested if taken orally and so would have to be injected, limiting its appeal. But such a compound could help people who don't respond to other drugs.

    Although he admits it's a long shot, Kim thinks 5-Helix might also serve as the basis for a new AIDS vaccine—ultimately, the only hope for curtailing the worldwide epidemic. The linear sequence of amino acids that make up gp41 varies a lot among different HIV strains, so antibodies against the unfolded protein wouldn't protect very efficiently. But the surfaces of the coiled protein that are exposed just before gp41 snaps into place are highly conserved—that part of the protein looks similar in all HIV clades. And that, says Kim, suggests that antibodies to 5-Helix, which displays some of the same coiled fragments of protein as gp41, might also attack the virus.

    Robert Lamb, a virologist at Northwestern University in Evanston, Illinois, says that using 5-Helix as the basis for an AIDS vaccine is an “exciting possibility” and worth trying. Conceptually, he says, the same sort of strategy would also apply to other viruses, including Ebola, that use a similar harpoon-protein mechanism to fuse their membranes with a host's.

  9. PALEONTOLOGY

    Mammoth Hunters Put Hopes on Ice

    1. Richard Stone

    CAMBRIDGE, U.K.—In an anticlimactic ending to last year's TV special, a block of permanently frozen ground hewn from the Siberian tundra appears to contain only scattered remains of a woolly mammoth. But researchers say that the team's brute-force method of hauling remains to a lab for study while they are still frozen holds promise for more-intact specimens unearthed on future expeditions.

    Sponsored by the Discovery Channel, a team led by Bernard Buigues, a Paris-based North Pole tour operator, chiseled the 23-ton block from the Taimyr Peninsula in October 1999 and airlifted it by helicopter more than 300 kilometers to the northern Siberian town of Khatanga. The previous year, Buigues had excavated the skull of the 20,380-year-old male mammoth, nicknamed “Jarkov” after the family of indigenous Dolgans who had found its tusks sticking out of the snow. Ground-penetrating radar readings hinted that substantial portions of the carcass remained underground. But after inspecting the block, a Russian project scientist argued that it was unlikely to harbor mammoth remains (Science, 29 October 1999, p. 876).

    After moving the block into a tunnel in Khatanga used to store reindeer meat and fish, Buigues and company began thawing it with hair dryers last October. Near the top of the block they found three thoracic vertebrae, two of which lay in anatomical position, and a pair of ribs lying haphazardly, like crossbones. But the bones were devoid of flesh. Indeed, the only flesh uncovered during the season's final thawing session, witnessed by Science, was a 10-centimeter-long strip of tissue that looked like beef jerky. “I was expecting a lot and got a little,” Buigues said at the time.

    The denouement comes as no surprise to many. But the revelation that the block does not contain a whole mammoth has drawn ridicule from some quarters. An editorial in the 6 January edition of The Times of London even suggested that the whole episode was a hoax. “Prehistoric hoaxes offer very good sport, as our dalliances with Piltdown man have long proven,” The Times said.

    However, Discovery Channel officials and project scientists reject that characterization. “Nobody ever said Jarkov was going to be Sue,” says Ross MacPhee, curator of mammals at the American Museum of Natural History in New York City, referring to the nearly complete Tyrannosaurus rex skeleton.

    Buigues's team takes some consolation from having succeeded in airlifting the remains, still frozen in place, to an environment where they could be thawed under controlled conditions. “Whether or not this mammoth is the epitome of frozen mammoths is immaterial,” says Larry Agenbroad, a geologist at Northern Arizona University in Flagstaff. “We can now go out and get more.”

  10. PALEOANTHROPOLOGY

    Oldest Human DNA Reveals Aussie Oddity

    1. Constance Holden

    Australian scientists say they have successfully extracted an extinct genetic sequence from an anatomically modern man who died on the shores of an Australian lake about 60,000 years ago. The sequence is so primitive that it raises questions about the leading model of human origins, the “Out of Africa” theory, which holds that our ancestors first arose in Africa, then spread throughout the world perhaps 100,000 years ago.

    DNA studies from living populations have repeatedly pointed to such a recent African origin. But the new data, published in the 16 January 2001 Proceedings of the National Academy of Sciences, present a “serious challenge” to a “simplistic” Out of Africa scenario, says co-author Alan Thorne, an anthropologist at Australian National University in Canberra. Thorne argues that the results better fit a model known as multiregionalism, favored by a determined minority of anthropologists, in which people coming from Africa interbred with earlier humans already living in various parts of the Old World.

    The researchers say they extracted mitochondrial DNA (mtDNA) from the remains of 10 ancient humans—a striking feat, as other scientists had extracted ancient human DNA from only a handful of subjects (including the 5300-year-old Alpine “Ice Man” and three 30,000-plus-year-old Neandertals). The 10 fossils—four from Lake Mungo in New South Wales, Australia, and six from Kow Swamp in nearby Victoria—range from 2000 to 15,000 years old, except for a Lake Mungo man known as LM3, who has been dated by three separate methods at more than 60,000 years old (Science, 21 May 1999, p. 1243). LM3 is “the oldest individual dated accurately and possibly the oldest human from which DNA has been recovered,” Thorne says.

    The key finding, Thorne says, is a sequence in LM3's mtDNA that differs both from that of the other fossils and from that of modern people. Now extinct in modern human mtDNA, it exists only as a remnant, or “insert,” on chromosome 11 in the modern nuclear genome. Scientists have long suspected this sequence to be a copy of old mtDNA that found its way into the cell nucleus, as other sequences are known to have done.

    Thorne says the data undermine studies that support the Out of Africa scenario with genetic evidence from living populations. By analyzing variations in modern DNA sequences and tracing their “roots” backward in time, scientists have concluded that everybody now alive stems from African ancestors who replaced earlier types of humans without interbreeding with them. Now, the most divergent, deep-rooted mtDNA sequence of any anatomically modern human has turned up thousands of miles from Africa. “We don't say that humans evolved in Australia,” Thorne says—but the logic behind earlier genetic studies could lead to just such an absurd conclusion, he says. Instead, Thorne thinks the new data support the multiregional hypothesis, which holds that Homo sapiens may have inherited DNA from precursors such as Homo erectus, who spread into Eurasia more than 2 million years before the presumed Out of Africa migrants did. Thorne and Milford Wolpoff of the University of Michigan, Ann Arbor (see p. 231), are central proponents of multiregionalism.

    “For many years people have been saying Out of Africa is correct because the genetic evidence is consistent,” says John Relethford of State University of New York College at Oneonta. But the Australian study “suggests that if we saw more ancient sequences we might get a very different picture than we get from looking only at the DNA of living populations.” Other now-extinct sequences, for example, might well include traces of DNA indicating that Homo sapiens interbred with Neandertals—evidence that has disappeared from modern genetic material.

    Most scientists, however, will need far more evidence to be talked out of the replacement scenario. Evolutionary biologist S. Blair Hedges of Pennsylvania State University, University Park, says the key piece of evidence, the LM3 sequence, must be replicated in independent laboratories in order to be convincing. Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Munich, who obtained the first Neandertal DNA in 1997, agrees. “We know from many failures in our laboratory that contamination can rear its head in many forms,” he says, and the Australian researchers did not meet his criteria—which include cloning, sequencing, and replication in independent labs—for ascertaining that the DNA sample is authentic. Although Pääbo says that at this point he can't evaluate the study's conclusions, he notes that extinct sequences such as LM3's might simply indicate that humans used to have more genetic variation than they do today. Still, “these scenarios do not change the observation that mtDNA found in humans alive today go back to a recent common ancestor in Africa.”

    But Thorne says that DNA from living populations alone will never reveal the true story of human origins. Finding this surprise in an ancient Australian “makes clear that it is the lineages that have been lost in the past that may hold the key,” he says.

  11. PALEOANTHROPOLOGY

    Skull Study Targets Africa-Only Origins

    1. Elizabeth Pennisi

    While Australian researchers invoke ancient DNA to discredit the notion that “Out of Africa” migrants completely replaced earlier humans, Milford Wolpoff is assaulting it with bones. Wolpoff, an anthropologist at the University of Michigan, Ann Arbor, has long championed multiregionalism—the dissident view that several populations of early humans evolved modern traits, merging into one Homo sapiens species through interbreeding. On page 293 of this issue, he and collaborators put the two rival scenarios to the test. Applying a statistical technique little used by anthropologists, they analyzed 25 ancient skulls from throughout the Old World and determined that three relatively recent ones had both local and African ancestry. “The implication of this finding is that replacement cannot be correct,” Wolpoff says. Most other paleoanthropologists, however, remain unconvinced.

    Borrowing an analytical technique called pairwise comparison from their colleagues who study DNA data, Wolpoff's team drew up a list of skeletal features and scored the presence or absence of each one in several sets of fossils. The fewer the differences, they assumed, the more likely a pair of skulls is to be closely related. The work is “a welcome attempt to quantify previous claims” of multiregionalists, says Chris Stringer of the Natural History Museum in London, although he disagrees with the study's conclusions. Adds Janet Monge, a physical anthropologist at the University of Pennsylvania in Philadelphia who says she's still undecided about multiregionalism, “It's as objective as any test that I have seen put forth on human evolution.”

    The researchers started with a 14,000-year-old skull from southeastern Australia and a pair of partial adult male skulls from Moravia in the Czech Republic—two distant places that the Out of Africa migrants would have had to reach in populating the globe. They compared the Australian skull with archaic human fossils from Ngandong, Java—likely ancestors if modern humans evolved locally—and with six fossils from Africa, close relatives if the Out of Africa hypothesis is correct. In analyzing the Moravian skulls, they used four Neandertal skulls from throughout Europe—the putative local ancestors—and five skulls of early modern humans from Qafzeh and Skhul caves in Israel, who would have been part of the replacing population from Africa.

    Wolpoff and colleagues examined the skulls for features such as the flatness of the forehead or the size of a bony projection behind the ear. “We know these traits are diagnostic for distinguishing the ethnicity of modern skulls,” Wolpoff says. Then, through pairwise comparisons, they ranked the skulls in order of decreasing similarity. The Australian skull wound up much closer to the Java fossils than to the African or Israeli fossils—possible evidence of Asian roots. The results for the Moravian fossils were less dramatic but indicated that dual European and African ancestry was possible, Wolpoff says.

    The work puts “another nail in the coffin of replacement,” says Geoffrey Clark, a paleoanthropologist at Arizona State University in Tempe, a longtime advocate of multiregionalism. Paleoanthropologists in the Out of Africa mainstream, however, leaped to voice their skepticism. “I and a number of other workers have previously analyzed these crania and have come to very different conclusions about their affinities,” says Stringer. Stringer says he reached pro-replacement conclusions after studying facial features of skulls—features he wishes Wolpoff and colleagues had been able to include in their work. Philip Rightmire of the State University of New York, Binghamton, criticizes the group's choice of specimens; he thinks that another Australian skull, which looks much different from the one Wolpoff picked, would have yielded different results. All in all, Ian Tattersall of the American Museum of Natural History in New York City says of the study, “I don't think it's going to change anybody's position.”

    But Monge says she welcomes Wolpoff's “provocative and evocative” work. Pairwise comparison will give her and her students a new way of looking at casts and fossils, she adds. “Often you don't see very much coming out from the [multiregional] side,” she points out, “so it's good to get these data out there.”

  12. THE FOSSILS

    Exquisite Chinese Fossils Add New Pages to Book of Life

    1. Erik Stokstad
    1. With reporting by Dennis Normile and Xiong Lei.

    Paleontologists are flocking to China, which has beefed up its support of the field to take advantage of troves of superbly preserved specimens

    SIHETUN VILLAGE, CHINAZhou Zhonghe came back to China for the fossils. Gazing out at what had once been a region of shallow lakes rich in fish, birds, and dinosaurs, the 36-year-old Zhou knows there is no better place for an avian paleontologist to work than these rolling hills of farmland in northeastern China.

    Six years ago, as a graduate student at the University of Kansas, Zhou was part of a team that first described a primitive, magpie-sized bird from China called Confuciusornis. Since returning to his homeland in 1999, Zhou has also worked on feathered dinosaurs from the same fossil beds here in western Liaoning Province. These discoveries may help end one of the most high-powered debates in paleontology—whether birds evolved from dinosaurs. Along with a profusion of other high-quality specimens in the region, they are also yielding a detailed picture of life 125 million years ago, during the Early Cretaceous. Says James Clark of George Washington University in Washington, D.C.: “It's one of the most exciting areas in the world right now for vertebrate fossils.”

    Liaoning is not the only paleontological hot spot in China. The Chengjiang formation in southwestern Yunnan Province boasts remarkably well-preserved fossils that are helping paleontologists document the Cambrian explosion of life some 530 million years ago. Chengjiang has already yielded creatures that are pushing back in time the appearance of key features of vertebrates, and it recently produced the world's oldest fish. Prizes like this have attracted massive interest.

    Smaller sites all across China are also drawing paleontologists who hope to fill in missing chapters of the history of life. When Johnny Waters of the State University of West Georgia first saw the fossilized echinoderms that a Chinese colleague had brought to a meeting in the United Kingdom in 1991, his eyes nearly bugged out. He and colleagues Chris Maples and Gary Lane of Indiana University, Bloomington, immediately arranged to visit the remote site in the desert of northwestern China that is yielding beautifully preserved specimens from the late Devonian, a time 355 million years ago when echinoderms were thought to have suffered a massive extinction. Digging in the barren, windswept outcrop that makes up the Hongguleleng formation in Xinjiang, they discovered more species than had ever been collected from that time period. “It gives us a whole different look at the recovery from the Devonian mass extinction,” says Doug Erwin of the Smithsonian Institution in Washington, D.C.

    Beautiful bones.

    Many fossils from Liaoning, like the dinosaur Caudipteryx, are well preserved.

    CREDIT: Z. ZHOU

    These and other findings have made China a Mecca for paleontologists. The country's complex geology gives it a uniquely diverse collection of fossils. Rising government support for the field is making it possible for Zhou and his colleagues to pursue these exciting opportunities, and an increasing number of collaborations is bringing in foreign scientists and resources. “This tremendous range of ages and environments is very exciting,” says Philip Currie of the Royal Tyrrell Museum in Drumheller, Canada. “In areas where [North American paleontology] is weak, we can look for answers in China.”

    The influx of money and talent comes just as China has begun to embrace Western-style research practices, including a system of competitively awarded grants built upon bottom-up proposals. And the effect is already clear. “There are a number of fronts on which superbly preserved fossils are making a difference in the way we think about the history of life,” says Andrew Knoll, a paleontologist at Harvard University.

    Earliest vertebrates

    Competition is fever-pitched in Yunnan Province, where many teams are looking for the earliest vertebrates. Paleontologists have long believed that this group first appeared during the Cambrian explosion, when most of the body plans of modern animals were laid down. But the record is sparse, because Cambrian creatures were mostly soft-bodied and their parts don't preserve well. Indeed, until the mid-1990s, the record of fossil vertebrates went back only about 475 million years, when small, jawless fish with bony plates lived in the Ordovician. In the past few years, however, Yunnan's Chengjiang formation has extended that record by a startling 60 million years.

    The formation, some 50 meters thick, contains extremely rich deposits of fossils and outcrops in sparsely vegetated hills that stretch for about 100 kilometers east to west. “You can find 20 specimens per day” in some places, says Jin Yugan of the Nanjing Institute of Geology and Paleontology (NIGP), which has a team working on the beds. The rocks predate the Burgess Shale—a rich collection of Cambrian life preserved in Canada—perhaps by as much as 10 million years, putting them closer to the origin of vertebrates. “The closer you can get to that [point],” says Yu Xiaobo of Kean University in Union, New Jersey, “the more significant your material.” The formation has been known for several decades, but it first drew major attention in 1995, when Chen Junyuan of NIGP argued that a 4-centimeter-long creature, Yunnanozoon, was a chordate, the group that includes vertebrates.

    Discoveries like this spurred other Chinese paleontologists to begin digging for fossils and to reexamine specimens that might have been overlooked. The pace quickened as Western paleontologists joined in. More chordates were reported in a November 1999 Nature paper by Shu Degan of Northwest University in Xi'an and Simon Conway Morris of Cambridge University in the United Kingdom. At 530 million years, the 3-centimeter-long Haikouichthys appears to be the world's oldest fish, while another new specimen, Myllokunmingia, has simpler gills and is more primitive. To Conway Morris and others, the presence of these jawless fish in the Early Cambrian suggests that the origin of chordates lies even farther back in time.

    Hoping to learn more, the Chinese government last year awarded $2.4 million over 5 years to eight teams of scientists from NIGP, the Institute of Vertebrate Paleontology and Paleoanthropology (IVPP) in Beijing, and several universities to further investigations at Chengjiang and Liaoning. “It's very strong support,” says Sun Weiguo of NIGP. But the riches have also created tensions. At least five rival teams are already working in Chengjiang, and “there is no cooperation between the different groups,” says Hou Xianguang of Yunnan University, who in 1984 discovered the first soft-bodied fossils at Chengjiang.

    Flight and fight

    All the same factors—ample money, competition, incredible enthusiasm, and important questions—are also visible some 3000 kilometers to the northeast in western Liaoning Province. The extensive rock layers of lake mud and volcanic ash bear evidence of feathered dinosaurs, primitive birds, and other rare animals entombed by occasional volcanic eruptions. Their rapid burial kept the skeletons intact—sometimes even including undigested lizards and mammals in the stomachs and unlaid eggs in the abdomen—and the fine sediment preserved impressions of skin and feathers. The region became world famous after primitive fossil birds were discovered in the mid-1990s at two sites near the town of Beipiao.

    This was a breakthrough for avian paleontologists. Since the discovery of the oldest known bird, Archaeopteryx, in 1861, few bird fossils had been uncovered. There was practically no way to learn how birds had evolved important aspects of their peculiar anatomy, such as their keeled sternum to which their powerful flight muscles attach. In the last decade, a few finds have emerged from Mongolia, Spain, Argentina, and Madagascar. But these are dwarfed by the sheer number of fossil birds from China, making Liaoning the hottest spot in the world for fossil birds.

    Pulled out of hillside quarries and eroding stream banks in dry farmland, the Chinese fossils point to a surprising diversity of birds in the early Cretaceous, the most recent of which, Protopteryx, was published last month (Science, 8 December 2000, p. 1955). The discoveries include several dozen taxa, some with an intriguing mix of primitive and advanced features. The birds shed light on the evolution of avian anatomy, such as the shoulder girdle, wing, and keeled sternum. “Now we have samples of an incredible mosaic of birds that give insight into how these morphological systems evolved,” says avian biologist Rick Prum of the University of Kansas Natural History Museum in Lawrence.

    The best known of these primitive birds, the magpie-sized Confuciusornis, was first described in 1995 by Hou Lianhai of IVPP, along with Zhou, Larry Martin of the University of Kansas, Lawrence, and Alan Feduccia, an ornithologist at the University of North Carolina, Chapel Hill. Unlike its scarce relative, Archaeopteryx, so many specimens of Confuciusornis have turned up that a paleontology museum outside Beipiao has cemented a dozen onto a wall for decoration. “For the first time we have an enormous sample of ancient birds,” says Luis Chiappe of the Natural History Museum of Los Angeles County.

    Chiappe says the surfeit will allow new lines of research, such as morphometric analysis to check for sexual dimorphism in the plumage and cross sections of bone tissue that might reveal how early birds like Confuciusornis grew. Cross sections are never allowed on rare specimens. Prum agrees: “The prospect of learning a lot about its biology is tremendous.” Indeed, Zhou, who in 1999 returned to IVPP, is so eager to explore the incredible paleontological wealth buried in western Liaoning Province that, last fall alone, he made the 400- kilometer trip four times.

    The extraordinary preservation of the Liaoning fossils—far superior to those almost anywhere in the world—has also made them key players in one of paleontology's most high-voltage debates. Most paleontologists believe that birds evolved from dinosaurs, because the two groups share many important skeletal features such as a wishbone and long arms. But feathers had always been considered the ultimate avian attribute. That's why signs of feathers on recently discovered Chinese dinosaur fossils have made such a stir.

    The first hint that dinosaurs might have been feathered came at the annual meeting of the Society of Vertebrate Paleontology, in October 1996. In the hallways, Chen Peiji of NIGP showed photos of a small dinosaur, named Sinosauropteryx, that appeared to contain impressions of fine bristles up to 4 centimeters long fringing its neck and spine. It wasn't clear whether the filaments were really feathers, however. Some paleontologists viewed them as transitional “protofeathers,” while others dismissed the filaments as frayed bits of decaying tissue.

    Unique window.

    Fossil beds in Liaoning give an unequaled view into Cretaceous life, like the bird Confuciusornis.

    CREDIT: D. NORMILE

    In June 1998, unambiguous feathers came to light. Ji Qiang, then director of the National Geological Museum, and his colleagues Currie, Mark Norell of the American Museum of Natural History in New York City, and Ji Shuan of the Geological Museum described two new species of theropod dinosaurs with downlike feathers on the body and tail. More spectacularly, the end of Protoarchaeopteryx's tail sported a fan of feathers that are vaned, suggesting the presence of barbules. The second specimen, named Caudipteryx, had feathers attached to the second finger of its hands.

    Skeptics of the bird-dinosaur link don't dispute the feathers, but they think Caudipteryx and Protoarchaeopteryx are flightless birds, not dinosaurs. The skeptics also pointed out that no feathers had been found in dromaeosaurs, the group of dinosaurs perhaps most similar to birds. Then in 1999, Wu Xiaochun, Xu Xing, and Wang Xiaolin of IVPP reported downy feathers on a 1-meter-long dromaeosaur named Sinornithosaurus. Last year, another dromaeosaur, named Microraptor, turned up with even more birdlike traits. “In terms of scientific significance for dinosaur evolution and the origin of birds, these fossils are as important as Archaeopteryx,” says Chiappe. “It's the major breakthrough in this field.”

    Key mammals

    Mammal paleontologists have made equally important discoveries in the Liaoning fossil beds, although the finds have tended to raise more questions than answers. The origin of mammals has always been a puzzle with most of the pieces missing, because these small animals fossilize poorly, if at all. All around the world, most Mesozoic animals are known solely from isolated fossils of teeth. As with dinosaurs and primitive birds, the extraordinary preservation at Liaoning has helped fill in the picture.

    In 1999, the field got its first relatively complete specimen of a triconodont, an extinct group of mammals previously known only from teeth, jaws, and a few skull fragments. The 125-million-year-old creature, dubbed Jeholodens, was described by Ji Qiang, Luo Zhexi of the Carnegie Museum of Natural History in Pittsburgh, and Ji Shuan. It's believed to be close kin to the common ancestor of all living mammals—both the more primitive, egg-laying monotremes like the platypus, and the therians, the group that includes marsupials and placental mammals. “One of the holy grails of paleontology is to find the ancestor of living mammals,” says Tim Rowe of the University of Texas, Austin. “Jeholodens is the closest thing.”

    The “stunning” completeness of the specimen reveals an odd trait: Jeholodens held its forelimbs under its body, while its pelvis retained the sprawling posture of reptiles. The find could mean that the upright forelimbs evolved once, in this common ancestor, and were later lost in monotremes, which have sprawling limbs in addition to their other reptilian traits. Or it could be that the modern forelimbs evolved in triconodonts only after that group split away from the lineage that led to living mammals. The modern forelimbs would then have to evolve a second time (along with modern hindlimbs) in the therian mammals.

    The action isn't just at mother lodes like Chengjiang or Liaoning, either. All across the country (see map, p. 234), Chinese and Western scientists are helping to solve paleontological problems. Take recent findings that shed light on the nature of the largest-ever mass extinction some 245 million years ago. “If you're interested in the Permian- Triassic extinction,” says the Smithsonian's Erwin, “you have to go to China.” That's because there are at least 50 good sections in south China alone—three times as many as in the rest of the world. Collaborative work between Erwin and a team led by Jin Yugan of NIGP has shown that the extinction was sudden, rather than drawn out. Isotopic changes measured by Erwin, Jin, and geochronologist Samuel Bowring of the Massachusetts Institute of Technology could mean that the extinctions took place in as few as 10,000 years (Science, 15 May 1998, p. 1007). A quick pace is consistent with a catastrophic cause of extinction, such as an asteroid impact, rather than a gradual change in sea level or climate.

    All this activity generates a self-reinforcing cycle, says Currie, a longtime China hand. The more that is published, he explains, the greater the buzz. The buzz leads to more collaborations, which result in more publications that attract more funding. “I don't see that this trend is going to stop,” he says.

    Indeed, the greatest threat to continued scientific productivity is an external one. At Liaoning and elsewhere, undiscovered fossils are threatened by looting and escalating prices on the black market (see p. 239). Although such activity could in theory exhaust this nonrenewable resource, both Western and Chinese paleontologists are optimistic that the new golden age will not lose its luster anytime soon. “There are many more important discoveries to be made,” says Sun Ge of NIGP. What's been found, he says, “is just the beginning.”

  13. PALEONTOLOGY IN CHINA

    A Peek at China's Paleontological Bounty

    1. Erik Stokstad

    China possesses an immense wealth of fossils. Its treasures range from some of the oldest known animals—such as the roughly 570-million-year-old Precambrian embryos of Guizhou Province—to 40-million-year-old early primates of the Eocene, and more recent finds as well.

    For decades Chinese geologists have mapped the fossil-bearing rocks in their country and determined their ages to foster exploitation of the country's vast energy and mineral resources. Now that work is also beginning to pay big dividends in fossils that are helping to answer a wide range of evolutionary questions. It has already shed light on the origin of vertebrates and the nature of mass extinctions such as the one that marked the end of the Permian period.

    The search spans the country, the third largest in the world, from the monsoon-drenched outcrops of southwestern Yunnan to the arid badlands of northwestern Xinjiang to the hills of northeastern Liaoning, with its famous feathered dinosaurs. This map illustrates some of the staggering array of well-preserved fossils that are attracting scientists from around the world.

  14. PLAYERS

    Research Kicks Into High Gear After a Long, Uphill Struggle

    1. Dennis Normile*
    1. With reporting by Erik Stokstad and Xiong Lei.

    Talented researchers are getting a chance to practice their profession, but will the reforms and added resources be enough to attract the next generation·

    BEIJINGChang Mee-Mann has come a long way since hauling baskets of rocks and dirt to build a dam in rural China. Chang, now 64, was just beginning her career here at the Institute of Vertebrate Paleontology and Paleoanthropology (IVPP) in 1966 when the Cultural Revolution brought scientific activities to a halt. The institute was shuttered, and Chang and her colleagues were sent to the countryside. “I thought I'd never do paleontology again,” she says.

    Digging in.

    Chang Mee-Mann waited decades for paleontology to be properly recognized.

    CREDIT: E. STOKSTAD

    But Chang bided her time. A decade later she resumed her career. Taking advantage of the increasing freedom to pursue basic research, she earned a Ph.D. in Sweden and began compiling what a colleague calls “the most comprehensive characterization of Devonian fish done by anyone.” For these efforts the Chinese Academy of Sciences (CAS) named her an academician, one of China's highest scientific honors. To Mark Norell of the American Museum of Natural History in New York City, Chang is “one of the greatest Chinese paleontologists ever.”

    Chang's career reflects the changing fortunes of the entire field. She and her colleagues have helped bring paleontology in China from near-extinction to international prominence. Buoyed by hard work and fortuitous geology, Chinese scientists have uncovered some of the most spectacular finds of the past decade. And they may be poised to make an even bigger impact. Funding is soaring, scientific institutes are being reorganized to sharpen their focus on research, and universities are stepping up their efforts to compete for top talent. As a result, the next generation of Western-trained paleontologists appears to be well equipped to tackle new challenges. “The work we are doing still cannot be compared with that done abroad both in depth and in breadth,” says Chang, but “the young people are moving in the right direction.” The field still faces some internal impediments to continued growth, however: bickering among competing institutions, looting of sites by local farmers (see p. 239), and a dearth of young people willing to enter the field.

    The current prominence of China's paleontology was a long time coming. Paleobotanist Zhou Zhiyan of the Nanjing Institute of Geology and Paleontology (NIGP), who received a Ph.D. in 1966, recalls the frustration of not being able to use the skills he had just acquired. “Before 1980, we all had to do things not related to paleontology,” he says. But Zhou's years of waiting paid off in 1989 with a spectacular find: the oldest gingko specimen ever found, dated at 170 million to 180 million years. “Before this discovery, many scientists doubted the gingko existed in Jurassic time, but now we have a very beautiful and very convincing specimen,” he says.

    Financial fuel

    Similarly remarkable specimens are turning up just about everywhere Chinese paleontologists have gone digging. The results have attracted foreign collaborators who, in the 1980s and early 1990s, brought badly needed financing and expertise (see p. 241). The next wave of finds attracted worldwide media interest and, finally, the attention of the Chinese government. Now the Chinese side often can afford to pick up some of the expenses for international collaborations. The government, says Xu Guanhua, a vice minister at the Ministry of Science and Technology, “must find ways to increase funding for a sphere where Chinese scientists have such great possibilities.”

    The jump in funding has already been impressive. Between 1996 and 2000, research grants awarded to NIGP went up eightfold, to almost $3 million. In addition, the institute's annual budget for salaries and maintenance has risen by two-thirds, to roughly $625,000. The institute is also in the midst of remodeling its 1920s era buildings to restore their original marble interior trim and terrazzo floors, add air conditioning, and extend phone lines to each office instead of the present arrangement of one hall phone per floor.

    Paleontology is also profiting from government programs designed to stem the country's brain drain (Science, 21 January 2000, p. 417). In 1999, when Zhou Zhonghe finished his Ph.D. in vertebrate paleontology at the University of Kansas, he had a publishing record that stood him in good stead for an academic career in the United States. To encourage him to return, IVPP was able to get him into the Hundred People program, which provided a plum salary and $242,000 over 3 years to get his research lab up and running. And Zhou is not alone—across the board, top paleontologists are enjoying a level of support that triggers envy among colleagues in other countries. “Even in North America, you're not getting this kind of money,” says Jin Meng of the American Museum of Natural History.

    Publishing prizes

    The bulk of the money is flowing through three institutes that dominate the field: IVPP and NIGP, both of which come under the CAS, and the National Geological Museum (NGM) in Beijing, which is part of the Ministry of Land Resources. As scientific activity recovered after the Cultural Revolution, much of the funding flowed from the top down, split up more or less by seniority. But competitively awarded grants now predominate, with emphasis on a good track record. Huang Weiwen, an IVPP paleoanthropologist, recalls a 5-year effort to get funding that succeeded only after he co-authored a Science paper with Richard Potts of the Smithsonian Institution in Washington, D.C. “After that, the door opened,” Huang says.

    Salaries, too, are now based at least in part on merit. Although base pay still depends on rank, explains NIGP director Sha Jingeng, publications, prizes won, and research grants awarded also play a role. For each paper that appears in Science or Nature, for example, NIGP pays a researcher about $600, and IVPP pays $400. That's a significant incentive, says IVPP director Zhu Min, who notes proudly that he paid out eight such bonuses in 1999.

    But CAS is raising the stakes as part of an academy-wide reform program (Science, 8 January 1999, p. 150). Officials want to consolidate institutes, reduce staff, get rid of the businesses many institutes run as sidelines, and relieve institutes of responsibility for such things as housing employees. The carrot is cash—as much as a doubling in salaries and better research support.

    Change agent.

    IVPP director Zhu Min has applied youthful vigor to reforming his institute.

    CREDIT: D. NORMILE

    NIGP was one of a handful of institutes selected in 1998 as models for the pilot stage of the program. “At that time, we had 250 people, but [under the restructuring] CAS gave us only 80 official positions, including administrative staff,” says Yang Qun, an NIGP deputy director. All researchers had to reapply for their positions, and those who scored highest on a rating based on performance made the cut. Those researchers not in official positions are permitted to continue their work but are not eligible for the higher salaries and grants offered through the Knowledge Innovation Program.

    Zhu hopes his institute will be chosen in the next round, but he's not taking any chances. The number of researcher slots had already been cut in half, to 50, using a process similar to NIGP's. He also intends to spin off a cast-making business and shed responsibility for employee housing.

    Zhu, 35, is an example of how CAS is aggressively moving younger people into top positions, thanks in part to the dearth of scientists in their 40s and 50s caused by the Cultural Revolution. Chang was Zhu's mentor, and he followed her into paleoichthyology, building on her work on Devonian fishes. He became director a year ago, just as a string of important papers on feathered dinosaurs began pouring out of the institute.

    Valuable research.

    NIGP director Sha Jingeng gives staff cash rewards for articles in leading journals.

    CREDIT: E. STOKSTAD

    The two CAS institutes are supposed to avoid stepping on each other's scientific toes, as they have different specialties. IVPP concentrates on lower vertebrates, including fishes, reptiles, dinosaurs, and birds; mammals; and paleoanthropology and archaeology. NIGP's five research divisions are focused on invertebrates and plants, along with a significant amount of work in geology, stratigraphy, and tectonics. But when it comes to important specimens, everyone is interested. NIGP has published a paper on a feathered dinosaur, for example, that irked IVPP researchers.

    Relations between the two CAS institutes and the NGM are even more tense. Ji Qiang, who has just stepped down as director of the museum to become principal scientist at the Institute of Stratigraphy and Paleontology within the Chinese Academy of Geological Sciences, has targeted many of the same hot areas of paleontology worked on by IVPP researchers and has proven adept at tracking down specimens dug up by farmers. Those attributes have generated tensions within the tightly knit community.

    The two CAS institutes and the national museum have dominated the field for years. But they are now facing some serious competition from universities, which are boosting their own paleontology research efforts. In a tactic new to China, universities are also raiding the institutes for talent. Northwest University in Xi'an and the Chinese University of Geology, which has campuses in Beijing and Wuhan, are already home to notable paleontology labs. Researchers at Nanjing University are planning an international effort that would unite paleontologists with geochemists and paleoecologists to try to understand major events like the explosion of life in the Cambrian era, half a billion years ago.

    One prominent paleontologist making the move into academia is Hou Xianguang, who discovered the first Chengjiang fossils in 1984. Last month he left NIGP after 22 years to join the new research center for Chengjiang biota at Yunnan University in Kunming. Hou says the university offered him “very favorable conditions for my research,” including more office and lab space, an apartment, and the promise of more funding. More importantly, he's betting that a move to Yunnan will mean better access to the sites and the specimens.

    Maintaining momentum

    As Chinese paleontology matures, policy-makers agree that it must find a way to sustain itself. One of the biggest challenges is filling the paleontological pipeline in an environment that offers far more lucrative career choices. “The lack of young students interested in paleontology is a big problem,” says NIGP's Yang. Hao Shougang, head of the paleontology section of the geology department at Beijing University, says that the number of undergraduate paleontology degrees awarded annually in his department has dropped from 15 or 16 in the late 1980s to two or three. “Fewer and fewer top students are willing to dedicate themselves to paleontology,” he says.

    Even those who sign on tend to drop out along the way. Wu Xinzhi, an academician at IVPP, says that only two of his 10 anthropology students who went abroad over the past 15 years have come back to China to work in the field. Several shifted into careers in computers or business, he notes.

    IVPP's Zhu thinks the organizational reforms and higher salaries will help lure back those who want to contribute. “Students can see that scientists can earn a decent salary. I'm optimistic,” he says. IVPP's Wang Yuan offers himself as an example. Even without a government subsidy, he returned to China in 1997 after obtaining a master's degree in the United States, because “there were more chances for me in China.”

  15. PROBLEMS

    Internal Fights, Looting Hinder Work in the Field

    1. Dennis Normile
    1. With reporting by Erik Stokstad and Xiong Lei.

    A wealth of opportunities is cheapened by black market sales and internecine squabbles over site access and specimens

    MAOTIANSHAN, YUNNAN PROVINCEWith its spectacular fossils, a well-trained cadre of researchers, and increasing funding, China could be the ideal place for paleontology in the 21st century. But scientists face a trio of problems: squabbles over access to sites and control of fossils, a lack of cooperation in the community, and widespread fossil looting. “It is a loss not only for China, but for the world,” says Chang Mee-Mann, a senior paleontologist at the Institute of Vertebrate Paleontology and Paleoanthropology (IVPP).

    A striking, two-story building down the road from the world-class site here offers mute testimony to what can happen when bureaucracies don't see eye to eye. The Chengjiang Field Station, boasting dorm rooms, work spaces, and a grand exhibition hall, was supposed to be a home away from home for scientists from the Nanjing Institute of Geology and Paleontology (NIGP), some 2000 kilometers to the northeast. But the 2-year-old facility has remained empty until recently, a victim of disagreement over stewardship of the site.

    Building ties.

    The new Chengjiang field station sat empty for 2 years until authorities agreed on how to both preserve sites and dig.

    CREDIT: D. NORMILE

    Local authorities have been reluctant to permit further digging at two of the most famous and productive Chengjiang sites—Maotianshan and Haikou. They want to preserve the site as a tourist attraction and worry, in the words of one scientist, that further digging will leave “nothing for visitors to see.” For NIGP scientists, however, closing off the site means leaving valuable fossils in the ground. A compromise is being worked out, says NIGP's Sun Weiguo, that would allow digging under “a long-term program to preserve the sites.” Meanwhile, the building is now open and digging at other Chengjiang locations will soon resume.

    Although provincial authorities clearly get to decide who digs, ownership of the fossils is unclear. A single sentence in a national law apparently gives authority over vertebrate fossils to the State Administration of Cultural Heritage, but a 1998 government reshuffling apparently shifted control to the Ministry of Land Resources (MLR). Confusion over the extent of its prerogatives can slow down research, however. Last summer, IVPP lost 2 months of work at an exceptionally rich site in western Liaoning Province after local MLR representatives halted digging and demanded the return of fossils previously collected from other sites. Work resumed after negotiations, but who will wind up with the specimens has yet to be clarified. National regulations now being drafted may resolve which agencies control sites and fossils.

    Group rivalry

    Outside China, one institution typically takes the lead in investigating a site and coordinating research efforts with those of other institutions. In return, the lead institute gives all qualified researchers a chance to study the collected specimens. In China, such coordination is lacking, and some researchers do not respect each other's turf. “We only know what other groups are doing because we all hire the same farmers to do the digging,” says Yunnan University's Hou Xianguang about activity at the Chengjiang sites.

    Self-protection.

    Zhou Zhonghe and other paleontologists hope this warning sign will discourage fossil thieves.

    CREDIT: D. NORMILE

    This lack of communication has led to embarrassing redundancies. In 1999, Gao Keqin and others from IVPP named a newly discovered aquatic reptile Hyphalosaurus. At the same time, Li Jianjun and colleagues of the Beijing Natural History Museum named its mirror image Sinohydrosaurus, completely unaware that they were working with the counterslab of the same specimen. “This sort of confusion arises because there are so many groups out there not cooperating,” says Hou.

    “Not cooperating” doesn't begin to describe the friction between IVPP and Ji Qiang, former director of China's National Geological Museum. Relations soured after Ji switched from Paleozoic marine life and plunged into the debate over the origin of birds, a primary research focus at IVPP. Ji says the competition for specimens and scientific recognition “is very good for research, because before 1996 there was only one voice on the origin of birds—IVPP's voice.”

    Tensions between the two institutions, including the sharing of fossils, reached the breaking point early last year. In an article in a Hong Kong newspaper, Ji criticized IVPP researchers for their work with the now infamous Archaeoraptor fossil, sensationalized in National Geographic but later proved to be a fraud (Science, 22 December 2000, p. 2221). In particular, Ji said that IVPP researchers had studied the specimen even though it had been smuggled out of China, a cardinal sin for Chinese paleontologists.

    Not so, says IVPP's Xu Xing, who replied in the Chinese press that he began studying Archaeoraptor only after it was clear it would be returned to China. That explanation is supported by the magazine's account of how it was duped. In the same newspaper article, Xu noted Ji's co-authorship of papers on two allegedly smuggled specimens of the primitive bird Confuciusornis in German and Austrian museums.

    Recent developments, however, may have calmed the waters. This month Ji will step down as director of the Geological Museum and return to the Chinese Academy of Geological Sciences, which is also under the MLR. Ji says his new post, principal scientist at the Institute of Stratigraphy and Paleontology, will give him a chance “to rejuvenate the paleontological research work” in the academy. Researchers hope the move paves the way toward better relations between the museum and IVPP.

    Illegal fruits

    A bigger problem than professional spats over jurisdiction may be the fact that many specimens are sold illegally to collectors. Scientists can never fully know what has been lost from looting and smuggling, but there are hints. In the early 1990s, dozens of dinosaur eggs, many with intact embryos, were unearthed in China and soon became hot items at fossil and curio markets worldwide. Today, says IVPP's Zhou Zhonghe, “all the best specimens of eggs with embryos are now outside China.”

    The immense value of specimens to farmers eager to escape the grinding poverty of rural China almost ensures that the looting will continue, however. Local governments are hard-pressed to protect the widely scattered sites, and police and officials can be bribed. Even the threat of a death sentence, so far levied only against those who have plundered cultural relics, isn't enough to deter the illegal trade.

    This presents scientists with hard choices. Although it is illegal to buy specimens with government money, Ji says that the Geological Museum has used a system of indirect payments. “We ask the farmers to donate fossils to the museum,” he explains. “Then, the museum gives them awards.” The first specimen of Sinosauropteryx, for example, netted the donor $750 in 1996.

    Director Zhu Min admits that IVPP reluctantly employs the same tactic, but only as a last resort. Staying above the fray, he notes, means that “scientifically valuable specimens will not be in the hands of genuine researchers.” At the same time, IVPP's Chang says that specimens bought from farmers “have lost much scientific information, such as the layer, location, and the association with other fossils.” Looters rarely save fossil fragments, which may be valuable to scientists but not to collectors. Indeed, attempts to cement unrelated bits and pieces together are so common that a recent monograph on Confuciusornis included a section on how to spot doctored specimens.

    Some localities have gotten serious about protection, with Yunnan officials posting full-time guards at some of the most prominent Chengjiang sites. In 1997, the secretary- general of the local Communist party personally supervised filling the quarry with boulders to protect it during the off-season. And in Guizhou Province, the local government has paid for highway patrols.

    But added security doesn't eliminate the problem. “It means peasants now dig less. But they haven't stopped,” says IVPP's Li Jinling, flipping through photographs of plundered outcrops. “I feel very sad for Chinese science.”

  16. PARTNERS

    Fruitful Collaborations Follow a Two-Way Street

    1. Xiong Lei*
    1. With reporting by Li Hui, Dennis Normile, and Erik Stokstad.

    Chinese scientists now hold many of the cards as foreigners seek access to a buried pot of fossilized gold

    NANJINGTwenty years ago, Jin Yugan was one of a handful of Chinese paleontologists allowed to collaborate with Western scientists. It wasn't easy. A senior stratigrapher at the Nanjing Institute of Geology and Paleontology (NIGP), Jin spent up to 6 months before each trip meeting such bureaucratic requirements as advance approval for every piece of correspondence. But the hard work was worth it, Jin says, because Chinese scientists were desperate for outside information, help with publishing papers in English, and the acclaim that flowed from such collaborations.

    Today, communication is a lot easier, and it's the rest of the world that is beating a path to Jin's door. Jin has even cut back on his overseas travel to spend more time analyzing his data on the Late Permian mass extinction, which is eagerly awaited by collaborators. The boost in government support also has given Jin and others “more opportunities and greater choice in finding collaboration partners,” adds Yang Qun, deputy director of NIGP.

    The new arrangement is a far cry from the 1920s and ‘30s, when foreign teams trooped around the country and then shipped home the best specimens. The war and the creation of the People's Republic ended that type of one-way interaction, and it wasn't until 4 decades later, after China began turning westward, that the next major influx of foreign scientists occurred. A series of expeditions called the Sino-Canadian Dinosaur Project began in 1986 and helped to open the door. Fueled by $100,000 in annual funding from the Canadian Ex Terra Foundation, scientists excavated more than 60 tons of fossils and identified many new species. “I felt sure that we could work with the Canadians on an equal footing,” says Chang Mee-Mann, then the director of the Institute of Vertebrate Paleontology and Paleoanthropology (IVPP) in Beijing. IVPP's Doug Zhiming and Zhao Xijin co-launched the expeditions with Philip Currie of the Royal Tyrrell Museum of Paleontology in Drumheller and Dale Russell, then of the Museum of Nature in Ottawa.

    Traveling man.

    NIGP's Jin Yugan has more offers from foreign collaborators than he can handle.

    CREDIT: D. NORMILE

    As China's scientific infrastructure expands, however, the preferred mode of interaction is smaller teams built upon mutual interests. “Personal connections in China mean everything,” says Chris Beard of the Carnegie Museum of Natural History in Pittsburgh. Large or small, foreign collaborations must work through a Chinese host to win approval for their scientific activities. The increased wealth of their Chinese counterparts is another, welcome change. “On a trip a couple of months ago, once we paid our airfare, they paid for everything else,” says Will Downs of Northern Arizona University in Flagstaff, who is working with IVPP on early mammals.

    The demand from the West is so great that there is a shortage of top Chinese paleontologists available to work with. Researchers at the IVPP “are just completely overbooked, all of them,” says Downs. But not all Chinese scientists are equipped to enter into collaborations. “First you have to know what you're doing,” says IVPP's Xu Xing, who studies feathered dinosaurs. “We don't just want to have our name out [in the newspapers].”

    Sun Weiguo, who studies early multicellular animals at NIGP, notes that some Chinese scientists seek fame merely on the basis of their access to key fossils. “If the majority of work is done by foreign scientists,” adds Xu, “that's not good for Chinese science.” Similarly, Chinese scientists complain about Westerners who give lip service to scientific collaborations to obtain access to the samples.

    True collaborations avoid those problems, says Doug Erwin of the Smithsonian Institution in Washington, D.C., who has worked with Jin. “If you collaborate as equals, then you can have a wonderful time.” And there's no excuse not to do it properly, adds David Dilcher of the University of Florida, Gainesville. “The door is open wide for good, constructive, collaborative research,” he says.

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