News this Week

Science  28 Sep 2001:
Vol. 293, Issue 5539, pp. 2364
  1. RESEARCH FUNDING

    White House Asks Community to Oppose Earmark Projects

    1. David Malakoff*
    1. *Association of American Medical Colleges; Association of American Universities; National Association of State Universities and Land-Grant Colleges; American Mathematical, Astronomical, Physical, and Chemical societies; American Association for the Advancement of Science (publisher of Science); American Society for Microbiology; The Science Coalition, and the National Academies.

    Twenty years ago, Congress slipped into a budget bill a small sum of money for research buildings at Catholic University of America in Washington, D.C., and Columbia University in New York City. The funds hadn't been requested by the Administration, and the projects hadn't gone through peer review. The move, which at the time sparked an uproar, has become de rigueur: Last year, Congress steered a record $1.7 billion into specific university projects that hadn't been requested, up 60% over 2000, according to the Chronicle of Higher Education (see graph below). Now, the Bush Administration is trying to stick its finger in the dike.

    Last week, senior White House budget officials called a meeting with a select group of academic and science-policy heavyweights to enlist their support in opposing the practice, known as earmarking. “It would be very helpful for the community to make its views known, since Congress responds more to constituents” than to White House complaints, said an official of the White House Office of Management and Budget (OMB) who was present. The Administration didn't get a blanket denunciation of a practice that has long divided the academic research community, but it made it clear that this is an issue it intends to pursue.

    Looking for a trim.

    White House budget chief Mitch Daniels is worried about rising academic earmarks (below), a small but growing slice of how the government chooses what science to fund (above).

    CREDITS: (TOP TO BOTTOM) DENNIS COOK/AP; SOURCE: OMB; SOURCE: CHRONICLE OF HIGHER EDUCATION

    Presidents traditionally oppose earmarks because they drain money from Administration priorities. Critics also argue that the practice undermines peer review, promotes poor-quality science, and erodes government science budgets. But most legislators support academic earmarks as a way to help smaller institutions—especially those in their districts—compete against wealthier research universities. Academic leaders, meanwhile, are torn between upholding the process of choosing the best science and pressure to raise money from every possible source.

    White House officials say they are targeting earmarks as part of a three-pronged effort aimed at strengthening federally funded research. (The other two thrusts are tightening up overall management practices and spelling out each agency's scientific priorities.) And although many of those who attended the 19 September meeting welcome the White House initiative, some doubt that it will succeed. “We know from past experience that having the science community rail against earmarks probably isn't enough to stop university presidents and members of Congress from seeking them,” says physicist Michael Lubell of the American Physical Society, one of 12 invited groups.*

    At the meeting, OMB director Mitch Daniels and his staff noted that earmarks are putting increasing pressure on some government science budgets. NASA officials this year had to trim many life science research grants by 5% or more to pay for earmarks, and up to 10% of the Environmental Protection Agency's $550 million R&D budget has been consumed by pork in recent years.

    Some groups, however, are reluctant to join forces with the White House before hashing out a clearer definition of the practice. “It's a very complex issue,” says Nils Hasselmo, president of the Association of American Universities (AAU), which represents 61 top research schools—including those that decry and those that benefit from earmarks. A shortage of federal funds for research building construction, he says, has forced many campuses into the earmarking game. And some researchers have sought Congress's help after the White House failed to request funds for projects that an agency has already approved (Science, 14 September, p. 1972).

    To decide whether such end runs should be banished, the AAU and other groups have invited OMB to a 3 October public forum on earmarking at the Carnegie Institution in Washington, D.C. Hasselmo, for one, hopes the meeting will “move us toward some reasonable agreement” on whether any research earmarks are acceptable.

    Even if such an agreement can be hammered out, however, some observers wonder if it could ever be made to stick. The AAU itself was unable to enforce a 1980s decree against earmarks among its own members, they note. But Bush Administration officials are hoping that pressure from the community, combined with a threatened presidential veto of pork-laden spending bills, will put the pig back in the barn.

  2. DEVELOPMENTAL BIOLOGY

    Organs Await Blood Vessels' Go Signal

    1. Caroline Seydel*
    1. Caroline Seydel is a science writer in Los Angeles.

    Blood vessels are the body's plumbing, supplying food and oxygen and removing waste. Now two papers published online this week by Science (http://www.sciencexpress.org/) show that blood vessels play a more active role than previously believed: They help direct the construction of the body they serve. The teams, led by Douglas Melton of Harvard University and Kenneth Zaret of the Fox Chase Cancer Center in Philadelphia, report that blood vessels induce development of the pancreas and liver—even before the blood vessels are functioning.

    Cancer researchers stumbled upon the first evidence that blood vessels do more than ferry food and waste around the body. In 1995, a team reported that endothelial cells, which make up blood vessel walls, produce growth factors.

    The new studies build on that work, showing that by sending another, as-yet-unidentified molecular signal, the embryonic blood vessels direct embryonic tissue not just to grow but to differentiate into complex structures. “The endothelial cells aren't just a bunch of pipes and tubing; they contribute to the formation of the organ,” says liver regeneration researcher Robert Costa of the University of Illinois, Chicago. “That's really the most important part of the discovery.”

    Melton's team began scrutinizing blood vessels after noticing something odd about how cells in the mouse pancreas differentiate into islets, clusters of cells that produce insulin. The researchers observed that the endoderm—embryonic tissue fated to become middle organs such as the lungs, liver, pancreas, and stomach—directly touches a major blood vessel, the dorsal aorta. “It begs the question, is there a signal there?” says postdoc Ondine Cleaver, a co-author of the paper. The developed pancreas monitors blood vessels to assess blood glucose levels and tweak insulin production accordingly. The team suspected that the pancreas and blood vessels talk to one another chemically during development as well.

    Time to grow up.

    Blood vessels (red) direct islets (green) to differentiate.

    CREDIT: E. LAMMERT ET AL.

    To test their hypothesis, the researchers first surgically removed cells fated to become the dorsal aorta from frog embryos. This dramatically reduced levels of insulin and two other pancreatic secretions in the developing embryos. To make sure the pancreas wasn't hobbled due to a lack of blood flow, Cleaver and fellow postdoc Eckhard Lammert grew undifferentiated mouse embryo tissue in culture with and without embryonic dorsal aortae. Only in the presence of the blood vessel did the tissue produce pancreas-specific markers, including insulin. Finally, the researchers overexpressed a blood vessel growth factor, VEGF, in mouse embryos. This increased blood vessel production as well as islet formation and insulin production.

    The Philadelphia group, meanwhile, approached the blood vessel question from another angle. Zaret and colleagues examined liver development in mice with a mutation in a gene called flk-1, which encodes a receptor for VEGF. When such mice are developing, the team found, no blood vessels form in the part of the endoderm destined to turn into the liver. What's more, “in the absence of such endothelial cells, the liver bud stops dead in its tracks and doesn't develop further,” Zaret says.

    To verify that an absence of blood vessels prevented the liver from developing, visiting scientist Kunio Matsumoto of Osaka University in Japan invented a new cell culture system that permitted blood vessels to grow among cultured liver tissue. Once the system was in place, the researchers compared mutant cells with normal cells. The flk-1 culture grew to the same size as the normal one. But whereas about 20% of the normal culture consisted of liver tissue, only 5% of the mutant culture became liver; the rest was connective tissue. Surprisingly, the endothelial cells' influence arose well before the cells turned into functional blood vessels, suggesting that the cells themselves—and not some component of the blood—were sending the growth signal.

    Understanding how cells differentiate will be critical to any future stem cell-based treatments for disease, such as growing islets in the lab for transplantation into diabetics. “If we're going to induce organs to form, we have to have a thorough understanding of how the embryo develops them,” says organ replacement biologist Michael Longaker of Stanford University School of Medicine in Palo Alto, California. “We will never do it in a more elegant way than the embryo.”

  3. PLANETARY SCIENCE

    New Visitors Set for Lunar Voyage

    1. Alexander Hellemans*
    1. Alexander Hellemans is a writer in Naples, Italy.

    NAPLES, ITALY— Like flared jeans and disco, exploration of the moon is back in fashion. Next week, at a meeting of the International Astronautical Federation in Toulouse, France, Japanese and European scientists will present new missions that will probe the satellite's surface and interior.

    Apart from two U.S. missions—Clementine in 1994 and Lunar Prospector in 1998—the moon has been largely ignored since Apollo 17 departed with a load of moon rocks in 1972. But plenty of good science remains to be done. “The moon still has many, many mysteries, such as its origin and evolution,” says Hitoshi Mizutani, head of planetary research at Japan's Institute of Space and Astronautical Science (ISAS).

    By far the most ambitious project is Japan's Selene—“we call it the Rolls-Royce for the exploration of the moon,” says Bernard Foing of the European Space Agency (ESA). Costing $350 million and carrying 200 kilograms of instruments, Selene will be launched jointly by ISAS and NASDA, Japan's space agency, in 2005. The craft's 14 sensors include x-ray and gamma ray spectrometers to chart elements on the surface and an alpha-particle spectrometer to analyze radiation emitted by radon gas and polonium. A stereoscopic camera will also map the lunar topology.

    Scientists expect that Selene will improve our understanding of the origin and evolution of the moon. Some observers, however, disagree. Although the mission “will create a massive data set on the moon, much of it unfortunately would not add materially to the things we already know,” says lunar researcher Wendell Mendell at NASA's Johnson Space Center in Houston. Mizutani counters that “the quality and precision of the Selene instruments will provide much better data than those obtained by previous or existing observations.”

    Fine-tuning.

    Europe's Smart-1 undergoes tests in the Netherlands.

    CREDIT: ESA

    A second Japanese probe, the $100 million Lunar-A, will swoop to within 40 kilometers of the surface in 2005 and launch two “penetrators”—80-centimeter-long projectiles that will pierce the surface to a depth of up to a few meters. Positioned on opposite sides of the moon, the sensors will monitor seismic waves traveling through its core. Analysis of the waves should reveal the size of the moon's core and determine whether or not it is liquid. Sensors on the penetrators will also measure heat flow through the crust, essentially taking the moon's internal temperature. “These geophysical data would be tremendously important toward understanding the moon as a planet,” says Mendell.

    The aim of ESA's more modest Smart-1 is to test new technologies, such as solar-powered ion propulsion, for later missions including ESA's Bepi-Colombo probe to Mercury. After the $80 million spacecraft is launched at the end of 2002, it will take 16 months to reach the moon, using only sunlight to drive it. Solar panels will provide the power to ionize xenon atoms and fling them out the back of the craft. “It is the first time that it will be used as a primary means for transportation,” says Foing, ESA's project scientist for Smart-1.

    Smart-1's tiny suite of six sensors, weighing only 15 kilograms in all, may help explain the moon's origin. In the most widely accepted theory, the moon is a bit of Earth broken off by a collision with a Mars-sized object. If so, the relative abundances of the moon's common constituents—iron, magnesium, and aluminum—should match those on Earth. Smart-1 will create a global map of abundances. The most important ratio is magnesium to iron, says Manuel Grande, a space physicist at the Rutherford Appleton Laboratory near Oxford: “That number really constrains whether the Earth and moon come from the same place.”

    Just as Cold War politics whipped up the moon frenzy in the 1960s, political forces may be behind the upcoming moon shots, some analysts contend. “The Selene mission … is really the first step toward a resource-oriented commercial development,” contends Mendell. Mizutani, however, insists it is far too early to talk about exploiting the moon. “We will need more basic study,” he says.

  4. STEM CELL RESEARCH

    Reports Give Green Light in Australia, Israel

    1. Leigh Dayton,
    2. Gretchen Vogel*
    1. Leigh Dayton writes from Sydney, Australia.

    BERLIN AND MELBOURNE— Two countries at the forefront of work on human embryonic stem (ES) cells, Australia and Israel, have just recommended policies to ease the way for their researchers.

    After 2 years of deliberation, an Australian government committee has endorsed legislation that would allow both ES cell research and the derivation of ES cells from unwanted embryos created during fertility treatments. The 10-member committee, made up of members of parliament, also called for a national licensing body to monitor and regulate all such research, whether publicly or privately funded. And although the parliamentarians unanimously condemned the use of ES cells for reproductive cloning, they left open the door to the creation of embryos as a source of genetically matched ES cells—so-called therapeutic cloning—by calling for a 3-year moratorium on the practice. The Australian government is expected to seek legislation to implement the recommendations.

    This stands in stark contrast to restrictive conditions imposed on U.S. researchers. On 9 August, President George W. Bush announced that federally funded scientists could obtain ES cells only from existing cell lines; shortly before, the U.S. House of Representatives passed a bill that would ban cloning for research purposes.

    In Australia, Catholic commentators condemned the report for failing to ban outright the creation of embryos for research. But medical ethicists such as Helga Kuhse of the University of Melbourne and Monash University believe the committee should have gone further. “I can't see why scientists should be limited to surplus embryos” from fertility treatment, she says. “Embryos are hard to come by, and, to me, the distinction between embryos created with somatic cells and those created from an egg and sperm is nontenable.”

    ES cell workers welcome the report, says Martin Pera of the Monash Institute of Reproduction and Development in Melbourne. Currently, scientists face a jumble of legislation that varies among state and territorial jurisdictions. For instance, Pera and his Monash colleagues derive ES cells in Singapore because it is illegal to do so in the state of Victoria. “This report finally provides a clear framework for Australian scientists,” he notes.

    In Israel, a national bioethics committee has approved both the derivation of ES cells and research into therapeutic cloning. The report, issued by the Bioethics Advisory Committee of the Israel Academy of Sciences and Humanities on 4 September, does not have the force of law, says committee member and molecular biologist Hermona Soreq of the Hebrew University of Jerusalem, but she expects the national science funding agency to follow its recommendations.

    This report lends important formal support for Israel's existing policy, says Nissim Benvenisty, an ES cell researcher at Hebrew University. Joseph Itskovitz of the Rambam Medical Center in Haifa, for instance, has already derived several ES cell lines in Israel.

    In 1999, the Israeli Knesset passed a 5-year moratorium on cloning procedures that lead to “the creation of a whole human being.” However, the ethics committee wrote that the law “does not rule out producing cloned embryos that will not be implanted,” giving the green light to therapeutic cloning. The full report will be published on the academy's Web site at http://www.academy.ac.il./.

  5. CONDENSED MATTER

    Quantum Condensate Gets a Fresh Squeeze

    1. Charles Seife

    Cooled to a few billionths of a degree above absolute zero, atoms in a Bose-Einstein condensate (BEC) represent an extreme state of matter. But physicists at the Massachusetts Institute of Technology (MIT) have subjected the atoms in condensates to even more outrageous ordeals, squeezing them into one-dimensional lines and two-dimensional planes. The experiments, reported in the 24 September issue of Physical Review Letters, open the door to investigating a new regime of physics in which the rules are easier to understand.

    In a BEC, atoms lose their individuality. Cool a clump of matter enough, damping out the random thermal motions of the particles, and the atoms can merge, becoming, in a quantum-mechanical sense, a single coherent object. For the past 5 years, scientists around the world have been experimenting with the strange properties of these atomic ensembles, listening to them ring with sound waves, building atom “lasers” with them (Science, 13 February 1998, pp. 986 and 1005), and using them to slow light to a crawl.

    But these experiments all probed three-dimensional BECs. One-and two-dimensional systems have “strikingly different physics,” says MIT physicist and team member Wolfgang Ketterle. “Critters or creatures in a one-dimensional world can't pass by each other, for example,” changing the behavior of the system as a whole, he says.

    Torture chamber.

    The BEC II device at MIT crushes an extreme form of matter into lower dimensions.

    CREDIT: W. KETTERLE/MIT

    William Phillips, a Nobel laureate at the National Institute of Standards and Technology in Gaithersburg, Maryland, says lower dimensional BECs are exciting for their potential use in studying phenomena such as solitons—stable waves—within BECs. “In 3D, [solitons] can break up into vortices and phonons. There are instabilities because of these possibilities,” he says. “In one dimension, there are fewer things that can happen,” making the solitons more stable.

    To make lower dimensional BECs, the MIT group started with ordinary 3D BECs made of sodium atoms. For the 1D BEC, the group simply trapped the condensate in strong magnetic fields and stretched it into a cigar shape. The extreme fields made it much easier for atoms in the condensate to flow along the cigar's long axis. As a result, atoms could move in only one dimension if shoved by an outside force. “If you bang it, it's going to respond axially; it's not going to respond radially,” says physicist Randall Hulet of Rice University in Houston. (Similar results with lithium atoms were published last month by a French group.)

    The 2D BEC took an extra step. Instead of staying in a magnetic trap the entire time, the atoms had to be transferred to an optical trap, where the condensate was confined by a sheet of light. The MIT team then watched as the condensates switched over from three dimensions to two or one dimension.

    Hulet and Phillips agree that Ketterle's results are only a beginning. Researchers would learn more by watching condensates form in lower dimensions, they say, instead of squeezing a 3D cloud into the required shape. Nonetheless, “it's a first step to being able to do interesting physics in a new regime,” Hulet says. Torturing a few sodium atoms is a small price to pay for such an opportunity.

  6. PALEOANTHROPOLOGY

    Tools Show Humans Reached Asia Early

    1. Ann Gibbons

    If Africa was the cradle of humanity, then Asia was the crossroads of early human migrations. Asia was the first continent that early humans explored on their exodus from Africa and was the jumping-off point for later treks to the New World, Australia, and perhaps Europe. But exactly when early humans first reached Asia has long mystified paleoanthropologists. The first signs of their presence are Homo erectus fossils dated to between 1.7 million and 1.9 million years ago in Dmanisi, Georgia, on Asia's western edge, and in Java, Southeast Asia (Science, 12 May 2000, p. 948). But there are still questions about some of those dates, and other traces of ancient Asians are questionable until about 1 million years ago.

    Now, in this week's issue of Nature, the case for an early movement out of Africa is further boosted by new work dating Chinese stone tools to 1.36 million years ago. What's more, the tools were found in relatively cold northern China, by an ancient lake bed 150 kilometers west of Beijing. To reach that spot, early humans must have migrated long distances over difficult terrain, armed only with simple tool kits.

    The new report is notable for its “very nice, clean” dating methods on pieces of stone that are indisputable tools rather than natural flakes, says geologist Frank Brown of the University of Utah in Salt Lake City. It also documents “the earliest known penetration of the northern latitudes by early Homo in Asia,” says paleoanthropologist Russell Ciochon of the University of Iowa in Iowa City. “This demonstrates that H. erectus was able to adapt to more seasonal and challenging environments than previously considered.”

    The stone tools—simple flakes, cores, and scrapers—were found 21 years ago by Chinese geologists in the hilly badlands of the Nihewan Basin, at the northeastern margin of the dust-blown Loess Plateau. Researchers had suspected that artifacts at a half-dozen sites in the basin were more than 1 million years old, but dating sediments in China has been notoriously difficult because there is no volcanic material for radiometric methods. So the Chinese and American team used high-resolution paleomagnetic dating, relying on known, ancient shifts in Earth's magnetic field to tie the tools to a particular period, says Rixiang Zhu, a geophysicist at the Institute of Geology and Geophysics at the Chinese Academy of Sciences in Beijing.

    Stone ages.

    New dates put these stone tools from China at 1.36 million years old.

    CREDIT: RIXIANG ZHU

    The members of Zhu's team hung from ropes alongside steep hillsides at two sites in the basin, sampling soil every 25 to 35 centimeters in a vertical column that cut through the horizontal layers of sediment, including the layer of grayish-white clay in which the tools were deposited. This clay layer was laid down during a long period when Earth's polarity was flipped. Sediments bearing the signature of this reversed polarity are sandwiched between a layer indicating normal polarity—a period dated radiometrically at Africa's Olduvai Gorge to 1.77 million to 1.95 million years ago—and another normal-polarity layer dated to 1 million years ago. From the location of the clay layer in the band of reversed-polarity sediments and an estimated sedimentation rate, Zhu and his team, including geophysicist Ken Hoffman of California Polytechnic State University in San Luis Obispo, concluded that the tools were at least 1.36 million years old. The team's efforts impressed dating expert Brown, who calls it “great work” that provides a “jumping-off point” for dating other basin sites.

    Although no human fossils have been found in the basin, the tools' antiquity shows that early humans had already managed to adapt to life at 40 degrees north, says co-author Rick Potts, a paleoanthropologist at the Smithsonian Institution in Washington, D.C. But he adds, “What were they doing at the margin of the range for hominids? How did they adapt to this northern climate?”

    Potts speculates that the climate may have been relatively warm at the time and that the toolmakers had to adapt to life in the north because the massive Qinling Mountains blocked them from migrating south. To reach the site, H. erectus had to cross the Tibetan Plateau and somehow get around the Himalayas. Regardless of how they got there, says archaeologist Kathy Schick of Indiana University in Bloomington, who has worked at tool sites in the basin since 1989, these dates show that “very early on, Homo had the capability to spread out of Africa and to move significantly northward across long distances with relatively simple tool kits.”

  7. FRENCH SCIENCE

    Budget Backs University Research, Job Creation

    1. Michael Balter

    PARIS— As fears of war and economic recession sweep the world, French scientists got at least a sliver of good news last week. New budget proposals would boost grant money for long-suffering university researchers by nearly 20%, while public research agencies would be able to hire 500 additional researchers and technicians.

    The big picture for science is more sobering. France's civilian R&D budget increase in 2002 would barely beat inflation, rising 2.2% to $8 billion. That modest growth would, however, put science in a better position than many other public sectors: The overall government budget is set to increase by a meager 0.5%. Not surprisingly, the mixed news is drawing mixed reviews: Whereas some French scientists welcome the spending plans, others complain that French R&D will gain little ground on R&D in the United States and other research powerhouses.

    Good news.

    With a 19.3% increase next year, French university research would be a big winner

    CREDIT: FRENCH MINISTRY OF RESEARCH.

    At an 18 September press conference announcing the new budget figures—which are subject to parliamentary approval later this year—French research minister Roger-Gérard Schwartzenberg said that his “number one priority” is to create opportunities for young researchers. Decrying a lack of positions that has forced talent abroad, Schwartzenberg remarked that “France's job is not to serve as a training institute of young doctorates for the benefit of the United States or other countries.” The job creation initiative, which aims to retain young scientists, has earned praise from France's National Union of Scientific Researchers, an organization that's usually highly critical of the government's priorities.

    But some prominent scientists are wringing their hands. “I am not optimistic that the government has taken [sufficient] measures to make research a top priority,” says cell biologist Jean-Paul Thiery of the Curie Institute in Paris. And Pierre Chambon, director of the Institute of Genetics and Molecular and Cellular Biology near Strasbourg, complains that salaries—which begin at $20,000 per year at agencies such as CNRS, the national basic research agency—are too low to hold on to the best scientists. “We are not competitive,” he says. “This is scary for the future.”

  8. MAGNETOSPHERIC PHYSICS

    Magnetic Storms Have Two Drivers, Not One

    1. Richard A. Kerr

    When the skies dance with auroral light, satellites stagger under an onslaught of charged particles, and electrical power systems on the ground collapse, you can blame the solar wind. Space physicists have long known that the gale of charged particles howling by Earth at supersonic speeds bears the ultimate responsibility for magnetic storms, but they have vacillated between two very different explanations of how the solar wind roils Earth's magnetosphere. Now, a study using the latest in magnetospheric probes—published in the 1 September issue of Geophysical Research Letters—may settle the sometimes contentious issue: Both explanations appear to be right.

    The events that precede the storms are not in dispute: The solar wind constantly peels back magnetic field lines from the sunward side of the comet-shaped magnetosphere into the tail, loading the tail with charged particles and magnetic flux. The controversy focuses on how that excess energy is released.

    In the 1960s, Syun-Ichi Akasofu of the University of Alaska, Fairbanks, and the late Sydney Chapman, a founding father of magnetospheric physics, argued that days-long magnetic storms are fed by a string of half-hour-long substorms, which appear as sudden brightenings of the aurora. When the excess energy in the tail reaches a critical point, researchers came to believe, something snaps in the maze of magnetic fields and electric currents that links all parts of the magnetosphere. That snap slings charged particles earthward, where they energize the inner magnetosphere, spawning a huge electrical current that rings the planet above the equator and wreaking havoc on humans' electromagnetic devices.

    Seeing the invisible.

    Magnetically trapped charged particles reveal themselves to an ENA instrument when a few particles are neutralized and escape.

    CREDIT: JHU/APL

    That explanation held sway in the 1970s and '80s, but in the 1990s another interpretation gained favor: magnetospheric convection. According to this view, the imbalance in the magnetosphere is redressed by magnetic flux and particles steadily drifting or “convecting” back toward the sunward side, energizing the nightside of Earth as they go.

    The new study, by Anthony Lui and his colleagues at the Johns Hopkins University Applied Physics Laboratory (APL) in Laurel, Maryland, falls squarely in the middle ground. The APL group assembled observations of a 22 October 1999 storm that had been studied by an international consortium of researchers. Observations had been made from the ground by magnetometers and arctic radars monitoring the effects of the equatorial ring current, magnetospheric convection, and substorm activity.

    To this mix the group added energetic neutral atom (ENA) data collected by the Geotail spacecraft in distant Earth orbit. ENA is one of the first remote-sensing techniques that can “see” large parts of the magnetosphere in a single look (Science, 10 June 1994, p. 1531). Satellite-borne ENA “cameras” form a picture of charged particles trapped in the inner magnetosphere—especially in the ring current—by capturing the few particles that manage to escape after picking up an electron from the outermost fringes of the atmosphere. Their resulting neutrality lets them cut free of the entrapping magnetic field lines.

    Lui and his colleagues found that the 22 October 1999 storm seemed to have a different driver at different times. At first, ENA data showed a sharp strengthening of the ring current as substorm activity jumped while magnetospheric convection remained subdued. That's “a very clear example of substorm contribution to storm buildup,” says Ioannis Daglis of the National Observatory of Athens. A few hours later, substorms were muted, but convection and the ring current steadily intensified. “This shows enhanced mantle convection can bring the ring current [charged-particle] population up, too,” says Lui.

    Not everyone is convinced yet. “In the end this paper may even be correct,” says Robert McPherron of the University of California, Los Angeles. “However, the data are much more difficult to interpret than the authors would have you believe. [And] the use of a single event to establish the conclusion is highly suspect.”

    In fact, more cases are on the way. The Imager for Magnetopause-to-Aurora Global Exploration (IMAGE) satellite, launched last year in March, has three instruments specifically designed as ENA imagers. Preliminary analyses of data from IMAGE and the Polar satellite, which also has an instrument useable for ENA, at Los Alamos National Laboratory in New Mexico show both drivers at work in other magnetic storms, says Geoffrey Reeves of LANL. These and other satellite remote-sensing results should be presented in the next few months.

  9. MALARIA RESEARCH

    Two New Steps Toward a 'Better Mosquito'

    1. Martin Enserink

    BARCELONA, SPAIN— Motivated by more than a million deaths from malaria a year, scientists have long fantasized about the ultimate method of eradication: replacing existing mosquito populations with ones unable to spread the disease. At a meeting* last week, researchers presented two studies that could help edge that dream closer to reality. Some researchers hailed the new studies as milestones, but skeptics warned that the strategy may never work in practice.

    Genetically engineering mosquitoes in any way—let alone making them resistant to infectious diseases—has been tricky. That changed a few years ago when researchers discovered a series of so-called transposons—short, movable stretches of DNA that can help insert new genes into a genome—that worked well in mosquitoes (Science, 20 October 2000, p. 440). Now, the field is making “massive strides forward,” says molecular entomologist Paul Eggleston of Keele University in the United Kingdom. Last year, for instance, a team at the European Molecular Biology Laboratory in Heidelberg, Germany, reported that it had genetically modified Anopheles stephensi, a species that transmits malaria in India. In a proof of principle, the team inserted a gene that encodes green fluorescent protein (GFP) and demonstrated that the gene functioned in its new environment.

    Changeling.

    An Anopheles gambiae larva carrying the GFP gene

    CREDIT: JOHN R. CLAYTON/CDC/APHL

    Now a team led by Marcelo Jacobs-Lorena of Case Western Reserve University in Cleveland, Ohio, has spliced into the same mosquito species a gene that confers resistance to Plasmodium, the parasite that causes malaria. The gene encodes a peptide, called SM1, that appears to block receptors in the mosquito's gut and salivary glands that Plasmodium needs to replicate inside the mosquito. In two experiments, mosquitoes carrying the gene lost their ability to infect mice with malaria; in a third study, they became much less effective vectors, Jacobs-Lorena reported.

    Also at the meeting, Mark Benedict of the U.S. Centers for Disease Control and Prevention in Atlanta announced that his team has found a way to create transgenic A. gambiae, the most common malaria vector in Africa and a much bigger killer than A. stephensi. Again, the team slipped the GFP gene into A. gambiae. Jacobs-Lorena calls the work “a real landmark,” because so many previous attempts to genetically alter A. gambiae had failed. Now, it's probably a matter of months before researchers produce a malaria-resistant version of A. gambiae, for instance by equipping it with SM1, says Eggleston.

    But Harvard medical entomologist Andrew Spielman cautions that huge scientific and practical obstacles remain to be overcome before transgenic mosquitoes can be deployed in the field. These range from finding a way to ensure that they replace existing populations to dealing with ethical problems regarding the protection of inhabitants of a test site. Because of these hurdles, it's “extremely unlikely” that this line of research will ever make good on its promises, Spielman asserts. Eggleston concedes that the field faces many problems. But even if the altered mosquitoes are never released, he says, they will teach researchers a great deal about how malaria parasites interact with their host.

    • *Third International Congress of Vector Ecology, Barcelona, Spain, 16–21 September.

  10. PALEONTOLOGY

    Unhatched Eggs Help Dinos Get a Head

    1. Erik Stokstad

    Rugged as they look, fossilized dinosaur skulls are frustratingly hard to find. Exposure, scavengers, and flash floods ensured that few of the information-laden artifacts survived their day. Miraculously, though, the most delicate skulls of all—those of dinosaur embryos—sometimes come to light. In the past 13 years, paleontologists have identified embryonic remains of five kinds of dinosaurs, but only one, a duck-billed dinosaur, had an intact skull. Intact embryos of the long-necked, lumbering sauropods remained unknown—until now.

    On page 2444, three paleontologists describe the first articulated skulls—not much bigger than a postage stamp—of titanosaurs, a group of sauropods known only from incomplete skeletons and very few skulls. “This is a really exciting find,” says Jeffrey Wilson of the University of Michigan's Museum of Paleontology in Ann Arbor. The embryos come from a site in Patagonia, called Auca Mahuevo, whose rocks are packed with thousands of dinosaur eggs between 71 million and 89 million years old. In 1998, Luis Chiappe of the Natural History Museum of Los Angeles County, Rodolfo Coria of the Carmen Funes Museum in Plaza Huincul, Argentina, and others described cantaloupe-sized eggs containing fragmentary bones—and the chisellike teeth of titanosaurs. Working with Leonardo Salgado of the Museum of Geology and Paleontology in Neuquen, Argentina, the team has now found six more embryos, some with intact skulls.

    Heads up.

    The first complete skulls from embryonic sauropods were discovered in eggs from this site in Argentina.

    CREDIT: AMERICAN MUSEUM OF NATURAL HISTORY

    The 4-centimeter-long skulls may help show which skeletal features of titanosaurs developed in tandem and which are independent. That's important, because scientists determine evolutionary relationships by comparing such features, or characters, and spurious connections can lead them astray. The embryonic titanosaur skulls confirm earlier suspicions that two key sauropod traits—the orientation of the braincase and the position of the nostrils—are independent, Chiappe and his colleagues say. Further study could tease apart even more characters to help paleontologists sort out the sauropod family tree.

    The embryos may also shed light on early sauropod evolution, about which relatively little is known. Although development doesn't necessarily replay evolutionary history, says paleontologist Eric Buffetaut of France's basic research agency CNRS, embryonic features may be reminiscent of more primitive sauropods. “If you can use embryos as proxy to reconstruct this early evolution, that's really original,” he says. Buffetaut hopes the discovery of sauropod embryos will encourage other paleontologists to examine eggs in their collections.

  11. CLINICAL RESEARCH

    India Acts on Flawed Cancer Drug Trials

    1. Pallava Bagla

    THIRUVANANTHAPURAM, INDIA— Reacting to numerous regulatory violations in the testing of an anticancer drug, the Indian government has suspended all human trials for 6 months at the Regional Cancer Center (RCC) here in the southern state of Kerala. It has also closed a loophole allowing the unregulated importation of experimental drugs by requiring organizations to obtain approval before the testing or marketing of any drug.

    These steps by the Ministry of Health and Family Welfare in New Delhi follow a 300-page report submitted earlier this month by an independent panel investigating a trial that RCC ran in collaboration with Johns Hopkins University in Baltimore (Science, 10 August, p. 1024). The report, which remains confidential, concluded that there was no “violation of human rights or use of any banned drug” but that not all of the required regulatory procedures were followed. In particular, it said that the RCC failed to obtain necessary approval from the Drug Controller General of India and clearance from the Health Ministry's Screening Committee for collaboration with a foreign agency in studying M4N, a methylated extract of the creosote bush being tested against oral cancers.

    Stoppage.

    India has suspended clinical trials at the RCC for 6 months.

    CREDIT: P. BAGLA

    “The report highlights irregularities in the way research was being conducted at RCC,” says Indian health minister C. P. Thakur. “We are now going to insist on a procurement of permission from the central government for all new drugs, whether for experiments or for their marketing.” The RCC's director, Krishnan Nair, acknowledged in an interview with Science that the center had not fully followed regulatory procedures.

    Along with the 6-month suspension, the ministry has ordered the institute to reconstitute its Institutional Ethical Committee along guidelines issued last fall by the Indian Council of Medical Research (ICMR) in New Delhi (Science, 3 November 2000, p. 919). In addition, it said that a representative of ICMR must sit in on discussions of proposed clinical drug trials.

    The government has also decided that all medical research institutions must abide by those guidelines, which currently apply only to ICMR institutions. A second inquiry, by the Kerala branch of the Indian Medical Association, concluded earlier this month that although there was “no evidence of exploitation, … it is doubtful whether all the [RCC] patients understood that they were participating in a human experiment.”

  12. FORENSIC ANTHROPOLOGY

    For Ice Man, the Band Plays On

    1. Ben Shouse

    BOLZANO, ITALY— Researchers threw a grand bash here last week to celebrate the 10th anniversary of the Tyrolean Ice Man's famous emergence from an Alpine glacier. But instead of giving Europe's oldest mummified human a cake with 5310 candles, they feted him with new insights into his origins as well as plans to compare his desiccated remains with those of South American mummies.

    Ever since two hikers spotted his wizened head and shoulders sticking out of the ice on 19 September 1991, the Ice Man—nicknamed Ötzi by the Austrians because he was found in the Ötztaler Alps—has been the Copper Age's biggest celebrity. In the early 1990s, Austria and Italy waged a custody battle over the remains until precise measurements showed that the find was made on the Italian side of the border. That led to an amicable agreement that opened up scientific study. Perhaps the most sensational find came just a few weeks ago: Computed tomography scans revealed what appears to be an arrowhead lodged in the Ice Man's left shoulder, suggesting that he may have been a victim of foul play (Science, 3 August, p. 795).

    A decade of work has painted a clearer picture of the Ice Man's roots. For starters, scientists have used isotopic analyses to pinpoint his place of origin. The ratio of strontium-87 to strontium-86 in his tooth enamel indicates that he grew up eating plants grown on soils derived from gneiss and schist, the same kind of soil found in the South Tyrol region of Italy—and unlike Austria's limestone-based soils, says geochemist Wolfgang Müller of the Australian National University in Canberra. In addition, preliminary analyses of oxygen isotopes suggest that the Ice Man lived at a higher altitude as an adult, Müller says. This is consistent with the idea that the Ice Man came from Juval, a Copper Age site in South Tyrol.

    Cold warrior?

    A pathologist probes a wound near the putative arrowhead that may have killed the Ice Man.

    CREDIT: INSTITUTE FOR ANTHROPOLGY, VIENNA

    Ongoing projects aim to use nondestructive techniques to examine the provenance and manufacturing methods of the Ice Man's copper ax; biopsy his prostate to learn about cancer in prehistory; and possibly try again to amplify his Y chromosomal DNA after one failed attempt. (This may contain clues to the spread of ancestral populations across Europe.) Some scientists also would like to dissect his shoulder to inspect the putative arrowhead—a decision that will be made after consideration in a future international forum, says Horst Seidler, scientific director of the Ice Man project.

    Behind the headline-grabbing news, Ice Man researchers have forged new bonds with archaeologists who study Peruvian mummies. At the meeting, Seidler unveiled an agreement with the Leymebamba Museum in remote northcentral Peru. The museum, which got half of its initial funding from the Austrian government, opened in May 1998 to house about 220 16th century mummies from the Chachapoya tribe. Lessons gleaned from the Ice Man in how to preserve ancient tissue can be applied to these mummies, Seidler says, and can also boost investigations into the genetic and cultural heritage of modern Peruvians. Up to four of the mummies may be shipped to Bolzano in 2003 in hopes of revealing something about the Ice Man himself.

    Seidler also announced a partnership with Chilean researchers working with the Prince of El Plomo. This Incan mummy was an 8-year-old child sacrificed near Santiago 400 years ago, then preserved in ice.

    New findings can't come too quickly for Bolzano, where the Ice Man has lent his name or image to a phone card, a postage stamp, a gelato flavor, and a musical called Frozen Fritz, which premiered a week before the conference. Linking up with the South American researchers should help broaden the region's scientific strengths, says Seidler: “Bolzano should be much more than just a place where the Ice Man is displayed.” But a decade on, Ice Man fever here is more passionate than ever—and unlikely to subside any time soon. “In 100 years,” says archaeobotanist James Dickson of the University of Glasgow, “we may be arguing over what time he sat down to his last meal.”

  13. SWEDISH BIOSCIENCE

    Karolinska Inc.

    1. Richard Stone,
    2. Lone Frank*
    1. Lone Frank is a science writer in Copenhagen.

    Under a dynamic “CEO,” Sweden's biomedical powerhouse is forging alliances intended to make it competitive with the Harvards and Cambridges of the world

    STOCKHOLM— Hans Wigzell has a way of winning over the harshest critics. At a reception in the Stockholm City Theater in 1989, actors accused Wigzell and his colleagues at the Karolinska Institute (KI) of seeking to create “Frankenstein monsters,” he recalls. “I told them, ‘You don't know anything about science.’” After several hours of back and forth, the actors' attitudes were completely reversed. The immunologist and his newfound friends even went on to create a play, with a biology theme, in which Wigzell plays himself. (A modest hit, the production has drawn 25,000 people over the past decade.) “Some colleagues said, ‘You can't do this, a Karolinska professor can't act like a clown,’” Wigzell says. “That made me completely convinced that we had to do it.”

    Such a headstrong nature, tempered by charm and candor, is serving Wigzell well in a more ambitious mission: shaking up the Karolinska, Sweden's top biomedical center. Since being elected institute president in 1995, Wigzell has moved aggressively to forge ties with industry, creating a series of holding companies that allow Karolinska to invest in biotech start-ups and to market its scientific talent. Insiders say Wigzell arrived at just the right moment. In the early 1990s, the Swedish government began slashing basic research spending. Karolinska had to change fast or lose its landmark status in the world's biomedical research landscape. “The ivory tower attitude is just not working anymore,” says KI's Claes Wahlestedt.

    “We have had to go as fast as possible to control our own destiny,” Wigzell explains. In addition to cutting scores of deals with companies and steering money into start-up firms, he has forced Karolinska researchers to compete for internal funding instead of spreading it evenly across departments. “It has been a revolution, but the changes were inevitable,” says immunologist Maria Masucci of KI's Center for Microbiology and Tumor Biology. Outsiders are impressed. “He's been transforming the Karolinska, taking it in a dynamic new direction,” says J. Craig Venter, president of Celera Genomics of Rockville, Maryland.

    Not everyone, however, is enamored with the Wigzell revolution and its emphasis on industry ties. “There's been a discussion out there about whether this is a form of prostitution,” admits KI university director Rune Fransson, a member of Wigzell's inner circle who has helped make his vision a reality. Many, however, laud Wigzell's tenure and look forward to what could be the crowning achievement of his presidency: Stockholm BioScience, Europe's largest science park, a multibillion-dollar venture that got a preliminary go-ahead last month.

    Still, Karolinska has a way to go to catch up with the likes of Harvard, says Hans-Olov Adami, chair of Karolinska's Center for Medical Epidemiology and an adjunct professor at Harvard. “KI is lagging behind,” he says, “but we know it and have a clear ambition to improve.”

    A Nobel and nobler tradition

    Karolinska was created after Sweden's defeat at the hands of Russia in the Finnish war, which ended in 1809. During the war, roughly one-third of wounded Swedish soldiers died in field hospitals, a record that prompted King Charles XIII to found the Karolinska Institute in 1810 to provide better training for army doctors.

    From early on, the Karolinska put great emphasis on basic research, but what really put it on the map was a clause in Alfred Nobel's will that gave Karolinska the task of picking the Nobel laureates in physiology or medicine. “Every important scientist comes through [on research stints] because of the Nobel aura,” says Wahlestedt.

    Controlling destiny.

    Hans Wigzell knew that with less government money, Karolinska had to team up with industry to maintain its landmark status.

    CREDIT: LARS SKOG

    Sweden's successive social democratic governments also treated Karolinska generously. “Medical research has been strongly supported for decades,” says Kjell Simonsson of the Karolinska Investment Fund. In the early 1990s, however, a sluggish economy prompted the Swedish government to cut research budgets. Wigzell's predecessor, Nobelist Bengt Samuelsson, saw the writing on the wall and began setting up a legal framework that would allow Karolinska to forge industry ties.

    In 1995, as senior Karolinska faculty members were casting around for someone to step up the pace of Samuelsson's reforms at this critical stage, Wigzell's name kept coming up. He had established his scientific credentials in tumor biology and immunology 2 decades earlier with his co-discovery of natural killer cells and development of a widely used chromium assay for measuring cell death. (With 500 peer-reviewed publications and counting, he still maintains a lab.) Wigzell also proved an adept administrator as director of the National Bacteriological Laboratory in Stockholm, the Swedish version of the U.S. Centers for Disease Control and Prevention. When Wigzell took over in 1988, the lab was in decline; he dissolved it and rebuilt it from scratch.

    Despite professing a desire to return to the lab bench, Wigzell was nominated and elected and took over Sweden's biomedical powerhouse in July 1995. His first task was to work the same magic that he had performed on the actors at the Stockholm theater. He set out to change the attitude “that KI is as good as it could get and shouldn't collaborate with anyone, … certainly not industry,” says Per Hall, vice chair of the Center for Medical Epidemiology at Karolinska.

    Industrial deals

    Although the institute director does not have the power to direct research, Wigzell took steps to stamp out mediocre work. In 1993, Samuelsson had melded 158 departments into about 30. Under Wigzell, the reforms have proved to be more than just a revised seating plan. Department chairs now control most of KI's federal funding, which provides enough money for a few months' salary. Professors must then compete for funds for the remainder of their paychecks. “It's not that easy to sack people,” says Fransson, who says the goal is to “be more elitist, allocating more money to fewer researchers.”

    Making KI's faculty leaner and fitter is all part of Wigzell's mission to put the institute on a sounder financial footing. With levels of government funding now harder to predict, Wigzell had to find other sources of income. He soon realized that KI's greatest growth potential lies in corporate ties. Five years ago, only about 2% of the institute's funds came from industry; that percentage has grown to 7% in this year's $285 million budget. He is aiming for a 20% share by 2004.

    As a first step, KI had to do a better job of licensing its inventions. As in Finland and Norway, Swedish researchers own their own research. But Wigzell realized that having researchers hawk their wares directly to drug companies wasn't working. “Big pharma doesn't want academic people coming to them; they don't know where they've been,” says KI's Folke Meijer. Instead, he says, “pharma wants to buy ideas after the proof-of-principle stage.” To make Karolinska's ideas more attractive, one of Wigzell's first initiatives as president was to pressure the government to pass legislation allowing universities to set up commercial entities. Within days of the law being passed, he had established KI Holdings AB, a commercial arm of the nonprofit institute. Since then, Wigzell and his top lieutenants have created several companies nested like Matryoshka dolls under KI Holdings.

    For example, Karolinska Innovations AB (KIAB) essentially serves as the university's tech-transfer office, filing for patents on behalf of inventors, then selling or licensing them, with a portion of the money flowing back to the inventors. As well as selling their ideas, KI is now encouraging researchers to go into business themselves. In 1999, Wigzell and company set up the Karolinska Fund, with five investors—a major Swedish pension fund, the Wallenberg Foundation, two insurance companies, and the Swedish Medical Association—pooling $50 million in venture capital. Three new buildings, to house a staff of up to 600, are rising to accommodate KI start-ups and should be finished by the end of 2004. Wigzell hopes that within a decade, as many people will be employed by KI companies as are employed by KI itself.

    One budding success story is a firm called Global Genomics. Molecular biologist Sten Linnarsson, working as a Ph.D. student in Patrick Ernfors's lab at Karolinska a couple of years ago, was disappointed with the results from experiments using Affymetrix gene chips. “This started my brain working on how to do this better,” Linnarsson says. He hit upon a method of combining gene detection using the polymerase chain reaction with computer algorithms designed to identify and quantify the genes in a sample. The young team—Linnarsson is 30 and Ernfors is 37—took the idea to KIAB. After agreeing to terms, KIAB filed for patent protection and helped the duo set up Global Genomics. Within a month after its formation, the company had secured venture capital.

    While nurturing start-ups, Wigzell has also sought closer ties with big pharma, such as by collaborating on the Center for Genome Research and Bioinformatics (CGB), a joint operation with Pharmacia & Upjohn Inc. Set up in 1997, the center was at first funded solely by the drug giant. “In the beginning, there was a lot of suspicion and natural skepticism from researchers around KI” who doubted that the center could retain its academic freedom, says Wahlestedt, CGB's director. But perceptions have changed, he says: “As we went along and they saw [that] we hire talented basic scientists and produce good science, … people were won over.”

    The industry ties have not just been restricted to Sweden or the pharmaceuticals business. Last year, Wigzell struck a deal with the Japanese firm Sumitomo, which sank $7 million into clinical research at KI related to Alzheimer's disease. The collaboration has opened a floodgate of other Japanese organizations looking for ties with Karolinska.

    Now, KI is embarking on an even grander industrial venture. The plan is to convert a huge unused railway yard, covering more than 500,000 square meters, into a business park dominated by biotech start-ups and research institutes, along with housing for scientists and students. Last month the city of Stockholm and Jernhusen AB, which owns the land, signed a letter of intent to develop BioScience. This “was the first and absolutely necessary decision” to proceed from the visionary stage to implementation, says John Skår, director of Karolinska's Center for Medical Innovations, who dreamed up BioScience. Along with Stockholm University and the Royal Institute of Technology, KI is now looking for roughly $2 billion in private investment and hopes to open the park for business by 2006. The three academic players expect BioScience to stimulate collaboration between themselves and industry, potentially creating thousands of jobs for scientists.

    Room for growth.

    Karolinska and its partners are seeking $2 billion to launch the mammoth Stockholm BioScience park (depicted in red).

    CREDIT: KAROLINSKA INSTITUTE

    Conflict resolution

    With this amount of traffic between academia and industry, potential conflicts of interest could become a serious issue. Wigzell is overseeing an effort to craft rules requiring full disclosure. Draft guidelines mandate a KI review if a scientist receives more than half his or her research support from industry. Already in place is a rule that the administration must sign off on any deal exceeding $10,000.

    When not leading KI, Wigzell serves on many corporate advisory boards around the world. And in March 1999 he was appointed science adviser to the Swedish government. Besides pressing for legislation that would benefit scientists, he tries to educate politicians by introducing them to scientific leaders. Recently, he took Harold Varmus to lunch with Prime Minister Göran Persson and dined out with Venter and Research Minister Thomas Östros. “Politicians need information they can trust,” Wigzell explains.

    Not all Karolinska staff members have enjoyed being caught up in the Wigzell whirlwind. “The leadership of Wigzell is about taking people by surprise, and not everyone likes that. He is a person you either love or hate,” says Masucci, adding that “it's a minority who are discontent.”

    But that minority spoke resoundingly when Wigzell's first term expired last June. Although he won reelection for a 2.5-year term that will see him into retirement, several prominent voices in KI's electoral assembly voted for a clinician to take the helm. The vote reflected disaffection within the clinical research ranks, which comprises about 60% of KI's scientific staff. Part of the frustration stems from increasing clinical and teaching demands. “There's no time for a clinician to keep up with the knowledge,” says Fransson, who notes that this problem is not unique to Karolinska. “If you were to find a shadow over Hans, this would be it.” In response, Wigzell is stepping up efforts to help KI clinical researchers benefit from the industrial ties. He's also designed a “merit portfolio” that attempts to account for teaching, scientific, and clinical achievements in marking career progress.

    Wigzell has also come under fire because few women have risen to Karolinska's higher echelons. “The new business-type organization tends to favor an old boys' network,” asserts Masucci. “This breeds discontent.” That view is shared by some prominent outsiders. “It was a nationwide scandal when he appointed 15 [department chairs] last February and they were all male. He did not do this by mistake,” charges KI board member Agnes Wold, a bacteriologist at Göteborg University.

    Others defend Wigzell's record. Tomas Cronholm, KI's trade union leader, notes that the university has just appointed equality ombudspersons to help female staff members and students. “He now takes this issue very seriously,” Cronholm says. Wigzell himself insists that he is working hard to raise the status of women at Karolinska. He even cites Kerstin Wigzell, Sweden's surgeon general (and his wife), as his role model. “She's taught me how to open up to people,” he says.

    That has undoubtedly helped Wigzell become a master at the art of bending people's wills to the task of raising Karolinska's fortunes. Says Brazilian Dulceaydee Gigliotti, who works in Wigzell's lab, “Only an unconventional Swede like Hans could bring about changes so fast. He broke the dogma.”

  14. SWEDISH BIOSCIENCE

    Working Sweden's Population Gold Mine

    1. Jocelyn Kaiser*
    1. With reporting by Lone Frank, a science writer in Copenhagen.

    One of Hans Wigzell's boldest scientific moves as head of the Karolinska Institute was to encourage a bright Swedish star in cancer epidemiology to uproot his entire department at Uppsala University and move to Stockholm. Since making the switch in 1997, Hans-Olov Adami's team has grown from 40 to 150, consolidating its position among the top epidemiology departments in the world.

    Adami had built a reputation at Uppsala on high-impact papers on everything from the cancer risks of hormone replacement therapy to survival rates for early prostate cancer. However, he says, Uppsala's financial support was flagging while Karolinska beckoned with a “much more vital, visionary, and dynamic” environment. “Our faculty locked ourselves up like cardinals and voted to move,” Adami says.

    Key to Adami's success is his group's access to Sweden's unique national databases, a gold mine of information for exploring how genes and the environment influence disease. The country's national health care system gives each person an identification number at birth and maintains health records in a registry. This allows for so-called “linkage” studies in which cancer cases can be assessed by occupation, for instance, or time of first pregnancy. Karolinska also maintains two high-powered research databases, including the world's largest twin registry with records on over 70,000 pairs.

    Doubly precious.

    Studies of identical twins Ruth and Annié Nyström and others in Karolinska's registry are yielding insights on genes, aging, and disease.

    CREDIT: GUNN ABERG

    Once ensconced at Karolinska, Adami did some recruiting of his own, luring behavioral geneticist Nancy Pedersen from another Karolinska department in 1999. She helped the group expand beyond cancer studies. All told, the team churns out a paper every couple of days, over 100 in 2000 alone. Among their recent contributions are studies probing the links between human papillomavirus and cervical cancer, and, for example, caffeine consumption and spontaneous abortions.

    The twins database, with the oldest living pairs in their 90s, is becoming ever more valuable now that “enough people are dying or being sick” from chronic diseases, Pedersen says. Some findings based on the twins have been controversial: For example, scientists recently challenged a paper suggesting that cancer risk is linked only weakly to genes (Science, 27 July, p. 601). “It was a good contribution, but it indicates how difficult these studies are,” says epidemiologist Robert Hoover of the U.S. National Cancer Institute. Another influential study suggested that intelligence is determined largely by genetics, even into old age (Science, 6 June 1997, p. 1560). The Karolinska team's skill at working these databases has produced “penetrating findings,” says Harvard epidemiologist Walter Willett, who expects to see a steady stream of intriguing papers from Stockholm in the years to come.

  15. EVOLUTION

    Evolutionary Pulse Found, But Complexity as Well

    1. Richard A. Kerr

    East African animals responded to abrupt climate change 2.8 million years ago, but climate's effect on human ancestors remains unclear

    Species come and species go. A huge asteroid or comet brought an untimely end to all the dinosaurs, giving mammals their chance, but why are we humans dominating the planet rather than some big, furry equivalent of Tyrannosaurus rex? The answer, according to one much-discussed theory, is climate change: The world took an abrupt step toward glaciation, the East African cradle of the human species dried to grasslands, and human ancestors coped with dwindling forests by evolving bigger and better brains (Science, 26 July 1996, p. 431).

    A new study of one of the best fossil records for testing the connection between climate and human origins lends some support to the theory: It finds an abrupt shift in East African species that coincided with a known climate change 2.8 million years ago. But the story emerging from East Africa is not a simple one, and the link to human evolution remains tenuous at best. “The record is really quite rich and very complex in terms of the variety of faunal changes at this time,” says paleontologist René Bobe of the Smithsonian Institution's National Museum of Natural History (NMNH) in Washington, D.C. He published the analysis of fossils from southern Ethiopia in the current issue of Paleobiology Memoirs with Gerald Eck of the University of Washington, Seattle.

    The fossils that Bobe and Eck analyzed were collected by an international consortium, which included Eck, in the 1960s and '70s. Each day in the field—in the Omo River valley of far southern Ethiopia—Eck and his crew would systematically collect all the fossils of certain types visible in a representative cross section of the Shungura Formation, an eroded pile of sediments almost 800 meters thick laid down by a meandering river. This systematic approach yielded a statistically workable number of reasonably representative fossils from a single formation. And the age of each fossil was particularly well known, which would allow dating of any response of animals to climate.

    Mammal treasure trove.

    East Africa's Shungura Formation holds a wealth of 2-million-to 3-million-year-old fossils, like this hippo mandible.

    CREDITS: G. ECK

    Bobe and Eck whittled the total collection of 22,335 specimens of mammalian crania, jaws, horns, teeth, and foot bones down to 4233 bovid fossils—the remains of grass-grazing animals such as antelopes, gazelles, wildebeests, and buffaloes—that met rigorous collection criteria. The two researchers then calculated how the abundance of each taxon varied between 2 million and 3 million years ago. “We found a significant shift in abundance [of bovid taxa] at about 2.8 million years ago,” says Bobe, “followed by continuing but more gradual change 2.8 million to 2.0 million years ago.” It was 2.8 million years ago that cycles of cooling and drying in East Africa intensified, producing a shift toward grassier environments (Science, 14 January 1994, p. 173). These changes, in turn, resulted in the jump in the number of bovids adapted to those environments, Bobe and Eck conclude.

    Paleontologist Elizabeth Vrba of Yale University has long argued that bovids around Africa underwent a “turnover pulse” about 2.8 million years ago, as the climate shift triggered a surge of both extinctions of existing species and originations of new ones. Although Bobe and Eck tracked changing abundances of various bovids rather than the turnover of species, “my results could be very compatible,” she says. “This is so close in timing to what has been proposed, it fits very well.”

    Paleontologist Anna K. Behrensmeyer of NMNH has also reported a shift in species in that era, but she found a different pattern: a gradual transition but no pulse in mammalian fossil data from the Turkana Basin just to the south of Omo (Science, 26 July 1996, p. 431). The three studies could be seeing different aspects of climate-related animal evolution—a spurt of extinctions and originations or gradual changes in abundance—depending on the type of analysis and the particular fossil collection, she notes. Still, Bobe and Eck's analysis suggests that “2.8 million years ago does seem to be a time of particular turnover” that coincides with the climate shift, she says. “Global-scale climate change was penetrating this area enough to be correlated with species turnover around 2.8 million years ago.” But then change continued, only it involved changing species abundances, not extinctions.

    Just how complex the climate-evolution link might be is further illustrated by an as-yet-unpublished study by John Barry of Harvard University and his colleagues about fossils from the late Miocene epoch in Pakistan. About 8 million years ago, when grasslands surged into dominance in Pakistan, the number of new species jumped, but extinctions didn't climb until half a million years later. Earlier, 10.3 million years ago, animals experienced “a big turnover” of both extinctions and originations similar to the pulse Vrba sees in Africa 2.8 million years ago, says Barry, but there is no sign of a climate-induced shift in grassland dominance in Pakistan at that time.

    Paleontologists agree that many more studies like these are needed to establish any firm link between climate and animal evolution. Extending the chain to human origins looks even more daunting—especially because the recent discovery of two very ancient hominid fossils has confused the picture of early human evolution (Science, 13 July, p. 187). “You find a couple new [hominid] fossils, and all of a sudden you have a whole new branch on the family tree,” says Bobe. “With the more recent [fossil] discoveries from Kenya, it's now very unclear” when a key branching in the hominid family tree once dated at 2.8 million years ago actually occurred. The “why” of human origins must await a clearer “how.”

  16. ECOLOGY

    Cave Biologists Unearth Buried Treasure

    1. Kevin Krajick*
    1. Kevin Krajick is the author of Barren Lands: An Epic Search for Diamonds in the North American Arctic.

    Researchers are bringing up a steady stream of odd cave creatures, which are shedding new light on the rules of life in the underworld

    Caves have always haunted the imagination. The ancient Greeks shuddered at tales of Cerberus, the three-headed monster guarding the entrance to hell, and countless myths and Hollywood fantasies include a spine-tingling staple: unknown creatures lurking in the next claustrophobic corridor, hungry and waiting for visitors. Now it turns out that bizarre, voracious denizens of the underworld are not wholly imaginary. Biologists slithering into ever deeper, tighter recesses are coming face to eyeless face with a fast-growing list of cave-dwelling spiders, centipedes, leeches, mites, scorpions, beetles, fish, snails, worms, and salamanders, along with thick beds of bacteria and fungi that sometimes make a living off the very rocks.

    Yet for biologists such discoveries involve more treasure than trepidation. Dominated by small insects, crustaceans, fish, and amphibians, cave fauna offer a glimpse into the usually inaccessible subterranean realm, where tiny air pockets and glistening crevices can be rich with life. And as more and more cave life comes to light, biologists are rethinking old generalizations about underground ecology and evolution, according to reports at a recent symposium on biospeleology (that is, cave biology), held in cave-combed Intervales State Park in southern Brazil.*

    Cave dwellers, or troglodytes, may be winning newfound respect, but reports at the meeting also highlighted the fact that they are among the most delicate, endangered of creatures. Naturally hemmed in, some species may consist of just a handful of individuals from a single cave; in the United States, home to 1000 of the 6000 known species, 95% are now threatened by mining, pesticides, and sewage, not to mention invasions of bacteria, mites, and even dandruff borne by tourists and researchers, says biospeleologist John Holsinger of Old Dominion University in Norfolk, Virginia.

    Flying food source.

    In many caves, bats deliver the chief source of nutrition: guano.

    CREDIT: STEPHEN ALVAREZ

    And that's just the known species, for the science of biospeleology is still in the early discovery phase. In the 1830s biologists started exploring caves in limestone, which underlies 15% of Earth's surface, but not until the 1970s, with advances in caving and research techniques, did they find creatures in other rocks and in climes that seemed unpromising. Now scores of species come to light annually, with no end in sight. Specialists estimate that 90% of known caves have never been biologically surveyed—and 90% of caves remain undiscovered altogether, because most lack visible surface openings. “That's the thrill: To pioneer, all you have to do is crawl in and look,” says William Elliott, a biospeleologist for the Department of Conservation in Missouri, where a growing cadre of amateur spelunkers report dozens of new caves each year. Elliott's own recent finds include a dozen new species of mites, millipedes, and amphipods; an all-black salamander; and a blind crayfish.

    Even with these revelations, what we see in caves may be only a taste of what actually lives in the underworld. Frank Howarth, an entomologist at the Bishop Museum in Honolulu, Hawaii, says that the lives of many troglodytes are undiscoverable, because they dwell in “microcaverns” and “mesocaverns”: endless tiny crevices, fissures, and tubes that may or may not open into what we think of as a cave—that is, anything big enough for people to fit in. “With the possible exception of the deep ocean, no other habitat is so foreign to human experience,” he says.

    Underworld lifestyles

    Caves provide generally predictable weather, but troglodytes face a scarcity of creature comforts—space, light, food—and a panoply of dangers, including rough vertical terrain, endless mazes, lethal gases, radioactive rocks, and catastrophic floods. Beyond the classic missing eyes and lack of pigment, many have adapted with eerily long legs and sensory organs, the ability to deal with 100% humidity, and incredibly low metabolic rates. Long-term studies of the small Orconectes australis crayfish in Shelta Cave, Alabama, for example, suggest that it reproduces at age 35 and lives past 100.

    Confinement amid rock layers prevents most animals from dispersing far, which keeps most species local and numbers vanishingly small. Richard Borowsky, a New York University geneticist who addressed the recent conference, says that 12 cave-fish species he has analyzed have a fifth or less of the genetic variation of surface relatives, suggesting that some gene pools may consist of as few as 100 individuals. But some aquatic cave species—called stygobites, for the mythical underground Styx, river of the dead—can travel freely in groundwater. For example, blind catfish and salamanders shooting up through artesian wells alerted researchers to the richness of southern Texas's Edwards Aquifer, a 10,000-square-kilometer complex of watery limestone caverns with some four dozen known species.

    Food is the other limiting factor. Because there is no photosynthesis in deep caverns, the main source is often meager dribbles from the surface: nutrients dissolved in seep water, or bugs or leaves swept down sinkholes. Although no known mammals dwell exclusively underground, in many caves the most significant source of nutrition is bats. Some caverns contain millions that forage topside but roost or nest below, depositing guano that fuels perhaps 40% of cave species, according to cave biologist David Culver of American University in Washington, D.C. In caves lacking bats, the occasional “accidental”—a raccoon that wanders in too far to escape, a log washed in during a storm—provides an orgiastic banquet that may resound through the food chain for centuries.

    Culver says troglodytes live up to their fantasy image in one respect: An unusual proportion are predators, armed to subdue struggling prey with nasty pincers or stingers. But they will eat anything, alive or dead. “They can't afford to be picky,” says Culver, who reviewed U.S. cave fauna in the journal Conservation Biology last year.

    Festival site.

    In Mexico's Cueva de Villa Luz, locals celebrate and feast on abundant cave fish (bottom).

    CREDITS: STEPHEN ALVAREZ

    Cave dwellers rely on stranger sources of nutrition, too. Some newly found troglodytic microorganisms appear to live on methane fumes belching from the deeps, manganese and iron dissolved in water, and, in some cases, the rocks themselves, phenomena detailed in an upcoming special cave issue of Geomicrobiology Journal. Because the food sources in such geologically fueled systems are basically endless, the caves explode with life. The first such discovery was Movile Cave, a blind cavern in Romania accidentally breached in 1986. There, geologically fueled bacteria and fungi feed a higher fauna of 31 endemics, from worm-sucking leeches to water scorpions.

    The latest is Cueva de Villa Luz (Cave of the Lighted House) in southern Mexico, revered by the local Soque people, who have long held yearly religious rituals there to catch and feast upon swarms of tiny bright pink fish. A 1998 expedition led by geologist Louise Hose of Chapman University in Orange, California, showed that the extraordinarily numerous fish—a new species—thrive because hydrogen sulfide in the air and water produces so much prey. Deep inside the cave are highly acidic “snottites,” mucusy, stalactite-like drips made of massed sulfur-eating bacteria. The walls host thick fluorescent bacterial and fungal tapestries, springy as raw oysters and crawling with bright red insect larvae. “Spider webs and eggs totally cover some of those slimes, and [there are] more spiders than you ever want to think about,” says microbiologist Penelope Boston of the University of New Mexico, Albuquerque. Bats, buzzing midges, and crane flies fill the sulfurous air—poisonous for humans, who suffer rashes, eye infections, and headaches.

    Hose says such ecosystems, once thought oddities, may be widespread. Work on the Edwards Aquifer by the Texas Memorial Museum now suggests that the food chain there may get a boost from sulfur-and methane-eating bacteria in the lower reaches. Other investigators are looking into smaller sulfur-fed systems in backcountry Wyoming and Kentucky. Hose has been asked by the government of Oman to explore a cave with another odd fish population, and Boston has gone the next step: She has a grant from NASA to investigate the idea that Mars, with soil rich in substances eaten by troglodytes, could have some very lively caves.

    Seeking stability

    Whether troglodytes exist below Mars's harsh surface or not, earthly troglodytes seem to have originally descended from surface dwellers, often fleeing climate and landscape changes. Once below, they may speciate further over the millennia as they adapt to underground niches.

    For example, the eastern United States holds 240 troglodytic Pseudanophthalmus beetle species. Their diversity suggests that their ancestors may have been common and widespread on the surface in leaf litter, shady ravines, and sinkholes during moist, cool conditions caused by intermittent glaciers farther north over the past 2 million years, says Holsinger of Old Dominion. He surmises that when the ice pulled back, the beetles did not like the resulting warmth and dryness, retreated ever deeper, and then split into local varieties as their populations separated. Biologists have spotted cave creatures in various stages of this speciation process. For example, a single millipede species, Cambala speobia, may be in the first stages of evolutionary adaptation to life underground. It was recently discovered in many Texas limestone caves and in cavelike spaces in loose boulder piles, all too far apart to be connected underground. Because Texas was much cooler and wetter just 1000 years ago, and the underground millipedes are still all alike, with no evidence of divergence from each other, they may have gone underground within recorded history, says Missouri's Elliott. “It's continuous: Animals are probably in the process of becoming troglodytes all the time,” he says.

    Underworld explorer.

    Penelope Boston samples “snottites”: slimy strings of bacteria.

    CREDIT: STEPHEN ALVAREZ

    Until the last 20 years or so, the notion of troglodytes as refugees from surface climate change neatly explained their distribution: They were most commonly found in so-called temperate zones, where climate periodically turns hostile, but they were thought to be scarce or absent in the tropics, where climate offers little reason to escape underground. But a string of studies has played havoc with that theory.

    In 1971, Howarth of the Bishop Museum began braving the depths of Hawaiian lava tubes. There, in a narrow passage, he met an eyeless 8-centimeter arachnid: the Kauai cave wolf spider, one of the largest troglodytes yet discovered. Predecessors missed them because they cluster in the deepest recesses, accessible only through scary U-shaped drains that exclude outside air. “It's not that I'm braver,” says Howarth. “They just didn't have modern electric lights or respirators.” In the years since, he and others have found 75 assorted Hawaiian lava-tube creatures.

    Many of these evidently descended not to escape anything but to get at underground goodies, says Howarth. The volcanic islands are constantly renewed by fresh lava flows that solidify with endless air spaces inside, which range from several stories high to capillary-sized and are largely interconnected. The new surface may host just a few scrubby trees, but 10 meters or more down, the trees develop luxuriant root systems hanging off cave ceilings, and along with fungi, these roots provide abundant food. Cave creatures colonize fast; 9 months after one eruption, Howarth found troglodytes in a brand-new tube, its walls still almost too hot to touch. Taking his lead, tropical biospeleology is now booming, with varied new communities being documented from Brazil to Malaysia and Thailand.

    Indeed, cave animals are now turning up in most of the environments where they were once thought absent, including formerly glaciated sites (the ice was thought to crush or freeze them) and ancient, arid rocks (once thought to lack sufficient limestone and water). For example, 3 years ago William Humphreys, a senior curator at the Western Australian Museum in Perth, began investigating the ancient rocks below the interior deserts of northwestern Australia and found water-filled caverns of calcrete, a form of limestone. In checking just a tenth of those aquifers, Humphreys has already found dozens of amphipod and diving-beetle species, all apparently endemic. “This must be the merest glimpse so far,” says Humphreys, who addressed the Brazil meeting. He has never entered the caverns; the only access is water pumped up through ranchers' wells and mineral-exploration boreholes.

    Survival down under

    Those boreholes may raise the biggest question of all: whether many of these creatures can survive growing intrusions by humans. When groundwater levels drop, aquatic habitats disappear, and many troglodytes appear exquisitely vulnerable to water pollution. One Australian company is proposing gigantic “water mines” that would empty aquifers into pipelines (Science, 2 June 2000, p. 1581), and Australia's mineral companies want more traditional open-pit nickel, gold, and iron mines. The story is similar the world over. So much water has already been pumped from Texas's Edwards Aquifer that nearly all the subterranean aquatic species are threatened, as are nine nonaquatic ones, which were put on the U.S. endangered species list last year. The Kauai cave wolf spider was declared endangered last year because of sewage from new houses, golf-course insecticides, and competition from an adaptable new invader: the American cockroach. In Alaska, loggers are stripping land around unexplored caverns, causing silt to rush in. At least 10 U.S. species are already gone, estimates Missouri's Elliott in the recent book Subterranean Ecosystems.

    Although surface activities are the main threat, tourism—and research—may be the final assault for some caves. Every hour, a human visitor sheds 60,000 skin fragments; millions of dust, hair, and clothing-lint particles; 24 liters of carbon dioxide; 170 watts of heat; and alien bacteria and fungi—to say nothing of the effect of a hiking boot on a half-centimeter insect. “This messes with the system pretty fast, with cascading results,” says Rod Horrocks, a manager at Wind Cave National Park in South Dakota. Horrocks says lights switched on for tourists have allowed photosynthetic algae—and newly emboldened rats—to take root, and lint in unvented spaces “makes some formations look like the back of your clothes dryer.” Even in the vast depths of New Mexico's Lechuguilla Cave, where only researchers enter, biologists' urine introduces nutrients, causing foreign bacteria and fungi to proliferate, according to a report by Diana Northup, a microbiologist at the University of New Mexico, Albuquerque, in the Journal of Cave and Karst Studies last year. As a result, Lechuguilla researchers now wear clean clothes, transport wastes out, and eat over drop cloths.

    Armed and ready.

    Many cave dwellers, like this spider, are predators.

    CREDIT: STEPHEN ALVAREZ

    Some “show caves,” such as Arizona's Kartchner Caverns, are trying to minimize the damage with trailside curbs to contain lint, airlocks and misters to keep humidity constant, and lights that come on only when people show up. But “this stuff doesn't always work,” says Gary Berdeaux, who runs Diamond Caverns in Park City, Kentucky, the country's oldest continuously operated show cave. “Unfortunately, show caves are sacrificial lambs.”

    At Diamond Caverns, at least a few cave creatures have managed to coexist with visitors. No one knows what lived there before August 1859, when the cave opened for business, but a few blind beetles and crayfish still hang on, occasionally scuttling ahead of guides' flashlights. “We like to see them,” says Berdeaux. “It means there's something left.”

    • *The 15th International Symposium on Biospeleology, 8–15 July.

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