News this Week

Science  08 Mar 2002:
Vol. 295, Issue 5561, pp. 1808
  1. NUCLEAR FUSION

    'Bubble Fusion' Paper Generates a Tempest in a Beaker

    1. Charles Seife

    The heat from the controversy alone is nearly enough to trigger a nuclear reaction. This Week in Science (p. 1868), scientists led by nuclear engineer Rusi Taleyarkhan of Oak Ridge National Laboratory in Tennessee claim to have seen evidence for nuclear fusion in a beaker of organic solvent. That stunning claim, if true, could eventually have important consequences for nuclear proliferation and energy production. But other scientists, citing another Oak Ridge experiment that seems to belie the claim, are likening the paper to cold fusion. Adding to the brouhaha is a series of exchanges between the magazine's editor-in-chief and nonauthors seeking to influence Science during its publication of the paper.

    Unlike nuclear fission, fusion is very difficult to initiate. Only at extremely high pressures and temperatures can atomic nuclei slam together hard enough to merge, or fuse, releasing energy in the process. A hydrogen bomb achieves those pressures by first setting off a small fission bomb to get the process going. A handful of labs are gearing up to do the same with enormous lasers or powerful magnetic fields (Science, 18 August 2000, p. 1126; 25 January 2002, p. 602). Small-scale “tabletop” fusion reactions, meanwhile, have remained far out of reach. And the scientific community is still wiping egg off its face from the 1989 debacle involving so-called cold fusion, in which some researchers erroneously claimed to have seen fusion catalyzed by a lump of palladium metal.

    It is against this backdrop that Taleyarkhan, nuclear engineer Richard Lahey of Rensselaer Polytechnic Institute in Troy, New York, and colleagues make their case for tabletop fusion. The work relies on a phenomenon known as acoustic cavitation, in which sound waves rattling through a fluid create tiny bubbles and then cause them to expand and compress. Under certain conditions, those bubbles give off tiny flashes of light as they collapse, a phenomenon known as sonoluminescence. Many scientists believe that the bubbles, compressed by the acoustic waves, reach great temperatures and pressures. Some speculate that under the right conditions, those bubbles might—just might—provide conditions extreme enough to trigger fusion.

    Pop!

    Embattled paper suggests that deuterium nuclei undergo fusion inside sonoluminescent bubbles.

    ILLUSTRATION: C.SLAYDEN

    Taleyarkhan and colleagues set out to test that idea. Starting with a small cylinder of acetone in which all the hydrogen atoms had been replaced with deuterium (a heavy breed of hydrogen that has an extra neutron), the team subjected the cylinder to acoustic waves. At the same time, they zapped the deuterated acetone with high-speed neutrons. The neutrons, which each carried about 14 million electron volts (MeV) of energy, struck the molecules of acetone and gave them a punch of energy. “You get vaporization on a small scale,” says Taleyarkhan. The pockets of vapor nucleate bubbles and cause them to grow to about 1 millimeter across—much bigger than they would normally get in an acoustic field. “They grow to be mammoths,” he says. “You can actually see the bubbles.”

    The catastrophic collapse of a millimeter-sized bubble to a few nanometers across heats the deuterated acetone to the point at which deuterium atoms collide and fuse, the authors argue. “I thought, doggone! I'm depressed I hadn't done that experiment,” says Lawrence Crum, a sonoluminescence expert at the University of Washington, Seattle, who acknowledges that he reviewed the paper for Science. (The magazine's editors do not reveal the identities of reviewers to Science's news staff.)

    When deuterium fuses with deuterium, two equally probable things can happen. First, the two can form an atom of hydrogen-3, or tritium, while the extra proton zooms off with about 3.02 MeV (and in the apparatus would be quickly absorbed by the acetone). On the other hand, the two can make a helium-3 nucleus, while the extra neutron flies off with 2.45 MeV; unlike the proton, it would escape the acetone bath. Taleyarkhan and his colleagues claim to have detected neutrons whose energies are consistent with 2.45-MeV emissions, and they also claim to have seen extra tritium in the solution. Both effects disappear when they replace deuterated acetone with acetone, turn off the acoustic waves, or change the temperature of the bath to make it less favorable for cavitation.

    Some physicists have greeted the work with deep skepticism. “The paper's kind of a patchwork, technically, and each of the patches has a hole in it,” says Mike Moran, a physicist at Lawrence Livermore National Laboratory in California who has performed similar experiments with deuterated water. Moran says electromagnetic interference by an acoustic-wave generator raised false hopes of fusion in his own lab, and he worries that something similar may have happened at Oak Ridge. A beaker full of deuterated acetone, he says, should show an increase in tritium when irradiated by fast neutrons, even without cavitation—whereas Taleyarkhan's data show an enhancement only while the solution is cavitating. “It's an inconsistency in the data,” according to Moran.

    Tougher criticism comes from Dan Shapira and Michael Saltmarsh, two physicists who are also at Oak Ridge. Late in May, after the lab had given Taleyarkhan and colleagues the go-ahead to submit their results to Science, Lee Riedinger, the lab's deputy director for science and technology, asked Shapira and Saltmarsh to check the work with a more sensitive neutron detector. They concluded that Taleyarkhan's results had been an illusion.

    Deuterated duo.

    Rusi Taleyarkhan (top) and Richard Lahey hope others will soon repeat their experiment.

    “There's no evidence for any neutron excess due to fusion,” Saltmarsh says. “If the tritium results in Taleyarkhan's paper are correct, and if you assume all the tritium is due to d-d fusion, then you expect a 10-fold increase in the neutron signal. We see a 1% effect.” One possibility is that the extra neutrons are left over from the 14-MeV neutrons fired into the cylinder, eventually winding up in the detector after skittering about the room. To rule out that scenario, says Saltmarsh, he and Shapira timed the flashes of light from the bubbles and compared them with the arrival times of the extra neutrons. The effect disappeared. “We didn't see any evidence for a coincidence between neutrons, gamma rays, and light emissions above background,” Saltmarsh says.

    Taleyarkhan and colleagues dispute Saltmarsh's interpretation of the data and are posting the details of their objections on the Web. Riedinger characterizes the ongoing dispute as “an active dialogue about what could be wrong with either set of measurements.” At the same time, he compliments Taleyarkhan's abilities and calls the work “very novel and interesting.”

    Sharper comments began to pepper Science's editors as Taleyarkhan's paper neared publication. Don Kennedy, the editor-in-chief of Science, says that Oak Ridge officials tried to withdraw their permission to publish the paper. “There was certainly pressure from Oak Ridge to delay, if not to kill, the paper,” says Kennedy. “I'm annoyed at the intervention, and I'm annoyed at the assumptions that nonauthors had the authority to tell us we couldn't publish the paper.”

    As knowledge of the pending paper spread, scientists outside Oak Ridge joined the fray. Late in February, physicist William Happer of Princeton University and Richard Garwin of IBM's Thomas J. Watson laboratory in Yorktown Heights, New York, each wrote Kennedy a letter about the paper. They say they were simply encouraging Science to publish the Shapira and Saltmarsh data as well, or at least not to hype the paper.

    “I like Science,” Happer says. “I'm a member of AAAS, and I don't want them to shoot themselves in the foot—or some other body part. All I told [Kennedy] was, for God's sake, don't put it on the cover.” Happer, who headed the Department of Energy's science office for 2 years in the early 1990s, adds that he is also trying to save the scientific community from another embarrassing fiasco. “I saw it happen with cold fusion. If we're really unlucky, Dan Rather will talk about it on the [CBS] evening news and intone how, providentially, the energy problem has been solved. We as a community will look stupid.”

    Garwin says that he was troubled by the quality of the research. The version of the paper he saw described how the authors constantly adjusted the experimental setup to keep it tuned properly—conditions ripe for allowing unconscious bias to seep into the data. Given these concerns, he says, “it would be unfortunate if Science magazine were to take any position on its correctness.”

    Kennedy says that publication in Science certifies only that Taleyarkhan's paper has cleared the magazine's own peer-review and editing process. After that, it's up to the scientists. “We're not wise enough to certify that every claim will stand up to the active effort of replication,” says Kennedy.

    The importance of replication, apparently, is one of the few things on which everybody can agree. “There's some small chance that they're right,” says Happer. “It should be published. The truth always comes out.” Taleyarkhan takes the same position, although he hopes for the opposite result. “I'm looking forward to helping people reproduce the experiment,” he says. But until then, confusion, not fusion, is likely to reign.

  2. INFECTIOUS DISEASE

    New Culprit Emerges in River Blindness

    1. Elizabeth Pennisi

    For decades, people have blamed a parasitic nematode for a disease that has blinded at least 250,000 people now living in Africa and South America. But the real culprit—or at least an accomplice—may be the ubiquitous Wolbachia, bacteria that colonize many hundreds of species, including the nematode indicted in river blindness.

    On page 1892, researchers report that Wolbachia stimulate the severe immune system response that slowly robs people of their vision in areas where the disease is endemic. The work “is one of the most exciting things that's happened in the past 10 years” in research on parasitic nematodes, comments Jan Bradley, a parasitologist at the University of Nottingham, United Kingdom. It “sheds a different light on the pathology of this disease,” and it has already sparked debate about how big a role this bacterium really plays.

    River blindness begins with repeated bites from black flies that are common along rivers and streams in tropical areas. The insects transmit nematode larvae that settle under the skin, mature, and produce millions of young larvae called microfilaria. Those of the species Onchocerca volvulus travel through the skin to the eyes, where they remain in the microfilaria stage and die after about a year. A victim of the disease can have “hundreds of worms wiggling in the eye,” says Bradley.

    Parasitologists have long assumed that the nematodes cause the inflammation that damages the eyes and cornea, probably by releasing proteins when they die that spark an immune reaction. The drug currently used to fight river blindness kills larvae, which slows the course of the disease but doesn't cure it because the adults remain.

    Occupied territory.

    Wolbachia (red) thrive in the filarial worms blamed for river blindness.

    CREDIT: AMY HISE

    Wolbachia, by contrast, garnered little attention, although researchers have known for some 30 years that they live inside the worms. In the late 1990s, parasitologists demonstrated that the nematodes need these bacteria to reproduce, and researchers began to wonder what would happen if they killed the bacteria. Last year, Achim Hoerauf, a research physician at the Bernhard Nocht Institute for Tropical Medicine in Hamburg, Germany, found that in infected people, antibiotics kill the bacteria and interrupt the parasites' life cycle.

    “The question then was what role might the bacteria be playing” in river blindness, says Eric Pearlman, an immunologist at Case Western Reserve University in Cleveland, Ohio. To find out, his group teamed up with Hoerauf and Mark Taylor, a parasitologist at the University of Liverpool, U.K.

    In one experiment, the German team sent Pearlman extracts of worms taken from either untreated patients or those who had received antibiotics. In the latter group, the antibiotic had killed most of the Wolbachia, leaving a solution of worm proteins devoid of bacterial ones. When Case Western's Amélie v. Saint André injected the extracts into the eyes of mice, she and her colleagues found that the worm-plus-Wolbachia extract caused much more damage, judging by how hazy the mice's eyes became, than worm proteins alone.

    Pearlman and his colleagues tested additional extracts, this time supplied by the Liverpool team. These came from two other filarial nematodes, one that doesn't carry Wolbachia and one that does. Only the latter clouded the mice's eyes. “It looks like Wolbachia is really causing a lot of the problem,” comments Barton Slatko, a molecular parasitologist at New England Biolabs in Beverly, Massachusetts.

    Thus it seems that “if one were to treat [patients] with antibiotics, potentially these microfilaria would no longer be able to incite an inflammatory response,” notes Thomas Nutman, a parasitologist at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.

    But as Nutman and others point out, it's not yet clear how practical or effective these antibiotics might be. Microfilaria proteins may also play a role in the disease. And Eric Otteson, a clinical parasitologist at Emory University in Atlanta, notes that the extracts came from dead or dying adult worms and not from the juvenile microfilaria that colonize the eye. Thus, he says, the researchers have made “a leap of faith” in assuming that extracts of larval proteins would have the same effect. Nonetheless, many parasitologists view the international team's effort as an important step in understanding a disease that deprives hundreds of thousands of people of their vision.

  3. AIDS RESEARCH

    Delays Jeopardize Italian Program

    1. Michael Balter

    With a queasy sense of déjà vu, Italian AIDS researchers are bracing for severe funding cuts for the second time in less than 2 years. Only this time, their plight is even more dire: As Science went to press, Prime Minister Silvio Berlusconi's government had yet to allot any funds for the national AIDS program in its 2002 budget. To make matters worse, a series of freezes and delays has prevented most researchers from receiving grants awarded for 2001.

    Annual funding for the AIDS program, which peaked at nearly $14 million 6 years ago, now stands at about $11 million. But extracting that money from the government, which has changed hands once a year on average since World War II, is another matter. “It has taken a little miracle to get this funding each year,” says Stefano Vella, chief of clinical AIDS research at the National Institute of Health in Rome and president of the International AIDS Society. In 1997, then-health minister Rosy Bindi froze the funds for several months. Then in 2000, she proposed slashing the AIDS research budget by 36% (Science, 7 July 2000, p. 28). Although the government of former Prime Minister Giuliano Amato reversed that cut, the money is again on the chopping block.

    Where's the beef?

    Girolamo Sirchia had promised to fund AIDS program.

    CREDIT: PIER PAOLO CITO/AP

    Italian scientists have been lobbying current health minister Girolamo Sirchia—who has overall responsibility for the program—and Berlusconi's deputy prime minister, Gianfranco Fini, for a budget at least at the 2001 level. Speaking last December in Milan on World AIDS Day, Sirchia promised that the money would be forthcoming. But since then, Vella says, “we have not seen anything.” Nor have Sirchia and Fini replied to a letter last month signed by 200 researchers, including most of the 15 members of Italy's National AIDS Commission, asking the government to commit the funds. Sirchia and Fini did not respond to repeated requests from Science for comment.

    The government's foot-dragging could cripple a program in which key discoveries in HIV research have been made, say scientists, including insights into how the virus interacts with the immune system. “Italian researchers have made substantial contributions to basic and clinical research on HIV/AIDS,” says Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. Italian researchers have published about 9600 papers on AIDS in international journals since the national program began 15 years ago. If the funds are not forthcoming, those contributions could begin to dry up.

    “My laboratory, as well as many others, is already in a very critical condition,” says immunovirologist Guido Poli of the San Raffaele Scientific Institute in Milan, who's still waiting for money he was awarded for 2001. If the Italian AIDS community were to starve for lack of funds, says Fauci, it “would be a significant loss to the global HIV research effort.”

  4. PALEONTOLOGY

    Earliest Signs of Life Just Oddly Shaped Crud?

    1. Richard A. Kerr

    The search for fossils in rocks formed before the Cambrian explosion of life 540 million years ago “has been plagued by misinterpretation and questionable results,” leading paleontologist William Schopf of the University of California, Los Angeles (UCLA), once noted. Now Schopf's own claim for the oldest known fossils—fossils that have entered textbooks as the oldest ever found—is under attack as a misinterpretation of intriguingly shaped but purely lifeless minerals.

    A paper in this week's issue of Nature argues that the microscopic squiggles in a 3.5-billion-year-old Australian chert are not fossilized bacteria, as Schopf claimed in a 1993 Science paper (30 April 1993, p. 640), but the curiously formed dregs of ancient hot-spring chemistry. “There's a continuum [of putative microfossils] from the almost plausible to the completely ridiculous,” says lead author Martin Brasier, a micropaleontologist at the University of Oxford, U.K. “Our explanation is that they are all abiogenic artifacts.”

    If true, the analysis calls into question the fossil record of life's first billion years. It would also raise doubts about the judgment of Schopf, the man chosen by NASA to set the standard for distinguishing signs of life from nonlife at the press conference unveiling martian meteorite ALH84001 (Science, 16 August 1996, p. 864). But Schopf says that such speculation is unwarranted. “I would beg to differ” with Brasier's interpretation, he says. “They're certainly good fossils.”

    The absence of simpler, smaller predecessors to the complex Cambrian biological record was a problem that bothered Charles Darwin. But paleontologists have since found uncontestable fossils in rocks as old as 2 billion years. They include multicellular algae and cyanobacteria, which could produce oxygen through photosynthesis. But the earlier record is sparser and far messier. Of the half-dozen groups of microfossils claimed to come from the Archean eon (before 2.5 billion years ago), Schopf's group was the star. It was not only the most diverse, with 11 distinct taxa of organisms, but Schopf also thought it contained some fossils that were probably cyanobacteria. At 3.465 billion years, it was also the oldest, coming just 400 million years after the last lethal bombardment of the young planet (Science, 25 June 1999, p. 2111).

    A new view.

    By compositing in-focus views from a range of depths, a putative microfossil described by William Schopf (b, c) extends and balloons into (a).

    CREDIT: M. BRASIER ET AL., NATURE

    Brasier's paper, the first serious reanalysis of Schopf's 1993 paper, rejects the suggestion of photosynthetic bacteria. From both chemical analyses and geological mapping near Marble Bar in northwestern Australia, Brasier and seven colleagues conclude that the so-called Apex chert containing the putative fossils was deposited not on the floor of a shallow sea but below the sea floor in the throat of a hot spring. Both lines of evidence, the group says, show that Schopf's samples came from a conduit that eventually clogged with chert and other minerals deposited from the hot brine it carried toward the sea floor. Photosynthesis below the sea floor seems unlikely, Brasier notes.

    Examining Schopf's sections of chert, which had been archived at the National Museum of Natural History in London, Brasier saw the same segmented, wormlike threads of dark organic matter pictured in the paper. But he saw a great deal more when he raised or lowered the microscope's focal plane to bring rock above and below into focus. A long, stringy “microfossil” with supposedly sharp terminations at either end in Schopf's image instead continued downward from one end, ballooning to many times its original width (see figure). Some strands seemed to branch, unlike chains of bacterial cells. Other structures ranged from vaguely suggestive of life to inscrutable jumbles of dark organic matter. “We found so many intermediate, chaotic forms,” says Brasier. “Parts that would look like a bacterium [at one focal depth] took on weird shapes” at other depths.

    Brasier and the team suspect that they were seeing organic matter shaped into sometimes provocative but meaningless forms by hot-spring minerals as they grew and transformed on cooling. The organic matter might be the remnants of heat-loving bacteria that lived in the vents but went unpreserved, the group concludes. Or it might have been synthesized under high temperature from volcanic gases under the catalytic prodding of the metals found in the chert.

    Schopf accepts the reinterpretation of the site as the root of a hot spring and concedes that none of his fossils are cyanobacteria. Schopf had always relied on early, far less detailed geologic mapping by others that assumed the Apex chert was a sea-floor deposit, and he hadn't done any chemical or mineralogical analysis. But he says that Brasier's interpretation of the dark shapes “is just a mistake; they haven't the experience looking at Precambrian microfossils, or such a depth of focus confuses them.” The very unbacterial branching of chains of bacterial cells, for example, is actually folding of chains, says Schopf.

    Schopf has some support in the Precambrian community. “There's always a process of sorting out signal from noise,” says Malcolm Walter of Macquarie University in Sydney, who has published with Schopf. “You illustrate only the well-preserved things,” he says, and leave the messier structures found by Brasier unillustrated.

    Other Precambrian paleontologists side with Brasier. “I thought it was a very persuasive paper,” says Andrew Knoll of Harvard University. The structures illustrated by Schopf as microfossils, he says, are “part of a greater galaxy of structures that clearly are not biological.” Bruce Runnegar, a colleague of Schopf's at UCLA, was never fully convinced by Schopf's original evidence. “They're suggestive” of life, he says, “but there's no absolutely distinctive morphology.”

    Whether the textbooks get rewritten will depend on an analysis of material from new sites, says Walter. “I doubt if it will be resolved by more clever work on these samples,” he says. “It gets resolved by more work on more rocks. There are plenty more rocks out there.”

  5. ASTRONOMY

    Stellar Flares Illuminate Young Sun's Outbursts

    1. Robert Irion

    A nursery of unruly stars in the Orion Nebula has yielded the best look yet at our sun's baby album. Based on data from NASA's orbiting Chandra X-ray Observatory, it appears that the sun threw more tantrums than expected, in the form of powerful x-ray flares that zapped the surrounding disk of gas and dust. These flares may have seeded the early solar system with fragile radioactive isotopes. However, it remains likely that some of the unstable compounds also drifted into our sun's domain from nearby exploding stars.

    More than 4.5 billion years of evolution have erased all traces of the sun's youth, so astronomers dig into that past by studying similar stars elsewhere. X-ray satellites had spotted outbursts from a few very young sunlike stars, but it wasn't clear whether such flares were universal. Chandra has put those doubts to rest with images of what researchers call “the richest field of x-ray sources ever obtained.”

    Chandra stared at a tight cluster of nearly 1100 x-ray blips at the heart of the Orion Nebula, the middle “star” in Orion's sword. Astronomer Eric Feigelson of Pennsylvania State University, University Park, and his colleagues identified 43 stars in this patch with masses between 0.7 and 1.4 times that of our sun and ages from 300,000 to 10 million years. Of those solar mimics, all but two actively emitted x-rays—and most of them flared during the 23-hour Chandra exposure.

    The ferocity of the eruptions surprised Feigelson. The Orion flares were about 30 times more powerful and 300 times more frequent than the most intense flares unleashed by our sun today. The team's analysis will appear in The Astrophysical Journal and is posted on the astrophysics preprint server (xxx.lanl.gov/abs/astro-ph/0202046).

    Hot flashes.

    X-ray flares from sunlike baby stars in Orion point to a fiery youth for our sun.

    CREDIT: NASA/E. FEIGELSON ET AL./PENNSYLVANIA STATE UNIVERSITY

    The study confirms that the sun was outrageously energetic as an infant, others say. “The statistics are overwhelming,” says astrophysicist Donald Clayton of Clemson University in South Carolina. And, because x-ray flares boost protons and other particles to near the speed of light, Clayton notes, “the early sun was an intense accelerator of solar cosmic rays. We no longer have to postulate.”

    Indeed, Feigelson thinks the sun, in its first million years, seared the solar system with a flux of high-energy particles 100,000 times greater than today. “They were like machine-gun bullets,” he says. “They would have created radioactive isotopes readily.” The radiation blasted chunks of atomic nuclei from mineral grains wafting through space as the solar system condensed, he explains. Such nuclear reactions could have spawned calcium-41, aluminum-26, manganese-53, and other isotopes that decay in a million years or so. The offspring of those fleeting compounds are locked in the oldest meteorites; the new findings would help explain the puzzling timing of how the isotopes existed just as asteroids formed.

    At a recent Chandra meeting,*Feigelson's team emphasized solar radiation as the main process over a rival theory that a nearby supernova fertilized the solar system's embryonic cloud with rare isotopes. However, the paper's primary reviewer insists that the story isn't so simple. Magnetic fields may have steered particles from the x-ray flares into space above and below the gas and dust in the chaotic early solar system, says astronomer Alastair Cameron of the University of Arizona in Tucson. Mineral grains probably grew quickly, he adds. If so, nuclear reactions were confined to the outer rinds, where they wouldn't have yielded much radioactive material. Moreover, Cameron notes, at least one isotope—iron-60—could not have arisen via the stripping action of cosmic rays, because it has more neutrons than stable nuclei of iron, rather than fewer.

    Clayton allows that a star might have blown up in the right place at the right time, supplying key isotopes. Earlier generations of supernovae also may have added to the potpourri. “I think the pendulum has swung toward solar cosmic rays,” he says. “But the real answer is likely to include parts of both.”

    • *“Two Years of Science with Chandra,” 5-7 September 2001, Washington, D.C.

  6. NEUTRINO DETECTION

    Japan Hopes Casings Will Do the Trick

    1. Dennis Normile

    TokyoSince the devastating 12 November 2001 accident that shut down the $100 million Super-Kamiokande neutrino observatory, scientists there have been searching for a fail-safe strategy to prevent a recurrence—and get them back to work. Now they think they have one: a protective casing for each of the thousands of tubes that help them spot the elusive neutrinos. But they still need government funding for the repairs.

    “I'm doing everything I can to win approval for restarting the experiment,” says Motohiko Yoshimura, director of the University of Tokyo's Institute for Cosmic Ray Research, which runs Super-Kamiokande. According to Yoichiro Suzuki, head of the observatory's solar neutrino team, “this is the best solution [that can be] obtained in such a short time.”

    Super-Kamiokande is a massive water tank lined with light-detecting photomultiplier tubes that catch the glow of the Cerenkov radiation that results when neutrinos smash into atomic particles in the water. The facility has already earned a place in the science history books by producing the first convincing evidence that neutrinos have mass, a finding that overturned decades of theoretical predictions. But that research has been on hold since November, when a chain reaction of implosions destroyed about 7000 of the 11,000 photomultiplier tubes in the 39-meter-diameter, 41-meter-high tank. The tank was being refilled with water after some of its burned-out tubes had been replaced (Science, 23 November 2001, p. 1630).

    Case closed?

    Researchers hope casings of fiber-reinforced plastic and acrylic will protect Super-Kamiokande's photomultiplier tubes from a repeat of last year's accident.

    CREDITS: ICRR

    In January, an investigating committee of scientists involved in the experiment, plus outside experts in fluid shock waves, concluded that workers standing on Styrofoam pads placed atop the tubes on the bottom of the tank probably caused microfractures in the neck of a single tube. Those fractures caused the tube to implode when the water pressure reached a critical limit, setting off the chain reaction throughout the tank (Science, 11 January, p. 247).

    To prevent a recurrence of such an accident, the Super-Kamiokande team would like to nest each tube within a protective case. Researchers have tested numerous materials and configurations, including breaking one of the encased tubes in 40 meters of water to see if it set off a chain reaction. The preferred casing consists of a fiber- reinforced plastic base topped by a dome of clear acrylic plastic so that the light of the Cerenkov radiation can reach the sensors within the tube. “Of the various proposals, this is the safest,” says Yoshimura, who chairs the investigating committee.

    The committee's findings must be vetted by an outside panel. But an even bigger hurdle, says Yoshimura, is obtaining the necessary funding from the Ministry of Education, Culture, Sports, Science, and Technology. “The budget would possibly have to be increased” to cover the cost of the cases, he admits, although the price tag is not yet known. The ministry isn't expected to take up the matter before next month.

    A green light would enable researchers to wrap the 5200 tubes now available—those that survived, plus a thousand or so spares—in protective cases and redeploy them throughout the tank. Although this arrangement provides reduced sensitivity, it's good enough to resume some research. Getting the facility back to full strength could take 5 years and between $15 million and $25 million.

  7. STEM CELL RESEARCH

    Canada Gives OK for New Cell Lines

    1. Wayne Kondro,
    2. Constance Holden*
    1. Wayne Kondro writes from Ottawa.

    OttawaCanadian and U.K. scientists have gotten the green light to proceed with human embryonic stem (ES) cell research.

    Researchers may derive new lines of stem cells from embryos left over from fertility treatments or tissue from aborted fetuses under guidelines announced Monday by the Canadian Institutes of Health Research (CIHR). (Such derivation is prohibited for publicly funded researchers in the United States.) But the guidelines, issued in draft form last spring (Science, 6 April 2001, p. 31), prohibit the creation of embryos for research purposes or for so-called therapeutic cloning.

    The guidelines “balance the safety and ethical issues of concern to Canadians with research and clinical opportunities and the desire of Canadians to proceed with the use of stem cells to treat disease,” says CIHR president Alan Bernstein. A new committee will review research proposals, and all new cell lines generated using CIHR funds will be listed at an electronic registry and will be available to all researchers.

    Canadian researchers and private disease-fighting groups hailed the new guidelines, which lift a voluntary moratorium for the past decade on human ES cell research. These new rules also are consistent with draft legislation before Parliament. But they have drawn the ire of some pro-life members of the governing Liberal party, who accuse Bernstein of trying to circumvent the parliamentary process.

    Bernstein says he does not see CIHR's move as a substitute for legislation: “What we're doing today is putting guidelines in place where there's been a vacuum. … [They] will be replaced if and when legislation comes in.”

    Canadian stem cell scientists are pleased that the government has set down a clear path. “A lot of scientists have been waiting to hear what's going on,” says Mick Bhatia of the John P. Robarts Institute in London, Ontario, who is gearing up to culture hematopoietic cells from ES cell lines acquired from WiCell in Wisconsin. Michael Rudnicki of the University of Ottawa points out that Canadian researchers have had plenty of time to think about how to pursue their aims and have a well-organized infrastructure—including a research network called StemNet and centralized fertility clinics with approved informed-consent procedures to supply embryos.

    In the United Kingdom, meanwhile, officials are moving forward with the world's most liberal stem cell policies. Last week the Medical Research Council (MRC) issued its first two licenses to researchers wishing to derive cell lines—to Austin Smith of the Centre for Genome Research in Edinburgh and Peter Braude of Guy's Hospital in London. A House of Lords committee has sanctioned the existing policies, even stating that therapeutic cloning might be permissible in cases of “exceptional need” when embryos are not available from fertility clinics.

    The United Kingdom is also planning to set up the world's first stem cell bank. MRC is soliciting bids from national laboratories, and a winner will be chosen this summer.

  8. ANIMAL BEHAVIOR

    Guppy Sex and Gluttony Guided by Orange Glow

    1. Virginia Morell

    What do females want? In peacocks, it's a male with a billowing train of colorful, eye-spotted feathers; in túngara frogs, it's a male with a low-baritone “chuck” call. And in guppies (Poecilia reticulata), it's a male with orange spots. But why females prefer males with these particular traits and not bright purple spots, for instance, has proved difficult to pin down. Now, behavioral ecologist F. Helen Rodd of the University of Toronto and her colleagues report that for guppies, at least, the attraction derives from a simple gut response: Orange looks like food.

    “It's very cool,” says Anne Houde, an evolutionary biologist at Lake Forest College in Illinois. “Other studies in other species have shown a preexisting bias for certain traits in mates, but this may be the first to show how that bias originated.” Earlier work on what makes an orange male so dashing “tried to show that [females] looked at the orange spots for some indication of good genes,” says Michael Ryan, an evolutionary biologist at the University of Texas, Austin. Although that may still turn out to be the case, he says, the females' initial attraction seems to arise from “something in their neural system that evolved for foraging” orange-colored foods.

    Rodd first noticed the fish's magnetic attraction to orange in the early 1990s while studying wild guppies in Trinidad. Her voyeuristic counts of courtship displays and mating attempts were disrupted every time a small, orange fruit from a cabrehash tree hit the stream. Sex immediately lost out to gluttony. Indeed, Rodd says, the orange fruits were about “the only thing” that ever interrupted the males' persistent mating displays.

    Yum.

    Orange fruit (top) and fruit-colored spots (bottom) catch a guppy's eye.

    CREDITS: F. H. RODD

    Struck by that observation, Rodd and her colleagues decided to test guppies' color preferences. They painted small plastic disks various hues and placed them in streams, then counted the number of times the guppies pecked at disks of each color. Orange was always the high scorer–even among a well-studied population of females that do not prefer males with orange spots. The team followed up their field tests with laboratory experiments using second-generation guppies raised from wild ancestors. In all cases, notes Rodd, “guppies of all age and sex classes preferred” orange disks, apparently because of their hard-wired appetite for the orange fruits, the researchers report in the 7 March issue of the Proceedings of the Royal Society of London, Series B.

    At first, the idea that females are attracted to food-colored males was “a little depressing,” says Rodd. “Are female guppies really that stupid? All it takes is a flash of orange that looks like a fruit?"

    There may be more in the flash, though, than meets the human eye. Like many orange-colored fruits and vegetables, cabrehash fruits are loaded with carotenoids, which contain vitamin A and may support the immune system. Males that eat more carotenoid-bearing foods have the most distinctive orange color in their display spots, points out Greg Grether, an evolutionary biologist at the University of California, Los Angeles, one of the study's co-authors. Because the fastest fish get the limited supply of fruits, Rodd adds, “the color of the spots could still be telling the females something about the health of the males.” Indeed, previous research revealed that female guppies dislike males with dull orange spots–an indication that they are or have been infected with certain parasites.

    Thus, the male's orange spots may be like infomercials, both grabbing the female's attention and giving her hard data about the quality of the male's genes. “Attracting a mate is a multistep process,” says David Reznick, an evolutionary biologist at the University of California, Riverside, who has led numerous studies of wild guppies. After catching a female's eye, the male does a bend-and-shake dance that “holds the female's attention and tells her something about [himself].” Far from being simpletons in their mating decisions, guppy females seem judicious. And that, Rodd says, should be a warning sign to other researchers seeking to understand female choice: “It's more complicated than we thought–even in guppies.”

  9. DENMARK

    Greens See Red Over Revisionist's New Job

    1. Lone Frank*
    1. Lone Frank is a science writer in Copenhagen.

    CopenhagenHas the Danish government put a fox in charge of the henhouse? That's what many environmental researchers are wondering after last week's appointment of Bjørn Lomborg, author of the controversial book The Skeptical Environmentalist, as director of Denmark's new national Institute for Environment Evaluation.

    Denmark's right-wing coalition government has created the institute to assess the effectiveness of environmental protection spending. Many researchers and activists worry that Lomborg's thesis—that most environmental problems are wildly overstated—will color the institute's thinking. “He is widely distrusted among the people whose research he will be dealing with,” says environmental biologist and biodiversity specialist Peder Agger of the University of Roskilde. But Lomborg says that researchers are missing the point of the new institute: “It's about getting the most for the money we spend.”

    Lomborg, a political scientist on leave from Aarhus University, created a furor last year by arguing in his book that indicators in areas from biodiversity to water conservation show that the planet is far better off than the public thinks. The Economist, for example, has praised him for questioning the validity of what Lomborg has called “the alarmist litany.”

    Lightning rod.

    Bjørn Lomborg's new job has sparked furor.

    Such compliments drive many environmental researchers crazy. “He's a media phenomenon spreading misinformation,” contends Agger. A series of essays in the January issue of Scientific American raises several questions about Lomborg's analyses, which are also under attack from the Union of Concerned Scientists. According to Stuart Pimm, an ecologist at Columbia University in New York City, “very serious environmental researchers have gone through chapters and found that he practically doesn't get a single point right.”

    The Danish Committee on Scientific Dishonesty is investigating a complaint from Danish biologist Kåre Fog that Lomborg has knowingly distorted the research he analyzes in his book. “He systematically leaves out any data and prognoses that are not in line with his views,” Fog says. The complaint, Lomborg replies, “has no merit whatsoever.”

    Given Lomborg's public views, many observers view his appointment as a declaration of war on the environment. Socialist Jørn Jespersen predicts that Denmark will lose its credibility in global environmental discussions because “appointing a man with no scientific background makes us a laughingstock.” Not surprisingly, Lomborg disagrees. In fact, he predicts that the institute “could be very powerful if politicians listen to us.”

  10. GENOMICS

    Taking Aim at Celera's Shotgun

    1. Jennifer Couzin

    The genome wars seemed to have subsided—until last week, that is, when one side took a belated swipe at the other's credibility. In a paper published in the 5 March online Proceedings of the National Academy of Sciences (PNAS), three leaders of the publicly funded Human Genome Project (HGP) assert that what appeared to be a dead-heat race to sequence the genome was actually nothing of the sort. Celera Genomics, the authors argue, broke down information from the public database into patterns that were easy to reassemble. The company's public relations machine then sold the effort as a triumph of the whole-genome shotgun approach, the authors add, making it appear different from the public frame-by-frame reading. (The two draft sequences were published in February 2001, Celera's in Science and HGP's in Nature.)

    And the scrimmage continues.

    Scientists are still battling over whether Celera's sequencing approach (right) is superior to the public consortium's (left).

    CREDIT: R. WATERSTON ET AL., PNAS

    Celera hotly denies the charges. “They say that we copied their answer, and that's completely false,” says Mark Adams, vice president for genome programs at the company, located in Rockville, Maryland. Alternating between despondence and frustration, Adams professes that “I'd really like to see [the rivalry] end.”

    The allegations come from Robert Waterston of Washington University in St. Louis, Missouri; Eric Lander of the Whitehead Institute's Center for Genome Research in Cambridge, Massachusetts; and John Sulston of the Wellcome Trust Sanger Institute in Cambridge, U.K. In their analysis, Waterston and his colleagues sought to mimic Celera's breakdown and reconstruction of the HGP data. Celera chopped up stretches of public data into short strands of sequence, Adams says, both to catch errors and to augment its own sequence data. The PNAS paper, on the other hand, argues that Celera disassembled, or “shredded,” the public data in such a way that it automatically reassembled into correct order—in other words, they charge, Celera added little but took the credit for a lot.

    Using chromosome 22 as an example, the critics simulated various shreddings of the HGP data. One, which they believed resembled Celera's disassembly pattern, yielded on reassembly a sequence essentially identical to the original. Celera's approach, they conclude, “implicitly preserves the underlying assembly information.” The results also suggest that the true whole-genome shotgun approach—which the three say Celera did not perform as claimed—may be problematic for lengthy sequences.

    The paper is rather an “arbitrary deconstruction of other people's work” that does not advance the science, says Richard Gibbs of Baylor College of Medicine in Houston. (Gibbs took part in the HGP and is now collaborating with Celera on the rat genome.) He adds that “the public consortium as a group” would not have signed off on this paper.

    But both Nicholas Cozzarelli, PNAS's editor-in-chief, and Philip Green of the University of Washington, Seattle, who, like Celera, wrote a commentary that will accompany the paper in an upcoming print edition, vigorously defend the paper's value. “It is important to correct the historical record,” says Green, given the enormous importance of a sequenced human genome. Yet even Green suspects that “the Nobel Prize is sort of underlying all these [controversies].” After all, “only three people can get it.”

  11. STEM CELLS

    In the Mideast, Pushing Back the Stem Cell Frontier

    1. Gretchen Vogel

    While researchers in many countries engage in political battles over human embryonic stem cells, Israeli scientists have moved to the vanguard of this scorching field

    Jerusalem and HaifaThe other passengers on the flight from Singapore to Australia never suspected that a small flask of reddish liquid tucked in Benjamin Reubinoff's shirt pocket contained what is now one of the hottest commodities in biomedical research. It was September 1998, and the fertility specialist was carrying one of the first preparations of human embryonic stem (ES) cells.

    Reubinoff was a long way from his home in Israel. In January 1998, the gynecologist at Hebrew University's Hadassah Medical Center in Jerusalem had come to Australia to spend a 1-year sabbatical with Alan Trounson and his colleagues at Monash University in Melbourne. Reubinoff had joined a high-risk project: Trounson's team had struggled for years to derive ES cells from human embryos. “We could get them formed but couldn't keep them maintained” for long, Trounson recalls, so the effort had stalled. Reubinoff knew nothing about the top-secret work when he first approached Trounson, a well-known embryologist and in vitro fertilization (IVF) expert, about a place in his lab. When Trounson filled him in, Reubinoff jumped at the opportunity.

    Reubinoff's enthusiasm and grit at the lab bench—along with that of developmental biologist Martin Pera of Oxford University—energized the project. Because the state of Victoria outlaws research using human embryos, Trounson was collaborating with Ariff Bongso at the National University of Singapore, where no such prohibitions existed. So in August 1998, Trounson dispatched Reubinoff to Singapore for another attempt at creating a stable line of human ES cells. Within a few weeks the team succeeded, deriving the cell line that Reubinoff then kept warm in his shirt pocket on the flight to Australia.

    Back at Monash, Reubinoff logged 15-hour days for months to concoct a recipe that would keep the vexing cells dividing but not maturing. “His persistence in the face of frustration really made the project work,” says Trounson. Reubinoff's sabbatical extended into a 2-year stay and a Ph.D. He also helped put Israel on the stem cell map.

    With their magical potential to transform into any cell type in the body, human ES cells have kindled hopes for new treatments for the millions of sufferers of Parkinson's disease, Alzheimer's, and other killers that share a hallmark feature: cell death. But because ES cells are culled from early embryos that are destroyed in the process, they are at the center of heated debates over research ethics and the sanctity of life.

    At the forefront.

    In 1998, Benjamin Reubinoff helped energize a pioneering stem cell project in Australia before coming home to the Hadassah Medical Center to establish his own research effort.

    CREDIT: (TOP TO BOTTOM) AVI HAYUN/HADASSAH MEDICAL CENTER; COURTESY OF B. REUBINOFF

    Indeed, in many countries, biologists have spent more time lobbying politicians and courting public opinion than they have in their labs learning about the cells. But that's not the case in Israel. Thanks to liberal regulations governing embryo research and broad public support, scientists here have been at the forefront of ES cell research. Reubinoff and gynecologist Joseph Itskovitz-Eldor of the Rambam Medical Center at the Technion in Haifa were key players in the landmark isolation of stem cells from human embryos in 1998. And of the first 12 publications on human ES cells, 10 included Israeli authors. “There's less of a pall over the work in Israel,” says stem cell expert George Daley of the Massachusetts Institute of Technology in Cambridge, who collaborates with Itskovitz-Eldor.

    Because of their head start, Israeli scientists have helped set the pace for the rest of the world. Researchers here, with U.S. collaborators, were the first to publish detailed descriptions of the differentiation of human ES cells in culture in October 2000, and they were the first to report the genetic modification of the cells 6 months later. The Israeli teams “are very important players” in doing the fundamental work of figuring out how the human cells work, says Ron McKay of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, a specialist on mouse ES cells.

    Far-flung connections

    When James Thomson of the University of Wisconsin, Madison, and his colleagues first announced the isolation of stem cells from human embryos in November 1998, the news took the scientific community by storm. Although several groups had been racing toward this goal, they had mostly kept their progress under wraps—to prevent tipping off competitors and to avoid the tumultuous public attention that has buffeted the young field ever since.

    Although the initial successes happened about as far from Israel as one can get—in Wisconsin and in Melbourne—both teams had Israeli collaborators. Thomson was working with Itskovitz-Eldor, who in 1997 had sent him more than a dozen frozen embryos donated by Israeli couples in IVF clinics. One of Itskovitz-Eldor's graduate students, Michal Amit, carried the frozen embryos to Thomson's lab and assisted in the project. Four of the five cell lines the team first described (Science, 6 November 1998, p. 1145) came from Israeli embryos. Just before publication, Itskovitz-Eldor carried cells from all five lines back to Israel.

    Itskovitz-Eldor and Reubinoff credit advances in IVF techniques for making the derivations possible. Scientists could not simply follow the recipe used to create most mouse ES cell lines. These are derived from blastocysts, which develop about a week after fertilization when the embryo forms a shell around a cluster of cells called the inner cell mass. The blastocysts were flushed from pregnant mice to get the inner cell mass, which gives rise to ES cells. As that method would never be morally acceptable in pregnant women, researchers knew they would have to find a way to derive ES cells from test tube embryos. In the mid-1990s, says Reubinoff, “there was a big question whether it could be done.”

    The problem was that researchers did not know how long human embryos could last outside the body. Until the mid-1990s, the normal routine at IVF clinics was to transplant embryos into a patient about 3 days after fertilization, before the inner cell mass develops. However, hypothesizing that embryos that survive to develop healthy blastocysts would be more likely to establish a successful pregnancy, IVF researchers in the United States and Australia developed methods to keep embryos alive longer in culture. Given the importance of IVF expertise and connections to the research, it isn't surprising that Israeli researchers were involved, says Reubinoff. “According to Jewish tradition, to procreate is very important,” he says. “There is a lot of support for infertility treatments and a very large number of IVF clinics in Israel.”

    Fundamental firsts

    When Thomson's team introduced the world to human ES cells, developmental geneticist Nissim Benvenisty of Hebrew University in Jerusalem leapt to take advantage of the breakthrough. As one of a handful of researchers who had studied how mouse ES cells transform into mature cells, Benvenisty had long been captivated by the potential of using human ES cells to probe early development and perhaps to treat diseases. “I had been waiting for years for someone to isolate human ES cells,” he says. The day he read about the Wisconsin findings, he phoned co-author Itskovitz-Eldor, just 2 hours away in Haifa, to discuss the work. The conversation went so well that Itskovitz-Eldor drove to Jerusalem later that week to hash out a collaboration.

    Their first project was to test whether human ES cells, like those from mice, can form clusters of differentiating cells called embryoid bodies. Initial studies by Thomson's group suggested they didn't. But by learning how to grow the cells suspended in liquid rather than flat on a dish, the labs found that they could. “[Benvenisty] is excellent at taking what has been done in the mouse cells and translating it to human cells,” says developmental geneticist Austin Smith of the University of Edinburgh, U.K.

    Benvenisty and company scored several other firsts. In October 2000 the team, along with cell biologist Doug Melton of Harvard University, published the first paper on how growth factors, such as bone morphogenic protein 4 and fibroblast growth factor, prompt human ES cells to mature into different cell types. They struck again last spring with the first report on the stable genetic modification of human ES cells. In that work, they inserted into stem cells a gene for green fluorescent protein, which glows in immature cells and shuts off as they begin to differentiate. The cell line should prove a boon to research, as it enables researchers to easily sort immature ES cells from those that have begun to transform.

    A northern leading light.

    Joseph Itskovitz-Eldor's lab in Haifa has managed to coax ES cell lines to grow on human “feeder” cells.

    CREDIT: COURTESY OF J. ITSKOVITZ-ELDOR

    Benvenisty's group is also collaborating with Melton to tackle a mountain on the stem cell landscape: targeting genetic changes to a specific gene or spot in the genome. This would allow researchers to knock out or modify specific genes. Success would bring them closer to the Benvenisty lab's ultimate goal: creating human ES cells that are not attacked by the immune system. Cells in the body display proteins called HLA antigens that help the immune system tell friend from foe. Like organ transplants, ES cells infused in a patient would trigger a potentially fatal reaction unless the immune system were suppressed, but suppression triggers a host of side effects that could doom a potential treatment. One way to avoid the problem, says Benvenisty, might be to knock out or shut off the HLA genes. Such modified cells could be a universal donor, like type-O blood, accepted by all patients' immune systems.

    Mouse-free ES cells

    A few hours north of Jerusalem, in a 13th-floor lab with a sweeping view of the sun lovers on Haifa beach and the Mediterranean's turquoise waters, Itskovitz-Eldor's team has notched its own set of firsts. The group has recently managed to overcome one practical hurdle standing in the way of using human ES cells as therapy. To keep cells undifferentiated, scientists grow them on a “feeder layer” of embryonic mouse cells, which generates an as-yet-unknown cocktail of proteins that signal cells to remain immature. That means all existing human ES cell lines have been exposed to mouse cells—and possibly to unknown pathogens. Itskovitz-Eldor's group has figured out how to remove mice from the picture by growing ES cells on feeder cells derived from human fetal tissue.

    Masters of translation.

    Getting human ES cells to perform like the well-studied mouse cell lines is what Nissim Benvenisty (far right) and his team at Hebrew University do best.

    CREDIT: COURTESY OF N. BENVENISTY

    Itskovitz-Eldor and Amit also continue to create new cell lines. They are working on a new method, in which embryos are allowed to develop several days beyond the blastocyst stage. The researchers hope their latest cell lines might grow in culture more easily or develop into target tissues more readily. Although Itskovitz-Eldor is reluctant to discuss the issue, the new technique might also fall outside the broad patents owned by the University of Wisconsin that cover cell-line derivation using Thomson's method.

    A few floors below Itskovitz-Eldor and his colleagues in Haifa, Karl Skorecki's lab in the Rappaport Institute at the Technion is studying lines of ES cells that have been tweaked genetically to churn out loads of telomerase, a protein that adds “caps” to the ends of chromosomes to protect them from degradation after multiple divisions. The team has shown that the enzyme, which is active in undifferentiated ES cells, normally shuts off as cells begin to differentiate. The hope is that differentiated cells in which telomerase stays active undergo more divisions, enabling researchers to grow larger batches of a tissue—a boon for the development of potential therapies.

    Four musketeers

    In a field known for its secrecy and competition, the Israeli teams stand out in another way: The four groups have linked up on a grant proposal to the Israeli Ministry of Science for up to 2 million shekels ($430,000). Their goal is to study how human ES cells develop into four key tissues: blood, pancreas, neurons, and liver. They hope that banding together on a broad proposal will convince the ministry to give them a relatively large chunk of Israel's limited medical research funding. “There is a lot of technology developed within the groups here,” says Reubinoff. “If we can join forces, we can move the field more quickly forward.”

    And as more researchers worldwide gain access to the cells, the Israeli labs are becoming ever more popular, with scientists from half a dozen countries (see map, p. 1819) making pilgrimages to Jerusalem or Haifa to learn from the masters. “For scientists to make this technology applicable one day to patients requires collaboration with the whole world,” Benvenisty says. And with stem cell advances pouring out of Israel, the steady flow of visitors seeking knowledge is unlikely to abate anytime soon.

    Stem cell central.

    Researchers from six countries (red arrows) have shuttled to Israel to study the fine art of stem cell science. So far Israel has shared its human ES cell lines with scientists in one country, the United States (blue arrow).

  12. STEM CELLS

    Are Any Two Cell Lines the Same?

    1. Gretchen Vogel

    Haifa and JerusalemAlthough the U.S. National Institutes of Health lists 72 human embryonic stem (ES) cell lines as “approved” for use by NIH-funded researchers, fewer than half a dozen so far have been distributed to scientists outside the labs where they were derived. That has hampered efforts to explore one of the field's burning questions: whether the cell lines, with their different pedigrees, act differently in culture.

    “Everything which is different is better,” explains Joseph Itskovitz-Eldor of the Rambam Medical Center at the Technion in Haifa, as subtle variations in some cell lines might point to novel properties that could be exploited to transform the cells into specific tissues at will. Guiding this maturation process has so far proved quite difficult—but it will be essential if scientists are to realize their dreams of using the cells to treat disease.

    First, however, researchers have had to determine whether human ES cells behave similarly to the well-characterized mouse ES cells. And that's not so straightforward. Although in 1999 researchers in Nissim Benvenisty's lab at Hebrew University in Jerusalem were able to grow human ES cells derived in Wisconsin into embryoid bodies—a hallmark of the maturation process in mouse ES cells—a team in Australia said its cells wouldn't form the aggregations. Was there something inherently different about the cell lines?

    Benvenisty's lab is now the only one in the world using cells from Wisconsin (three lines) and Australia (one line) side by side. The team's results are still preliminary, but they appear to suggest that cells under the same conditions do respond similarly.

    Promising sign.

    Human embryonic stem cells (top) form aggregations of maturing cells called embryoid bodies (bottom).

    CREDITS: COURTESY OF N. BENVENISTY

    At the same time, each line has its own “personality.” So far, says Maya Schuldiner, a graduate student in Benvenisty's lab, the most finicky cells in their hands are from the H1 line from Wisconsin. This happens to be the only cell line, out of five derived there, that WiCell—the company that the University of Wisconsin, Madison, set up to distribute the cells—is sending to scientists. The cells are difficult to sustain, Schuldiner says, and multiply only reluctantly.

    Approaching the coin from the other side, Itskovitz-Eldor's lab is probing for slight differences among various lines. In his lab, graduate student Michal Amit is screening dozens of subclones—lines propagated from a single ES cell—for those that might form cardiac muscle cells more readily. According to Amit, some lines spawn cardiac muscle cells only rarely, whereas others consistently form beating clusters. The team hopes to use gene chips to discover whether different patterns of gene expression among the cell lines help determine their fate.

  13. 2002 OCEAN SCIENCES MEETING

    Salt Fingers Mix the Sea

    1. Richard A. Kerr

    Oceanographers made more than 2200 presentations at last month's Ocean Sciences Meeting from 11 to 15 February, sponsored by the American Geophysical Union and the American Society of Limnology and Oceanography. But three examples may give the flavor of the highly interdisciplinary Honolulu gathering: the “fingered, not stirred” mixing of the ocean, the “rotten steppingstone” route of mussels into the deep sea, and a mood swing in the North Pacific.

    To make a great martini, you have to mix it well. But as James Bond knows, there's more than one way to mix a drink. Oceanographers have long wondered what powerful analogs of a cocktail shaker or swizzle stick are at work combining the ingredients of the sea, mingling warmer waters with colder, saltier with fresher. Three decades ago, theory and then dogged observation established that large bodies of water can mix without stirring or shaking, as interweaving fingers of water flow up and down between distinct layers of seawater. Driven solely by thermodynamics, this “salt fingering” was real enough. But was it powerful enough to be a player in ocean mixing?

    At the meeting, physical oceanographers Raymond Schmitt, James Ledwell, John Toole, and Kurt Polzin of the Woods Hole Oceanographic Institution (WHOI) in Massachusetts reported the first direct measurement of the power of salt fingering. By following the spread of an inert chemical tracer, they found that salt fingering was mixing waters east of Barbados 10 times more effectively than stirring by currents and eddies was. “It's a nice vindication of salt-finger models” of mixing, says Schmitt.

    The decades-long pursuit of ocean mixing had long frustrated physical oceanographers. They could see that mixing happens. Sun and wind drive globe-girdling currents that ultimately send cold, dense water into the deep sea, but the sea has not filled to the brim with cold water. Instead, in some places cold currents must rise to mix with warmer, shallower waters and complete the circulation loop. But when oceanographers measured the amount of turbulent stirring in most parts of the ocean, it was a tenth of what was needed. Finding where and how the sea mixes is crucial to understanding, among other things, how the ocean cools the planet by taking up heat as well as absorbing the greenhouse gas carbon dioxide.

    No swizzle stick.

    This turbulence sensor helped show that salt fingering, not stirring, was mixing tropical waters.

    CREDIT: TOM BOLMER/WOODS HOLE OCEANOGRAPHIC INSTITUTION

    Some oceanographers, and Schmitt in particular, saw salt fingers as part of the solution. Whee warm, salty ocean water lies above cold, fresher water, as it does in the tropics and subtropics, centimeter-wide salt fingers were seen mixing bodies of water hundreds of kilometers across without stirring. The stirring takes place because heat diffuses 100 times faster than salt in seawater. Where salt fingering occurs, centimeter-wide columns of water stack side by side, forming layers a few tens of centimeters thick. The columns form a sort of heat exchanger in which warm, salty water in some of the “tubes” passes its heat to adjacent colder, fresher water, becoming heavier and sinking. Meanwhile, the colder, fresher water in adjacent tubes warms up, lightens, and rises. The variation of temperature and salinity across salt fingers persuaded Schmitt that the tubes were doing some serious mixing, but others remained unconvinced.

    East of Barbados, layers of salt fingers made an obvious target for the WHOI group. In addition to measuring turbulent mixing and water properties, the researchers traced the movement of a patch of water as it mixed over more than 300 days last year. In January 2001, they released 175 kilograms of a tracer, liquid sulfur hexafluoride, from a sled towed at a constant depth of 400 meters as it crisscrossed a 25-kilometer-square patch of ocean. The chemical formed a 20-meter-thick layer between two layers of salt fingers. When the group came back in November, the tracer—which can be easily detected even if diluted to 1 gram in a cubic kilometer of seawater (Science, 8 January 1993, p. 175)—had mixed more than 120 meters above and below the release level. That was 10 times more than the turbulent stirring measured there could have caused, says Schmitt.

    “The result was pretty definitive,” says physical oceanographer Robert Pinkel of the Scripps Institution of Oceanography in La Jolla, California. The question now becomes just how prevalent salt fingering is, he says. It's common in the tropics and subtropics, under outflow tongues of water like the current that flows from the Mediterranean at Gibraltar, and at weatherlike “fronts” in polar regions, Schmitt notes. “I think it could be quite substantial” worldwide, he says. Now that the mixing power of salt fingering has been demonstrated, the search should be on.

  14. 2002 OCEAN SCIENCES MEETING

    Mussels on the Move

    1. Katie Greene

    Oceanographers made more than 2200 presentations at last month's Ocean Sciences Meeting from 11 to 15 February, sponsored by the American Geophysical Union and the American Society of Limnology and Oceanography. But three examples may give the flavor of the highly interdisciplinary Honolulu gathering: the “fingered, not stirred” mixing of the ocean, the “rotten steppingstone” route of mussels into the deep sea, and a mood swing in the North Pacific.

    Sulfur-spewing hydrothermal vents at the ocean floor may seem like a strange home for surf-loving animals such as mussels, but more than 14 species of mussels thrive on vents thousands of meters under the Atlantic and Pacific. Scientists have linked the deep dwellers to their shallow cousins since the mid-1990s, but how mussels made the evolutionary trip from seashore to ocean bottom was mostly speculation until now. At the meeting, Amy Baco and Craig Smith of the University of Hawaii, Manoa, and colleagues described how they used mitochondrial genes to chart the mussels' evolutionary course. Shallow-water mussels, they showed, hopped from sunken wood to whale bones before settling in to cold bottom seeps—regions where hydrocarbons or salts ooze out of the ocean floor—and hydrothermal vents.

    Smith first proposed that sunken organic remains might serve as a way station for mussels colonizing the deep back in the 1980s, when he noticed mussels growing on rotting whale bones. At the meeting, Smith described how colonies that set up shop on whale bones can last for decades, sending out their free-swimming larvae to colonize other organic remains. Such environments are more common than one might think: Smith estimates that nutrient-rich whale skeletons crop up every 9 km on average along gray whale migration routes, and sunken, water-logged wood is common off forested coasts.

    Ocean oasis.

    One-centimeter-long Idas washingtonia mussels colonize a whale rib on the ocean floor off California.

    CREDIT: HELMUT KUKERTIS

    Studies of mussel nuclear DNA eventually unearthed a common ancestor for the mussel species from sunken wood and from whale bones, vents, and seeps. But the nuclear DNA hadn't changed enough between the species to tell when the different populations diverged. Because mitochondrial DNA mutates faster than nuclear DNA, Baco sequenced two mitochondrial genes from three to four species from each of the four environments—a thorough species spread, comments marine biologist Rick Gustafson of the National Marine Fisheries Service in Seattle. The evolutionary tree Baco and Smith drew from these genes confirmed that most deep-water species moved from rotting wood to whale falls, then to seeps, and finally to hydrothermal vents.

    Evolutionary biologist Robert Vrijenhoek of the Monterey Bay Aquarium Research Institute in Moss Landing, California, believes that clams and other animals may echo the evolutionary path Baco described. But he cautions that the progression from surface to bottom may not be a one-way street. Once the mussels have developed the ability to survive down deep, there may be quite a bit of crossover between vents and seeps, he says. “Other evidence,” he adds, “suggests mussels may be a bit more clever and opportunistic bunch,” moving back and forth between vents and seeps. But the general trend is clear, Baco says: A rotting set of steppingstones led mussels to the bottom of the sea.

  15. 2002 OCEAN SCIENCES MEETING

    Coastal Cool-Down

    1. Katie Greene

    Oceanographers made more than 2200 presentations at last month's Ocean Sciences Meeting from 11 to 15 February, sponsored by the American Geophysical Union and the American Society of Limnology and Oceanography. But three examples may give the flavor of the highly interdisciplinary Honolulu gathering: the “fingered, not stirred” mixing of the ocean, the “rotten steppingstone” route of mussels into the deep sea, and a mood swing in the North Pacific.

    Over the past century, the North Pacific Ocean has swapped hats every 20 to 30 years, exchanging a cool cap for warm wool—or vice versa—as sea surface temperatures rise or fall along the coast of North America and in the tropics. This change in the mean state of the ocean thermostat—called the Pacific Decadal Oscillation (PDO)—is only one symptom of a broader climate change that influences weather patterns across North America and might jack up or down the number of El Niños in a given decade.

    At the meeting, physical and biological oceanographers gathered to discuss the 1999 flip in sea surface temperatures, which chilled waters along the edge of the Pacific and in the tropics, and its impact on ecosystems off the western coast of North America. The driving forces behind the PDO are still being debated, and the recent shift may be temporary background noise in the climate system, says atmospheric scientist Nathan Mantua of the University of Washington, Seattle. But even if the waters quickly warm up again, the 3-year chill has already sharply affected marine life, says climate researcher Arthur Miller of the Scripps Institution of Oceanography in La Jolla, California: “The biology is telling us loud and clear that things have changed in the Pacific Ocean.”

    The last major regime shift, in 1976, took oceanographers by surprise. Most believed the ocean had only one long-term stable state. It took them almost a decade to recognize the 1976 change as a shift between two equally valid equilibrium states for the ocean. Fish catches gave the first hint. After 1976, a booming salmon fishery off the coast of Oregon crashed even as Alaskan salmon surged, suggesting that the temperature changes, and changes in the amount of nutrient-laden water brought up to the coast from the deep, had altered the availability of food.

    Some like it cold.

    Average ocean temperatures in the Pacific flipped from hot (left) to cold (right) in 1999, affecting ecosystems.

    CREDIT: (STEVEN HARE/INTERNATIONAL PACIFIC HALIBUT COMMISSION

    Oregon coho salmon began to recover in 1999, inching out of the extremely low survival rates that had plagued the fishery through the 1990s. Upwelling—the process of bringing up deep water to the coast—had picked up as temperatures dropped. But this time around, oceanographers are poised to understand changes not just to salmon but also to the food web that supports them.

    Bill Peterson, a biological oceanographer at the National Marine Fisheries Service in Newport, Oregon, has been monitoring the population of euphausiids (commonly known as krill) off the Oregon coast every 2 weeks since 1996. These large zooplankton make up much of the salmon's ocean diet. In the year beginning in 1999, the average water temperature off Oregon plummeted 5 degrees Celsius, and Peterson described the dramatic boom in both krill and the copepods they feed on. “It happened practically overnight,” he said. The warm-water species that had dominated Oregon's coastal ecosystem for a decade disappeared, replaced by species normally seen farther north.

    Frank Schwing, an oceanographer at the Pacific Fisheries Environmental Laboratory in Pacific Grove, California, said at the meeting that the changes in circulation in 1999 may have increased the flow of nutrients to the bottom of the food chain, triggering an explosion in the amount of life the waters could support. And Elizabeth Logerwell, a fisheries biologist at the Alaska Fisheries Science Center in Seattle, presented results from a model coupling ocean physics with bottlenecks in salmon populations. According to the model, she says, the increase in salmon population could be due either to the newly available zooplankton or to the fall in water temperatures, because many of the salmon's ocean predators prefer warmer waters.

    Whatever their cause, the changes to coastal ecosystems may be short-lived. Physical oceanographer Michael McPhaden of the Pacific Marine Environmental Laboratory in Seattle suggests that the pattern might merely be evidence of a particularly long and strong La Niña—a cold upwelling in the tropics that sometimes follows an El Niño. “The 1997-98 El Niño was the largest on record,” he says, so it's not a stretch to assume that the subsequent La Niña, a strong one, was also surprisingly persistent and far-reaching. Peterson, however, is unconvinced. “Three, 4, 5 years—how long does it need to last before it's called a shift?” he asks. Most Las Niñas persist only for a year or two, he argues, and these conditions have been around for 3.5 years.

    Forecasters suggest that an El Niño is brewing in the Pacific even now. The experimental parameters are changing again, and the results may knock the oscillation back into its warm state. “History can only help so much in predicting the future,” says Mantua. “In this complex system, nature is always surprising us.”

  16. NEW YORK ACADEMY OF SCIENCES

    How Fast Can an Old Dog Learn New Tricks?

    1. Jeffrey Mervis

    With its membership shrinking and its flagship magazine closed, the New York Academy of Sciences searches for new ways to serve a global community

    The New York Academy of Sciences proudly calls itself “one of New York City's oldest and most enduring cultural institutions.” For 185 years, it has been a gathering place for the region's scientific elite, and it now performs a long list of civic functions, from sponsoring public lectures and the city's annual student science fair to studying how to clean up New York Harbor. But its name carries a cachet far beyond the confines of New York. Physicist and human rights activist Andrei Sakharov chose the academy's imposing, four-story mansion on New York City's upper-crust east side in 1988 to make his first public U.S. appearance and to thank the academy for helping secure his release from the Soviet Union. And from Bucharest to Bangkok, framed letters hang proudly on the walls of research labs proclaiming their owners' membership in the far-off academy.

    But the institution's long and illustrious history didn't prevent it from experiencing a near-implosion last fall. Faced with a mounting financial crisis, Rodney Nichols, the academy's president and chief executive officer, proposed selling its landmark headquarters to a Middle East potentate. He also shut down the academy's award-winning magazine, The Sciences, after a 40-year run. These steps—plus growing resentment of Nichols's efforts to make the academy a player on the national science policy scene—triggered a near-insurrection by some former leaders. Nichols resigned in November after nearly 10 years as the academy's head.

    The academy's immediate future now rests in the hands of Nobelist and Rockefeller University biologist Torsten Wiesel. Wiesel has pulled the building off the market, has trimmed budgets, and is focusing on serving the academy's members, steps which seem to have steadied the ship. The big question is whether a membership organization created to foster scientific discourse can survive in a world in which more and more communication occurs electronically—and for free. “I'm skeptical whether this or any other organization of its type can continue to rely on a membership base,” says board member Lawrence Buttenwieser, a New York lawyer and philanthropist. Although most scientific organizations face similar problems, the New York Academy may not be able to afford any wrong answers. “It's important to overcome a sense of skepticism about the future of the academy,” says Wiesel. “People are still worrying about its mission.”

    Controversial choices

    The academy's financial condition has probably never been as solid as its imposing headquarters might suggest. Nichols, a longtime administrator at nearby Rockefeller University, benefited from an explosive growth in international members, from fewer than 10,000 in 1989 to nearly 25,000 in 1995. Unfortunately, the overseas rise masked a steady slide on the domestic side, from 32,000 members in 1989 to 14,500 last year. And when the international tide began to turn in the late 1990s—dropping to 11,000 last year—Nichols found himself with a projected operating deficit of $1.5 million, a crisis for an organization with a $10 million budget.

    Standing tall.

    Torsten Wiesel has taken the academy's landmark building off the market.

    CREDIT: ANTONIO MARI

    The plunge in membership—from a peak of 46,300 in 1995 to 25,600 today—was only one part of a dismal financial picture. The Sciences had for years been losing about $750,000 annually. Programmatic activities, ranging from a Web site for teachers to studies of the major pollutants in New York Harbor, generally cost more to run than they generated in grants, says Chief Financial Officer (CFO) Thomas Kelly. Only the Annals—well-regarded reports on 25 to 30 scientific conferences held each year—operated in the black.

    The budget crisis prompted two radical steps. In October 2000, Nichols decided to sell the headquarters building, which he calls “a looming hazard.” Built in 1919 as a residence and donated to the academy in 1949 by a Woolworth heir, it was too small to serve a growing staff or to host large meetings. Nichols estimated that the sale would net $20 million, creating an endowment for new and ongoing programs.

    The decision, disclosed last spring, caused an uproar. “The proposed sale … and move to some characterless building is a shocking idea,” wrote past president Fleur Strand, professor emerita of biology at New York University, in a recent letter to Wiesel. “This would inevitably translate into a further loss of membership.” But the sale never went through. The would-be buyer, the emir of the oil-rich state of Qatar in the Middle East, walked away from the deal just a few weeks after the 11 September terrorist attacks.

    As this drama was unfolding, Nichols presented the board with a budget for the upcoming 2001-02 fiscal year that eliminated The Sciences. “We needed a vehicle to tell people what was happening at the academy, and [The Sciences] didn't do that,” he says. In addition, he notes, fewer than 1% of the people who dropped their membership ($95 a year for U.S. members and $115 for everybody else, with discounts for students) remained subscribers. “People said they loved it, but they didn't like it enough to pay $20 [the U.S. nonmember rate] a year,” says Nichols.

    The board went along, but many members lamented the loss of what they said was a primary reason to join the academy as well as an effective way to communicate with the public. Moreover, Nichols's moves to dispense with these twin icons fed simmering resentment about his management style. “It was symptomatic of his aloof, top-down approach,” complains Brian Ferguson, a professor of anthropology at Rutgers University in Newark, New Jersey.

    Ferguson and other active members were already seething about a proposal to transform the 23 discipline-based sections, the foundation of the academy's membership infrastructure, into interdisciplinary groupings. The old structure reflected “a 19th century view” of science, says Nichols. Many members worried, however, that the new arrangement was a stalking horse for Nichols's plan to become a bigger player in national science policy debates.

    Toward that end, Nichols created the offices of education and science/technology policy, expanding the academy's menu beyond its traditional diet of conferences and publications. In 1998 he launched the harbor project, involving state and federal governments, industry, and environmental groups. It was in the academy's best tradition, according to Nichols and his supporters. Bill Green, a former Republican member of Congress and past chair of the governing board, points to a precedent: In the 1830s New York asked the academy to help find a new source of water to slake its growing thirst. Its report, he notes proudly, led to the establishment of the Croton Reservoir, which continues to serve the city.

    But the harbor project will deliver less substantial results. A shortage of funds forced Nichols to narrow the focus from whether to dredge the harbor to studies of five major sources of pollution, and its first report, on mercury, is only now nearing completion.

    Alarmed by these developments, some senior academy members, including past presidents and section heads, drafted an alternative slate of candidates in September with the intention of seeking seats on the academy's 21-member board. Although their names never appeared on a ballot, the campaign was a major slap at Nichols's leadership. Soon after, Nichols told the board that he had decided to step down, and on 6 November the academy said that Wiesel, who in September succeeded Green as board chair, would also serve as interim executive director.

    Nichols says he left to pursue new challenges, including an extensive schedule of travel and writing on global science policy issues. “The timing [of the failed building sale] was a coincidence,” he says. “An element of staleness and frustration had crept into the job after 9 years, and I was ready to do new things.”

    A full plate

    There's no shortage of challenges for Nichols's successor. As president emeritus of Rockefeller University and head of the International Human Frontier Science Program based in Strasbourg, France, the 77-year-old Wiesel wasn't looking for another job. But he says he felt an obligation to pick up the pieces after Nichols departed.

    Info flow.

    Officials hope that online access to the Annals series will offset the loss of The Sciences as a member benefit.

    Wiesel has already announced several steps intended to return the academy to its roots as a forum for scientific discourse, declaring that his primary focus will be to “rebuild membership from within.” That's a signal that members' interests and needs will come before efforts devoted to national or global issues. “I don't think that policy issues can be ignored,” he says. “But if you are running a restaurant, you'd better be sure the local population eats there.”

    This month Wiesel also harvested the fruits of a project to put the past 3 years of the Annals online. It will save production costs and provide a convenience for members (who previously received one free report a year and five more for $15 each, compared with a retail price of $100 to $150). Access is free to all until June, when the archive becomes a member benefit.

    Those new policies have been accompanied by some serious belt-tightening. The academy's conference, education, and policy offices have been merged into one unit, and what was once a five-person development office, which CFO Kelly says “spent $2 for every dollar it brought in,” has been reduced to a single person. Staff members located in another building are being moved into the mansion, for an annual savings in rent of $250,000.

    Kelly expects that these and other steps will trim the deficit to $535,000 for the fiscal year ending 30 June. That figure includes a $500,000 charge for amortizing new computer equipment, Kelly says; without it, the operating budget is nearly balanced. And he projects a $600,000 surplus in 2003, when all the savings will have kicked in.

    Internally, Wiesel hopes to shore up a governing board that has been accused of being too acquiescent. “It's easy for boards to fall asleep at the switch,” says Cecily Cannan Selby, who chaired a 1998 academy conference on the status of women in science and engineering. Selby, a former university administrator and member of several corporate boards, faults Nichols for not consulting more with staff and members and says that his salary—at $275,000 more than double the pay of any other staffer—threw the scales off balance and “diminished the strength of the organization.” Some members also bristled at the inclusion on the board of business leaders and nationally known science policy figures burdened with other commitments.

    One such prize catch was Green, who represented Manhattan for 14 years in Congress. Green's family foundation pledged $1 million in 1998 to kick off the academy's first major capital drive if the academy could match it. But Green says he's withdrawn that pledge because the drive never really got off the ground. He's also resigned from the board because of policy differences with Wiesel. “I felt that we should have kept the building on the market,” he says. “It's a wonderful building, but it's also an albatross. So in fairness to Torsten, I felt that I should stand aside and clear the path for him.”

    Another board member, former presidential science adviser D. Allan Bromley, a staunch backer of Nichols, also plans to step down: “I think it's appropriate for me to resign, because I was there at the request of Rod.” Not so Buttenwieser, another Nichols recruit. “Holding on to such a large nonproductive asset [the building] is a mistake,” he says. But “I'm not going to walk away just because I'm skeptical.”

    Officials are hoping that online access to the Annals will prove to be a major drawing card for prospective members. But if the numbers continue to fall, whether in reaction to the loss of The Sciences or for some other reason, then the financial picture could again darken.

    Wiesel agrees that “the main thing is to stem the decline in membership.” Once that occurs, he says, the new executive director can build a new team, solicit contributions from private donors, and chart a new course for the academy. Wiesel thinks that the academy will rebound, but he's not making any promises. “My term as chair ends in September 2003,” he says. “It should be clear by then how it's going.”

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