# News this Week

Science  23 Sep 2005:
Vol. 309, Issue 5743, pp. 1972
1. SCIENTIFIC ETHICS

# Discovery of Pluto Contender Contested in Planetary Court

1. Richard A. Kerr

When a group of astronomers announced back in July that it had discovered a distant, icy body rivaling Pluto in size, the claim seemed exciting enough. But now it has become entangled in charges of unethical behavior. Planetary astronomers are feeling their way through uncharted territory as they try to sort out conflicting claims to the discovery.

All but one of the facts in the case are uncontested, thanks in part to the crystal-clear memory of the Internet. As first reported by The New York Times, astronomers José Ortiz and Pablo Santos-Sanz of the Institute of Astrophysics of Andalucia (IAA) in Granada, Spain, telescopically imaged an object, now temporarily designated 2003 EL61, on 3 nights in March 2003. But they did not analyze the images right away. In the meantime, Michael Brown of the California Institute of Technology in Pasadena and his colleagues independently imaged the same object, analyzed the images, and recognized that it was slowly moving against the field of stars, proving that it is a distant member of the solar system. This was in December 2004. By 20 July this year, after more study, Brown's abstract describing the object in general terms was posted on an open Web site for an upcoming September meeting.

On 25 July, Santos-Sanz pointed out the object in their 2003 images, according to Ortiz writing in a 15 September posting to the Minor Planet Mailing List. The next day, according to electronic archives, the unsecured observing log of the telescope Brown's team used was accessed three times using a computer at the IAA. The log shows exactly when and where Brown and his colleagues had pointed the telescope at EL61 at various times during the previous 6 months. In his posting and in a 16 September e-mail to Science, Ortiz acknowledges for the first time that he and Santos-Sanz did in fact access the telescope log after Googling Brown's code name for the object mentioned in the meeting abstract.

The day after accessing the observing log, Santos-Sanz used the same computer to report to the Minor Planet Center (MPC) in Cambridge, Massachusetts, that he and Ortiz had discovered what would be designated 2003 EL61. The day after that, 28 July, the telescope Web log was again accessed, this time by a second computer at the IAA. Later the same day, Ortiz used this second computer to notify the MPC of new observations of EL61 made by a second group at Ortiz's request. This prompted MPC—a part of the International Astronomical Union (IAU)—to designate the object 2003 EL61, effectively crediting Ortiz and Santos-Sanz with the discovery and thus the privilege of suggesting a name for the object. As yet unaware that the Spanish astronomers had accessed the observing log, Brown e-mailed his congratulations to Ortiz on the 29th.

MPC may have been right to credit the Spanish astronomers at the time, Brown now says, but “I see no reason to believe they made the discovery themselves.” Normally, when astronomers hunt for objects in the solar system, they examine their search images within days. That the Spanish researchers happened to find the object more than 2 years after the search but a few days after the observing log became available to them “is just an incredible coincidence,” says Brown.

In other fields, such charges of unethical behavior might end up in a formalized adjudication process. In planetary astronomy, there is no such process. Instead, the MPC director chooses winners and losers in astronomical exploration, and the chips fall where they may. MPC Director Brian Marsden “has historically been the czar on these matters,” says planetary astronomer Richard Binzel of the Massachusetts Institute of Technology in Cambridge. “It's whoever Brian wants to bestow the discovery on.”

Brown concedes that priority in the case of EL61 probably cannot be proved one way or the other, but he has no doubt that “they violated one of the central tenets of science, which is that you cite your sources,” as he told Marsden in an e-mail message on 15 August. “I request that Ortiz et al. be stripped of offial [sic] discovery status and that the IAU issue a statement condemning their actions.”

After 6 weeks of silence, Ortiz has begun to defend himself. In the mailing list posting, he stands by the order of discovery events. Their analysis had been delayed by technical problems with the images, he says. And in the e-mail to Science, he says that their Googling of the code name and accessing the log in the course of a “revision process” is “perfectly legitimate. That is no hacking or spying or anything similar.” As to their failure to mention the other group's earlier discovery, he says he had no room for such details, and in the posting, he adds that they weren't even sure the two groups had been looking at the same object.

Marsden doesn't buy that. The failure to mention Brown's observation, he tells Science, “just seems ethically improper. The whole story is quite bizarre.” But as the judge, jury, and executioner in this case, he awaits a stronger defense from Ortiz. “I haven't done anything,” he says. “I'm trying to give Ortiz and his people every chance to prove their case.” In the next couple of months, after consulting with members of the IAU committee responsible for naming small solar system bodies, Marsden will decide who the discoverer of 2003 EL61 is. And that will probably be that.

2. JAPAN

# Tokyo Professor Asked to Redo Experiments

1. Dennis Normile

TOKYO—Japan's most prestigious university is investigating the basis of several papers published by a faculty member over the past 7 years. Officials at the University of Tokyo say it's the first case of its kind in the institution's history.

The matter involves a group led by Kazunari Taira, a professor of chemistry and biological chemistry in the Graduate School of Engineering. Taira was unable to produce the raw data or experimental notes to support a string of papers from his lab that were published in top-tier journals, according to an interim report by an investigative committee looking into the matter. Taira has promised to redo the experiments, which he says were done by a research associate who entered the data directly into a computer.

The case has caught university officials flat-footed. “We don't have an example of how such a situation would ordinarily be handled,” says Yoichiro Matsumoto, a mechanical engineer who led the investigating committee. Both Matsumoto and a university spokesperson say that this is the first time such an allegation has surfaced at the university, known as Todai.

The investigation was triggered by an April letter to the university from the Japan RNA Society. According to a report released last week by the investigating committee, the society questioned the reproducibility of the results reported in 11 papers that appeared between 1998 and 2004 in journals that include Nature, Nature Biotechnology, and the Proceedings of the National Academy of Sciences U.S.A. The committee said the letter, which has not been released, raised questions about whether a gene discovery technique developed by the Todai group works as described. The society also noted that Taira had retracted a 19 June 2003 Nature paper because of a misidentification of a key gene and issued a correction to the methodology described in a 9 September 2004 Nature paper. Two society officials declined to discuss the letter.

To start its probe, the investigations committee surveyed researchers both in Japan and around the world. Of the nine who replied, none had reproduced the research results, although it's not clear how many had attempted to do so. The committee then selected four papers for a detailed examination and concluded that Taira could not provide raw data or notebooks to support the papers. The committee concluded that the reliability of the research results could not be verified.

Taira told Science that the key experiments leading to the questioned results were done by Hiroaki Kawasaki, a research associate. Kawasaki had entered all the raw data and notes directly into a computer, Taira said. However, those files were not properly backed up and now cannot be reconstructed, he added. Taira said that he was unaware Kawasaki was not keeping proper notes. “There is no excuse” for the lax oversight, he said.

Still, Taira is standing behind the results. The gene discovery technique hinges on the use of a synthetic ribozyme, which is a short RNA enzyme, to inactivate genes. Taira says several groups around the world have developed similar approaches and that other groups in Japan have used their ribozyme to identify genes. “This technology has been checked by other professors at other universities, and it has worked,” he says.

Shigeo Ohta, a biochemist at Nippon Medical School in Kawasaki, says he used a ribozyme from Taira's group as the basis for a 2003 paper that identifies a gene that may contribute to Alzheimer's disease. “Of course we believe the published results are accurate,” he says, adding that his group plans to double-check the results in light of the Todai investigation.

Matsumoto says the committee has not questioned all of the work from Taira's lab. But he says “it's a big mistake” for a group leader to overlook proper recording of experimental details. Taira acknowledges that he will need to reproduce the experiments to put the matter to rest. Kawasaki did not reply to an e-mail message, but Taira says his research associate “feels he can carry out the experiments and prove they are OK.”

The university has agreed to give Taira until the end of March to redo the experiments. Matsumoto says the university went public with its investigation—holding a press conference on 13 September—because the committee felt it owed the RNA Society an answer.

3. PEER REVIEW

# Suggesting or Excluding Reviewers Can Help Get Your Paper Published

1. David Grimm

CHICAGO, ILLINOIS—It's the closest most scientists will come to picking their own jurors. Amid all the checklists, bibliographic information, and file-attachment instructions, the manuscript submission forms of many journals ask authors a simple question: Are there any individuals you would like to suggest or exclude as potential reviewers?

Having a say over who will review one's work should be a good thing. Authors may be better placed than editors to know who is best qualified to evaluate their findings, and they may have valid reasons for keeping sensitive results out of the hands of a close competitor. Yet many decline to suggest reviewers, and only a small percentage opt to exclude them.

That may change, thanks to the results of three studies presented here last week at the Fifth International Congress on Peer Review and Biomedical Publication, organized by the Journal of the American Medical Association and the British Medical Journal (BMJ) Publishing Group. Either suggesting or excluding reviewers, the studies show, can significantly increase a manuscript's chances of being accepted.

“The studies point out a potential for bias in the peer-review system,” says R. Brian Haynes, a clinical epidemiologist at McMaster University in Ontario, Canada, and the editor of two clinical journals. “If that's the case, this is something we should be taking a closer look at.”

Journal editors who use author-suggested reviewers tend to disagree about their value, says Sara Schroter, a senior researcher at the BMJ Publishing Group. So she and colleagues compared author-suggested reviews to those solicited by editors at 10 journals owned by the company, including Heart, Tobacco Control, and BMJ itself. In a 9-month survey of 788 reviews for 329 manuscripts, the team found no significant difference in the quality (as measured by widely agreed upon criteria judged to be essential for a good review) or timeliness of reviews between the two groups. However, they did find that, compared to editor-suggested reviewers, author-suggested reviewers were more likely to recommend manuscript publication (55.7% versus 49.5%) and less likely to recommend rejection (14.4% versus 24.1%).

“Editors and authors can be confident that either group will do an adequate job at reviewing the manuscript,” says Schroter. “But editors should be a bit more cautious about relying on the recommendations of author-suggested reviewers.”

Schroter's findings are reinforced by a study conducted by journal consultant Elizabeth Wager and colleagues at BioMed Central, an open-access publisher of online journals. Wager's team compared editor-chosen and author-suggested reviews submitted to 40 of BioMed Central's journals. Using criteria similar to Schroter's, the researchers found little difference in quality between the two groups of reviews. And, like Schroter, they found that author-suggested reviewers were more likely to advocate manuscript acceptance (47% versus 35%) and less likely to recommend rejection (10% versus 23%).

Opting to exclude reviewers may have an even more dramatic effect on a manuscript's success. Lowell Goldsmith, a dermatological geneticist at the University of North Carolina, Chapel Hill, and the editor of the Journal of Investigative Dermatology, and colleagues looked at 228 consecutive manuscript submissions to the journal in 2003. The team found that the odds of acceptance were twice as high for manuscripts for which authors had excluded reviewers compared to those whose authors had not done so. “Excluding reviewers ends up being very, very important,” says Goldsmith. “People know their assassins.”

What's driving these numbers is not clear. If authors tend to suggest sympathetic reviewers and exclude nitpicky ones, for example, the findings could spotlight biases in the peer-review process. Similarly, bias may be introduced by reviewers in journals at which reviews are not anonymous. Says Wager: “Author-suggested reviewers don't want to be the person that killed their recommender's last study.”

But David Nordstrom, an epidemiologist at the University of Minnesota, Twin Cities, and an adviser on grant applications and peer review, isn't as cynical. “I take a fairly benign view,” he says: Author-suggested reviewers tend to be familiar with the author's field and may be in a better position to recognize the potential impact of a paper. And Haynes says that more-established researchers, who may have the hubris to exclude reviewers, may also have a better chance of getting manuscripts accepted.

Are such author-tailored reviews likely to increase? Matthias Egger, an epidemiologist at the University of Bern in Switzerland and an associate editor of the International Journal of Epidemiology, says it's hard to predict. Many authors are loath to exclude reviewers because it goes against their ideal vision of what science should be about, he says: “Scientists like to believe that personal factors shouldn't play a role in science.”

At the same time, he says, there are valid reasons to single out reviewers. Some scientists hold grudges, Egger says. Others may have conflicts of interest or are just not qualified to evaluate certain topics. So suggesting or excluding reviewers may help limit bias rather than introduce it. “I've never excluded a reviewer,” he says, “but perhaps it isn't such a bad thing to do.”

4. GENETICS

# Mouse With Human Chromosome Should Boost Down Syndrome Research

1. Greg Miller

After more than a decade of frustrated efforts, researchers have finally pulled off a genetic engineering first, creating a strain of mice with a nearly complete copy of human chromosome 21. The strain's unusual genome mimics the genetic makeup of people with Down syndrome, the most common inherited form of mental retardation.

“This is going to have a huge impact on Down syndrome research,” says Roger Reeves, a geneticist at Johns Hopkins University in Baltimore, Maryland. Adds Julie Korenberg of Cedars-Sinai Medical Center and the University of California, Los Angeles: “This mouse not only solves problems, but it raises the next round of questions and creates a way to solve them.”

People with Down syndrome have an extra copy of chromosome 21, resulting in mild to moderate mental retardation and abnormal facial features. About 40% of Down syndrome children have heart defects, and many have weakened immune systems. Efforts to model Down syndrome in mice have been complicated by the fact that the mouse versions of the genes on human chromosome 21 are inconveniently scattered across three mouse chromosomes. About two-thirds lie on mouse chromosome 16, the rest on chromosomes 10 and 17. One of the most popular mouse models now in use has an extra bit of mouse chromosome 16 that contains the counterparts of roughly half the genes on human chromosome 21.

To create a more complete mouse model, researchers led by Elizabeth Fisher of the Institute of Neurology in London and Victor Tybulewicz of the National Institute for Medical Research, also in London, took a radically different approach. Rather than trying to duplicate regions of the mouse genome corresponding to human chromosome 21, they tried to put the human chromosome into mice. It wasn't easy.

The team built on a technique pioneered by a Japanese group to add fragments of human chromosomes to mice. They extracted chromosomes from human fibroblast cells and transferred them into mouse embryonic stem (ES) cells. A marker gene indicated which ES cells had picked up chromosome 21—usually just one or two cells out of a batch of tens of millions, Tybulewicz says. The team injected the ES cells into early mouse embryos, which were carried to term by a foster mom. Additional tinkering was needed to create a strain of mice that passed the extra chromosome on to their offspring.

That strain, called Tc1, has about 92% of human chromosome 21, the team reports on page 2033. It also has several characteristics of Down syndrome. Although there's no test for mental retardation in mice, the Tc1 mice have deficits in spatial learning and memory similar to those found in Down syndrome patients; they also have a deficit in “long-term potentiation,” a neurophysiological process thought to underlie learning and memory. Perhaps most significant, the mice have heart defects like those seen in Down syndrome patients. “That's a first,” says Stylianos Antonarakis, a geneticist at the University of Geneva in Switzerland. “No other mouse so far has the heart defect.”

Korenberg says the Tc1 mice are a vast improvement over the existing mouse models because they have not only many more of the genes on human chromosome 21 but also have the human DNA that regulates these genes. “This is a first mouse I would consider a superb model,” she says.

But there are some wrinkles, says Charles Epstein of the University of California, San Francisco. He and others suspect that the largest drawback will be that the Tc1 mice don't have an extra copy of human chromosome 21 in every cell. Fisher's team reports, for example, that about a third of brain cells lack the extra chromosome. Mouse-to-mouse variations in which cells have the extra chromosome could complicate future experiments. William Mobley of Stanford University says he's concerned that some of the genes from human chromosome 21 that didn't make it into the Tc1 mice are likely to play an important role in Down syndrome. Even so, he and others says they can't wait to get their hands on these mice.

5. INFECTIOUS DISEASE

# Old Drugs Losing Effectiveness Against Flu; Could Statins Fill Gap?

1. Martin Enserink*
1. With reporting by Gong Yidong in Beijing.

ST. JULIAN'S, MALTA—With the threat of a deadly pandemic looming large, flu drugs are coming under increased scrutiny. At a meeting here last week* researchers reported disheartening data showing that the most aggressive of the circulating human flu strains has become resistant to an older class of flu drugs, rendering the drugs all but useless in the yearly battle against seasonal flu and deflating hopes they might be used to fight a pandemic.

But help might come from an unexpected source, according to another study: the cholesterol-lowering drugs called statins. Very preliminary data suggest that these drugs, cheap and widely available, might help prevent serious complications from a flu infection. If that's true, statins would offer a glimmer of hope for countries that, unlike the United States (see ScienceScope, p. 1977) and other wealthy nations, can't afford pandemic vaccines or oseltamivir, the pricey drug of choice for pandemic stockpiles.

Researchers had long known that amantadine and rimantadine, drugs that block a viral protein called M2, easily trigger resistance in the flu virus and that resistant strains can spread from person to person. But even after decades of use, resistance rates were low, says Rick Bright of the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia—until recently. Bright set out to determine when and where the upward trend started, screening more than 7500 flu samples, collected all over the world since 1995, for mutations that confer resistance against both drugs.

For H3N2, the most virulent of the three strains that return each winter, a dramatic pattern emerged. Until 2002, no country had resistance rates higher than 10%. But in 2003, the rate shot up to 58% in China, then jumped to 74% in 2004. Hong Kong, South Korea, and Singapore followed with similar explosions, and samples taken during the 2005 flu season in Europe and the United States show that resistance has climbed to 14.3% and 11.5%, respectively.

The cause of the upswing is unclear, but Bright says over-the-counter sales of amantadine in China may have played a role. The drug is an ingredient of several anticold and antiflu cocktails sold in China. The leading product, called Gan Kang, is widely available for about $1.50, and a recent report in China Business put its 2004 sales at$80 million, or more than 50 million courses. Widespread use may have favored resistant virus strains, says Bright, and the dramatic jump in 2003 may be a result of the SARS panic that year.

Fairly inexpensive, amantadine and rimantadine are primarily used against seasonal flu in the United States and Japan, says Arnold Monto of the University of Michigan, Ann Arbor.

The finding may deal a fatal blow to plans, under way in a few countries, to add amantadine to pandemic stockpiles. That option had already become less appealing after the discovery that H5N1 avian flu strains isolated in Thailand and Vietnam were resistant to the drug—a finding some have linked to veterinary use of the drug in China (Science, 24 June, p. 1849). The finding that a human strain now shows widespread resistance—and the fact that pandemic viruses may arise when avian and human strains swap genes—makes it even less appealing.

Instead, most governments are choosing oseltamivir, a drug that blocks a viral protein called neuraminidase. So far, resistance to that drug is rare, and resistant viruses don't seem to grow as well. Still, the CDC study “shows that we should watch and worry,” Monto says.

But many countries have other concerns: They don't have the means to buy large stashes of antiviral drugs or, for that matter, pandemic vaccines. That's where the inexpensive statins might come in. Over the past decade, researchers have discovered that these drugs not only lower cholesterol but also reduce levels of immunomodulators called cytokines, dampening inflammation. This is thought to contribute to their protection against cardiovascular disease, but it may also explain why in three studies so far, patients on statins appeared to fare better in bacterial infections in which inflammation plays a major role, such as sepsis and pneumonia.

Because flu viruses trigger cytokine release as well, and complications from flu include heart disease and pneumonia, David Fedson, a retired medical director of Aventis, wondered whether statins might be useful in treating flu. At Fedson's urging, clinical epidemiologist Eelko Hak and colleagues at University Medical Center Utrecht in the Netherlands began looking for evidence in a Dutch database of 60,000 primary-care patients. Such data collections are invariably incomplete; whether a patient was tested for flu or bacterial infections often isn't recorded, for instance. Nonetheless, Hak found tantalizing clues. During flu epidemics between 1996 and 2003, patients who had had at least two statin prescriptions over the previous 12 months had a 26% lower risk of pneumonia and other severe respiratory ailments. In non-flu seasons, statins didn't reduce the risk, suggesting that the drugs offer specific protection against flu complications.

That doesn't position statins as the next generation of flu drugs yet. The results will need to be confirmed in other patient populations, Hak says; pharmacoepidemiologist Christoph Meier of the University Hospital in Basel, Switzerland, says he will report results from a similar study shortly. Data from old clinical trials with statins should be reexamined, adds Hak, whose colleagues in Utrecht are also planning in vitro studies to determine how statins might have a protective effect. Clinical studies would have to show whether statins should be taken prophylactically—as millions of people do—or once a person is exposed or infected.

Questions aside, the findings generated interest among meeting participants such as Frederick Hayden, an antiviral expert at the University of Virginia, Charlottesville: “It's definitely something that should be explored.”

• * The Second European Influenza Conference, 11-14 September.

6. PLANT SCIENCE

# New Gene Boosts Plant's Defenses Against Pests

With a little help from friends, crop plants may one day be better able to deter herbivores. By tweaking a cellular pathway for producing organic compounds, researchers have, in a proof-of-principle experiment, endowed Arabidopsis thaliana with the power to recruit mites as allies against leaf-munching enemies. The insertion of a strawberry gene into the mustard plant leads to two new compounds that attract predatory mites that devour herbivorous spider mites, Iris Kappers, a plant biochemist at Wageningen University in the Netherlands, and her colleagues report on page 2070. “They show it is possible to manipulate the movements of biological control agents through genetic engineering of plants,” says Merijn Kant, a plant physiology at the University of Amsterdam.

Through a series of reactions involving multiple enzymes, plants make terpenoids, complex organic compounds that are important to development and growth, as well as to plant-animal interactions, such as pollination and pest deterrence. About 15 years ago, chemical ecologists discovered that lima beans, when infested with spider mites, emit at least one terpenoid that draws spider-mite predators to the scene; strawberries and other plants turned out to use the same defense. Since then, several groups have tried in vain to provide Arabidopsis with this capability by adding genes for the various enzymes necessary to make a particular attractant. “It's [been] notoriously difficult,” says John Pickett, a biological chemist at Rothamsted Research in Harpenden, United Kingdom.

Whereas the earlier experiments put enzymes into the plant cell's cytoplasm, Kappers and colleagues at Plant Research International in Wageningen targeted the one they had chosen—a sesquiterpene synthase from strawberries—into the cell's mitochondria, which contain farnesyl diphosphate, a key building block for one mite attractant. The researchers attached an extra piece of DNA, one encoding a peptide subunit that directs a protein to mitochondria, to the enzyme's gene. This was “very clever targeting,” says Ted Turlings, a chemical ecologist at the University of Neuchatel, Switzerland.

In contrast to the lackluster performance of similar synthases active in the cytoplasm, the mitochondrial-located enzyme exceeded expectations, producing about 25 times more of the expected attractant than had other transgenic Arabidopsis plants, the group reports. To their surprise, the researchers found that a second predatory mite attractant, one derived from the first by the removal of four carbon atoms and one alcohol subunit, had also accumulated in their transgenic plants—and sometimes in greater quantities than the intended one.

Kappers and her colleagues tested the effectiveness of the organic compounds by releasing predatory mites into the center of a circle of Arabidopsis potted plants that alternated between wild and transgenic varieties. In the experiment, 388 predatory mites headed for the transgenic plants and 197 headed for the wild-type plants. “This is the first study” to show that the strawberry synthase gene can produce effective attractants in other plants, says Turlings.

Still, Ian Baldwin, a chemical ecologist at the Max Planck Institute for Chemical Ecology in Jena, Germany, is concerned that because such plants would continuously emit attractants, predatory mites won't know when and where prey are available. That uncertainty could cause the plant-mite relationship to break down over time, Kappers agrees. So she's looking for the genes responsible for producing mite attractants only after herbivores attack. Nevertheless, says Kant, the new study “is a major step forward in our ability to manipulate this phenomenon ultimately to our own benefit.”

7. VENICE

# A Sinking City Yields Some Secrets

1. John Bohannon*
1. John Bohannon is a writer in Berlin, Germany.

Like New Orleans, Venice is slowly subsiding. Several decades and $10 billion of research have not settled the debate over what to do about the “Venice problem,” but studies of the city's famed lagoon are providing insights for other coastal cities on pollution and climate change VENICE, ITALY —With a few expert motions of his oar, Fabio Carrera sends the long batèla boat gliding around a corner in this maze of canals. Suddenly, a dim patch of stars is the only light and the gentle swish of water the only sound. The experience evokes a centuries-old past, when Venice was one of the most powerful city-states in the Western world. But times have changed. One clue is the outboard motors protruding from beneath the tarps of moored boats. Another comes in the approach to the tunnel beneath Santo Stefano Church. Although it is low tide, Carrera has to stoop to clear the moist stone ceiling. “At high tide, this passage is completely inaccessible,” says Carrera, an urban information scientist and native Venetian who now divides his time between Worcester Polytechnic Institute in Massachusetts and his watery hometown. Elsewhere in the city, the acqua alta overflows the streets, fills the ground floors of buildings, and nibbles away at bricks and plaster. New Orleans isn't the only coastal city threatened by encroaching waters. Little by little each year, Venice is being swallowed by the sea. Although this has been a problem since the Middle Ages, an accelerating rise in sea levels linked to global warming has turned the sporadic flooding from a nuisance into a looming catastrophe. Crisis already hit once, in 1966, when most of the city's streets were submerged under a meter of water. After 3 decades of debate, construction has now begun on a series of enormous tidal gates to defend the city. The$5 billion plan is controversial, with some critics arguing for different protective measures and others predicting that the coming decades of sea-level rise will render the gates obsolete (see sidebar, p. 1979).

But there's good news as well. The “Venice problem” has made the city a hot spot for scientific research, and there's no shortage of questions to tackle. “Every time we focus on one aspect of the practical problem, we discover another gap in our knowledge,” says Pierpaolo Campostrini, an electrical engineer who directs CORILA, the organization that orchestrates Venice's scientific activities. Venice is providing other coastal cities with insights on what global climate change looks like at the local level. The city and its lagoon have also become a model system for studying how physical, biological, and urban processes interact in a marine setting.

If Italy's Ministry of Education, Universities, and Research has its way, Venice will soon receive 1.5%—$60 million—of the$5 billion allocated for the tidal gates. City officials hope that the fivefold increase in national funding for basic science institutions will attract young people by creating more academic and high-tech jobs in a city whose population is rapidly shrinking. But whether science can revitalize the city or save it from the encroaching sea remains an open question.

## At the battlefront of climate change

Zipping across the chalky green water in a motorboat, Campostrini points out a 16th century stone fortress with windows half-submerged. “It's not enough to estimate sea level as a global average,” he says. Determining a particular city's risk—and what to do about it—requires an understanding of how climate change plays out locally. Even so, Venice is a “microcosm of the larger changes” taking place, says Trevor Davies, an atmospheric scientist at the University of East Anglia in Norwich, U.K.

For instance, Venice's record of sea-level change is now the most comprehensive in the world. Modern records of watermarks go back to the late 19th century, and researchers are finding ways to push the data farther back in time. A Venetian tradition of painting scenes with the help of camera obscura projections, the pinhole predecessor to photography, has left researchers with accurately scaled images of the green algae lines on walls that mark the average high-water level. A team led by Dario Camuffo, a climatologist at the University of Padua, Italy, has used them to extend sea-level records back another 300 years. Archaeologists are going back to the Middle Ages by estimating water levels based on the buried remains of former walls and bridges. And geologists are estimating the local sea level 2000 years ago by dating the remains of salt marsh plants that once poked above the water.

To fit these data into the global picture, researchers must also account for Venice's steady sinking due to a combination of moving continental plates and compressing sediments. The effect of a “little Ice Age” that hit Europe in the Middle Ages appears as a spike in sea levels even higher than today, whereas the levels at the time of the Roman Empire were about 1.5 meters lower. The most troubling trend, says geophysicist Alberto Tomasin of the University of Venice, is that sea levels have risen rapidly over the past 50 years.

Rising sea level isn't the only way climate change is affecting the city. Venice is a perfect natural lab for studying these effects, says Davies, because changes in weather patterns are “amplified” as changes in the frequency and severity of flooding events. Davies and Isabel Trigo, a climate scientist at the University of Lisbon, Portugal, have been teasing apart the different factors that cause the flooding.

The first task has been a postmortem of the 1966 disaster. Even without global warming, Venice would be prone to flooding, both because it was built only a couple of meters above the water and because of the city's location at the end of the narrow Adriatic Sea. The mountains to the north create low-pressure systems that suck the water level higher up around the lagoon, and wind tends to blow in from the sea, piling the water higher. And because of the shape of the Adriatic, sometimes swells generated by storms in the Mediterranean fall in phase with the tides, doubling the load of water that rushes into Venice's lagoon. These factors all conspired in 1966, causing the second tide of the day to push into the lagoon before the first could drain out, swamping the city.

With these mechanisms mapped out, Davies and Trigo are finding that climate change can also have a protective effect at the local level, at least in the short term. Venice would be in much deeper trouble by now, says Davies, were it not for a northward drift of the Atlantic storm track over the past 40 years, a trend linked to global warming. As a knock-on effect, storms in the Mediterranean have become less severe, likely saving the city from more 1966-style catastrophes. What happens if climate change nudges the Atlantic circulation farther off track is hard to predict. By studying Venice, says Davies, “you can start to draw out these subtle effects.”

## Deep knowledge of a shallow lagoon

In the past 3 decades, Rome has spent more than $10 billion studying and coping with the “Venice problem.” In comparison, Italy's national research foundation receives about$1 billion per year. “By the mid-1990s, people began saying that the Venice funding was a torta,” a giant cake free for the taking, recalls Philippe Pypaert, an environmental scientist at the United Nations Educational, Scientific, and Cultural Organization's European science bureau in Venice. In 2000, the newly established CORILA began reining in the projects by controlling the flow of funds and organizing projects under a few broad goals. “Things are under much better control now,” says Pypaert.

Still, Campostrini says that climate change and flooding aren't Venice's only problems. The city's art and architectural treasures require protection and restoration, and there are environmental threats to the surrounding lagoon, which is a bustling seaport and one of Europe's largest protected wetlands.

To help understand the troubles besetting the lagoon, scientists of every stripe are building a model that can not only help them manage the fragile environment but also shed light on the physical and biological aspects of a wetland. “This is our ultimate goal,” says Roberto Pastres, a marine scientist at the University of Venice, but it's easier said than done.

Just predicting how the water behaves is mind-boggling. Water flow alters the lagoon's shape by moving sediments, which then changes the flow, and so forth. Add to that feedback loop the many urban and biological influences, and the hopeful modeler faces “an impossibly complex system,” says Giampaolo Di Silvio, a hydraulic engineer at the University of Padua.

Fortunately, the researchers already have enormous amounts of information, from the movement of sediments to the distribution of sea life. “The Venice lagoon is the best studied in the world,” says Di Silvio. One of the big questions to be answered with the final model, of course, is how the lagoon will react to the new tidal gates. But it will also help scientists around the world study how pollutants are shuttled through marine systems and the factors that lead to oxygen-choking algal blooms. The model may also help answer fundamental questions involving biodiversity and nutrient transport in sea-land systems.

Turning Venice into a science mecca could also save it from a ruinous brain drain. “Venice is in danger of becoming a dead city, like a museum,” says Carrera. Driven away by the high waters and high prices, the population has plummeted from 150,000 in the 1950s to 64,000 today. Nearly half of the city's income now comes from the 14 million tourists who flock to Venice each year, with most of the rest coming from port traffic. “We desperately need more young people,” says Campostrini, and “one way to attract them is to build up the university and high-tech sectors.” Otherwise, Venice may end up being saved from the sea but abandoned by its own people.

8. VENICE

# Holding Back the Sea

1. John Bohannon

Understanding climate impacts is useful. But the goal is to protect Venice. Dams would do the trick, says Campostrini, but the city would lose its income as a port and the lagoon would die without the daily tides. Injecting water into the underground aquifer that was nearly drained 40 years ago would lift the city, but uneven rising could also destroy it.

The compromise solution, called MOSE, is a series of 78 hollow, 300-ton steel gates. The gates will sit flat underwater at the lagoon's three inlets. But in anticipation of a flood, air will be pumped into the structures to make them stand upright and block tides up to a meter higher than those of 1966. Dredging has begun for the massive concrete foundations, but they won't be operational before 2011.

The two questions hanging over MOSE are how often they will be used and how high sea levels will rise. By official estimates, the gates will be needed only two or three times a year. But critics say it could be as often as 50, enough to make the lagoon a sewage-contaminated swamp. And if the worst-case scenario of a 1-meter sea-level rise by 2100 comes true, the gates could be useless.

Outsiders' opinions are as mixed as those of Venetians. “Something like the MOSE gates are needed because controlling tidal surges is the only solution,” says Caroline Fletcher, a coastal scientist at the University of Cambridge, U.K. But building gates is not enough, according to John Day, an ecologist at Louisiana State University in Baton Rouge who, until 2 years ago, led a long-term study of the Venice lagoon. Day says his study, one of many supported by national funds devoted to Venice, revealed that returning the flow of diverted rivers back into the lagoon would not only deposit sediments to compensate for subsidence but also would support lush wetland vegetation that would act as a buffer to slow the surges. With this natural defense, says Day, the gates would not be needed nearly as often. “Venice's situation is unique, as is New Orleans's,” he says, “but they share the long-term problem of subsidence and wetland loss.” Day contends that the consortium of industrial partners behind the MOSE project “[doesn't] want to hear about” natural versus engineered solutions.

Meanwhile, some Venetians argue that the entire debate has fallen far from the mark. “The take-home lesson from all this,” says Fabio Carrera, an urban information scientist who divides his time between Venice and Worcester Polytechnic Institute in Massachusetts, “is that the cheapest solution is to stop global warming, but no one seems to be talking about that.”

9. AFTER KATRINA

# Displaced Researchers Scramble to Keep Their Science Going

1. Jocelyn Kaiser*
1. With reporting by Adrian Cho, Eli Kintisch, Jeffrey Mervis, and Elizabeth Pennisi.

Despite huge personal losses, New Orleans scientists are hurrying to recreate their labs and lives with some help from the government

Tulane University biochemist Arthur Lustig is still reeling from Hurricane Katrina. He spent 4 days hunkered down in his New Orleans lab before being evacuated by helicopter, then another miserable night in a shelter. His house was likely lost to flooding, and he's not sure whether the 20 years' worth of yeast strains he uses to study telomeres survived the power outage.

But things could be a lot worse. Showered with invitations from colleagues around the country, Lustig is now living with his wife's family in Chicago and working at Northwestern University, with lab space for his four students and one postdoc. “It's a traumatic time. But I think most of us have a positive attitude that we can get over this,” Lustig says.

Thousands of scientists face similar challenges. The flooding that displaced New Orleans residents after Katrina slammed into the Gulf Coast on 29 August exiled faculty members, graduate students, and postdocs from a half-dozen institutions in New Orleans. Thanks to Internet message boards and cell phone calls, many are regrouping in temporary labs and office spaces at other universities. “People have been really wonderful. They realize [Katrina] is a huge impact on careers,” says Arthur Haas, chair of biochemistry and molecular biology at the Louisiana State University (LSU) Health Sciences Center in New Orleans. Scientific societies have also rushed to help, posting Web sites for those who haven't yet found spots (www.aaas.org/katrina).

For some, the disruption may be short-lived. Tulane medical school officials hope to get a handle soon on mold in air conditioning ducts, the main obstacle to reopening buildings in their now-dry part of the city. But many researchers have already enrolled their children in schools elsewhere and don't expect to return until January, when university classes resume. Although they are trying to view the forced exile as a minisabbatical, it's hard to be too optimistic about their research. “Will it slow us up competitively? Absolutely,” says Lustig.

Against all odds, researchers did what they could to preserve their research materials. In the days after the storm, researchers from Tulane and LSU ventured back by boat, truck, and helicopter with armed guards to top off the liquid nitrogen covering storage containers and retrieve samples hastily ordered by priority. Tulane gene-therapy center director Darwin Prockop organized a convoy from Baton Rouge on 10 September to salvage their National Institutes of Health (NIH)-funded adult human stem cell bank, with staff lugging 36-kg Dewars up four flights of stairs to collect racks of vials.

Tulane scientists saved transgenic mice but had to euthanize most other animals; LSU animal caretakers destroyed or lost to flooding about 8000 animals in four vivariums, says Joseph Moerschbaecher, vice chancellor for academic affairs at LSU's Health Sciences Center. Also lost at Tulane were freezers of blood and urine samples, including those from the Bogalusa (Louisiana) Heart Study, which has followed thousands of children since 1972 to tease out heart disease risk factors. “It's a national tragedy,” says Paul Whelton, Tulane senior vice president for health sciences.

Other scientists fear that mold has destroyed animal and plant collections built up over decades. Tulane ecologist Lee Dyer sneaked back and put desiccant and mold killer in drawers containing preserved insects. University of New Orleans (UNO) butterfly expert Phil DeVries and his wife, systematist Carla Penz, fear a severe toll on 30 years' work: preserved butterflies, hundreds of photographs, as well as rare identification books and countless field notebooks. Physical scientists, for their part, are worried about damage to sensitive equipment such as electron microscopes.

With their campuses closed until January, many scientists have accepted offers of temporary digs at other institutions. Xavier University microbiologist Shubha Ireland feels especially lucky. She was offered a spot in a molecular biology lab at Oak Ridge National Laboratory in Tennessee. ORNL officials also secured a part-time administrative job for her husband Rick, a lawyer. And a local real estate developer donated a new four-bedroom house for the family to stay in for 6 months. “It's like a dream come true,” says Ireland.

Although some scientists expect to use the time mainly to write papers, many others are determined to get back to the bench as quickly as possible. “Nobody is going to miss a beat—at least not in my group,” says Zeev Rosenzweig, a chemist from UNO now living in McLean, Virginia, and working at the nearby National Science Foundation (NSF). Rosenzweig moved up by 2 years the start date of a rotating position as officer for NSF's analytical and surface chemistry program and intends to relocate most of his group to the Washington, D.C., area.

Some hope their research will benefit from the unexpected move. UNO physicist Leonard Spinu was invited by a colleague from his native Romania to the National High Magnetic Field Laboratory at Florida State University in Tallahassee, which has some of the best facilities anywhere for his research on magnetic nanomaterials, he says. Tulane neuroscientist Andrei Belousov says his time in the lab of Sacha Nelson at Brandeis University in Waltham, Massachusetts, could spark new collaborations. “I hope it's something we can work together on, not simply charity,” says Belousov.

Still others are preparing to rebuild essential research materials. Haas, who lost 20 years' worth of samples for studying the ubiquitin system, expects to spend time re-expressing recombinant proteins at LSU's biomedical research center in Baton Rouge. “We've just got to bang out clones,” he says.

Especially hard-hit are graduate students. Tulane's Vincent Shaw, whose adviser is evolutionary biologist Duncan Irschick, found a temporary spot at Brown University in Providence, Rhode Island. But he and his labmates left behind the analyses needed to finish a paper in press, experimental animals now likely to be dead, and freezers full of thawed samples. “Researchwise, I am in a bad place,” says Shaw.

Funding agencies are working to smooth these temporary transfers and help displaced researchers get back on track. NSF and NIH are relaxing rules to accommodate those caught in the catastrophe. “We want to protect researchers so that they don't get stuck with the tab” for incurring expenses related to relocation or repair of federally funded projects, says NSF's Jean Feldman, who oversees a hotline that is getting 50 calls and e-mails a day.

In addition to information, the hotlines provide some therapy, says her NIH counterpart, Carol Alderson. “Some PIs [principal investigators] are resilient and just want to know what it'll take to get back to work,” says Alderson. “Others sound like the people you hear on television; they've gone through the worst, and they don't think that their institution will ever recover.”

Although federal agencies have promised to be as flexible as possible, there's a limit to how far they can bend. NIH, for example, has struck deals with Tulane and LSU allowing faculty to temporarily submit grant applications directly, but NSF says any proposal must still come from the institution. At the same time, both agencies plan to be lenient about enforcing application deadlines, with NSF decreeing a 1-year extension for any scientist in the three-state region whose grant would have expired this month or next.

Although grateful for the outpouring of help, New Orleans administrators worry that some universities are seeing the disaster as a chance to snap up talented faculty. At least a few have already taken permanent positions. “We do not want to see a brain drain. It would be terrible for the region,” says Tulane's Whelton. “Our full aspiration is to get back in business and have an even stronger institution than when we left. And we'll need all the help we can to get to that point.”

10. AFTER KATRINA

# Katrina Leaves Behind a Pile of Scientific Questions

1. John Bohannon

Amid the cleanup in Katrina's wake, scientists are rushing into the field to gather data before they disappear. It's a sobering exercise. Havidan Rodriguez, who is leading a team from the Disaster Research Center at the University of Delaware, Newark, that is asking evacuees along the Gulf Coast how their basic needs are being met, says the task “is turning out to be more difficult” than similar efforts in Sri Lanka after the 26 December 2004 tsunami. “The breakdown of infrastructure is far greater,” he says, “and the poverty is endemic.”

One major focus is to reconstruct how the hurricane overcame New Orleans's defenses. The Hurricane Center (HC) at Louisiana State University (LSU), in nearby Baton Rouge, has become the de facto headquarters for that effort. After a whirlwind tour of the region, the center's researchers reported that the storm surge reached a height of 9 meters in some places. They are also updating a model of the floodwater's impact on the city. If the pumps hold out and no new tropical storms hit, says HC coastal scientist Hassan Mashriqui, the city should be fully drained by the end of the month.

Another priority involves tracking the consequences of dumping the city's contaminated floodwater into the surrounding environment. Initial tests by the Environmental Protection Agency and the Louisiana Department of Environmental Quality have allayed the worst fears: Fecal bacteria counts are high, but according to a preliminary analysis, it would take exposure of “a year or longer” to the chemicals at measured concentrations to cause serious health effects. Toxic algal blooms are another fear; the LSU Earth Scan Laboratory has been using an Indian satellite to search Lake Pontchartrain for signs of growth. Colder temperatures next month are expected to make blooms less likely and reduce the risk of further storms.

To help cover the costs of these and other projects, the National Science Foundation (NSF) is providing supplementary funding to existing grants. This week, NSF hoped to award about 30 “exploratory” research grants of between $10,000 and$30,000 chosen from some 120 proposals it received. A second competition closes this week for a larger pot of money. The timing could not have been worse, says NSF's Dennis Wenger, because “Katrina hit right at the end of the fiscal year.” But “we're making it work.”

11. STEM CELLS

# Scientists Chase After Immortality in a Petri Dish

1. Gretchen Vogel

Efforts to turn embryonic stem cells into sperm and eggs are answering long-standing questions about how the body prepares its genes for the next generation

Sperm and egg cells are the body's best shot at immortality. Although these so-called germ cells play no part in day-to-day survival, in most species they offer the only route for the genome to make it into the next generation. In keeping with that pivotal role, germ cells seem to play by their own rules, developing separately from cells that build all the other parts of the body. Now scientists who study embryonic stem (ES) cells—another type of immortal cell—are attempting to figure out how to coax them to become germ cells in a dish.

If they succeed, the implications would be profound. Such technology would not only provide an unprecedented opportunity to study the development of these crucial cells, but it might also enable scientists to pursue nuclear transfer experiments without needing to harvest egg cells from women donors—a huge obstacle. And in the most futuristic applications, such techniques could someday allow scientists to create sperm and egg in a dish, possibly helping infertile people reproduce or—in a scenario that makes some shudder—leading to designer gametes and made-to-order babies.

Designer gametes may be a distant prospect, but 2 years ago, scientists did seem on the verge of converting ES cells to germ cells. Three different groups reported that sperm- and egglike cells could arise spontaneously in colonies of differentiating mouse ES cells. But the researchers soon tempered their expectations. Although several groups have repeated the earlier results—and new studies suggest even more unexpected sources of germ cells (see sidebar, p. 1983)—mature sperm and egg cells appear only rarely, and no one has managed to show that any of the lab-grown cells can produce a live organism.

Nevertheless, the work is providing insights into how early germ cells determine their fate, how they turn specific genes on and off in a still-mysterious process called imprinting, and how important the environment surrounding differentiating cells—sometimes called the stem cell niche—is for their survival and normal development.

“This is really unique biology that no one has been able to study before,” says Renee Reijo Pera of the University of California, San Francisco, whose lab is trying to turn human ES cells into sperm and oocytes. She and her colleagues hope to sort out the genes that control gamete formation in humans—something that has been nearly impossible to study in the lab.

The first hints that such studies might be possible appeared when researchers noticed that ES cells left to grow and differentiate on their own produce a range of cell types: patches of muscle cells that contract in rhythm, groups of neurons, bits of cartilage, and even blood. Several years ago, Hans Schöler and his colleagues, now at the Max Planck Institute of Molecular Medicine in Münster, Germany, set out to see if any of the cells in the random mix might be immature oocytes or sperm.

Because maturing germ cells are difficult to distinguish by their appearance, the scientists developed a mouse ES cell line harboring a gene for green fluorescent protein that lit up only when a key germ-cell gene was expressed. After a few days of unguided differentiation, a few of the clusters sported glowing green cells; after a few more days, these clusters began to look like ovaries. The cells survived in culture for several months, and, perhaps most surprising, seemed to trigger the production in culture of hormones similar to those produced during the female mouse's menstrual cycle (Science, 2 May 2003, p. 721).

A few months later, two separate teams published papers in the Proceedings of the National Academy of Sciences and Nature describing how they had coaxed mouse ES cells to grow into sperm cells (Science, 12 December 2003, p. 1875). Toshiaki Noce, Yayoi Toyooka, and their colleagues at the Mitsubishi Kagaku Institute of Life Sciences in Tokyo showed that immature germ cells transplanted into the testes of live mice could become full-fledged sperm, although they didn't manage to fertilize any eggs. Meanwhile, Niels Geijsen and George Daley, both now at Harvard Medical School in Boston, Massachusetts, showed that spermlike cells produced in their lab could fertilize eggs and prompt the formation of early embryos. None of the lab-made germ cells managed to produce a pregnancy, much less a live-born mouse.

That next step has proved difficult. Although several labs can consistently get early germ cells to form, only a tiny percentage enter meiosis—the complicated process of germ-cell division that produces a sperm or egg with a single copy of each chromosome instead of the normal complement of two. “It's still a very rare phenomenon,” Daley says.

Nevertheless, a few new ideas are emerging from the studies. For example, Reijo Pera's lab has been focusing on the very first cues that set germ cells aside for separate development. At a June meeting of the International Society for Stem Cell Research, she and her lab described what they call “germ cell particles,” clusters of proteins and RNA that seem to distinguish early germ cells from those destined to become somatic cells.

In insects and fish, germ cells develop from a region of the oocyte called the germ plasm, which is particularly rich in RNA and RNA-binding proteins. Mammals, however, seem to set their germ cells aside slightly later in development—and independent of any specific region in the oocyte. Reijo Pera and her colleagues have found human versions of the germ-plasm proteins and RNAs in the human germ cell particles; now they are trying to determine what triggers their formation. The work should turn up new insights into what the proteins and RNAs do, says Geijsen. Even in model animals, he says, “no one really understands what the germ plasm is and does.”

Geijsen and his lab are also focused on the early stages of germ-cell development. When a sperm and egg come together to form a complete genome, many of the genes inherited from the mother or father are specifically turned on or off. This process, known as imprinting, begins in immature germ cells; Geijsen hopes the chance to make unlimited numbers of such cells will enable him to identify some of the molecules that control it.

New results hint at ways to increase the efficiency of producing early germ cells for such studies. Alan Trounson and Orly Lacham-Kaplan of Monash University in Clayton, Australia, reported last month that they can turn clusters of differentiating ES cells called embryoid bodies (EBs) into what Trounson calls “ovarylike” structures by bathing the EBs in media that has first been exposed to newborn mouse testicular cells. In a paper published online in Stem Cells, the researchers reported that they coaxed more than 80% of their EBs to form the ovarylike structures: clusters of cells surrounding larger cells that express several oocyte proteins. But Trounson says they have not managed to fertilize any of the oocytelike cells. Nor do they understand what, exactly, the conditioned media contains—much less how it might be influencing the growing cells.

That result could shed light on another mystery: how the gender of germ cells is determined. Why the proteins produced by testicular cells could produce ovarylike structures is not yet clear, Trounson says, but several studies have suggested evidence for germ-cell gender-bending. Schöler and others have found that male ES cells—carrying one X and one Y chromosome—can become oocytes, and Reijo Pera notes that doctors occasionally find so-called testicular eggs in male patients. Female ES cells can't make sperm, however. “The Y chromosome is fundamentally required” for sperm maturation, says Reijo Pera.

Another fundamental requirement for full germ-cell development, apparently, is the so-called niche, the cells and signals that surround the maturing germ cells in the testes and ovaries during development. Studies in fruit flies have shown that developing oocytes interact closely with nurse cells that help guide their movement and maturation. Similar interactions are probably key in mammals as well and may explain why so few of the lab-grown germ cells make it past the earliest stages of development. “Meiosis will not work if you don't have the right cell-cell communication,” Schöler says. But he is optimistic that the cell clusters that he and others see in their lab dishes will reveal those signals. “We have the right material” to find the answers, he says—and to move another step toward understanding the germ cell's immortality.

12. STEM CELLS

# Another Route to Oocytes?

1. Jennifer Couzin

Embryonic stem cells may be one path to new eggs, but a scientist at the University of Guelph, Canada, thinks she's found another, unexpected one. At a July meeting of the Society for the Study of Reproduction in Quebec City, Canada, reproductive and molecular biologist Julang Li described to a startled audience how she and her colleagues had transformed skin stem cells drawn from fetal pigs into cells that looked remarkably like oocytes. Since then, her work, now under review at a journal, has sparked discussion among scientists, who consider the results preliminary and agree that more in-depth testing is necessary. But the oocytelike cells are nonetheless “extremely interesting and exciting,” says developmental biologist John Eppig of the Jackson Laboratory in Bar Harbor, Maine, who heard her talk. “It seems that it's going to be possible to get germlike cells from a variety of different types of stem cells,” he adds.

In her presentation, Li described a series of experiments; in each case, she and her colleagues isolated about 5 million skin stem cells from 40- to 50-day-old fetal pigs. (Full gestation normally takes 114 days.) The scientists put these cells into a solution Li declined to describe. Most stuck to a petri dish and were discarded. Some, however, floated together and formed aggregates. Up to a third of the aggregates appeared to have a large cell in their center. These were transferred to another concoction containing gonadotropin, a hormone that can stimulate oocyte production; Li would not reveal all its ingredients because the culture is detailed in a pending patent application.

Of the aggregates transferred, 1% to 10%, depending on the batch, ballooned into very large cells, 80 to 100 micrometers in diameter. In their shape and other morphology, the cells closely resembled oocytes, although they tended to be slightly smaller. The cells also expressed a half-dozen genetic markers common to eggs. Li reported that some of these cells spontaneously went on to become embryolike structures called parthenotes, which appear when an unfertilized egg begins developing on its own. Parthenotes were also seen by Hans Schöler, now at the Max Planck Institute of Molecular Medicine in Münster, Germany, and his colleagues, who were the first to convert stem cells—in their case, derived from embryos—into cells similar to eggs (see main text).

More than anything, the smooth, circular images Li beamed across a screen were what convinced her audience she was on to something. Eppig noted what looked like a “distinctive” zona pellucida, a transparent membrane that forms around the developing ovum. He also considers the cells superior, in their likeness to oocytes, to those Schöler's team created. Indeed, the images so closely resemble eggs that they may be expressing more oocyte-associated genes than Li tested for, suggests Hugh Clarke, an expert in mammalian oogenesis at McGill University in Montreal, Canada.

But more research is needed to prove that these cells are eggs, say Clarke and others, such as examining their chromosomes and possibly fertilizing them to see if they form a traditional embryo. Eppig notes that despite some hints, it's also far from certain that the cells can enter meiosis and divide. Still, they suggest that when it comes to coaxing germ cells to form, there may be more than one place to start.

13. DIVISION FOR PLANETARY SCIENCES MEETING

# Martian Methane: Rocky Birth, Then Gone With the Wind?

1. Govert Schilling*
1. Govert Schilling is an astronomy writer in Amersfoort, the Netherlands.

CAMBRIDGE, U.K.— In the medieval city where Isaac Newton worked on the gravitational laws, about 850 scientists gathered from 4 to 9 September for the 37th meeting of the American Astronomical Society's Division for Planetary Sciences.

Last year, a spectrometer on board the European Space Agency's Mars Express spacecraft detected methane above areas of the martian surface where there also appears to be subsurface ice (Science, 1 October 2004, p. 29). Many researchers hailed the find as possible evidence that bacteria are living in the ice and producing the gas. After all, almost all the methane in Earth's atmosphere is produced by living organisms. Indeed, says planetary scientist Sushil Atreya of the University of Michigan, Ann Arbor, many alternative explanations for the existence of the methane don't work. Volcanic activity would also produce sulfur dioxide, which is not observed. A freak cometary impact in the past few thousand years could have delivered methane to the martian surface, but then the gas wouldn't be concentrated in specific regions.

But, Atreya announced at the meeting, it's too soon to invoke martian microbes as the source. Instead, a little-known geochemical process known as low-temperature serpentinization could be the culprit. In this process, which has been observed on Earth's ocean floor, liquid water chemically alters basalt to produce the gas. Atreya thinks it might produce huge amounts of martian methane, which would then be quickly destroyed by oxidation, ultraviolet sunlight, and possibly also by electrical activity of atmospheric dust.

Atreya says basalt reacts with liquid water to produce minerals known as serpentines, releasing hydrogen in the process. The hydrogen then reacts with carbon dioxide to produce methane. The process operates at temperatures of about 40° to 90° Celsius and is distinct from the high-temperature hydrothermal activity also seen on Earth's ocean floors. At a few kilometers beneath the martian surface, low-temperature serpentinization in reservoirs of liquid water could produce up to 200,000 tons of methane per year, Atreya says—more than enough to explain the concentrations of some 10 parts per billion seen in the atmosphere.

So where does all the methane go? Given that methane concentrations vary widely over the martian surface, it must be destroyed too quickly for the gas to spread out evenly. The explanation may lie in the electrostatic charging of dust particles, says Atreya. In small dust devils and larger dust storms, electric fields as strong as 25 kilovolts per meter could be produced. Such voltages would break up water molecules, and the hydroxyl molecules created would then oxidize methane. If this removal mechanism is indeed operating on Mars, it could mean that the production rate of methane is actually much higher than has been assumed until now.

Indeed, Michael Mumma of NASA's Goddard Space Flight Center in Greenbelt, Maryland, observed Mars with telescopes on Earth and found much higher methane concentrations (up to 250 parts per billion) in some equatorial regions. However, Atreya says “something is weird” about these observations. Such high concentrations would almost blind Mars Express's sensitive spectrometer, a problem that does not occur. Mumma is currently reanalyzing the data using new and better calibrations, but so far there's no indication that the high values will go away, he says.

As for the origin of the gas, Mumma says he's not sure that Atreya's low-temperature serpentinization scenario applies to Mars. “I'd keep the biological option open,” he says. A definitive check on the origin of methane will likely have to wait for NASA's Mars Science Laboratory, scheduled for launch in 2009. Says Mumma: “This is going to be a long tale.”

14. DIVISION FOR PLANETARY SCIENCES MEETING

# Snapshots From the Meeting

1. Govert Schilling*
1. Govert Schilling is an astronomy writer in Amersfoort, the Netherlands.

CAMBRIDGE, U.K.— In the medieval city where Isaac Newton worked on the gravitational laws, about 850 scientists gathered from 4 to 9 September for the 37th meeting of the American Astronomical Society's Division for Planetary Sciences.

A rapidly rotating rugby ball. A recently discovered miniplanet in the outer solar system is almost twice as long as it is wide, says David Rabinowitz of Yale University. The object, known as 2003 EL61, has the shape of a squashed rugby ball, measuring 1960 × 1520 × 1000 kilometers. The elongated shape results from the object's rapid rotation; its period of 3.9 hours is the fastest ever measured for a large solar system body. Using the 10-meter Keck Telescope at Mauna Kea, Hawaii, Rabinowitz and his colleagues have also detected a small satellite orbiting the miniplanet at a surprisingly large distance of almost 50,000 kilometers. It's unclear how the system could have formed or whether the rapid rotation and the strange satellite are somehow related. Says Rabinowitz: “2003 EL61 may not quite be as big as Pluto, but it's much more interesting dynamically.”

Irregular satellites explained? No one really knows how to explain the large number of “irregular” satellites that swing around the giant planets in slow, eccentric, tilted orbits. Most likely they're asteroids, long ago slowed by gas drag and captured by the rotating disks of gas and dust from which each of the planets formed. But computer simulations show that such captured objects quickly spiral into the nascent planet unless something boosts their orbits well outside the cluttered inner parts of the planet-spawning disk.

Now, Brett Gladman and Matija uk of the University of British Columbia in Vancouver think they've found such a mechanism. According to their numerical simulations, an orbital resonance between Jupiter and Saturn that occurred in the distant past would have “pumped up” the orbits of Saturn's irregular satellites to a safe distance from the planet. A similar past resonance between Saturn and Uranus may have preserved the latter planet's irregular satellites, says uk. However, he admits that Jupiter's troop of irregulars is not so easily explained.

15. DIVISION FOR PLANETARY SCIENCES MEETING

# Several New Twists for Saturn's Rings

1. Govert Schilling*
1. Govert Schilling is an astronomy writer in Amersfoort, the Netherlands.

CAMBRIDGE, U.K.— In the medieval city where Isaac Newton worked on the gravitational laws, about 850 scientists gathered from 4 to 9 September for the 37th meeting of the American Astronomical Society's Division for Planetary Sciences.

They may appear serene and eternal, but Saturn's rings are changing, and changing fast. Over the past 25 years—the mere blink of an eye in planetary evolution—one particular ringlet in the innermost, tenuous part of the ring system moved 200 kilometers inward and became one-tenth as bright. “That's radical,” says Carolyn Porco of the Space Science Institute in Boulder, Colorado, head of the imaging team for NASA's Cassini spacecraft. Porco's team discovered the rapid change by comparing Cassini ring photos with images the Voyager spacecraft sent to Earth in 1980. “This is one of the reasons why we wanted to come back,” she says. The dramatic change suggests that this part of the ring system could be young and rapidly developing, although no one yet knows how to interpret the observations.

Other ring results presented at the meeting are equally baffling. For instance, Cassini's temperature measurements of the rings indicate that ring particles are 15° cooler on their night side than on their day side. According to Linda Spilker of NASA's Jet Propulsion Laboratory (JPL) in Pasadena, California, this means that all particles—from a few centimeters to a few tens of meters across—rotate too slowly to bake evenly on all sides. “We always thought that mutual collisions would lead to a wide variety of rotation rates,” says Spilker. Maybe the particles are fluffy and porous, she adds, which would dampen the effects of collisions.

Weirdest of all is Saturn's thin, braided, kinky F ring, which lies just outside the main ring system. Cassini's images show that various strands of the F ring are actually one and the same narrow dust ring, tightly wound into a spiral. This unique structure—unrelated to the spiral density waves that have been seen in other parts of the ring system (Science, 9 July 2004, p. 165)—may be caused by a small moonlet discovered by Cassini in an eccentric orbit that appears to cross the F ring. That orbit is a mystery in itself: The F ring is believed to contain many large boulders and moonlets, which would make it hard for a small satellite to survive multiple crossings. Even so, the tiny object (denoted S/2004 S6) has been observed for almost a year.

Cassini has also spotted more bright knots close to the F ring, some of which are very elongated. “We have a hard time deciding which of these objects are real moons and which of them are clumps of dust,” says Porco. Even S/2004 S6 may turn out to be a loose clump rather than a solid object. Future observations of Saturn will surely reveal new small satellites. Says Cassini's project scientist Dennis Matson of JPL: “The complexity in the rings is just dumbfounding. We will continue to bring you excitement.”

16. DIVISION FOR PLANETARY SCIENCES MEETING

# Volcanoes, Monsoons Shape Titan's Surface

1. Govert Schilling*
1. Govert Schilling is an astronomy writer in Amersfoort, the Netherlands.

CAMBRIDGE, U.K.— In the medieval city where Isaac Newton worked on the gravitational laws, about 850 scientists gathered from 4 to 9 September for the 37th meeting of the American Astronomical Society's Division for Planetary Sciences.

Hiking on Titan would be the ultimate extreme sport. Data from the European Huygens lander show that the surface of the large saturnian moon is a jagged landscape of extremely steep valleys, overshadowed by towering ice cliffs. “It's quite dramatic,” says planetary scientist Jonathan Lunine of the University of Arizona's Lunar and Planetary Laboratory in Tucson. “You would need an ice ax to scale the 30-degree slopes.” It would be tougher than climbing a glacier, he adds: “The ground beneath your feet would feel more like a crumbly rock slope.” But at least early travelers to Titan could consult the first three-dimensional maps of parts of the moon's surface, which Lunine presented at the meeting.

The Huygens lander touched down on Titan on 14 January. During its parachuted descent, it took numerous snapshots of the panorama beneath. Lunine's team has now combined these into stereoscopic images of a 1.5-by-3.5-kilometer swath of terrain, showing deep, precipitous valleys carved out by “methane monsoons,” as Lunine's colleague Ralph Lorenz calls them after a description in Arthur C. Clarke's 1975 novel Imperial Earth. Taking into account Titan's seasons, atmospheric properties, and solar radiation, Lorenz estimates that the “monsoons” happen every few centuries and last for months. They're like the episodic rainstorms in the Arizona desert, but on a different time scale, he says.

The methane in Titan's atmosphere must be continuously replenished because ultraviolet sunlight is constantly breaking down the gas. Researchers do not yet know whether methane has been stored in the mantle since Titan's formation or whether it is being produced by geochemical processes beneath the surface. According to planetologist Gabriel Tobie of the University of Nantes, France, various forms of outgassing—such as cryovolcanism, which brings water-ammonia ice containing trapped methane to the surface—would then release the gas into the atmosphere episodically. Indeed, radar images of Titan's surface obtained by NASA's Cassini spacecraft—Huygens's mother ship—show evidence of volcanic domes, craters, and flows. Some of the latter resemble flows on the slope of Mauna Loa, Hawaii. “There's major resurfacing going on,” says volcanologist Rosaly Lopes of NASA's Jet Propulsion Laboratory in Pasadena, California.

Researchers' views about Titan's surface have also changed since Huygens's landing in January. During touchdown, a protruding penetrometer on the bottom of the lander first encountered much resistance and then went through softer material, leading scientists to conclude that Titan was like a crème brûlée with a thin, brittle crust. Now, John Zarnecki of the Open University in Milton Keynes, U.K., head of the Surface Science Package team, thinks it's more likely that the penetrometer hit an ice pebble similar to the ones seen in Huygens's pictures and then pushed it aside.

It will be a while before travel agents offer trips to Titan, but Jean-Pierre Lebreton, Huygens's project scientist at the European Space Agency, hopes to go back soon. “Huygens has paved the way for future missions to the surface of Titan,” he says.