News this Week

Science  30 Nov 2007:
Vol. 318, Issue 5855, pp. 1360

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    New Estimates Scale Back Scope of HIV/AIDS Epidemic

    1. Jon Cohen

    On the surface, it looked like very good news. Two United Nations groups reported last week that the estimated number of people infected with HIV worldwide has fallen from 39.5 million to 33.2 million, a drop of 16% from last year. The annual number of new infections has also plummeted since 2006, says the report, from 4.3 million to 2.5 million. The new analysis suggests that global incidence peaked in the late 1990s at just over 3 million per year.

    A large part of the steep decline, however, reflects the fact that numbers for previous years had been overestimated. The new figures are based on improved methods to estimate HIV prevalence and a better understanding of the disease's dynamics, the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the World Health Organization (WHO) explain in their December 2007 update. Behavior change contributed to the drop in some locales but overall was not a major factor.

    Epidemiologists at UNAIDS categorically deny that the agencies had jacked up previous estimates to increase funding for HIV/AIDS, as sources alleged in a Washington Post story on 20 November. “We find that accusation absurd,” says UNAIDS epidemiologist Paul De Lay. Tim Brown of the East-West Center in Honolulu, Hawaii, an epidemiologist who has worked closely with UNAIDS on its estimates, also rejects the charge. “There was no inflation of the numbers,” says Brown. “We were trying to use the best scientific information available at the time.”

    Seventy percent of the downward shift comes from Angola, India, Kenya, Mozambique, Nigeria, and Zimbabwe. Of these, India accounts for the biggest change—a drop from 5.7 million to 2.5 million—which was first reported this summer (Science, 13 July, p. 179).

    Ups and downs.

    Estimates of the number of HIV-infected people worldwide have dropped because of new methodologies, but taking these into account, a revised look back shows that the number has steadily increased (bottom).


    Evidence suggests that declines occurred in Kenya and Zimbabwe in part because people engaged in less of the risky behavior that can expose them to HIV. In other countries, the lower figures reflect data from a growing number of sites that report results from HIV tests. (India alone went from 155 in 1998 to 1100 in 2006.) Additionally, 30 countries since 2001 have done household surveys that document HIV prevalence in large swaths of the population. These population-based surveys revealed that urban prenatal clinics, which have served as a major source of countrywide estimates in the past, generally inflate actual infection rates by about 20%, prompting experts to lower the latest estimates. One reason for the inflation is that in places such as South Africa—which has more infected people than any country—young women are more likely to be infected than young men. Another is that such surveys do not capture the status of women who are not sexually active or routinely use condoms.

    Executive Director Peter Piot explains that UNAIDS now realizes the importance of using different tools to track the epidemic in different locales. “We should be connecting all these different approaches very, very early on,” says Piot. Specifically, in countries that have a “generalized” epidemic, in which the virus infects more than 1% of adults, population surveys are probably the most accurate gauge, he says. But in countries with an epidemic “concentrated” in groups such as sex workers, injection drug users, and men who have sex with men, it makes more sense to focus on those high-risk groups.

    Not all estimates decreased. In eastern and central Asia, prevalence increased 150% since 2001, with nearly 90% of the new infections occurring in Russia and Ukraine. Similarly, prevalence doubled in Vietnam between 2000 and 2005, and the report says the epidemic in Indonesia “is among the fastest growing in Asia.”

    The update also reported the surprising finding that, on average, it takes 11 years rather than 9 for HIV infection to cause symptomatic disease in untreated people. This slower disease course affects calculations of the new infection rate and of mortality. Anti-HIV drugs, which more than 2 million infected people now receive in poor and middle-income countries, also have contributed to decreasing mortality, which dropped from 2.9 million deaths in 2006 to 2.1 million in 2007.

    AIDS epidemiologist Thomas Quinn, who directs the Johns Hopkins Center for Global Health in Baltimore, Maryland, stresses that like all infectious-disease estimates, the new figures have their own degree of uncertainty. “I certainly hope this change in statistics doesn't alter anyone's concerns about how we're going to manage this epidemic,” says Quinn. “It doesn't really matter whether it's 33 million or 39 million when it's that high of a number. It's a massive epidemic that continues to grow.”

    Kevin De Cock, head of WHO's HIV/AIDS program, says the 16% reduction in prevalence will not change the amount of money needed for anti-HIV drugs. “We're not going to see a substantial reduction in treatment needs, and for various reasons, it's likely to go up,” he says. Two forces in particular will offset the cost savings from the prevalence reduction, he says: People are surviving longer without treatment, and people in developing countries are beginning to start treatment earlier. “Where this will end up is not entirely clear,” he says.

    The same holds true for estimating HIV's incidence and prevalence. “I hope we don't have to adjust in a big way in the future,” says Piot of UNAIDS. “But we're no longer simply documenting the natural history of HIV infection. There are treatment and prevention effects to consider now. That's great, but it's a nightmare to document.”


    Tense Meeting Produces Some Hope for Flu-Sharing Deal

    1. Martin Enserink*
    1. With reporting by Dennis Normile.

    It's too early to call it a breakthrough. But a marathon meeting in Geneva, Switzerland, last week has resulted in what participants hope will be a way to salvage the international system for sharing influenza virus samples. After 4 days of feverish debate and diplomacy, often stretching late into the night, participants agreed to embark on an overhaul of the system that Indonesia and other developing nations had demanded. They also agreed to some immediate measures, including a way to help countries keep track of what happens to their samples. “It's more progress than I have seen at any meeting to date,” a member of the U.S. delegation says.

    At stake during the Intergovernmental Meeting on Pandemic Influenza Preparedness was the Global Influenza Surveillance Network (GISN), which helps monitor viral evolution and prepare the production of vaccines against seasonal and pandemic flu strains. Indonesia has for the past year refused to share samples from its human H5N1 influenza victims with the network, saying those viruses are its own property and demanding guarantees that it will get the benefits—such as pandemic vaccines—that sharing can help produce.

    Other developing countries, such as Egypt, Nigeria, Vietnam, and Thailand, have stopped short of boycotting GISN but sympathize with Indonesia. The result was a “very tense and polarized meeting,” says Christianne Bruschke, a bird flu expert at the World Organisation for Animal Health in Paris.

    In the end, participants from more than 100 countries agreed to a 50-plus-page document that will form the basis for a new set of principles and rules for the sharing system, to be worked out at the next meeting in 2008. The text still has many dozens of disputed passages and even conflicting ideas, which nobody believes will be easy to resolve. “But at least now we have a process to start solving the problem,” says Edward Hammond of the Sunshine Project, a nongovernmental organization based in Austin, Texas, that has supported the developing nations.


    Indonesia has been the hardest hit by H5N1 avian influenza.


    In a separate two-page statement that was awaiting approval from African countries as Science went to press, the meeting also agreed to set up a database to help countries track where their viruses, “and the parts thereof,” go after submission to a GISN lab. Details are unclear—one key question, for instance, is whether those “parts” include genetic information—but the system would alleviate complaints that viruses sent in by affected countries are shared among labs and vaccine companies without the countries' knowledge. In addition, the statement announces that WHO Director-General Margaret Chan will set up a new advisory body to address the sharing issue.

    “As a tangible demonstration of good will,” the statement also says, virus sharing will continue until the issue is resolved. Whether Indonesia will resume its contributions is unclear, however. The country's laws require so-called material transfer agreements to ship biological samples, says Indonesian delegation member Widjaja Lukito, a physician at the University of Indonesia in Jakarta. But those aren't currently issued within GISN, and the meeting did not reach an agreement on them.

    Hammond says the country hasn't been “entirely coherent” in its demands. “Indonesia has brought us to this point, but they're not showing the leadership to take it to the next level,” he says. “It may be the Brazilians and the Nigerians and the Thai that move this issue forward.”


    Hominid Harems: Big Males Competed for Small Australopithecine Females

    1. Ann Gibbons

    Among living people, men are usually bigger than women—but not by much, averaging 5% to 10% larger. Now a study on page 1443 finds that the males of an extinct species of hominid in South Africa took longer to grow up than females—and got much larger. This suggests that these robust australopithecines chose a risky mating strategy: Top males invested energy in bodybuilding in order to possess a harem of females, much like silverback gorillas do today.

    Although this species, Paranthropus robustus, is not on the human line, the study is the first to offer solid evidence of the mating strategies of an early hominid, says paleoanthropologist J. Michael Plavcan of the University of Arkansas in Fayetteville, who was not part of the study. The males' facial features were on average 17% larger than females', suggesting a haremlike mating strategy. “You don't get that kind of sexual dimorphism unless you are polygamous. Males don't get that big unless they get a big payoff,” Plavcan explains. That suggests diverse social strategies in the hominid family and perhaps the relatively recent adoption of low sexual dimorphism by humans. “This is not the human pattern,” says lead author Charles Lockwood of University College London.

    Lockwood made the discovery while examining 19 skulls and 16 jawbones of P. robustus from caves in South Africa, where they had been consumed by predators between 1.5 million and 2 million years ago. The adult males clustered into two groups: smaller specimens with less dental wear and larger ones with worn teeth and more robust features, such as pillars of bone alongside the nose. Lockwood cites this as evidence that the smaller males were younger and hadn't reached full size. In many primates, males don't achieve full maturity until years after equal-aged females have started to have offspring. This pattern is found in primates in which one male dominates a group of females and wards off other males. In contrast, female humans and chimps are only slightly smaller than their male counterparts, reflecting different mating strategies. “I think [the study] is very convincing,” says biological anthropologist Steven R. Leigh of the University of Illinois, Urbana-Champaign.

    The finding challenges a theory that early hominids had a relatively low level of sexual dimorphism, inherited from a common ancestor shared with chimpanzees, says Plavcan. Instead, the primitive condition may have been more gorillalike, and our female ancestors may not have closed the gap until recently, perhaps in Homo erectus in the past 2 million years.

    Bachelor boy?

    Male robust australopithecines took longer to grow up and mated later than females, leaving young males on their own.


    But those who have championed the early theory remain skeptical. Paleoanthropologist C. Owen Lovejoy of Kent State University in Ohio isn't convinced that P. robustus males were actually much bigger than the females. He warns that using dental wear to estimate age can be risky, as is estimating soft-tissue body mass based on skeletal size. And researchers hold conflicting opinions on the amount of sexual dimorphism in what most consider our closest australopithecine ancestor, Australopithecus afarensis. Lockwood plans to apply this type of analysis to that and other species to detect when the sexes grew closer in size, a signal that males were investing more in offspring and in longer-term bonds with females. “This is the $64,000 question: When did human dimorphism get smaller?” says Plavcan.


    Smithsonian Struggles to Strike a Balance With Sponsors

    1. Elizabeth Pennisi

    When the Smithsonian National Museum of Natural History (NMNH) opens a new exhibition hall on the oceans next fall, a key component—an elaborate educational Web site—will still be on the drawing board. It lost its sole sponsor last week when the American Petroleum Institute (API) withdrew a promised $5 million gift in the wake of questions about whether the Smithsonian should take money from oil companies. The withdrawal comes at a time when the Smithsonian's leaders are about to launch a capital campaign to shore up the institution's 19 museums and more than a half-dozen research centers. The fuss about API's gift hints at how challenging the campaign may be, and the episode has sent the Smithsonian's leaders scrambling to avoid future embarrassments.

    “We will take a look at the guidelines to make sure they are clear enough,” says Smithsonian acting Secretary Cristián Samper. In addition, the institution's governing Board of Regents plans to get involved earlier in negotiations with potential donors. “It was [a] mistake in not raising the questions [about the API donation] sooner,” notes Roger Sant, head of the board's executive committee.

    The natural history museum's $75 million ocean initiative includes a $49 million exhibit, an endowed research chair, and research support, in addition to the threatened Web site, which should have extensive educational and research components as well as daily updates. “I am hoping it will become the site everyone in the world will go to when they want to learn something about the oceans,” says NMNH marine biologist David Pawson, who is helping to design the site.

    The U.S. government has agreed to foot about 60% of the total bill for the oceans initiative, and more than a dozen private donors are chipping in. In 2005, the natural history museum approached API—an oil and gas industry trade association that sometimes supports outside research and education programs—for help in funding the Web site. A detailed agreement was hammered out by the end of August 2007: API's logo would appear for 2 seconds during the Web site's opening sequence and there would be a link on the site to API's own ocean information, but the institute would have no say in the content or publicity surrounding the site.

    Mixed message.

    A disagreement between Smithsonian acting Secretary Cristián Samper (left) and Regents member Roger Sant about a gift for a natural history museum (below) Web site led to the withdrawal of $5 million.


    Everyone up the Smithsonian chain of command, including Samper, signed off on the plan. “My assumption was that it would be approved,” says Paul Risser, acting director of NMNH. But when, as required for any gift of more than $1 million, the agreement was sent to the Board of Regents for the final go-ahead, Sant and board member Senator Patrick Leahy (D-VT) questioned whether it was appropriate for API to be a sponsor in light of the problems created by oil spills. An article about these concerns appeared in the Washington Post on 3 November. In mid-November, API withdrew its gift with a one-sentence letter to Risser. “Once it became discussed in public, in some ways [the loss] was inevitable,” Risser explains. He is confident, however, that new sponsors will step in. API officials would only say that conditions had changed recently at the Smithsonian, prompting API to withdraw the gift.

    Typically, Smithsonian scientists are quick to complain about possible blemishes to the Smithsonian's reputation. They sharply criticized former secretary Lawrence Small's business-oriented style and the naming of exhibit space and auditoriums after corporate and private donors. Yet in this case, Science found, researchers weren't objecting. “Most people were sorry to see it fail. I am sorry,” says Pawson. NMNH paleontologist Brian Huber agrees, adding, “It's unfortunate that we send these mixed messages [to donors].”

    The API fiasco comes at a time when the Smithsonian is being squeezed for funds to replace or renovate old buildings and exhibits and revitalize programs. The federal government pays for about 70% of the institution's $1 billion budget, which includes capital and operations expenses. However, the cost of repairing and renovating buildings alone over the next 6 years is expected to top $2.5 billion; based on previous appropriations, some are predicting a $1 billion shortfall. Moreover, Samper has been pressing hard for improvements to exhibits. “[That cost] is probably the same order of magnitude as the facilities deficit,” says Sant.

    On 19 November, the regents approved in principle the first pan-Smithsonian capital campaign, the details of which will be worked out next year, when a permanent secretary is in place. The flap over the API donation suggests that this fundraising effort could be full of land mines. “The Smithsonian, because it's such a national icon, does have a higher level of scrutiny,” says Risser. “There's a need to set rules on what we will and will not accept.”


    Pilot NSF Program Flies Into Stiff Community Headwinds

    1. Jeffrey Mervis

    A novel program at the U.S. National Science Foundation (NSF) to support innovative ways of communicating science faces an uncertain fate. The 4-year-old Discovery Corps Fellowship (DCF) program has attracted few applicants, and in a time of tight funding, a new program solicitation that's about to hit the streets could be its last. Fellows say one big obstacle is that the scientific community, for all its handwringing about a scientifically illiterate public, still views outreach as a dubious activity for those on an academic career path.

    “My department chair calls it ‘that weird thing you do,’” says a current postdoctoral fellow at a major research university who requested anonymity. “It's like we're wearing a scarlet O on our chests.” For many faculty members, outreach can be “something that you shove off onto somebody else … so we can stick to the science,” says senior fellow Carl Batt, a chemistry professor at Cornell University. But that's the wrong attitude, according to Batt, who works on self-assembling nanoscale arrays and has developed a touring show on nanotechnology called “Too Small to See.” “I run a huge research lab, and I still have the time,” he says.

    The DCF program, which gives 2-year, $200,000 grants to both postdocs and experienced investigators for research and outreach, was begun by Arthur Ellis when he headed NSF's chemistry division. Ellis saw it as a potential model for the $6 billion foundation, which embraces outreach as one of its core missions. “New Ph.D.s were telling us that they wanted to do something different as a postdoc—something with a science component but not strictly research,” recalls Ellis, now vice chancellor for research at the University of California, San Diego. “And senior investigators had ideas that they wanted to pursue, but they couldn't find the right way to go about it. Traditional models work well for most people,” he adds, “but DCF was supposed to attract those who wanted to go in a different direction.”

    Polished science.

    Discovery Corps fellow Tami Clare teaches silvering to high school students at the Philadelphia Museum of Art in a workshop on the chemistry of metalworking.


    Tami Lasseter Clare, a postdoctoral fellow at the Philadelphia Museum of Art, is one of those people. She knew after one interview that she didn't want to work for the chemical industry, and a full-time academic position didn't sound appealing, either. Instead, her love of art and historical preservation landed her a part-time position at the art museum, doing work that included restoring a set of century-old bronze sculptures atop city hall. Now she's designing new protective coatings for metallic works of art as well as teaching high school students about the chemistry of such coatings. “It might lead me back into academia,” she says about her career plans, “but in a much more interdisciplinary way.”

    Other fellows—the class of 2007–08 consists of five postdoctoral DC fellows and four senior fellows—are doing everything from running biofuels workshops for high school teachers to developing movie-quality visualizations on the origins of life and how cells evolve. Liam Pingree, a chemistry postdoc at the University of Washington, Seattle, has enlisted art students and Web site designers to help him put placards about solar power on city buses in the hope that daily commuters will be drawn to a Web site with more information on the topic. But Pingree, who hopes his research on the structure and function of organic solar cells will win him a tenure-track faculty position, admits that sometimes he has to curb his enthusiasm for his bus project. “You don't want to be flagged as someone who does outreach,” he says. “Somehow, it makes you look like something less of a scientist.”

    NSF's Kathy Covert, who runs the DCF program, says it takes time for scientists to become familiar with any new NSF initiative, especially one that deliberately goes against the grain. “This is different enough that it has what chemists might call a really low sticking coefficient,” she says. Still, she's disappointed that only 29 people applied for funding last year, and she doesn't know whether DCF will survive despite her best efforts to promote it. “If that's the most we can get from this vast community of chemists from academia, industry, and the national labs, then …” her voice trails off.


    Germany Finally Picks a National Science Academy

    1. Gretchen Vogel

    The world's oldest scientific academy has a new job. Ending years of discussion, German Science Minister Annette Schavan unexpectedly announced earlier this month that the Leopoldina, founded in 1652 and named after Holy Roman Emperor Leopold I, would serve as the new German Academy of Sciences and as science adviser to the federal government.

    Germany currently has a system of eight regional science academies, an engineering academy called acatech, and the Leopoldina, which draws its members from across the nation as well as from 30 foreign countries. But science leaders and federal officials have worried that there is no single organization set up to advise the government on scientific questions and to represent the German science community in international affairs.

    Schavan's announcement, which came as part of a radio interview on 16 November, took Germany's research community—and the academies, including the Leopoldina—by surprise. The Leopoldina's president, Volker ter Meulen, a virologist at the University of Würzburg, was at a conference in India and says his cell phone connection was so intermittent that he was unable to comment—or speak with Schavan—until his return more than a week later. Representatives from the other academies quickly complained in German newspapers that they had been snubbed.

    A plan for a new national advisory body, to be made up of members elected from the eight regional academies plus acatech and the Leopoldina, “was ready a year ago,” says Gerhard Gottschalk, president of the Union of the German Academies of Sciences and Humanities, which represents the regional academies. “We received no reaction.” On the radio show, Schavan made her reaction clear, saying that the Leopoldina was “predestined” to take on this new role.

    This is not the first time the Leopoldina has been offered the job. Shortly after reunification, the science minister at the time asked the academy, based in Halle in the former East Germany, if it would be willing to serve as a national academy. But although it had received praise for remaining independent under Communist rule (Science, 15 October 1999, p. 394), Leopoldina's leaders declined the promotion, saying the organization was not yet ready.

    Decision time.

    German research minister Annette Schavan announced that the Leopoldina should become Germany's national academy of sciences.


    In 2003, Germany's Science Council recommended that a new body be formed, with representatives from all the existing academies. For nearly 4 years, the academies and German research organizations discussed various possibilities, settling on the proposal Schavan rejected.

    Despite bruised egos among the other academies, many in the scientific community welcome Schavan's decision. The proposal “would be the realization of a long-discussed idea, without the need to found a new institution,” said Matthias Kleiner, head of the German research funding organization the DFG. Ter Meulen says that although he had no problem with establishing a new institution, the idea “didn't convince the politicians.” “All those involved were tired” of the discussions, he says. “It is now time to stop going in circles.”

    The Leopoldina is already well-connected internationally, with ter Meulen currently serving as chair of the European Academies Science Advisory Council, which brings together the national science academies of European Union member states. In preparation for the G8 meeting in Germany in May, the Leopoldina organized a meeting of the national academies from 13 countries on climate change.

    To bolster any weaknesses, the Leopoldina should cooperate with the other academies, Schavan says, especially with acatech on issues involving technology and engineering and with the Berlin-Brandenburg Academy of Sciences and Humanities for questions involving the humanities and social sciences.

    The science minister said in her announcement that she plans to be “generous” with new funding for the academy, but she did not give any solid figures beyond saying that the federal government will provide 80% of the budget and the state of Saxony-Anhalt, where the Leopoldina is located, will cover the rest. Funding and organizational details are expected to be ironed out at a meeting of Germany's state and federal science ministries in February.


    Should Oceanographers Pump Iron?

    1. Eli Kintisch

    Companies and countries are planning a series of controversial experiments to help determine if seeding the ocean with iron can mitigate global warming

    Ambling down to the winch room after a midday nap, German oceanographer Victor Smetacek realized immediately that the instruments aboard the RV Polarstern were registering something important. The water hundreds of meters below a massive algal bloom that Smetacek was monitoring was surprisingly turbid, with particles clumping up everywhere. A handful of samples revealed that the clumps consisted of dead algae.

    The phenomenon surprised the 50 scientists on the European Iron Fertilization Experiment operating in the Southern Ocean 2000 km off the Antarctic coast. Six weeks earlier, the participants in the 2004 cruise had dumped nearly 3 metric tons of iron into the frigid sea. The algal bloom from the iron was expected. But the widespread, rapid sinking of dead matter was a surprise. “We were quite stunned,” Smetacek says. “I went up and down the ship … shouting, ‘The bloom is sinking, the bloom is sinking!’”

    EIFEX offered preliminary confirmation of one method for sucking carbon dioxide from the atmosphere. The researchers hoped to demonstrate that iron would fertilize the growth of phytoplankton, which, like nearly all plants, form carbon compounds from CO2. If the algal bloom promptly sank to the sea floor, taking the carbon with it, fertilizing the oceans with iron might help remove some of the greenhouse gases that humans are pouring into the atmosphere. But Smetacek's excitement soon gave way to frustration: The EIFEX team was focused on the surface plankton bloom and lacked instruments to measure what was happening deep underwater or to collect more than a few samples. “We were not prepared for what we saw,” says Smetacek. Next time, he vowed, that wouldn't happen.


    He may soon get another chance. Last month, scientists from the National Institute of Oceanography in Goa, India, visited Smetacek's lab at the Alfred Wegener Institute for Polar and Marine Research in Bremerhaven, Germany. The Indian team is planning a 2009 cruise to explore the impact of a fertilization experiment on krill stocks and to determine how much of the algae's carbon actually reaches the depths without being recycled through the food web. Dubbed LOHAFEX—loha means iron in Hindi—the cruise is one of a new generation of iron fertilization experiments (see A Growing Field table).

    Earlier projects like EIFEX confirmed that iron fertilization stimulates algal blooms. The new experiments will explore what happens to those blooms and whether they can be carbon sinks for atmospheric carbon dioxide. There's a lot scientists don't know, including why some blooms fall so rapidly, how much of them are devoured by microbes and other sea life on the way down, and which locations and plankton species do the best job of sequestering carbon. Larger experiments could more effectively track carbon that makes it to the deep and help to quantify the impact of the technique on climate.

    The strong interest of commercial companies and governments is driving academic experiments like LOHAFEX. Companies are hoping to make money by selling credits for carbon sequestered, using the Kyoto international climate system, smaller trading schemes, or voluntary ones. On 6 November, a ship leased by one company, Foster City, California-based Planktos, set sail from Florida toward an undisclosed area in the equatorial Atlantic that it plans to fertilize. (The secrecy is due to threats from environmental activists to disrupt the mission.) Climos, a competitor based in San Francisco, California, says on its Web site that the technique has “the highest greenhouse gas mitigation potential of all available methods.”

    These plans are generating a backwash of concerns. Scientists have been divided for years about not only whether large-scale ocean fertilization is feasible but also whether it should be done at all. One worry is that such ocean engineering could disrupt ocean food webs. Another is that jump-starting ocean ecosystems with an iron jolt could lead to emissions of methane and N2O, both potent greenhouse gases that could limit the total climate benefit of a big uptake in carbon. At a recent meeting at Woods Hole Oceanographic Institution (WHOI) in Massachusetts, several scientists questioned whether large-scale fertilization could ever provide the data needed for a credible credits program. And earlier this month, the parties to the international antidumping London Convention declared that “given the present state of knowledge regarding ocean fertilization, such large-scale operations are currently not justified.” (Experts say that the treaty may be easy to circumvent, however, and that it's not clear iron fertilization is even a form of “dumping.”)

    Location, location

    Behind the current buzz about ocean fertilization is one of the biggest oceanographic discoveries of the past 50 years, namely, that iron from terrestrial dust controls the growth of extensive marine ecosystems. Scientists had long puzzled over why huge swaths of surface oceans lacked phytoplankton, the plants that form the foundation of global ocean ecosystems, despite relatively high levels of two important nutrients—nitrate and phosphate. In 1990, biogeochemist John Martin of Moss Landing Marine Laboratories in California proposed an answer: Iron is the limiting factor in determining the abundance of life in the ocean, and those marine deserts contained too little of it.


    The first successful test of this “iron hypothesis” was carried out in 1993—just months after Martin's death—by oceanographers on a cruise southwest of the Galápagos Islands in the Pacific. Since then, nearly a dozen experiments in the southern, equatorial, and northern Pacific and South Atlantic oceans have shown that iron, dissolved into seawater, could catalyze algal blooms. Some blooms were so huge, they were visible by satellite.

    Oceanographers don't understand exactly how iron influences the blooms. But ice cores suggest that the oceans have taken up as much as 100 billion tons of carbon during a series of ice ages. Smetacek calls the quest to understand how the oceans took in so much carbon “the Holy Grail” of paleoceanography because of its significance for the history of Earth's climate.

    But iron fertilization experiments have not simply opened a window into the past, he says. They have also given researchers the unique ability to perturb an ocean ecosystem with small amounts of a single chemical and then watch the effects. “All the rest [of oceanography] are simple observations,” says Smetacek. “This is the way to really understand the system.”

    Can that system be used to fight global warming? The first order of business, according to oceanographer Philip Boyd of the University of Otago in Dunedin, New Zealand, is to get a better handle on where to conduct such experiments. “Location, location, location,” Boyd said at the Woods Hole meeting. The key is to find ocean sites that are fertile enough to grow algae on the surface but that offer the environmental, ecological, and physical traits needed for the carbon to sink quickly to the deep and stay there.

    Planktos later plans to take advantage of warm waters and nutrients in the equatorial Pacific in hopes of spurring rapid algal growth. Russ George of Planktos says the company will be looking for areas that feature the best nutrient cycling. But WHOI marine geochemist Ken Buesseler questions whether it would be appropriate to sell credits based on work at the site. “It's quick and easy [there] to get a quick green patch,” he says. But nutrients from the deep are recycled infrequently in those areas, he adds, and those nutrients “would have been used anyway” by carbon-sipping plants growing naturally.

    To avoid that potential problem, the India-funded team is focusing on the Southern Ocean. Although the cold and seasonally dark conditions are less conducive to algal growth, its surface nutrients are more regularly replenished by upwelling. That allows successive iron-fertilized blooms to take in carbon using nutrients that would have otherwise returned to the deep.

    Larger experiments of longer duration could make it easier to track the humanmade blooms, which get stretched and diluted by currents, downwelling, and storms. During a 12-day experiment in 1999, says Boyd, “we invest[ed] about half our time just keeping track of where [the patch] is.” Scientists have calculated that the next generation of experiments should be bigger by a factor of 10 and occur within a relatively enclosed, recirculating area called an eddy to keep the fertilized area intact.

    Counting the carbon

    The trick to sequestering carbon is to have it fall below what oceanographers call the 100-year horizon. That's the point, starting at 500 m, beyond which the water will not come into contact with the surface for a century. That duration is the international standard for commercial carbon-storage projects. As much of the carbonaceous material grown on the surface falls, microorganisms and animals called zooplankton below invariably eat it, creating, among other things, CO2 that eventually returns to the surface within a year. By getting more carbon beyond the 100-year line, fertilization buffs hope to bypass that process.

    Scientists don't know exactly why some of the dead algae clumps and falls, and only three of the 11 experiments to date have shown evidence of carbon being transported below the surface. It's possible that the experiments were too short or too small for scientists to measure the amount of carbon transported. A more ambitious effort should, many scientists think, send more carbon to the deep. Researchers also need better measurements to quantify how much carbon is gone for good after a bloom dies or gets eaten up. Climos plans to deploy devices, called sediment traps, just below the 100-year horizon to catch that harvest.

    To know where the magic line is, says oceanographer Andrew Watson of the University of East Anglia in Norwich, U.K., modelers need a better understanding of how water moves within their ocean models. “The physics is as important as the biology,” he says. Another task is to monitor more accurately the potent greenhouse gases produced by microbes in such an altered ocean ecosystem. Although only two of the 11 experiments thus far have detected nitrous oxide and none methane, any company that hopes to claim carbon credits from a fertilization project must first measure these gases and subtract their impact.

    There's also the problem of tracing carbon that doesn't make it past the 100-year line, says John Cullen of Dalhousie University in Halifax, Canada. The water below the surface moves turbulently and gets mixed up, so any N2O generated later could turn up far from the original. “There could be ill effects we simply could not see,” says Cullen. “It's a legitimate concern,” agrees Margaret Leinen of Climos. But she believes that observational data suggesting a problem with N2O levels are “equivocal” and that modeling studies show that only a portion of the positive impact of the bloom would be offset by the additional levels of the potent greenhouse gas.

    View this table:

    A sea of unknowns

    Scientists must find a way of linking specific downstream impacts to specific experiments. Otherwise, says Buesseler, once several companies begin working in the same region, “it starts to get very difficult to work out who's responsible for some of these effects.”

    Those consequences could be considerable. The next generation of experiments must improve monitoring of nitrate and phosphate to measure whether an algal bloom could deplete these nutrients from the site of the experiments or adjacent areas. Overfed bacteria, for instance, can create dead zones that could deplete fish stocks. So the next experiments need better technology to track nutrients and oxygen levels indicative of dead zones. Right now, the error bars are too large. The problem is “somewhere between trivial and bad,” says Climos adviser Anthony Michaels of the University of Southern California in Los Angeles. Researchers are also on the lookout for toxic algae strains from blooms.

    Leinen says “a mix of indicators” on robots and boats could help track the algal blooms. It would be a big improvement over the first generation of experiments, she says, which had little ability to monitor their blooms over a broad tract. The increasing variety of buoys, undersea gliders, and autonomous samplers can now follow a bloom and report data to satellites at regular intervals. But the tools are still limited. Remote sensors can't yet measure N2O and have limited battery life. The thousands of buoys needed to keep an eye on greenhouse gases returning to the surface for roughly a year would be prohibitively expensive, notes Watson.

    Even if individual projects could account for the carbon that they're sequestering, says oceanographer James Bishop of the University of California, Berkeley, their combined impact could alter the carbon uptake of the world's oceans in ways that are very hard to quantify. That could stymie efforts to balance the terrestrial, atmospheric, and ocean segments of the global carbon budget, he says, and make it harder for policymakers “to know if carbon management is working.”

    Despite considerable reservations, a growing number of oceanographers expect ocean fertilization to be among the proposed solutions to global warming. “China has 500 years of coal and intends to burn it at 3 cents a kilowatt hour,” Brian Von Herzen of the Climate Foundation said at the Woods Hole conference. In response, he says, “as a community, we can do nothing. Or [we can] play an active role by exploring this second generation of [fertilization] experiments.”

    Cullen predicts that scientists will be unable to quantify the greenhouse impacts of fertilization but that policymakers will want to use the method anyway. Before that happens, Cullen says, scientists should have collected as much data as possible. “It's the only ocean we have,” he says. “Society needs clearer answers on what the risks are.”


    MIT Engineer Shakes Korean Academia to Its Core

    1. Dennis Normile

    Radical measures from the new president of the Korea Advanced Institute of Science and Technology are roiling a tradition-bound system


    To gain stature beyond Korea, KAIST has lured students from Vietnam, China, and Rwanda, among other countries.


    DAEJEON, SOUTH KOREA—When the Korea Advanced Institute of Science and Technology (KAIST) announced on 19 November that an entrepreneur had donated $2.5 million to the university with promises of more to follow, it marked the latest in a string of coups for the new president, Suh Nam Pyo. A mechanical engineer on leave from the Massachusetts Institute of Technology (MIT) in Cambridge, Suh has raised an unprecedented amount—$12.5 million—in a country where donations to universities are rare. He's challenging other traditions as well. For example, KAIST's latest tenure review turned down several candidates, a shocking move by Korean standards.

    Suh says he is aiming to make KAIST “as good as the best [universities], including MIT.” Many faculty members agree that Suh's “overall philosophy and vision are correct,” says KAIST systems biologist Lee Sang Yup. But there are concerns about how Suh will implement that vision at the 36-year-old university.

    The KAIST community has reason to be cautious. In 2004, the university hired Nobel physics laureate Robert Laughlin as president—the first foreigner to lead a Korean university—with a mandate to transform KAIST into a world-class institution. Laughlin, on leave from Stanford University in Palo Alto, California, proposed privatizing KAIST and charging tuition, focusing on commercialization, and tripling undergraduate enrollment (Science, 25 February 2005, p. 1181; 20 January 2006, p. 321). But when Laughlin's plans failed to materialize, “the faculty was disappointed,” says KAIST molecular biologist Chung Jongkyeong. In 2006, the board of trustees decided to seek a new president.

    The board turned to Suh. Born in Gyeongju, South Korea, in 1936, Suh moved to the United States with his family as a teenager and earned a doctorate in mechanical engineering from Carnegie Mellon University in Pittsburgh, Pennsylvania. As an MIT professor, Suh has won plaudits for his engineering design theories, earned more than 50 patents, and helped start several companies. In the early 1980s, he was assistant director for engineering at the U.S. National Science Foundation, and he headed MIT's Department of Mechanical Engineering from 1991 until 2001.

    Since arriving at KAIST in July 2006, Suh has opened undergraduate education to non-Korean students for the first time by insisting that many courses be taught in English. Suh decided that students who maintain “B” or better grades would continue to pay no tuition, whereas those with a “C” or below must pay about $16,000 per year starting in February. “We want students to take responsibility for their actions,” Suh says.

    Agent of change.

    KAIST's faculty supports Suh Nam Pyo's reforms, so far.


    A new admissions process may also have broad impact. Previously, KAIST, like most of Korea's top universities, selected the top scorers in a written exam. Most high school students spend their free time prepping for these tests in cram schools. But Suh says that scores “are a one-dimensional measure” that fails to identify leaders. So candidates for KAIST's next incoming class were invited to campus this fall for interviews, to give presentations, and to engage in discussions while being observed by faculty members, who made selections based on scores and personal impressions. “We're looking for future Einsteins and future Bill Gateses,” says Suh.

    An even more radical step was putting teeth into tenure reviews. Traditionally, faculty members in Korea gain tenure after logging enough years. Suh insisted that KAIST professors up for tenure gather endorsements from experts in their field around the world. In September, 11 of 33 applicants were denied tenure and were given a year to find new jobs.

    The tenure review “is the beginning of an educational revolution,” says KAIST chemist Ryoo Ryong. But he and others worry about the fate of those denied tenure. Suh understands their predicament but is standing firm. The professors who didn't make tenure “are very good people, but in terms of the standard we set, they're not as good as we expect our professors to be.” He is asking other universities to consider giving these professors a chance.

    At the same time, Suh is looking to inject fresh blood—including foreigners—into the 418-strong faculty with a plan to add 300 professors over the next 4 to 5 years. (To expand the school, Suh is striving to win government approval for a doubling of KAIST's base governmental support of $108 million.) His first catch is Mary Kathryn Thompson, who completed her Ph.D. in mechanical engineering at MIT last year. “It's an exciting time to be here,” says Thompson, who just started studying Korean when she arrived last August.

    Although they support Suh's initiatives, some faculty members chafe at his blunt public comments implying that Korea's professors take life too easy. “I cannot agree,” says Choi Yang-Kyu, an electrical engineer. “Most professors here are working very hard.” Biomolecular engineer Kim Hak-Sung adds: “President Suh should have sticks and carrots, not just sticks.”

    Carrots don't come cheap. “I'm spending most of my time trying to raise money,” Suh says. Part of that effort is wooing private donors. “Giving to universities is not prevalent in Asia, but it is something I'm trying to nurture in Korea,” he says. That's a precedent all of Korea's universities might want to embrace.


    Camel Scientists Ask: What's Sinking the Ships of the Desert?

    1. Robert Koenig

    A wave of deaths among Saudi Arabian camels is the latest reason for a surge in research into these rugged, unusual, and highly valuable animals

    When more than 2000 camels perished in Saudi Arabia this year, the mysterious die-offs caused a nationwide furor. Investigations were launched and camel “beauty contests” suspended. And when evidence mounted that the killer was not an infectious disease but rather a toxic substance in the animals' feed, a government council demanded punishments and reforms.

    Camels are serious business in the Middle East and North Africa. And, increasingly, camel research has become a hot topic. “Camels are amazing animals,” says Ulrich Wernery, scientific director of Dubai's Central Veterinary Research Laboratory, which has a staff of 15 camel experts and a herd of 50 dromedaries. (The camelid group includes one-humped dromedaries, Asia's two-humped species, and South America's llamas and alpacas.) Educated in Germany, Wernery first treated camels during a veterinary stint in Somalia in the 1970s, and he has been hooked ever since. “They have fantastic qualities, able to survive without water for 2 weeks in temperatures of 50° centigrade in the shade. They can drink water that is 3% salt.” The animals also make unusual antibodies that may have applications including human diagnostics and snake antivenins (see sidebar, p. 1373).

    But just as scientists in North Africa and the Middle East are expanding research into these seemingly impregnable desert juggernauts, the animals appear to be increasingly vulnerable to disease and toxins. Although epidemiological data are scarce—especially in the camel-rich but politically troubled nations of Somalia and Sudan—some scientists argue that the illnesses striking camels are changing. “We are seeing new diseases in camels, and we often don't have a good explanation,” says Bernard Faye, chair of the newly formed International Society of Camelids Research and Development (ISOCARD).

    Desert mystery.

    The recent deaths of more than 2000 camels in Saudi Arabia, such as this one near the capital city of Riyadh, belies their image as rugged desert juggernauts.


    Dromedary die-offs

    In North Africa, there have been several unexplained dromedary die-offs during the past decade, but the incidents have not shown a consistent pattern so far. In the late 1990s, hundreds of camels perished in Ethiopia, followed by isolated incidents of dying animals showing similar symptoms—pneumonia and fevers, for example—in Kenya and Sudan over the past 7 years. Faye, who is working with Kenyan scientists to investigate the deaths there, says a small ruminant virus that normally infects cattle and sheep was the likely cause, but other pathogens were also found in the dead animals. “The biggest problem is getting blood and organ samples,” says Faye, a veterinary scientist with the French Agricultural Research Centre for International Development in Montpellier.

    Another scourge of dromedaries, camelpox, is also a perennial suspect. The disease has been controlled with a vaccine in some regions, but Saudi scientists say it does not protect all camel populations. Other persistent or emerging camel diseases being scrutinized by North African investigators include tuberculosis, sleeping sickness, brucellosis, and rotavirus infections. There are no vaccines for such camel diseases, complains biochemist Mohamed Bengoumi of the Hassan II Institute of Agronomy and Veterinary Medicine in Rabat, Morocco.

    In both North Africa and the Middle East, scientists have also noted an increase in the number of “food intoxications,” camel deaths or sickness caused by harmful substances in plants or in the livestock fodder the animals eat. Bengoumi says camels are highly susceptible to high-nitrogen plants as well as fungal mycotoxins, neither of which are typically found in dry regions.

    Faye collaborates with camelid scientists from Mongolia to Morocco, and he suspects that climate change in the Sahel region—the transition between the Sahara desert and wetter areas of central Africa—may be altering disease patterns among camels there. “There are two major factors affecting camels in North Africa: desertification and changes in the rainy seasons that tend to increase insect disease vectors,” he says.

    Other scientists suggest that changes in how people use camels—these days, more for their milk and meat and less for long-range desert transport—could make the animals susceptible to new illnesses. Yet another reason may be the expanding geographical range of dromedaries, now found as far south on the African continent as Nigeria and Tanzania.

    Although he shares the perception that camel pathologies are slowly changing, Ghaleb Alhadrami, dean of the agriculture college at United Arab Emirates University in Al Ain, which hosted ISOCARD's first conference last year, says there is not enough evidence to link any shifts to climate change. He speculates that increased stress from keeping ever-larger herds in confined spaces and from camel racing—a multimillion-dollar industry in the Middle East—weakens the immune systems of many camels. But Alhadrami, like other researchers, says more data are needed, especially from North Africa. “There are few reliable statistics on camel disease trends,” Bengoumi notes.

    Furor in Arabia

    Although mysterious camel deaths have occurred elsewhere in the Middle East and North Africa, no recent event matches the extent of this year's Saudi die-off, during which at least 2000 dromedaries perished in a region mainly south of Riyadh, Saudi Arabia. One unofficial estimate placed the death toll at 5000.

    Initial reports focused on the possibility of an infectious disease or intentional poisonings. But after an investigation by the nation's agriculture ministry—which sent camel blood and fodder samples to both Saudi and outside labs—government officials asserted that the camels succumbed to contaminants found in their bran fodder: the antibiotic Salinomycin, a supplement in chicken feed that is toxic to camels, and a fungal species whose mycotoxins can damage some animals' nervous systems.

    The Saudi government has shared few details of its investigation with outside experts, which has puzzled camel scientists who felt they could have contributed. “Many questions remain open,” says Faye. He suggests that the deaths may involve several factors, possibly including viral infections that suppress camels' immune systems. But Saudi Arabia's deputy agriculture minister for research, Abdullah Al-Obeid, says the lab tests showed no evidence of infectious disease. Steps are now being taken to improve the transport and storage of fodder for the nation's half-million camels, he says.

    Dune science.

    Camel researcher Bernard Faye, shown riding a dromedary in Morocco, wants to know why patterns of disease among the animals are changing in North Africa.


    Although Wernery's lab hasn't yet studied tissue samples from the recent deaths, he says, “neither mycotoxins nor any known disease could have killed 5000 camels in that short span of time.” He favors the antibiotic explanation, noting that the Saudi die-off appeared similar in symptoms to the deaths of about 120 racing camels in Dubai a few years ago. The cause was also later determined to be salinomycin in the fodder.

    Whatever its origins, the Saudi debacle may help energize camel studies in the region. ISOCARD has been attracting new members, and Sudan has opened a camel research lab in Khartoum. In Saudi Arabia, Al-Obeid says his ministry plans to strengthen camel research, which is under way at several centers, including King Faisal University, where infectious-disease expert Abdulsalam Abdulan Bakhsh is investigating camel maladies.

    Also, in January, the newest phase of the Camel Breeding, Protection, and Improvement Center—built with help from the U.N.'s Food and Agriculture Organization—will open in northern Saudi Arabia. Its technical director, veterinary scientist Mukhtar Taha Abu-Samra, says the facility will boast a camel hospital with seven diagnostic labs, a radiology and ultrasound room, and a surgery theater. By training camel specialists and upgrading research programs, he says the center aims to “bridge major gaps” in our knowledge of dromedaries.

    Certainly, many gaps remain. Camels' desert survival skills include kidneys that release very little urine in order to preserve water, an intestinal system that recycles water, and a nasal “air-conditioning system” that cools the blood vessels heading to their brains. And scientists suspect they will find more quirks of dromedary physiology, some that might even eventually benefit human medicine.

    “Camels are wonderful research subjects,” says Wernery, “and we can learn a great deal from them.”


    'Camelized' Antibodies Make Waves

    1. Robert Koenig

    When biologists at the Vrije University in Brussels by chance substituted leftover camel serum for mouse serum in a laboratory experiment, they made a startling discovery: The camel antibodies were fundamentally different from their murine counterparts.

    “We were amazed,” recalls Belgian biochemist Serge Muyldermans. Instead of being composed of two “heavy-chain” subunits and two “light-chain” subunits, the camel antibodies have only two heavy chains, making them smaller and more durable than typical antibodies.

    Since this discovery—first reported in 1993—more than 130 papers have been published on the properties of camel antibodies and their uses, which include diagnostic tests and biodefense assays. At least two companies are trying to develop clinical products using antibodies from camels or related species, such as llamas and alpacas.

    Muyldermans says these camelid antibodies pose lower risks to humans than antibodies from other animals, and they can survive elevated temperatures, are highly soluble, and can penetrate more quickly than normal antibodies through cell layers in tissue to reach their targets. Because of those and other qualities, drug companies are already using camel antibodies to speed identification of leads for therapeutics. And at the University of Munich in Germany, Heinrich Leonhardt's group is fusing fluorescent markers to camelid antibody fragments and using them to target and trace molecules in living cells.

    The heat resistance of camelid antibodies has attracted the interest of the U.S. Naval Laboratory and the Southwest Foundation for Biomedical Research. They are testing the antibodies in biosensors designed to detect bioterrorism agents in hot environments. Another group, at Washington University School of Medicine in St. Louis, Missouri, has used the antibodies to develop a simple test to measure the caffeine content of hot beverages.

    Ulrich Wernery of Dubai's Central Veterinary Research Laboratory, speculates that dromedaries developed heat-resistant antibodies to survive in harsh desert conditions. But Muyldermans says scientists don't truly know why the animals have such odd antibodies, which probably resulted from mutations about 50 million years ago, after camelids split from ruminants and pigs.

    One unusual application of camelid antibodies comes from Wernery's lab, where camels are used to produce antibodies to the venom of poisonous animals. The researchers obtain the antivenin by exposing a group of 15 dromedaries to venom from cobras, spitting vipers, and other poisonous snakes. Some people have severe reactions to traditional antivenins produced in horses, but Wernery says, “there is no problem with camel antivenins.” The first clinical trial is scheduled for next year in Nigeria.

  11. SPACE

    Columbus Injects Science Into Station

    1. Daniel Clery*
    1. With reporting by Dennis Normile.

    With Europe's Columbus laboratory on the launch pad—and Japan's research module due next year—our outpost in space is about to get a scientific makeover


    Next week, Florida's weather and aging space-shuttle technology permitting, Europe's main contribution to the International Space Station (ISS) will thunder into orbit. The European Space Agency's (ESA's) Columbus laboratory, a multipurpose experimental module, should dramatically increase the capacity for research on the station—and perhaps quiet those who have called the space station a job-creation scheme for aerospace companies rather than a productive scientific platform.

    The €1 billion Columbus, which will be attached to the space station during the course of the three spacewalks of the 11-day mission, is the crowning achievement of ESA's human space-flight effort—its first crewed facility in space. “Columbus opens a new page for us. Now we will have real estate in orbit,” says Bernardo Patti, ESA's Columbus project manager. But it has been a long and frustrating process for European scientists and engineers to get this far. Columbus arrives at the station some 5 years later than originally planned, because of construction delays and 2003's Columbia shuttle disaster. And, like the rest of the space station, Columbus is more modest than what was on ESA's drawing board early last decade.

    Despite the scaled-back ambitions, European researchers believe Columbus will bring something new to the station. NASA's ability to use the space station as a laboratory has been hamstrung by the increasing cost of its construction, problems with the shuttle, and President George W. Bush's 2004 realignment of the U.S. agency toward exploring the moon and Mars. As a result, most NASA research on board the space station concerns the effects of long-duration space flights on the human body.

    ESA managers say Columbus will restore part of the station's original rationale, providing a platform for basic research in biology, fluids, and materials, as well as for medical research and technological development. “We haven't followed the United States in narrowing our objectives,” says Alan Thirkettle, ESA's space-station program manager.

    The launch next spring of the main part of Japan's Kibo laboratory should continue to expand the station's scientific potential, as will 2009's planned increase of the station's resident crew from three to six. This doubling, and dwindling construction demands upon the crew, should create “an order of magnitude more experiment time,” says Thirkettle. Adds physicist Gregor Morfill of the Max Planck Institute for Extraterrestrial Physics in Garching, Germany, “Columbus and the Japanese module will complete the transformation of the space station from a political point in space to a real laboratory.”

    Standing tall.

    Columbus is Europe's main contribution to ISS, but it came close to being left behind.


    Indeed, with the words of space-station critics fresh in their minds, scientists and space-agency officials are hoping they can finally show what the station is capable of. “Now we have to prove ourselves,” says Patti.

    Being there

    After President Ronald Reagan formally invited international partners in 1984 to join NASA in building a space station, Europe developed a plan consisting of several elements: a laboratory attached to the station; a free-flying module that would house automated experiments and occasionally dock with the station for repairs and restocking; and a polar-orbiting Earth observation satellite that would share computer and communications technology with the station. European astronauts would travel to and from the station in Hermes, a minishuttle that could carry three people and 3 metric tons of cargo.

    The first cost estimates produced by contractors in 1989 were much higher than ESA had expected, and European governments began to put the squeeze on ESA's space-station program. The Hermes shuttle and free-flying module were abandoned. The polar satellite was handed over to ESA's Earth observation directorate. The program that emerged in the mid-1990s comprised the Columbus module—smaller than originally planned but still containing 10 phone-booth-sized payload racks—and a series of pilotless cargo ships called Automated Transfer Vehicles (ATV). Launched atop a European Ariane 5 rocket, an ATV would carry about 7.5 metric tons of air, water, food, fuel, scientific equipment, and personal items to resupply all parts of the station. Once emptied, filled with waste, and jettisoned, it would burn up on reentry. The first ATV is due to fly in February.

    The ATV is also part of the complex barter arrangements through which NASA's international partners buy into the space station. “It pays our rent,” Thirkettle says. To reimburse NASA for the shuttle launch of Columbus, European companies have built two “nodes”: connecting modules for the station. The first is Node 2, also known as Harmony, which the shuttle carried aloft last month. Columbus and Japan's Kibo will both dock to Node 2. In addition, to pay for the air, water, power, and other station services that Columbus needs, five of its 10 payload racks will be devoted to NASA's use.

    Although construction of the 19-metric-ton, 7-meter-long Columbus was well under way by the late 1990s, its trials were far from over. In 2001, with station costs spiraling out of control, legislators in Congress and NASA officials began to consider building the ISS to the minimum viable configuration. “They questioned the entire premise of the station and didn't give a damn for the partners,” says Thirkettle. The crisis passed, but delays in building Russian elements of the station bumped Columbus's planned launch from 2002 to 2004.

    Then the Columbia shuttle disintegrated during reentry in February 2003, and all station construction was put on hold. Two years later, with the shuttle fleet still grounded, NASA again debated drastically cutting back the number of shuttle flights to complete the station. Some scenarios would have left Columbus and Kibo on the ground. “This lasted for a few weeks. It was very, very messy,” Thirkettle says.

    But then, he notes, Michael Griffin was appointed NASA administrator and turned out to be a keen proponent of the station. As Science went to press, Columbus was in the hold of Atlantis and on the pad ready for a weeklong launch window starting 6 December.

    A lab in space

    Planning, designing, and building such a space facility takes roughly a decade, so Columbus's technology was never going to be cutting-edge. But the 5-year delay has made Columbus even more outdated, with computer technology and data-transfer speeds falling behind what's available on Earth. Patti says ESA has upgraded Columbus's avionics system and installed a 100-megabit-per-second computer network. Equipment with such speeds can now be bought in any computer store, but Columbus's network will still be the fastest in space.

    Personnel issues have also been a challenge, as ESA tried to retain essential staff and keep “the scientific community on the ball and interested,” says Thirkettle. A significant number of researchers who prepared experiments for Columbus were Ph.D. students at the time and have since graduated and found other jobs.

    Just as in the United States, many researchers in Europe think the science they get from a crewed facility in space is not worth the huge cost of building it. The money spent on the space station and Columbus, they argue, would have been better spent on robotic probes. Astronomers dislike the station, for example, because with whirring machinery and people moving around it isn't still enough to point a telescope accurately. “It goes up and down like a roller coaster,” says George Fraser, director of the Space Research Centre at the University of Leicester in the U.K.

    But Patti says many researchers in Europe, mostly at universities and government labs, are eager to conduct microgravity research. He hopes a few years of good results out of Columbus will trigger more curiosity among industrial researchers. According to Marc Heppener, head of science and applications in ESA's human space-flight directorate, the last call for experiment proposals in 2004 attracted three times as many as the agency could fund.

    People power.

    With Columbus (illustration) and a Japanese lab module in place, and larger crews by 2009, space-station science should take off.


    Max Planck's Morfill attests to the promise of Columbus, having already had experiments performed by cosmonauts on the Russian segment of the station. His area of interest is “dusty plasmas,” microscopic particles mixed into a plasma that can be coaxed into repeating patterns, akin to a macroscopic crystal and other states of matter. These experiments could be automated, Morfill says, but “with cosmonauts doing the experiments, … you're able to go into regimes not anticipated before. It's been enormously successful. We've got 100 publications out of it.”

    Columbus will take off with a full complement of experiments already installed. Its racks include a fluid science laboratory, a set of physiology modules, and a basic biology lab, among others. On the outside of Columbus, there are two sites for external experiments. Initially, one will hold a facility to expose various pieces of technology to the harsh conditions of space; the other will be home to a solar telescope.

    Although some Columbus experiments will follow NASA's lead and examine the effects of microgravity on humans, many others will be more fundamental. “Columbus should return fascinating data that will advance physiological science in general,” says physiologist Kevin Fong of University College London, who has just completed a 9-month fellowship at NASA's Johnson Space Center. Experiments will look at, for example, how bone remodels after a break. Removing gravity allows researchers to see the remodeling process more clearly. “No one really understands this at a fundamental level,” Fong says.

    Researchers in Japan are looking forward to a similarly eclectic mix of experiments once Kibo arrives at the station next year. The size of a luxury tour bus and weighing nearly 23 metric tons, Kibo, which means “hope” in Japanese, will be the biggest of the space station's research modules. It will take three shuttle flights to deliver all its components: a pressurized module with racks for experiments conducted by astronauts, an exposed platform, and an external storage compartment. Japanese scientists have plans for eight internal experiments covering various aspects of protein crystallization, fluid mechanics, and cell biology. Later, three payloads will be fixed to the exposed facility, including an x-ray scanner to catch novae and gamma ray bursts, an atmospheric monitor, and a material-exposure facility. “From the beginning, science was intended to be a key factor for the ISS. I'd like to see that direction pursued,” says astrophysicist Shoji Torii of Waseda University in Tokyo, who is designing an instrument for Kibo.

    Once Columbus and Kibo are in place, fans of the space station will finally have a chance to do the unique science they promised. That opportunity is all ESA's Thirkettle wants. “I'm looking forward with anticipation, not trepidation,” to the launch of Columbus, he says. “Now we have an opportunity to really exploit this gorgeous piece of hardware.”

  12. Return of the Matrix

    1. John Travis

    A few cell biologists are trying to convince skeptics that they have missed a molecular matrix that helps a dividing cell move its chromosomes around

    Good alignment.

    During cell division (artist illustration), the spindle's microtubules (green) line up the chromosomes (blue) before separating them.


    It's tough to get money to study something that most biologists doubt exists. Kristen Johansen of Iowa State University in Ames learned that firsthand in 1999 when the U.S. National Institutes of Health (NIH) in Bethesda, Maryland, rejected her grant application to investigate a hypothetical cellular structure called the spindle matrix. As one reviewer bluntly put it, recalls Johansen, “‘If it existed, it would have already been discovered.’”

    The spindle itself is well-known to cell biologists. This array of protein filaments separates a dividing cell's two sets of chromosomes during mitosis, ensuring that each daughter cell has the right DNA. In the 1960s, a few scientists proposed that the spindle required a molecular underlayer—a spindle “matrix”—in order to work. But the idea never took hold, as cell biologists concentrated instead on the spindle filaments that they could observe and manipulate.

    Fortunately for Kristen Johansen and Jørgen Johansen, her collaborator and husband, the grant reviewers at the National Science Foundation (NSF) were more open-minded than NIH's about the spindle matrix. Since 2001, NSF has funded the pair as they try to breathe new life into this old idea. So far, the Johansens have pinpointed four matrix protein candidates. They are now working with mutant fruit flies to verify that these proteins are important to spindle function. Another researcher has identified at least one more matrix contender through her studies of spindles in a cell-free system. “I don't think anyone rejects [the spindle matrix] out of hand anymore,” says Kristen Johansen.

    However, because these proteins appear to be pulling double shifts—also having crucial roles in the nucleus of a nondividing cell—researchers have had trouble assessing just how important these proteins are to the spindle during cell division. And, says Jonathan Scholey of the University of California, Davis, until these “matrix” proteins are proven to have a role in cell division, he and many other cell biologists will remain skeptical. “It's certainly an interesting topic that merits further research and discussion,” he says. “There has been progress, … but the jury is still out.”

    Splitting up.

    In a dividing cell, spindle filaments (red) first attach to DNA (blue) at chromosome structures called kinetochores (green). Then the spindle somehow moves the DNA apart so that each daughter cell has its own set of chromosomes.


    Unexplained forces

    The spindle's filaments, known as microtubules, are made of the protein tubulin. After a cell has duplicated its DNA and begun breaking down its nucleus in preparation for dividing, free tubulins polymerize into these filaments, arranging into an oval network. The cell relies on the spindle to segregate the two sets of chromosomes before it can pinch in at the middle to create two distinct cells.

    Since the 1920s, cell biologists have produced stunning pictures of spindles. They really started to see spindles in action in the 1970s, when they observed live cells in which the protein tubulin and DNA were lit up with fluorescent markers. Once the spindle forms, chromosomes line up perpendicular to the spindle's main filaments, at the midpoint between the spindle's two ends, or poles. Sites on each chromosome called kinetochores attach to microtubules, which extend out to the poles. The chromosomes then start their march toward the spindle poles.

    The spindle images that grace journal covers and textbook pages are so attractive that few cell biologists felt a need to look for something more to explain chromosome segregation, contends Yixian Zheng, a Howard Hughes Medical Institute investigator at the Carnegie Institution for Science in Baltimore, Maryland. “Nothing is as good looking as microtubules and kinetochores,” she says.

    But what actually moves the chromosomes? Microtubules can lengthen or contract through the addition or removal of tubulin subunits. At first, researchers thought such changes might move the DNA. If a microtubule anchored at a spindle pole slowly shortened, it could reel in a chromosome. Alternatively, microtubules extending from the cell's middle could push a chromosome out toward the pole as they added more tubulin subunits.

    There are also motor proteins such as dynein attached to spindles, suggesting another way to move chromosomes. These molecules utilize a cell's energy to change shape and inch along a substrate. They can transport tethered cargo and may push or pull chromosomes—or microtubules bearing DNA—toward the opposite ends of the cell.

    Most mitosis researchers contend that microtubule growth and contraction, perhaps in combination with motor proteins, are all a dividing cell needs to get chromosomes to the right places. But a few cell biologists, chief among them Arthur Forer of York University in Toronto, Canada, and Jeremy Pickett-Heaps of the University of Melbourne, Australia, have long argued that microtubules and motor proteins don't fully explain the movement of chromosomes along a spindle. As evidence, they point to what happens when they use a beam of ultraviolet light to sever spindle microtubules in dividing cells. “You would expect a chromosome to stop moving,” says Forer. Yet both the chromosome and the severed microtubules keep sliding toward the cell edge. “It looks like something is pushing them,” adds Forer.

    For a motor protein to do the pushing, it “has to attach to something,” Forer points out. That something, he, Pickett-Heaps, and others argue, is the spindle matrix.

    Reasonable doubts

    Over the past decade, researchers have proposed various matrix ingredients, but none have yet convinced the skeptics. For example, Timothy J. Mitchison of Harvard Medical School in Boston and his colleagues reported in the 2 December 2004 issue of Nature that a polymer composed of sugars and nucleotides was needed to assemble the spindle. But his team has since found no evidence that the polymer is part of a spindle matrix; Mitchison calls himself “agnostic” on the matrix hypothesis.

    The Johansens entered the matrix debate in 1996 when an antibody intended for a membrane protein instead bound to chromosomes in the nucleus. During the early stages of mitosis, these proteins left the chromosomes and, before any tubulin had started to form microtubules, created a suspiciously familiar filamentous oval. “It looked like a spindle was forming within the nucleus,” recalls Kristen Johansen.

    The researchers ultimately identified the tagged nuclear protein, dubbing it skeletor. Since then, they have fished out megator, chromator, and EAST, three other nuclear proteins that, like skeletor, redistribute into a filamentous oval before the spindle itself takes shape. These ovals persist even if a chemical that breaks up microtubules is added to a dividing cell. To the Johansens, these results are suggestive of a nontubulin mesh of molecules that provides a platform upon which the spindle can assemble. The mesh may also offer a substrate for motor proteins to move along.

    And this summer, Forer's group, working with the Johansens, reported in the 1 July 2007 Journal of Cell Science that a muscle protein called titin appears in many of the same places within a dividing cell as skeletor, megator, chromator, and microtubules. Given that titin's distribution seems to mirror the spindle, Forer considers the protein an excellent candidate to provide musclelike elasticity to a spindle matrix.


    In nondividing cells, the proteins chromator and megator reside in the nucleus, either on chromosomes (top, left) or dispersed (top, right). But as cells start to divide, each protein rearranges into an oval spindlelike structure (bottom).


    All this is provocative but far from proof that there is a spindle matrix composed of titin, skeletor, or anything else. One problem is that scientists have looked carefully for gene mutations that perturb spindle assembly, shape, or function, and thus far, none of the genes for the Johansens' proteins has popped up. “What has been lacking up till now, and what people are clamoring for, is better evidence for a direct role of the matrix in spindle function,” acknowledges Kristen Johansen.

    That proof isn't easy to come by, she and other spindle-matrix fans stress. Because some of the key proteins have additional jobs in the nucleus—megator is part of the complex that regulates traffic across the nuclear membrane, for example—mutating them or depriving cells of the proteins may simply cause cells to die or have other problems that obscure any spindle defects.

    Smoking gun?

    Still, in work to be presented at the American Society for Cell Biology meeting in Washington, D.C., next week, the Johansens and their colleagues will describe strains of fruit flies with subtle mutations in chromator's gene. These flies exhibit spindle defects—poorly organized microtubules or improper chromosome segregation, for example—as cells divide. The researchers further show that introducing the normal gene into cells corrects the problems. Finally, they provide evidence that chromator actually binds to microtubules and to a motor protein. “Hopefully, when these experiments are complete, we will be close to having a ‘smoking gun,’” says Kristen Johansen.

    Zheng has taken another approach in an attempt to sway spindle-matrix skeptics. She adds a protein called RanGTPase to the extracts of frog eggs, which triggers the formation of spindles. With this simplified system, Zheng can concentrate on spindle function alone.

    Last year, using this strategy, Zheng and her colleagues added a new name to the list of candidate spindle-matrix proteins: lamin B (Science, 31 March 2006, p. 1887). According to Zheng, this filamentous protein looks a bit like the putative matrix proteins studied by the Johansens. It's likewise found in the nucleus, as part of the protein mesh that underlies the nuclear envelope.

    Other researchers had shown that when this envelope breaks down at the beginning of mitosis, lamin B disperses and some of it ends up on spindle filaments. Using her egg-extract system, Zheng and her colleagues showed that lamin B is required for spindle creation and forms a matrix that harbors spindle assembly factors.

    Zheng is now chasing down other possible spindle-matrix proteins using her system. And she proposes that as a nucleus dissolves for mitosis, many of its components likely become part of the spindle matrix. Still, she knows all too well how unfashionable the spindle matrix remains: Zheng recently lost her NIH funding and decided to downplay mention of her work on the matrix in a recent NIH grant application. “We're not at the tipping point yet,” she says.