News this Week

Science  03 Mar 2006:
Vol. 311, Issue 5765, pp. 1224
  1. AVIAN INFLUENZA

    As H5N1 Keeps Spreading, a Call to Release More Data

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

    PARIS—An impassioned call by a prominent Italian influenza scientist has renewed the debate about how to balance global health against scientists' needs to publish and countries' demands for secrecy. On 16 February, Ilaria Capua of the Istituto Zooprofilattico Sperimentale delle Venezie in Italy asked more than 50 colleagues around the world to release all sequence data for the H5N1 avian influenza strain into the public domain. Comparing sequence data from every H5N1 isolate as soon as they become available is crucial for understanding how the virus moves and evolves, Capua argues.

    Showing her cards.

    Ilaria Capua says she will submit H5N1 sequences from her lab to public databases immediately.

    CREDIT: ANNA FOGAROLO/CLICK FOTO AGENCY

    Putting her money where her mouth is, Capua entered H5N1 sequence data from two recently infected countries, Nigeria and Italy, into the GenBank database the same day. She also rejected an offer by the World Health Organization (WHO) to join a select circle of 15 labs that share bird flu sequences on a password-protected Web site.

    Capua's lab is a reference center for the U.N. Food and Agriculture Organization (FAO) and the World Organisation for Animal Health (OIE), and officials at those agencies say they support her call. But some scientists say sharing data instantly is complicated by the need for credit, and WHO argues that without some form of confidentiality, some countries would not submit samples at all.

    Sharing information about H5N1 has been tricky from the start. WHO, FAO, and OIE encourage countries to send virus samples to specialized reference labs that can confirm the outbreak and study the virus further. Some have been reluctant to do so because they worry about intellectual-property rights or not receiving a fair share of the scientific credit; China, for instance, has not shared any avian samples for a year, a WHO spokesperson says. But even when reference labs do get their hands on a virus, they don't always release the data immediately.

    For instance, in the past few months, H5N1 samples from about 15 European countries have been sent to the Veterinary Laboratories Agency (VLA) in Weybridge, U.K., a reference lab for OIE and the European Union. Lab director Ian Brown says he's sharing sequence and other data with governments and the international agencies; to show support for Capua's campaign, he also submitted the sequence of a virus from an outbreak in Turkey that he says is a “progenitor to the European epidemic” into GenBank last week. However, until a paper about the European outbreaks—which he says could be submitted in a matter of weeks—has been accepted, Brown says he needs to hold on to the European sequences. “The staff in this institute is working 24/7 to provide this service,” he says. “I don't think it's unreasonable to expect … for their endeavors.” It also takes time to negotiate the conditions of release with dozens of individual governments, Brown says.

    Capua counters that just isolating and sequencing a virus that comes in the mail does not give researchers the right to sit on the data—especially not at a government lab. “Most of us are paid to protect human and animal health,” she says. “If publishing one more paper becomes more important, we have our priorities messed up.” Governments can often be persuaded to release the sequences, adds Capua, who repeated her call at an OIE meeting in Paris on Monday and also plans to submit it to ProMED, an e-mail list about emerging infectious diseases.

    WHO agrees that in an ideal world, scientists would share their data widely and voluntarily, says Wenqing Zhang of the agency's Global Influenza Programme. But because that's not happening, the agency created a special secured section at the Influenza Sequence Database at Los Alamos National Laboratory in New Mexico in 2004. Currently, some 15 labs have passwords to access these data, says Zhang, including WHO's eight reference labs. The system is invaluable for WHO, she adds, as it helps the agency track the virus and adjust risk assessments if necessary.

    Virologist Yi Guan of the University of Hong Kong, which has a huge H5N1 collection, says he would be prepared to release more data publicly before publication but is looking for WHO to establish a new policy. Until then, WHO's secure server at least ensures that policymakers and most of the scientists who advise them have access to vital information. But Capua says everyone with an interest should be able to browse all the data. When she was offered access in exchange for submitting her Nigerian sequence last month, she declined. And the system gets mixed marks within WHO as well. “Personally, I'm not in favor of it,” says WHO scientist Michael Perdue.

    Whether scientists' fears of being scooped are justified is difficult to say. In theory, once sequences are posted in the public domain, anybody could write a paper about them. In practice, journal editors will ask manuscript authors to get permission if they write a paper about unpublished data they did not submit to GenBank themselves, says Caroline Ash, who edits infectious diseases papers at Science. But Brown says he'd rather not take that risk.

  2. AVIAN INFLUENZA

    Evidence Points to Migratory Birds in H5N1 Spread

    1. Dennis Normile

    With the H5N1 avian influenza virus racing across the globe, scientists are debating new evidence on the role of migratory birds. As Science went to press, the virus had just been confirmed in a third African nation, Niger, one of the world's poorest countries. It had spread further in Europe and Asia, with 13 countries confirming outbreaks in just the past 2 months. And France reported the European Union's first outbreak in domestic poultry.

    Increasingly, scientists are attributing this remarkably fast spread to migratory birds, but dissenters remain. One set of data that points to a role for wild birds comes from recent, unpublished analyses of influenza viruses recovered from outbreaks stretching from Russia and Kazakhstan to Nigeria, Iraq, and Turkey. A World Health Organization report issued last week,* which drew upon these analyses, concluded that all of the viruses involved in these outbreaks appear to be related to the strain identified from Qinghai Lake in northwestern China, where an outbreak killed 6000 wild birds last spring. And instead of the constant evolution typical of avian viruses, the Qinghai variant appears to have remained unusually stable for nearly a year. “This finding raises the possibility that the virus—in its highly pathogenic form—has now adapted to at least some species of migratory waterfowl and is … traveling with these birds along their migratory routes,” the WHO report concludes.

    That case is strengthened by the first documented identification of the H5N1 virus in healthy migratory birds, reported in the 21 February issue of the Proceedings of the National Academy of Sciences (PNAS). Some researchers have expressed skepticism that migratory birds play a major role in the spread of H5N1, arguing that infected birds would die before traveling very far (Science, 21 October 2005, p. 426). The new findings, from a collaboration led by Yi Guan, a virologist at the University of Hong Kong, and virologist Robert Webster of St. Jude Children's Research Hospital in Memphis, Tennessee, suggest that's not always the case. Since early 2003, the team has collected more than 13,000 cloacal and fecal samples from migratory birds at Mai Po Marshes in Hong Kong and Poyang Lake in Jiangxi Province, China. In early 2005, they isolated the H5N1 virus from six apparently healthy migratory ducks at Poyang Lake. The team also collected serologic samples from 1092 captured migratory ducks and found that 3.1% had antibodies to H5N1, indicating a prior infection.

    The group's findings confirm that wild birds can carry the virus great distances. Their sequencing analyses show that the viruses isolated from Qinghai Lake are genetically linked to the two strains recovered from the wild ducks at Poyang Lake. Guan says this doesn't mean ducks from Poyang carried the virus to Qinghai but does suggest that these viruses are circulating among migratory birds.

    Investigation.

    A veterinarian looks for signs of bird flu infection in a swan, found dead earlier in the day, at a lab in Arras in northern France on 22 February.

    CREDIT: PASCAL ROSSIGNOL/REUTERS

    Guan and his colleagues also have data suggesting that once an outbreak is established, the main route of transmission appears to be through poultry. The group has regularly sampled poultry brought to markets in six provinces in southeastern China since 2000. Among the more than 51,000 birds studied, they found the virus in 1.8% of all ducks and 1.9% of all geese, as well as 0.26% of chickens. Sequencing of 121 influenza samples collected from birds in China, Indonesia, Malaysia, and Vietnam showed that the viruses fall into regional sublineages. Viruses recovered from wild ducks at China's Poyang Lake were related to two sublineages from different regions in southern China. Guan says that together, this suggests that the viruses have been endemic among ducks and geese in different regions long enough to evolve distinct phylogenetic signatures and that circulation among poultry, not reintroduction from wild birds, is keeping the virus going in China. If migratory birds had repeatedly seeded the outbreaks, there would likely be fewer distinct regional differences in the viruses. Guan adds that this conclusion offers hope that the cycle of transmission can be broken if the virus is eradicated from poultry flocks.

    The WHO report and PNAS study don't convince everyone that wild birds explain H5N1's alarming spread. “There is no single bird species that migrates due west-east,” notes Richard Thomas, a spokesperson for Birdlife International. Guan counters that the spread could involve a complex interaction of humans transporting poultry and the movements of dozens of species of wild birds. “It is not easy to trace this step by step,” he says.

    The difficulty is seen in Europe, where dead swans symbolize the spread of the virus. Because they obviously succumb to the virus, no one thinks swans are carrying it great distances. “Swans become infected by other aquatic [bird] species,” says Albert Osterhaus, a virologist at Erasmus University Medical Center in Rotterdam, the Netherlands. But he admits that as yet, surveillance efforts in Europe have not found H5N1 in any healthy wild birds. “We do not, at this moment, have the complete epidemiological picture,” Osterhaus says. He adds that more surveillance of wild birds is needed along with lab experiments to study the behavior of the virus in different migratory species.

  3. GENOMICS

    DOE Hits Potholes on the Road to Systems Biology

    1. Elizabeth Pennisi

    The Department of Energy's bold plans to expand its genomics efforts drew some critical comments from a panel of the National Research Council (NRC) last week. The panel would like DOE to spend more money and take a different approach.*

    The $70-million-a-year Genomes to Life Program, begun in 2000, has led the way in sequencing microbes involved in bioremediation, carbon sequestration, and bioenergy, as well as in deciphering genomes of other key organisms. Late last year, DOE announced that the next phase of the program, renamed Genomics: GTL, would focus on systems biology, and last month President George W. Bush requested $119 million in 2007 for those efforts. DOE plans to fund four centers, each with a different technological bent: large-scale characterization of proteins, imaging complex molecules, proteomics, and systems biology. Each center would serve academic and corporate scientists. DOE plans to build these centers over the next 2 decades and has already invited proposals for the protein-production facility.

    Get to work.

    Compost bacteria may prove useful in binding up carbon from greenhouse gas emissions.

    CREDIT: SIMKO/VISUALS UNLIMITED

    Before DOE goes forward, however, the NRC panel wants each center to focus on a specific problem, say, bioenergy or bioremediation, and encourage scientists from all relevant disciplines to lend a hand. Such “one-stop shopping … is a change from DOE's more typical historical model of providing just a user facility, like the synchrotron,” says Jennie Hunter-Cevera, a microbial physiologist and president of the University of Maryland Biotechnology Institute in Rockville. But she and others say focusing the centers on problems rather than technologies would encourage more interaction among researchers.

    The NRC panel argued for a tripling of the program's current annual budget, to as much as $200 million, but it also suggested ways to cut costs, get the centers up and running more quickly, and increase interaction with outside researchers. One solution: Occupy empty space in an existing biotechnology corridor and ask public and private institutions to foot the bill for renovations or construction. The committee urged DOE not to locate the centers at its 16 national labs because security at the labs might limit access.

    Program managers for Genomics: GTL say they need more time to review the recommendations. But Betty Mansfield, a biologist at Oak Ridge National Laboratory in Tennessee who was involved in the early planning for the genomics program, worries that the panel's suggestions won't save money. She says that DOE rejected the idea of having centers focus on particular problems because “you end up with redundant technology. And with that redundancy comes increased costs.”

  4. SCIENTIFIC PUBLISHING

    Canadian Editors Fired in Row With Association

    1. Paul Webster*
    1. Paul Webster is a freelance writer based in Toronto.

    TORONTO—The editor of Canada's premier medical research journal and a top assistant have lost their jobs after a long-running feud with the publisher over editorial independence.

    John Hoey, editor of the Canadian Medical Association Journal (CMAJ), and Senior Deputy Editor Anne Marie Todkill were dismissed without notice last week by CMA officials. Graham Morris, head of CMA's media division, says, “I felt it was time for a fresh approach.” Morris claims the journal's independence was not an issue but adds, “The last call will be my call” in any dispute over content. This week, the Council of Science Editors condemned CMA's action. CSE President Richard Horton, editor of The Lancet, called it “a blatant example of the misuse of power, in promoting an agenda that goes beyond the legitimate authority of the journal's owners.”

    The dismissals came after a series of clashes between Hoey and his bosses. In November 2002, the journal ran a letter from 20 members of the journal's editorial board saying that then-CMA President Dana Hanson posed a “clear and present danger” to the journal's editorial independence after Hanson had demanded Hoey retract an already-published editorial on medical legislation. Two months ago, Hoey described in an editorial how CMA officials had ordered him to revise an unpublished investigative article on questions Canadian women were being asked when trying to buy the nonprescription emergency contraceptive Plan B after the Canadian Pharmacists Association complained about the investigation.

    Hoey then called in Jerome Kassirer, who was forced to retire in 1999 as editor of The New England Journal of Medicine amid a similar debate over editorial independence with its publisher. Kassirer says he believes CMA violated guidelines from the International Committee of Medical Journal Editors that publishers “should not interfere in the evaluation, selection, or editing of individual articles” and that editors are obliged to speak out. “It's my belief the Canadian Medical Association has commandeered the journal,” says Kassirer, who as a CMAJ board member signed the November 2002 letter.

    Another signer, Donald Redelmeier of the Institute for Clinical Evaluative Sciences in Toronto, says that Morris “expressed no concerns” about Hoey at a board meeting last fall and that “customarily, we organize more tranquil succession timing.” He and others worry that the firings could affect the flow of submissions to the journal. “We knew there was a fearful row going on,” says Drummond Rennie, a deputy editor of The Journal of the American Medical Association. “There is no quicker way of destroying the reputation of a medical journal than suddenly firing the editor.”

  5. UNIVERSITIES

    Despite a Chilly Reception, the 'European MIT' Advances

    1. Daniel Clery

    CAMBRIDGE, U.K.—Facing down skeptics in the academic community, European Union (E.U.) officials are forging ahead with a proposal to create a new research-intensive university on the continent. They say their objective is to remedy problems in European higher education by building a flagship modeled on the Massachusetts Institute of Technology (MIT). Rather than a single site, however, a plan published last week by the European Commission, the E.U.'s executive, calls for a network of centers across the 25 member states. But the idea continues to meet with near-universal hostility from scientific and education leaders. The commission “has failed to analyze what the issue is and how you would address it,” says glaciologist Geoffrey Boulton of the University of Edinburgh, U.K., who has studied the plans for the League of European Research Universities (LERU).

    Academics argue that there is no need for a new European Institute of Technology (EIT). “There are a lot of very good institutions [in Europe] that are grossly starved of funds,” says Peter Cotgreave of the Campaign for Science and Engineering in the U.K., a pressure group. And they worry that the commission's new enthusiasm will attract attention—and funding—away from the new European Research Council (ERC), due to begin work next year. With the E.U. research budget still undecided, “we could take our eyes off a rather crucial ball,” says Boulton.

    Flying the flagship.

    European Commission President José Manuel Barroso is a strong supporter of the European Institute of Technology.

    CREDIT: HAZIR REKA/REUTERS

    Planners dreamed up the EIT early last year as part of the Lisbon Strategy, a faltering scheme to make Europe the leading knowledge economy by 2010. After a public consultation in the fall, the commission's outline last week argues that “Europe still falls short in turning R&D results into commercial opportunities.” According to commission president José Manuel Barroso, who has championed the idea, “Excellence needs flagships; that's why Europe must have a strong European Institute of Technology.”

    The commission proposes a small governing board that would identify worthy areas of interdisciplinary research and set up “knowledge communities.” These would borrow staff, students, and facilities from universities, research centers, and industrial labs across the E.U. for as long as 15 years. The EIT will, the commission asserts, be a high-quality “brand,” and institutions will compete to join. E.U. heads of government will discuss the plan at the end of March and, if they give it the nod, commission officials will draw up the legal documents. The EIT could be recruiting academic staff by 2009.

    Although the attention on higher education is welcome, many dispute the idea that MIT's success can simply be transplanted onto European soil. “MIT is just a very good university, and many European universities are very successful in the same areas,” says Boulton. Funding is another concern. The commission says the EIT will be funded by the E.U., national governments, and industry, and that not much will be needed before the end of the decade. But E.U. finances are already squeezed; the research budget—currently being debated by the commission and the European Parliament—will fall short of last spring's request.

    One concern is the potential impact on funding for the ERC, a new grants agency. Unlike the E.U.'s Framework Programme, the ERC will have an independent scientific council and make awards based primarily on scientific excellence. “Although its funding is small, within a decade the ERC could be a very fundamental driver of research in Europe,” says Boulton. “The ERC is a genuinely bottom-up proposal, something that's been debated and developed over 3 or 4 years,” says John Smith, deputy secretary general for research at the European University Association. Adds LERU Secretary-General David Livesey: “Everyone agrees the ERC is the right thing to do at the moment. That's the flagship.”

  6. SCIENCE INDICATORS

    NSF Presents the Wide World of Science

    1. Jeffrey Mervis

    China has arrived as a scientific powerhouse. Or has it?

    The factors behind China's rapid rise to third place in overall research spending, behind only the United States and Japan, are documented in the latest compendium of international trends in science issued last week by the U.S. National Science Foundation (NSF). Its biennial Science and Engineering Indicators (nsf.gov/statistics/seind06) features analysis, statistics, and tables on everything from academic research spending to zoo attendance. As always, the two volumes are a gold mine of information. But the 2006 edition also comes with a refreshingly frank caveat.

    SOURCE: SCIENCE AND ENGINEERING INDICATORS 2006

    One essay, for example, points to the danger of comparing research expenditures around the world and raises questions about one common metric called purchasing power parity (PPP). “It is difficult or impossible to assess the quality of PPPs for some countries, most notably China,” it notes. “Although PPP estimates for [industrialized] countries are quite reliable, PPP estimates for developing countries are often rough approximations.” In particular, China's R&D expenditures, reported at $84 billion in 2003, could be inflated by a factor of 4 or 5, it adds.

    Another essay, on “unmeasured R&D,” reminds readers that some sectors—businesses with fewer than five employees, for example—go unreported. Others, notably research done by nonprofit organizations and state and local governments, are extrapolated from surveys nearly a decade old.

    A companion piece to the indicators report (nsf.gov/statistics/nsb0602) by the National Science Board, NSF's presidentially appointed oversight body, offers several suggestions for improving U.S. science and math education. It says higher pay for teachers, improved public literacy, and tests that measure both conceptual knowledge and problem-solving skills are needed to tackle what it calls “America's pressing challenge.” The science board is also weighing launch of a commission that would examine the subject.

    SOURCE: SCIENCE AND ENGINEERING INDICATORS 2006
  7. SCIENCE AND DIPLOMACY

    Indian Chemist Receives a Visa and an Apology

    1. Pallava Bagla

    NEW DELHI—In an abrupt turnaround, the United States last week “home delivered” a visa to Goverdhan Mehta, former director of the Indian Institute of Science in Bangalore, after holding up his application and questioning him about the potential use of his research in chemical weapons. The case raised concern in the scientific community. U.S. officials apparently hoped to smooth ruffled feathers before President George W. Bush's visit to India this week.

    Offended.

    Goverdhan Mehta.

    CREDIT: P. BAGLA/SCIENCE

    But Mehta is not mollified. His response to the U.S. offer: “Thank you, but no thank you. I have already canceled my tickets and have no intention of going to the United States,” he told Science, which first reported the incident (Science, 17 February, p. 933). “I am not allergic to the United States and would be willing to go at a later date.”

    The U.S. Embassy issued a statement on 24 February saying that the ambassador to India, David C. Mulford, “called Professor Mehta … to notify him and express both his apologies and satisfaction that a visa would be issued immediately.” The processing of the visa had been suspended pending a review in Washington, D.C., the embassy said, but it was later approved. Mehta says that when he first applied in early February, the consular office in Chennai questioned him and suggested that his research could be used in chemical warfare, then turned him away. It was the “most humiliating experience” in his life, Mehta says. A consular agent came to Mehta's laboratory on 24 February and collected the passport, which was delivered to the lab on Saturday with a visa stamp.

    Another scientist who was recently turned down for a visa, Placid Rodriguez, former director of the Indira Gandhi Center for Atomic Research in Kalpakkam, also received a U.S. entry visa on 24 February in what he describes as a “huge turnaround.” He feels that “all's well that ends well.”

    Mehta says, “I appreciate the apology extended by the U.S. ambassador.” But he remains concerned: Scientists must be able to participate “in international activities without being subject to any such restriction or humiliation.”

  8. ANIMAL RESEARCH

    Protesters March to a Different Drummer

    1. Eliot Marshall

    OXFORD, U.K.—A placard-waving crowd took to the streets here on 25 February with an unusual message: Support animal research. Several hundred people showed up, among them a few speakers from the University of Oxford faculty, including neurosurgeon Tipu Aziz (surrounded by a crowd, right). The idea for the rally came from 16-year-old Laurie Pycroft, who describes himself as an Internet blogger and fan of science. Angered by an encounter in January with protesters seeking to halt construction of Oxford's $34 million life sciences lab, Pycroft decided to respond with a pro-lab march. The idea caught on. The same day, opponents of the lab staged a rally several blocks away; police kept them apart. Oxford has been the main target of animal-rights protests since the University of Cambridge gave up on plans for a primate facility 2 years ago. Last fall, the Animal Liberation Front took credit for torching an Oxford boathouse (Science, 5 August 2005, p. 872); ALF recently declared on its Web site that anyone connected to the university is “a legitimate target.”

    CREDIT: E. MARSHALL/SCIENCE
  9. CONSERVATION BIOLOGY

    The Lost World of the Kihansi Toad

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

    Can a unique amphibian be saved after its environment has been transformed? Scientists do their best but fear the worst

    BRONX ZOO, NEW YORK CITY—Past the snake exhibit, where gigantic pythons lurk behind thick glass, in the back rooms of the Reptile House, sits a humid, low-ceilinged isolation chamber. Here in five plastic terraria, 159 mustard-colored, fingernail-size amphibians are making what could be their last stand on Earth.

    The Kihansi spray toad is 12,800 kilometers from home: Kihansi Gorge, in Tanzania's remote Udzungwa Mountains. For millions of years a great waterfall filled this gorge with perpetual spray and wind, creating a singular environment where the toad and other endemic creatures lived. In 2000, a hydropower dam cut off 90% of the water, and the ecosystem withered. Since then, scores of scientists in many disciplines have performed elaborate, unprecedented deeds to salvage the toad and its lost world. They have managed to raise the toads in captivity, documented the ecosystem's myriad responses to the dam, and engineered in the gorge what may be the world's largest sprinkler system. Their story shows that although human technology can easily upset nature, even the best science may not suffice to restore it.

    In splendid isolation

    The cool, high peaks of the Udzungwas jut from a sea of dry savanna, forming part of the Eastern Arc Biodiversity Hotspot, a crescent-shaped archipelago of nine mountain ranges. Here are some of the world's oldest rainforests, where long isolation and stable climate have given biota tens of millions of years to evolve. Thousands of plants and animals are endemic to the nine ranges, to one range, or, as in Kihansi, one locale. The spray toad has what may be the smallest range of any vertebrate—2 hectares. Some biologists think it has lived in the gorge or nearby for at least 10 million years.

    The gorge begins where the Kihansi River plunges 100 meters off an escarpment, then rushes another vertical 750 meters through 4 kilometers of violent twists and cascades. The river flows year-round, whereas the region's other streams disappear in dry season. The slippery cliffs and the water's ferocity long excluded people, allowing the mist-world creatures to live undisturbed and undiscovered.

    Steep drop and dependable flow also are ideal for hydropower. In 1983, engineers envisioned diverting water via a dam above the gorge to a turbine-filled tunnel; flow would bypass the gorge and return to the riverbed at the bottom. A survey of the modest 20-hectare proposed reservoir suggested an environmentally benign project, and in 1994, construction began on the $270 million effort, initially funded by World Bank loans. Development banks in Norway, Sweden, and Germany later joined but insisted that downstream biota be surveyed too.

    Thus in 1996, with the dam infrastructure already partly built, biologists including herpetologist Kim Howell of the University of Dar es Salaam managed to climb down into several steep, mist-engulfed meadows. Here they found an estimated 50,000 of the skinny, endearing toads, hiding in deep moss mats. Although they have relatives in the region, several unusual features set the toads apart, including flaps over nostrils (possibly to keep out excess spray) and live births (eggs might wash away). Their chit-chit-chit-chit call can ramp up to high frequencies inaudible to humans, possibly to overcome constant low-end waterfall roar, says evolutionary biologist Corinne Richards of the University of Michigan, Ann Arbor. The toads ate hundreds of wetland insect species, most still unidentified. Biologists also found at least four new endemic plants in the gorge, including a new coffee species, plus rare trees and threatened primates and birds.

    But even as they explored the gorge world, biologists had scant hope for preserving it. “As soon as we found this place, we knew it would be going extinct,” says one foreign consultant—who, like several others, feared being quoted by name because of the fierce politics surrounding the dam. To compensate, biologists sought possible toad transplant sites but turned up nothing. They recommended letting half the river's flow continue to the gorge, but that recommendation was not followed. In 1999, European newspapers got wind of unpublished studies, along with the published description of the toad, Nectophrynoides asperginis. Groups such as Friends of the Earth accused the banks and Tanzania of violating the International Convention on Biological Diversity, which forbids projects that would wipe out species.

    The government and lenders compromised. With an added $6 million loan to cover conservation studies and mitigation, the gorge would get 10% of its previous flow. Part was to be channeled into a several-kilometer-long, gravity-fed pipe system snaking down rock walls to the toad meadows, where hundreds of spray nozzles would spurt mist—a setup meant to mimic natural spray with a fraction of the water. Covering a quarter of the toads' original habitat, the sprinklers are “probably the most highly engineered recovery system for any species ever,” says William Newmark, a conservation biologist at the Utah Museum of Natural History advising the World Bank.

    But the sprinklers were not ready when the water was to be choked off in early 2000. The shutoff proceeded anyway, and by the time the sprinklers came on 9 months later, the ecosystem had dried up catastrophically. Common plants from adjacent dry areas had invaded former spray meadows; mosses had declined almost 95%; insect diversity had dropped; and only 2000 toads were left alive.

    Doing the downstream conservation work only after the dam was well under way was a “huge mistake: Planning was not preceded by a thorough and complete environmental impact assessment,” admits conservation biologist Wilfred Sarunday, coordinator of Tanzania's Lower Kihansi Environmental Management Project, which oversees studies and mitigation at the gorge.

    In captivity

    Fearing the toads would soon be extinct, in December 2000, the Tanzanian government allowed the Wildlife Conservation Society to collect 500 animals for breeding in a halfdozen U.S. zoos. But captive amphibians are difficult to raise, and the animals soon were plagued with lungworms, infections, bone problems, intestinal parasites, and nutritional deficiencies. They would not breed predictably. By spring 2004, the Bronx and Toledo (Ohio) zoos had the only survivors—about 70.

    Holding on.

    Kihansi toads now thrive only in zoo terraria (top), where keepers managed to get them to breed.

    CREDITS (TOP TO BOTTOM): T. HERMAN/BOWLING GREEN STATE UNIVERSITY

    The Bronx Zoo took two unusual steps. It called in the Coriell Institute, a Camden, New Jersey, human genetics outfit that preserves cell lines for research. Their staff created cell lines from dying toads, in hopes that technology would one day permit cloning the cells back into whole creatures. But the cell lines all died. The zoo also farmed out a dozen tiny corpses to Valerie Clark, a Cornell University chemist who studies potentially valuable bioactive substances harbored by amphibians. It was “our last chance” to analyze the toads, says Clark, who plans tests.

    Then, in 2005, the captives perked up. Keepers had devised treatments for various ailments and discovered that although the standard zoo ultraviolet lamps were too big and crude, the toads liked basking in the narrow beams of little 12-volt track-light bulbs. Slowly, the toads started having babies—so small that keepers at first thought they were ants. Now there are about 300 toads between the two zoos.

    Meanwhile, in Kihansi, things briefly got better—then much worse. After the sprinklers came on in early 2001, wetland plants slowly regenerated, according to a paper last year in Biodiversity and Conservation by Claire Quinn of the University of York, U.K. Some severely affected toad prey such as an endemic Ortheziola scale insect also increased, says Peter Hawkes, a consulting entomologist in Pretoria, South Africa. Most encouraging were the toads; internal reports indicate that by June 2003, some 20,000 were hopping about.

    A month later, the toads crashed. In August 2003, 40 were seen; in January 2004, only five. Since then, they have virtually disappeared. Once or twice a year, site workers say they hear calls, and in May 2005, a biologist claimed to see one individual. Some scientists say it is still too early to talk about extinction in the wild, but many are pessimistic. “Seeing one spray toad is like … [seeing] one passenger pigeon,” says James Gibbs, a herpetologist at the State University of New York at Syracuse who monitors the gorge for the World Bank. “The place is not what it used to be. Nobody wants to say it out loud, but it may be too late.”

    Biologists point to several possible suspects. The immediate cause may have been chytrid fungus, a deadly skin infection implicated in amphibian crashes around the world, says herpetologist Ché Weldon of North-West University in Potchefstroom, South Africa. His data show that the fungus was absent earlier but present by the crash. One candidate for bringing it in: the imported sprinkler pipes. Another: the boots of dozens of scientists, who traveled in from four continents. Others point out that the 2003 crash coincided neatly with a brief opening of the dam's floodgates to flush sediments. Tests showed these contain pesticides used by a growing number of maize farmers upstream, in concentrations that could kill the toads.

    But these are just immediate causes. At bottom, many believe that the gorge environment is broken and can't be reassembled: The changes weakened the toads, and chemicals or infections just finished them off. For instance, the waterfall had constantly replenished spray-meadow soils with wet silt; the sprinklers just sprinkle water, leaving soil crumbly and susceptible to erosion. The waterfall's force also generated ceaseless wind—not supplied by sprinklers—whose now-vanished role in the ecosystem remains unknown. “It's not clear how successful the artificial system is,” says water-resources engineer John Gerstle of Hydrosphere Resource Consultants in Boulder, Colorado, who managed much of the environmental work at the gorge until 2004. “It is hard to mimic a situation when you don't necessarily understand it.”

    The situation has brought down continuing ire on scientists and their employers. Friends of the Earth President Brent Blackwelder recently wrote to the World Bank: “[Y]our monitoring team is passively documenting the extinction of this unique ecosystem.” Sarunday, who still hopes that the system will recover, insists that the banks and Tanzania have “acted in good faith.” In one letter to the group, then-World Bank Vice President for Africa Callisto Madavo wrote that measures at the gorge were “designed to ensure an optimal balance between biodiversity conservation and economic development.”

    The gorge also highlights tensions between developed nations, who funded the dam, and Tanzania, which now gets a third of its electricity from it. Tanzania is one of the most conservation-oriented African nations, but most observers doubt it would have borrowed $6 million for environmental work without pressure from “donor” nations, who want the money repaid. “Most [Tanzanians] say: Who cares about a toad? We want our electricity,” says Tanzanian ornithologist Norbert Cordeiro, now at Chicago's Field Museum. When the captive toads were flown on a jet to New York, one Tanzanian newspaper pointed out that few human citizens could expect to do the same. Others question the presence of a seven-person crew doing daily care on the sprinkler system without proof that the toad is there or could ever safely return.

    There is perhaps one positive outcome. Tanzania is still rich in biodiversity, and Kihansi has helped develop homegrown expertise to preserve it. The loan has helped Tanzanian and foreign scientists study the gorge together, plus train Tanzanian grad students, hire professors, and buy textbooks and computers. This has “played an important role in capacity-building for local scientists,” says Henry Ndangalasi, a botanist at the University of Dar es Salaam. The nation is “mindful of the importance of scientific knowledge,” says Sarunday. “The goal of Tanzania is to achieve economic prosperity and have a protected environment at the same time.”

  10. CELL BIOLOGY

    Great Balls of Fat

    1. Mary Beckman*
    1. Mary Beckman is a writer in southeastern Idaho.

    Lipid droplets, long-ignored globules inside cells, are earning recognition as possible organelles involved in cholesterol synthesis and much more

    In the breast cells that produce milk, they're called milk fat globules. In plants, they go by the name oil bodies. In fruit flies, lipid storage droplets. Yeast, lipid particles. Cell biologist Richard Anderson prefers the name adiposomes. Immunologist Peter Weller baptized them eicosasomes.

    CREDIT: SCIENCE VU/VISUALS UNLIMITED

    Whatever their name, these intracellular blobs of triglycerides or cholesterol esters, encased in a thin phospholipid membrane, are catching the attention of more and more biologists. It turns out these lively balls of fat have as many potential roles within cells and tissues as they have names. Pockmarked with proteins with wide-ranging biochemical activities, they shuffle components around the cell, store energy in the form of neutral lipids, and possibly maintain the many membranes of the cell. The particles could also be involved in lipid diseases, diabetes, cardiovascular trouble, and liver problems.

    This is a far cry from earlier perceptions of lipid droplets, the name most scientists use for the particles. Biologists once considered lipid droplets just inert storage vessels for energyrich fats. Yet recent studies indicate that the cell keeps a tight rein on their function with molecules that regulate what the particles do, where they go, and what other cellular compartments they cavort with. And a new technique that allows better imaging of lipid droplets in live cells promises even more surprises.

    “I've been in cell biology for more than 30 years, and lipid droplets have always been this bag of lipid,” says Anderson, who conducts membrane research at the University of Texas Southwestern Medical Center in Dallas. “What is new is the focus on the droplet as an organelle.”

    Knocking out the fat

    The first inkling that lipid droplets were more than a cell's beer belly came in the early 1990s. Cell biologist Constantine Londos of the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, and colleagues identified a novel protein, perilipin, on lipid droplets in fat precursor cells. They also discovered that the cells, when they are stimulated to metabolize the droplet's fat reserves, attach phosphate groups to this protein, suggesting that the cells precisely control the protein's activity during the process.

    Whereas perilipin is found almost exclusively in the lipid droplets of fat cells, other researchers soon identified two structurally related proteins—adipose differentiation-related protein (ADRP or adipophilin) and TIP47—associated with lipid droplets in other types of cells. These three became the charter members of the PAT (perilipin/ADRP/TIP47) family of lipid-droplet proteins, whose ranks have since swollen to include more than half a dozen molecules spanning mammals, flies, and amoeba. Researchers in the late 1990s also found a handful of proteins in yeast lipid bodies that are involved in lipid production and degradation.

    But what really grabbed everyone's attention were the mutant mice reported in 2000 by Lawrence Chan, an endocrinologist at Baylor College of Medicine in Houston, Texas. Lacking all perilipin thanks to a mutation introduced by Chan's team, these rodents ate more food than normal but burned off two-thirds of the fat a typical mouse would have gained on the same diet. “Their metabolic rate is as if they are exercising all the time,” says Chan.

    These perilipin knockout mice were a “big breakthrough,” says Londos. (His team reported creating its own strain of such mice a few months after Chan's paper was published.) Biochemical experiments by Londos's teams revealed that under normal circumstances, perilipin coats lipid droplets in fat cells and guards their luscious store of lipids. When cells are starved or chemically induced to chew up their fat, an enzyme drapes a phosphate group on perilipin. This changes the protein's shape, exposing the droplet's neutral lipids to degradative enzymes. Finding a way to keep perilipin phosphorylated might prove to be a useful antiobesity therapy, suggests Chan. Londos, however, cautions that “the freewheeling fat breakdown in the perilipin knockout animals” leads to free fatty acids in the blood, a precursor to insulin resistance.

    The functions of ADRP and TIP47 on lipid droplets are less well understood. Knocking out ADRP in rodents produced mice that seem to be healthy; cells in the animals compensated by overproducing TIP47, says Londos. His group has since deactivated the genes for both ADRP and TIP47 in mice, but they haven't published the research yet. “You'll have very sick animals if you can't package your lipids,” Londos cryptically notes.

    Trimming down.

    Mice that can't respond to the appetite-regulating hormone leptin grow obese (right). Mice lacking the perilipin protein that coats lipid droplets burn off the excess fat and become almost as slender (middle) as normal mice (left).

    CREDIT: PRADIP SAHA AND LAWRENCE CHAN (MICE)

    Chan is also looking more closely at the ADRP knockout mice to see if researchers missed some subtle problems. Citing yet-to-be-published data, he says that mice lacking ADRP have lower amounts of triglycerides and less fat in their liver cells and are far less likely than typical mice to suffer a fatty liver, a condition commonly found in overweight individuals.

    A cholesterol connection?

    Cholesterol researchers joined the lipid-droplet field in 2001, when three research teams reported that caveolin, a cholesterol-production protein that typically resides in the cell membrane, could be found on the particles under certain conditions.

    Just what the protein does there isn't yet clear, however. In one study, cell biologist Robert Parton of the University of Queensland, Australia, engineered cells to make a mutant version of caveolin and found that these proteins amass in lipid droplets, increase the amount of neutral lipids in the cell, and interfere with cholesterol production. This suggested a role for lipid droplets in making cholesterol, instead of just storing its raw materials. But not everybody is convinced because there's no obvious mechanism: Researchers aren't sure exactly how caveolin could help lipid droplets produce cholesterol or get it out of the cell. “I think the clincher finding has yet to be made on the role of caveolin [with lipid droplets] in cholesterol synthesis,” says cell biologist Deborah Brown of Stony Brook University in New York.

    Protein protector.

    Perilipin (green) surrounds bubbles of neutral lipids (red) in fat cells.

    CREDIT: TANCY ET AL., IUMBM LIFE 56, 379–385 (2004)

    Caveolin has similarities with other proteins that interact with lipid bodies. “If you squinted hard enough at [its structure], caveolin would look like a PAT family protein,” says Brown. But other proteins recently found to hang out with lipid droplets are more diverse. In 2004, several groups surveying the protein profile of lipid droplets revealed that these particles contained dozens of proteins, including ones involved in fat metabolism and in moving membranes between compartments within a cell.

    Anderson, who led one of the groups, was so impressed by the droplets' protein ensemble that he argued the particles deserved the name adiposomes to indicate their status as true, metabolically active organelles. Researchers have also found strands of messenger RNA snuggled up to the fatty balls. “Lipid droplets are much more complex than people imagined,” says Parton.

    The finding that proteins that shuttle membranes around the cell kibitz with lipid droplets startled biologists. Previous reports had placed one such protein, Rab18, in an unrelated cellular compartment. But when cell biologist Toyoshi Fujimoto of Nagoya University Graduate School of Medicine in Japan overproduced Rab18 in liver cells, ADRP disappeared from lipid droplets, and the particles then maneuvered through the cell until they nestled up next to the rough endoplasmic reticulum, the membranous structure upon which ribosomes produce proteins and deposit them into the ER for additional processing. Fujimoto says Rab18 could control whether droplets associate with the ER. “We suppose ADRP shields lipid droplets from other organelles so the droplets don't get attached,” he says.

    Rab18 or one of its cousins may also control fat cells' ability to access the fatty contents of their lipid droplets. Cell biologist Dawn Brasaemle of Rutgers University in New Brunswick, New Jersey, says that when fat cells are eating up their triglycerides for energy, the droplets shatter into smaller fragments, and their protein composition changes massively. “I think a Rab will be a part of that,” she says.

    Foaming cells and fatty livers

    The medical world has long known that lipid droplets can be problematic: The so-called foam cells that lodge in arteries and contribute to heart disease are not much more than immune cells stuffed with overly large lipid droplets. But recent studies have linked several rare inherited disorders with defects in the function or control of lipid bodies. For example, mutations in the gene encoding a protein called CGI-58 lead to a rare syndrome in which lipids overload a variety of tissues, causing symptoms such as muscle degeneration and scaly skin. Brasaemle and colleagues have found that CGI-58 normally associates with perilipin on lipid droplets but falls off when cells start to metabolize their fat stores.

    There are also hints that viruses and bacteria exploit lipid droplets in cells. Livers of mice infected with some varieties of hepatitis C virus bleb with fat, and virologist John McLauchlan of the Medical Research Council Virology unit in Glasgow, U.K., has found that the HCV capsid protein associates with lipid droplets inside liver cells. Also, cell biologist Raphael Valdivia of Duke University in Durham, North Carolina, reported at a meeting last year that when the bacterium chlamydia reproduces inside cells, it coats itself in hijacked lipid droplets.

    Fatty liver.

    The capsid proteins of hepatitis C virus (green) and lipid droplets (red) fraternize (bottom left) in an infected human liver cell (bottom right).

    CREDIT: J. MCLAUCHLAN/INSTITUTE OF VIROLOGY, GLASGOW

    Peter Weller, who studies lipid droplets at Beth Israel Deaconess Medical Center in Boston, Massachusetts, has also connected the particles to inflammation, an immune reaction that can either damage or protect the body. Weller and his colleagues initially noticed a mere correlation: Immune system cells stimulated to make lipid droplets, by adding free fatty acids to their growth medium, also made eicosanoids such as leukotriene. Inhibit lipid body formation, by withholding such acids, and production of these inflammatory signals dropped.

    Then, in 2001, Weller chemically treated immune cells so that any newly synthesized leukotriene would bind to nearby proteins, thus illuminating the eicosanoid's site of production within the cells. When they stimulated lipid body formation, “lo and behold, the leukotriene was on the lipid particle,” says Weller, indicating that its production occurred on the droplets' surface. “For us, it was the smoking gun.” More recently, Weller and Patricia Bozzo of the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil, have shown the same with other eicosanoids known as prostaglandins.

    Disease clue.

    Mutations in CGI-58 (green), which coats lipid droplets (orange) in fat cells, cause scaly skin and muscle problems.

    CREDIT: SUBRAMANIAN ET AL., J. BIOL. CHEM. 279, 42062–42071 (2004)

    Additional inflammation mediators fraternize with lipid droplets. Back in 1994, electron microscopist Ann Dvorak of Beth Israel identified cyclooxygenase (COX)—an enzyme that produces prostaglandins—residing on lipid droplets. She has since shown that aspirin interferes with lipid-droplet formation, but in a manner that doesn't depend on the drug's inhibition of COX. “We hope such results might offer some opportunity to find new anti-inflammatory therapies,” says Weller.

    As interest in lipid droplets grows, biologists are searching for better ways to probe the function of the particles. They usually kill cells to isolate and examine the droplets. “One of the things that's hampered their study is there's [been] no technique to study lipid bodies on the long term,” says microscopist Emmanuel Beaurepaire.

    But in the January 2006 issue of Nature Methods, he and his colleagues at École Polytechnique in Palaiseau, France, describe a way to perform real-life imaging of lipid droplets in developing fruit flies and in growing liver cells. While developing light microscopic techniques to visualize mitochondria within cells, they noticed that particular wavelengths lit up lipid droplets surprisingly well.

    Whether this new imaging technique will reveal all the secrets of these fatty particles is far from clear. Scientists still don't know if these drops form from other organelles or crop up by themselves. “The biology of lipid droplets is so immense and untapped,” says Brasaemle, noting that the first conference will be devoted to them in the summer of 2007. As one of the earliest researchers in the field, Brasaemle is glad that the particles have finally come into their own: She points out that they're discussed in the latest copy of a widely used biochemistry textbook. Ah, but under what name?

  11. WOMEN IN SCIENCE

    Getting Women Scientists Back on the Career Track in Japan

    1. Dennis Normile

    Japan is one of the richest countries, but it's also one where women have little chance of succeeding in science; several new programs aim to end this dubious distinction

    TOKYO—Five years after she gave up research to be a full-time mother, Kumiko Usuda is trying to pick up her career where she left off. The Ph.D. astronomer quit working when her first child was born and stayed home until her second child was comfortable with a babysitter. Now living in Hilo, Hawaii, where her husband, also an astronomer, heads engineering for Japan's Subaru Telescope, Usuda does voluntary outreach work for the observatory as she updates her thesis research on molecular gases in galaxies for publication. She would like to arrange observing time at radio telescopes and attend conferences. But it's hard. Although the observatory has given her office space, “there is no financial support for business trips,” she says.

    Timing is everything.

    Yoko Iijima had her first child in between postdoc stints. Other women in their 20s temporarily step off the career ladder.

    CREDITS (TOP TO BOTTOM): D. NORMILE/SCIENCE; SOURCE: INTERNATIONAL LABOUR ORGANIZATION

    Help is on the way. Next month, Japan's government will launch a new category of grants open only to parents returning to the scientific workforce after extended childrearing breaks. It is part of a package of initiatives that also includes grants for institutions to develop schemes to help women balance research careers and family life. The underlying objective—set out in a draft 5-year policy plan—is to have women claim 25% of all new science and engineering positions at governmental institutions.

    Usuda appreciates what the government is doing: “I'm so happy somebody is thinking about my situation,” she says. But many worry that the measures will barely dent the formidable bar riers that women face. A shortage of daycare facilities and a tradition of long working hours make research careers difficult for mothers with young children. The biggest challenge may be raising the consciousness of senior—primarily male—administrators. Labs and universities “are far from ever thinking of what it takes to be a mother and a scientist,” says Kuniko Inoguchi, minister of gender equality and social affairs and a former professor at Sophia University in Tokyo.

    The Japanese government has taken up the gauntlet out of embarrassment, not chivalry. In 2004, women made up only 11.1% of the scientific workforce, the lowest proportion among the 30 member countries of the Organisation for Economic Co-operation and Development. (Portugal has the highest rate, more than 40%; the U.S. f igure is 26%.) “This is a very dubious honor for Japan,” says Akira Kawamoto, director for science and technology policy in the cabinet office.

    The percentage of women scientists has remained low despite rising achievement. In 2004, women made up 23% of those enrolled in science and engineering doctoral programs, up from less than 15% in 1995. Yet few women f ind permanent academic jobs. At Japan's national universities, the proportion of women holding associate professorships is stuck at about 10%.

    To boost the numbers, the Council for Science and Technology Policy (CSTP), the nation's highest science advisory body, set targets for the proportion of newly available permanent positions that go to women in the Third Science and Technology Basic Plan, expected to be adopted by the cabinet this month. Targets vary by field: 30% for health and life sciences, 30% for agricultural sciences, 20% for physical sciences, and 15% for engineering. The percentages are based on the proportions of women currently earning Ph.D.s in each area. “We assume that the ability of men and women are equal, so we can naturally expect that the rates [of women earning Ph.D.s] should be reflected in the rates of women becoming professors or assistant professors,” says Kawamoto, who oversaw the drafting of the plan.

    The initiative is getting mixed reviews. Plant biochemist Yoko Iijima, a postdoc at the Kazusa DNA Research Institute in Chiba, thinks candidates “should be chosen based on abilities, irrespective of gender.” Others argue that gender is an ever-present factor. Mariko Kato, an astronomer at Keio University in Tokyo, says that during initial postdoc fellowships, the male-female ratio closely reflects the proportion of men and women earning Ph.D.s. But as the years pass after graduation, more men find permanent positions, leaving a disproportionate number of women cycling through postdocs or other temporary jobs. Nobuko Wakayama, a protein crystallographer at the National Institute for Materials Science in Tsukuba, says that it is typically the older male scientists who set the tone for institutional decisions on hiring, promotion, and funding. And “they tend to look down on women researchers,” she says.

    Kawamoto says the targets will make institution heads accountable for helping the nation boost the number of women in responsible research positions. “To change [attitudes], this sort of top-down target is necessary,” he says. Although the cabinet office can only rely on “moral pressure,” Kawamoto says, it will publicize which institutions are making progress and which aren't.

    Beating the “M” curve

    To address the day-to-day issues that weigh on women scientists, the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) in the fiscal year beginning in April is launching a trio of new initiatives.

    How to balance work and family demands is a challenge for women everywhere. But in Japan (and Korea), scarce daycare and a cultural bias in favor of mothers staying at home with small children result in an unusual pattern of midcareer dropouts. In most industrial countries, the percentage of women in the workforce stays fairly constant at all ages. In Japan and Korea, however, the percentage peaks for women in their early 20s, dips to a low point for those in their early 30s, and then recovers to the earlier level as they enter their late 30s. This “M” curve of workforce participation plotted against age is deceptive, says CSTP member Reiko Kuroda, a University of Tokyo biochemist. “Women are not able to come back to positions where the quality of the work is the same as before the break,” she says. Kuroda suspects that returnees typically end up in jobs with less responsibility and fewer chances to advance to leadership positions.

    MEXT officials hope two new programs will get the kink out of the curve. One will challenge institutions to devise novel approaches to balancing motherhood and work. Many women feel pressured to quit a research post rather than take maternity leave because they worry that a prolonged absence will inconvenience colleagues. One possibility is to provide money to hire temps for women on maternity leave. The ministry expects to select proposals from 10 institutions based on a competitive review. Winners will share $12.6 million over 3 years.

    The second program will offer research reentry grants to men and women who, like Usuda, put careers on hold to start a family. The $2.2 million program will provide 30 scientists with 2-year fellowships, which are expected to be steppingstones to permanent posts.

    Unheralded dilemmas.

    The new initiatives fail to tackle cultural issues such as late-night lab discussions that mothers must miss, says Miwako Ishido.

    CREDIT: D. NORMILE/SCIENCE

    The third program reaches further up the pipeline. MEXT plans to set up exchanges between high school girls and role-model women scientists and develop brochures on research careers. The ministry has $300,000 for the program in the fiscal 2006 budget. If the programs are successful, it's likely they will be expanded, says MEXT's Masaaki Tanaka.

    Women welcome the programs but tend to see them as small steps when leaps are called for. “I really think highly of these initiatives,” says cell biologist Miwako Ishido. However, she says, they do little to tackle “the range of cultural issues that make it difficult” for women in research.

    Maternity leave isn't likely to improve much, some say. Most women who want to start families are postdocs. “Many women worry that taking maternity leave while on a postdoc won't look good on their resumé,” says Iijima. She planned her pregnancy so as to give birth between the completion of a postdoc fellowship at the University of Michigan, Ann Arbor, and the beginning of her current postdoc at Kazusa. “All of my friends are in a dilemma over when to have kids,” she says. Ishido adds that many institutions have an age limit—typically 35—for candidates for permanent positions, adding a twist to the child-rearing puzzle.

    One of the biggest headaches remains unaddressed: “We need childcare centers in labs and universities,” says Inoguchi. Only two of Japan's dozen or so top research universities have on-campus daycare. Tohoku University opened the first last fall, and Nagoya University will follow suit in April. The Nagoya nursery will keep children until 9 p.m. But that may not be late enough for what Ishido calls “the night-owl culture” of Japan's labs. Researchers typically arrive late in the morning and work until midnight. “All the most interesting lab discussions take place late at night,” she says.

    The slow pace of change in the academic community has already pushed many talented women in other directions. Ishido, who earned her Ph.D. at Kyoto University and did a postdoc stint at the Scripps Research Institute in San Diego, California, chose to get off the postdoc treadmill when she returned to Japan last year. She now splits her time between benchwork at a biotech start-up and evaluating high-tech investment opportunities for a venture-capital firm. “This trend of talented women pursuing opportunities outside academia is likely to push universities to change,” she says.

    But the extra nudge from the new clutch of programs is welcome. Usuda says she regularly checks the Web site of the Japan Society for the Promotion of Science, where details of the grants for women returning after career breaks are due to be posted. The new programs may not usher in an era of equality, but they send a strong message that the status quo is no longer acceptable.

  12. JAPAN

    A $214 Billion Plan of Action

    1. Dennis Normile

    TOKYO—Women researchers are not the only beneficiaries of Japan's Third Science and Technology Basic Plan (see main text). The blueprint for the next 5 years, expected to be finalized and adopted by the cabinet this month, is designed to tackle unfinished business across the R&D spectrum.

    The first plan, adopted in 1996, set an ambitious goal of doubling public research spending to ¥17 trillion ($145 billion) over 5 years. That target was achieved. The second plan in 2001 called for ¥24 trillion for R&D, which would raise annual expenditures to about 1% of gross domestic product (GDP). Due to Japan's fiscal woes, however, spending fell short, totaling about ¥21 trillion. For the third plan, policymakers are again eyeing a 1% of GDP benchmark, up from 0.67% in 2003. That translates into ¥25 trillion ($214 billion) for R&D over the next 5 years. Spending increases will depend on economic growth averaging 3.1%, a figure that may be in reach with Japan's economy on the mend.

    Highlights of the draft plan include:

    Priority areas. The S&T plan aims to continue previous policies of concentrating funding increases in four priority areas: life sciences, information technology, environmental sciences, and nanotechnology and materials sciences. It will also continue to focus on four areas of secondary priority: energy, manufacturing technology, social infrastructure, and frontier sciences (a catchall category).

    Fostering competition. To create a more competitive research environment, the plan calls for increasing funding for peer-reviewed grants for individuals and small teams by 30%—up from about $3.3 billion in fiscal 2005—over the next 5 years. And to promote the best institutions, the plan seeks to make universities and labs compete for funds. Currently, they receive most of their funding as block grants based on factors such as enrollment. The goal is for about 30 institutions to break from the pack as world class according to number of citations, says Akira Kawamoto of the cabinet office.

    Research fraud. Although details are still being worked out, the final plan is likely to call on universities and institutes to set up offices to investigate allegations of misconduct.

  13. IOANNIS MIAOULIS PROFILE

    A Passion for Teaching Leads to Engineering Change in Schools

    1. Yudhijit Bhattacharjee

    Most U.S. students aren't exposed to engineering until college. Massachusetts is different—and Ioannis Miaoulis is a big reason why

    Eighteen years ago, Ioannis Miaoulis took a wrong turn on his way to Tufts University and ended up in the parking lot of a middle school outside Boston. Instead of asking for directions to the Medford campus, where he was an assistant professor of mechanical engineering, Miaoulis walked into the principal's office and offered to demonstrate the principles of superconductivity, a hot field that he was exploring. One week later, Miaoulis was showing eighth grade students how a magnet could float in the air above a superconductor.

    The new world.

    Ioannis Miaoulis says students need to understand engineering as well as science to succeed.

    CREDIT: BOSTON MUSEUM OF SCIENCE

    That classroom session launched the Greekborn researcher on a parallel career in science education that has made him a passionate advocate for technological literacy. Disturbed by a curriculum that contained “so much about flowers and rocks and nothing about planes and power plants,” Miaoulis started a statewide campaign to introduce engineering concepts into schools. In 2001, Massachusetts education officials made their state the first to include engineering in its curricular standards and student assessments. “Miaoulis was the one who made that happen, no question about it,” says Massachusetts education commissioner David Driscoll. “He sold engineering to us in a way that demystified it and made a compelling case for teaching it to kids from an early age.”

    Today, Miaoulis, 44, has expanded that campaign into a national effort. In 2003, he left academic life to become president of the Museum of Science in Boston. It houses his National Center for Technological Literacy (NCTL), a nonprofit organization with $32 million from businesses and the federal government that has developed an elementary school curriculum and an engineering course for high school students. Last fall, schools in a dozen states began trying out the elementary school curriculum, and high schools in seven states are piloting the advanced course. “My dream is to have the humanmade world be a part of the curriculum of every school in the country within the next 9 years,” says Miaoulis. “I say nine because last year I said 10.”

    A prized speaker at education summits around the country, Miaoulis promotes the cause of precollege engineering education like nobody else. His monomaniacal focus can even be a little annoying to others in the field. “He thinks he discovered the idea of teaching engineering to kids,” says Kendall Starkweather, executive director of the International Technology Education Association (ITEA) in Reston, Virginia. ITEA was founded in 1939, and in 2000, it issued national standards for technological literacy. But Starkweather doffs his hat at Miaoulis's achievements. “The bottom line is that he has succeeded in getting one state to adopt engineering standards and helped to focus national attention on the E and T in STEM.”

    A passion for teaching

    Miaoulis's own acquaintance with engineering started at home: His father was a civil engineer. After moving to the United States as a teenager, Miaoulis got both his bachelor's and doctoral degrees in engineering from Tufts and eventually joined its faculty. But he was disturbed by the public's ignorance about what engineers do, as well as its higher regard for scientists. “People who drive trains and repair VCRs are considered engineers,” he says. Even the old building that houses the National Academy of Engineering “has a janitor's closet that says ‘Engineering’ on it,” he notes.

    At Tufts, Miaoulis's passion for teaching made him immensely popular and raised engineering's profile on campus. For example, to teach heat transfer, he became a cooking instructor, providing students with lamb recipes alongside energy-rate equations. His tasty lessons reduced the traditionally high attrition rates for first-year engineering students to the point at which the department began to attract majors from the liberal arts.

    But Miaoulis wasn't content to confine his teaching talents to a college campus. Working with local public schools in the late 1980s made him realize that “98% of the curriculum is focused on the natural world, even though 98% of the things that most people interact with in their daily lives (apart from their own bodies) are humanmade.” It seemed crazy to him that students “spend days learning how a volcano works but no time learning how a car works.” Then he delivers the punch line: “How often do they find themselves in a volcano?”

    When Miaoulis was appointed to a panel revising the state's science and technology standards in 1998, he saw the opportunity to do something about his pet peeves, but he knew he needed allies. So he reached out to the state's association of technology education teachers, many of whom had been losing jobs as schools closed down printing and automotive shops to fund computer labs. “Going to science teachers did not seem like a good idea because teachers that are well-fed and secure—why would they change anything?” he says. “I thought, if I partner with tech-ed teachers and make the case that adding engineering could upgrade their whole profession and save their jobs, I'd have the backing of that entire community.”

    Brushing up on technology.

    Second graders at Barbieri Elementary School in Framingham, Massachusetts, learn about the technology behind everyday items such as a toothbrush.

    CREDIT: Y. BHATTACHARJEE/SCIENCE

    It didn't go that smoothly. Many tech-ed teachers without engineering degrees worried that they'd be left behind. Others thought that science teachers would be asked to carry the load because of the strong math and science foundation needed. Indeed, state officials did try to throw technology out of the standards, arguing that shop skills such as metalworking and woodworking did not belong in higher level academic standards. Miaoulis convinced them that tech ed would become as academically relevant as physics when blended with engineering. “He showed a lot of political savvy during the process,” says Driscoll. “He made a connection with people—from the governor to state education officials—and he was relentless in a nice way.”

    Technical difficulties

    Since his successful advocacy for precollege engineering in Massachusetts 5 years ago, Miaoulis has delivered talks in more than 25 states and lobbied hundreds of politicians and school administrators. But no state has yet followed Massachusetts's lead. Even within the state, most middle and high schools have been hard-pressed to implement the new standards. One hurdle is the lack of clear guidelines in the standards and the absence of curricular materials for the middle school grades, which NCTL is currently developing. But a tight budget and a finite school year also pose serious problems, says James Surowski, head of the science department at Forest Park Middle School in Springfield, Massachusetts.

    “In the 185 days available during our school year, an eighth grade science teacher already has to cover the Earth's history, change in ecosystems over time, the Earth and the solar system; … the list goes on,” says Surowski. “Now the same teacher—we can't hire a specialty engineering teacher—must make time for technology topics as well. The pond just got a lot wider and a lot shallower.” Laura Bottomley, who leads the American Society for Engineering Education's K-12 project, notes that “we have trouble getting schools to teach science, let alone engineering.”

    Some Massachusetts teachers worry that many high school students may not have a sufficient foundation in mathematics and physics to benefit from the engineering course. “We're currently designing a model deck for which students need to calculate live loads and dead loads, which requires algebra,” says Richard Skrocki of Shepherd Hill Regional High School, who is implementing the high school engineering course developed by NCTL. “I can see that some of my students who are weak in math are having difficulty. But I don't have the time to teach them algebra before proceeding with the class.”

    At the same time, other educators say that NCTL's engineering course for high schools is not rigorous enough. “When they teach students music, they don't give them cardboard models of musical instruments. Why should engineering be any different?” asks Richard Blais, vice president of Project Lead the Way (PLTW) in Clifton Park, New York, which offers a demanding middle school and a precollege engineering program.

    Miaoulis, who calls PLTW's course the “Cadillac” program, admits that the NCTL curriculum, including the use of cardboard models in the deck-building assignment, is more basic than what many engineers would like to see. But he thinks it gives them a good sense of engineering design and problem solving. “Once this thing catches on,” he says, “we can create more specialized courses that involve calculus and advanced physics.”

    In the meantime, Miaoulis tries to help teachers fit engineering into their existing curricula. After taking a 2-week summer course offered jointly by Tufts, the Museum of Science, and Worcester Polytechnic Institute, Debbie Warms asked her seventh graders at Charlton Middle School to create assistive devices for students with disabilities. “They had to use math skills such as measurement, ratios, and proportions, and solve equations with a variable and geometry,” says Warms, who found the exercise timeconsuming but worthwhile.

    That blending of disciplines is exactly what engineering can bring to precollege education, says Miaoulis: “It can bring to life not just the math and science but also the social studies, the English skills.” As an example, he points to NCTL's pilot elementary school curriculum that combines history, geography, and culture into an engineering lesson. In one book, Yi Min learns about the use of materials engineering in building and preserving the Great Wall in her native China. Another lesson follows Aisha, a young Boston girl, as she explores a local potato chip factory with her father and learns about industrial engineering.

    Miaoulis believes that approach will boost undergraduate engineering enrollment and increase diversity by making the subject more relevant to students' lives. And he's unapologetic about the program's potential impact on other subjects now being taught. “Okay, you might have to cut other things from the curriculum a little bit,” he says. “But then, so be it. Look at what you add.”

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