News this Week

Science  14 Mar 2008:
Vol. 319, Issue 5869, pp. 50
  1. SCIENTIFIC MISCONDUCT

    Two Papers From Korean Lab Found to Lack 'Scientific Truth'

    1. Jennifer Couzin,
    2. Dennis Normile

    An investigation by a prominent South Korean university has revealed that two papers by its researchers do not contain any scientific truth. Both will likely be retracted by the journals in which they appeared, Science and Nature Chemical Biology. The papers describe a new way to identify drug targets by tracking protein movements in living cells. Their well-known senior author, Tae Kook Kim, studied in the United States and founded a company in Daejeon, South Korea, in 2004 to commercialize the findings.

    Kim, in a brief e-mail to a Science reporter, said he would cooperate with the investigation to open the truth very soon. He added that a certain party has twisted this current situation to take an advantage of it.

    An inquiry by the Korea Advanced Institute of Science and Technology (KAIST) in Daejeon, where Kim is a faculty member, is not yet complete. But Gyun Min Lee, chair of KAIST's Department of Biological Sciences and head of the internal investigation committee, informed Science by e-mail that our initial investigative results are strong enough to convince us that the two papers do not contain any scientific truth. Another member of the committee, Yeon-Soo Seo, a biochemist at KAIST, declines to say precisely what it has found until the investigation is complete.

    KAIST launched the inquiry after scientists at Kim's company, CGK Co., had difficulty coaxing the technology, called magnetism- based interaction capture (MAGIC), to work. One co-author of both papers and a former Ph.D. student in Kim's lab, Yong-Weon Yi, contacted Science and Nature Chemical Biology in December to ask that his name be removed from the papers. The journals then quietly began asking questions of their own. Science was reassured by Kim that he didn't think there were problems with the paper, says Katrina Kelner, Science's deputy editor for biological sciences. The journals' inquiries were continuing when KAIST announced its preliminary findings on 29 February.

    Too good to be true?

    Papers describing a technique known as MAGIC for tracking proteins in a living cell have been called into question.

    At CGK, which raised 2.5 million from three Korean venture capitalists in 2006, concerns about the technology had run deep for months. CGK has tried to reproduce the technology but in vain, the company said in a written response to questions from a reporter for Science. In mid-February, CEO Jin Hwan Kim informed KAIST officials of the company's difficulties with MAGIC, prompting KAIST to launch a departmental investigation the next day.

    The school followed a protocol established by the Ministry of Science and Technology after a scandal over fraudulent stem cell publications by Seoul National University professor Woo Suk Hwang (Science, 19 May 2006, p. 980). Seo says investigators approached Tae Kook Kim, who couldn't provide notebooks or original data for the experiments. The task force interviewed members of Kim's team and met twice with Jaejoon Won, the first author of both studies. After the second interview, Seo says, Won sent a written statement to the committee that, Seo says, admitted serious scientific misconduct in both papers. The committee reported its findings to KAIST President Nam Pyo Suh on 28 February. The school then suspended Kim and notified the journals. Science posted an Editorial Expression of Concern about the paper online on 3 March, and editors at Science and Nature Chemical Biology say they're hoping to hear from all the authors, or learn the outcome of the investigation, before retracting the papers.

    Both journals say the papers garnered praise. Reviewers were very enthusiastic, says Kelner. Notes Terry Sheppard, chief editor of Nature Chemical Biology: The referee comments, I thought, were quite consistent with a favorable response.

    But in response to a reporter's questions, CGK listed eight problems with MAGIC, in which magnetized nanoparticles are prodded to interact with proteins in cells. Among them were the type of magnetic nanoparticle used and the resolution of the microscope that authors say generated the published images. It cannot produce the results shown, according to CGK.

    Science began routine screening of images for manipulation in 2006, after publishing Kim's paper in July 2005. The Nature journals instituted image screening a few months after publishing their paper from Kim and his colleagues in the summer of 2006.

    Kim's mentors were stunned to learn of KAIST's initial findings. I certainly would never have expected this, says Tom Maniatis, a molecular biologist at Harvard University who supervised Kim's postdoc work in the mid-1990s. Maniatis described Kim as an extremely hard worker, very efficient, very focused, echoing comments from Kim's Ph.D. adviser, Robert Roeder of Rockefeller University in New York City. The work Kim performed in Maniatis's lab, on interferon genes, has held up, as have his experiments under Roeder.

    After his postdoc, Kim landed a coveted fellowship at Harvard's Institute of Chemistry and Cell Biology, as well as a post with Seoul National University's Institute for Molecular Biology and Genetics. It was at this time that he began focusing on ways to identify drug targets. MAGIC does this by coating a magnetized nanoparticle with a small molecule of interest; the particle is then gulped up by a cell. Proteins are tagged one after another with fluorescent labels, and scientists apply a magnetic field to the cell. This forces the nanoparticle to move, and researchers can observe whether a particular protein moves with it, indicating that the small molecule has bound to the protein. The 2006 Nature Chemical Biology paper showed that MAGIC could pick up two proteins that reset a cell's aging clock.

    Although the MAGIC technology was eye-catching, it apparently wasn't hugely popular. I don't know anybody who was using MAGIC, says Brent Stockwell, a chemical biologist at Columbia University who knew Kim somewhat when the two were at Harvard. Stockwell recalls reading the Science paper and wondering whether it seemed too good to be true. Because the technique melded different disciplines, he adds, it would be hard to find anyone who would have expertise in all of them.

    Over the past year, Kim had become embroiled in a patent dispute between KAIST and CGK over rights to MAGIC. Last July, KAIST suspended Kim for 6 months for allegedly bypassing the school's normal patent procedures, and Kim had been aggressively job-hunting, seeking references from Roeder and Maniatis. I must have sent out 30 letters in the last month, Maniatis says.

    Kim was still listed as CGK's scientific director and founder on the company's Web site this week. But CGK says it has developed an alternative to the MAGIC technique and hopes to build a business around it.

  2. BIOMEDICAL RESEARCH

    $300 Million in Private Money for New Investigators

    1. Jocelyn Kaiser

    Concerned that young investigators are barely treading water, the largest U.S. biomedical research charity this week unveiled a plan to throw a lifeline to some of them. The Howard Hughes Medical Institute (HHMI) in Chevy Chase, Maryland, will spend 300 million over 6 years to support researchers it considers promising but who are struggling to obtain their first independent federal research grant. Hughes aims to fund up to 70 this year.

    Pipeline problem.

    HHMI President Thomas Cech worries about an academic brain drain; Ohio State's Jill Rafael-Fortney testified about challenges facing new investigators.

    CREDITS (LEFT TO RIGHT): HHMI; OHIO STATE UNIVERSITY

    HHMI President Thomas Cech sees the new program as an emergency effort to help young scientists who have been disproportionately affected by 5 years of flat budgets at the National Institutes of Health (NIH) in Bethesda, Maryland. As success rates for NIH research grants scrape a historical low, Cech and other leaders worry that many new investigators are abandoning academic research. Underscoring the community's concerns, a Senate committee this week held a hearing to look into the Broken Pipeline in life sciencesthe title of a report released the same day by a coalition of universities describing the difficulties faced by 12 young investigators.

    HHMI plans to help scientists with a lab and 2 to 6 years' experience as assistant professorspeople who typically have an early career award but currently have only an 18 chance of being awarded their first basic NIH R01 research grant. Cech says that when he visits top research universities, the early faculty are struggling and depressed. The one-time, 6-year appointments will average about 700,000 per yeartwice the size of an NIH R01 grantsplit between research, salary, and institutional support.

    Hughes's rescue is a drop in the bucket compared with the challenge NIH perceives. NIH aims to give R01 awards to the historic average of 1500 new investigators annually, starting last year, up from 1353 in 2006. Other NIH programs have geared up: Pathway to Independence will give out about 170 awards this year for training and research, and New Innovators will award up to 24 5-year grants to new investigators for high-impact research.

    Young investigators say help is badly needed. Human geneticist Jill Rafael-Fortney of Ohio State University, Columbus, who testified this week before the Senate Health, Education, Labor, and Pensions Committee, is waiting for a renewal of her first R01 or a new grant to study a muscular dystrophy gene that also plays a role in heart failure. The second proposal has gotten great scores, and it's just missing the pay line, or cutoff, for funding, she says. If her R01 applications fail, and a multi-PI grant she's on doesn't come through, it will mean a 50 cut in her salary. I'd probably have to leave my job, she says.

    Hughes expects to fund at least one more competition 3 years from now to help young people through this rough period, Cech says. We hope we won't have to do it any more than twice.

  3. U.S. CONGRESS

    Physicist Wins Open Illinois Seat

    1. Eli Kintisch

    Developmental biologist Donald Brown of the Carnegie Institution of Washington in Baltimore, Maryland, doesn't get many fundraising calls from candidates for Congress. But when experimental physicist Bill Foster called Brown in January, he gave the Illinois Democrat his ear, and soon after, 1000. Last weekend, Foster, a former researcher at Fermi National Accelerator Laboratory (Fermilab) in Batavia, Illinois, won a special election to fill the seat held by former House Majority Leader Dennis Hastert in a race that attracted national attention. And hundreds of scientists around the country gave their time and money to help put Foster over the top.

    Bigger science.

    Bill Foster (center) will join two other physicists in Congress.

    CREDIT: ASSOCIATED PRESS

    The combination of my scientific and business backgrounds spells problem solver, says Foster, who ranks the economic downturn and pulling U.S. troops out of Iraq as his highest priorities and says more funding for basic science is a problem he also wants to tackle. Bill's background as a scientist not from Washington helped him, says his campaign manager, Tom Bowen.

    During his 22-year career at Fermilab, Foster, 53, also was part-owner of a prosperous lighting firm. Unhappy with the cancellation of a particle physics project he led and bitten by the political bug, Foster left the lab in 2006 to work on the successful congressional campaign of another neophyte, Democrat Patrick Murphy, for a seat in suburban Philadelphia. Calling himself the campaign physicist, Foster learned the ropesand devised software to organize the efforts of volunteers knocking on some 140,000 doors.

    Foster's lab ties helped him jump-start his own campaign. Nobelist and former Fermilab director Leon Lederman introduced Foster to Chicago power brokers and assembled a list of 28 Nobelists who publicly endorsed Foster. After work hours, Fermilab physicist and county alderman James Volk recruited colleagues to get involved. Lab engineer Thomas Peterson told voters in a campaign commercial that Foster brings people together. Volk and others braved the bitter weather to collect signatures and knock on doors to get out the vote, he says.

    The community also dug into its pockets, giving roughly 160,000 according to campaign documents. Amounts ranged from 250 from former Department of Energy official and Massachusetts Institute of Technology physicist Mildred Dresselhaus to 2000 from Fermilab Director Pier Oddone. Foster was his own biggest contributor, spending 1.4 million, and the Democratic National Committee put in a similar amount to help Foster capture what had been a traditional Republican stronghold.

    Brown says he's proud of his role in helping Foster win the Democratic primary last month and then defeat Republican Jim Oberweis on 8 March by a margin of 53 to 47. It's a great omen for the Democrats, he says. This Administration has been terrible for science.

    Despite being the newest member of Congress, Foster won't be able to leave the campaign trail. That's because he faces Oberweis again on 4 November in a race for a full 2-year term. And scientists such as Fermilab physicist Michael Church, who contributed 400, say Foster can count on their support again. It'll be a tough election, and he'd need all the help he can get, says Church.

  4. SCIENTIFIC WORKPLACE

    Indian Government Offers Helping Hand to Women Scientists

    1. Pallava Bagla

    NEW DELHIIn 2000, when Vijayalakshmi Ravindranath was appointed director of the National Brain Research Centre in Gurgaon, the neuroscientist made history. Ravin-dranath became the first woman to lead any of the 65 institutes under India's Ministry of Science and Technologyand today she is one of only two women who have broken the ministry's glass ceiling. When it comes to promoting women scientists in India, she says, our record is dismal.

    It may be surprising that women scientists are struggling in the nation that elected Indira Gandhi prime minister in 1966. But at a conference in New Delhi to mark International Women's Day on 8 March, more than 1000 scientists spoke of barriers to advancement and debated how to attract more women into research careers. At the meeting, science minister Kapil Sibal announced what he calls fledgling steps to empower women to have their rightful role in science, including new regulations to allow women with young children to work more flexible hours.

    The statistics are sobering. Although women have earned 37 of all science Ph.D.s awarded by Indian institutions, they hold fewer than 15 of science faculty positions. Out of India's 114,000 or so government scientists, fewer than 16,000 are women. Only one of the Indian Council of Agricultural Research's 175 institutes has a female director: the National Research Centre for Women in Agriculture in Bhubaneswar.

    The hurdles women scientists face are not unique to India. Women are unable to cope with the triple burden of home, work, and societal prejudices, including gender-related nepotism, says Mahtab S. Bamji, a nutritionist with the Dangoria Charitable Trust in Hyderabad and chair of a science ministry task force assessing the status of women in science in India. The panel will release its findings later this year.

    At the conference, Sibal announced that his ministry's 65 institutions would provide flexible working hours for women scientists with children younger than 3 and establish crches in all institutions. In addition, Sibal said, some of the 33 female members of the Indian National Science Academy (which has a fellowship of 774) will receive research grants of up to 25,000 a year over 5 years.

    Women scientists applaud the measures. But in the long run, as India's first woman president, Pratibha D. Patil, argued at the conference, gender parity will come only when discrimination against women has stopped.

  5. NEUROSCIENCE

    Hiding From Biting Insects in Plain Scent

    1. Mitch Leslie
    Dinnertime.

    Unprotected by DEET, this man's arm draws hungry mosquitoes.

    CREDIT: CLIFF PARTLOW/GETTY IMAGES

    For backpackers, the insect repellent DEET makes hikes bearable by protecting against mosquitoes and other blood-sucking pests. For people who live in malaria-prone areas, it can be a lifesaver. Although people have been spraying and dabbing DEET on for more than 50 years, nobody knew exactly how it works until now. Researchers report online in Science this week (www.sciencemag.org/cgi/content/abstract/1153121) that instead of driving away biting bugs, DEET actually conceals us from them. The compound dulls the insects' sensitivity to certain body odors, explains co-author Leslie Vosshall, a molecular neurobiologist at Rockefeller University in New York City.

    Although DEET's insect-deterrent abilities are formidable, it can be toxic, especially to infants. Unraveling how DEET fends off attacks is a first step toward developing more specific alternatives, says neuroscientist Richard Axel of Columbia University, who wasn't involved in the research. The work affords the possibility of rational approaches to confounding the olfactory system of insects. But first, more behavioral studies of mosquitoes are needed, cautions medical entomologist Willem Takken of Wageningen University in the Netherlands, as Vosshall's behavioral experiments focused on fruit flies.

    To female mosquitoes, our body odors mean food. These insects sniff out lactic acid in our sweat and carbon dioxide and 1-octen-3-ol alcohol in our breath. It's wildly attractive to mosquitoes, says Vosshall.

    She and her colleagues netted key evidence about DEET's mode of action from fruit flies, whose neurobiology is better understood than that of mosquitoes. For these behavioral studies, the researchers gave the flies a chance to enter either of two small vials. If both tubes held food, flies piled into them in about equal numbers. If one tube also contained DEET at the 10 concentration found in many sprays, the insects preferred the DEET-free vial. However, when the choice was between an empty tube and an empty tube dosed with 10 DEET, the flies made no distinction, suggesting that they weren't just shunning the compound. With DEET wafting around, they apparently couldn't smell the food, says Vosshall.

    To bolster this suspicion, her team took a close look at fly odor receptors. The team engineered frog eggs to make these receptors, a technique that effectively can turn a frog egg into a fly nose, says Vosshall. Exposure to certain odor molecules activated the receptors and triggered a surge of positive ions into the egg. But DEET reduced the flow, indicating that the receptors are less responsive in DEET's presence. The compound hides food scents by blunting the sensitivity of specific odor receptors, the researchers conclude.

    But that conclusion is premature, says Takken, until the researchers determine whether mosquitoes react the same way as do fruit flies in the tube-choice tests.

    However, Vosshall and colleagues did show that their results held true for mosquito receptors and neurons. Using the frog-egg method, the team discovered that DEET suppresses three body-odor-detecting receptors from Anopheles mosquitoes, which transmit malaria. They also saw a dampening of electrical activity in mosquito neurons that typically respond to 1-octen-3-ol, confirming that DEET disrupts the insects' perception of some attractive smells.

    Calling DEET a repellent is a misnomer, says Vosshall: It doesn't smell bad to insects; it masks or inhibits their ability to smell you.

  6. DEVELOPMENTAL BIOLOGY

    Proposed Frog Ban Makes a Splash

    1. Gretchen Vogel

    A proposal to ban the sale of African clawed toads in the United Kingdom has that country's developmental biologists worried about the availability of their favorite research animaland conducting studies to surmount the reason for the ban. In November, the U.K. Department for Environment, Food and Rural Affairs (Defra) issued a list of potentially harmful non-native species that it wants to ban from sale or trade. To the surprise of scientists who work with the animal, the toad, Xenopus laevis, was on the list. Defra says the animals can carry the chytrid fungus blamed for mass amphibian die-offs around the world. It also noted that escaped African clawed toads can compete withand sometimes eatnative amphibians.

    Environmental menace?

    African clawed toads can spread disease.

    CREDIT: CATHERINE LEDNER/GETTY IMAGES

    The U.K. biomedical charity The Wellcome Trust and other scientific groups quickly lodged protests and filed briefs against the proposed ban. Defra's list came out of left field, says developmental biologist Matthew Guille of the European Xenopus Resource Centre in Portsmouth. The two sides are likely to settle on a new licensing scheme that would limit, rather than ban, sale of the animals. But the issue has made biologists more aware of potential dangers their toad colonies pose to the environment.

    For decades, developmental biologists have prized Xenopus for its large, robust embryos that make it possible to observe and manipulate key stages of development. In recent years, the frogs have become even more valuable to researchers, as scientists have learned to create mutants and interrupt the function of specific frog genes. A ban on the sale of the animals would mean that researchers would have to keep their own breeding frogs on hand, making it much more difficult and expensive to manage colonies, Guille says.

    Defra admits being surprised by the scientists' reaction. We didn't realize it was quite such a big deal, says Matthew Ashton, who is coordinating the agency's response.

    The scientists support Defra's aims, if not its ban. We are biologists. I have no wishnor do my colleaguesto be the people who are responsible for the die-off of a whole lot of native amphibians, Guille says. The Xenopus research community already had relatively strict standards in place to prevent wild release of their animals, he says, but in response to the proposed ban, researchers have started to test for the fungal disease, which doesn't make X. laevis obviously ill. Guille says that so far, levels in laboratory frog colonies seem to be low. Although there is no evidence that the fungus compromises studies by affecting Xenopus development, we'd all feel a lot better if we knew we had an infection-free colony, he says. There is no recognized treatment, he says, but the fungus seems to disappear on its own when animals are kept at low density.

    Ashton says Defra's final decision on the Xenopus ban is expected in October.

  7. EDUCATION

    Spanish Scientists Question Accreditation Plan

    1. Elisabeth Pain
    1. Elisabeth Pain is a contributing editor for Science Careers.

    Many in Spain's scientific community are lobbying the country to change a new accreditation system for professors, complaining that it emphasizes nonresearch activities such as patenting, consulting, university management, and work in governmental and state agency offices. In a letter last month to the Spanish Minister of Education and Science, endorsed by more than 760 Spanish scientists, Joaqun Marro Borau, a statistical physicist at the University of Granada, expressed the concern that many of the best scientists would never be able to become full professors in Spain with this marking scale and that many competent scientists will autoexclude themselves from the process.

    Some Spanish officials have questioned the political motives of the letterat least one signer had connections to the opposition party that lost last week's electionsand others argue that scientists are rushing to judgment. When accreditations start to be given out to scientists and they see that someone of their profile gets it, they are going to calm down, says Flix Prez Martnez, coordinator of faculty evaluation for Spain's National Agency for Quality Assessment and Accreditation (ANECA).

    Marro denies any political motive to the letter. And the debate over accreditation dates back to 2001 when Spain, in an attempt to bypass the old-boy network, mandated that aspiring professors first get their competences accredited. But everyone soon agreed that that process was flawed.

    The new accreditation scheme replaces oral examinations with faster, electronic applications. But a complex scoring system, released in January, has come under fire for giving too much credit to nonresearch-related activitiesan applicant to full professorship must get 80 out of 100 points, although research can provide a maximum of 55 points. But the authors have misinterpreted the importance of this marking scale, says Spanish Secretary of State for Universities and Research Miguel ngel Quintanilla Fisac. Evaluators, adds Prez, can give scientists points for management activities such as coordinating European research projects and sitting on editorial boards for journals.

    All agree that the revised application procedure remains cumbersome. Applicants must back each achievement with written proof, for example. They've made it so bureaucratic, difficult to comply with, and confused [that] it seems unbearable, says Maria ngels Garcia Bach, an associate professor at the University of Barcelona.

    ANECA says that it's open to adjusting the process further. I believe that we still need to improve and ask the ANECA to make [the system] more agile, Quintanilla says.

  8. INNOVATION

    U.K.'s Royal Society Ventures Into Funding Start-Up Companies

    1. Daniel Clery

    The Royal Society, the United Kingdom's academy of science, is taking the unusual step of getting into the venture capital business. Last month, it announced the creation of an Enterprise Fund, with the aim of funneling money into start-up companies seeking to commercialize the fruits of academic research. The society says that although it does much to support science and teaching, as well as contributing to policy debates, it could be more active in applying science for public benefiteither by simply boosting the U.K. economy or tackling problems such as carbon capture, renewable energy, and water purification. If there are difficulties getting science into the marketplace, the society has a role helping with that, says Andrew Mackintosh, a chemical physicist-turned-businessman who has been brought in to run the fund.

    Although the society's plan has largely earned plaudits, some worry that the institution could ultimately tarnish its famous name, and others argue that any money raised under the society's name should go to traditional research. Nick Dusic, head of the Campaign for Science and Engineering, a U.K. pressure group, welcomes the injection of start-up funding but says the society mustn't lose its independence in advising government and disbursing funds.

    Some see the Enterprise Fund as a return to the society's roots, as many of its early activities were spurred by the business concerns of the day. The society was a more commercially oriented organization back then, says Peter Littlewood, head of physics at Cambridge University and a Fellow of the Royal Society. In the run-up to its 350th anniversary in 2010, the society is seeking to raise 100 million (200 million) for a variety of special projects, 20 million of which is destined for the Enterprise Fund. The society has so far raised 3 million for the fund from philanthropists, and Mackintosh says he hopes to begin making investments this year.

    The equity investments may range from 250,000 to 2 million but would typically be about 500,000 and extend over longer time scales than are usual for venture capital funding. The fund will be commercially run and legally independent from the society, and any profits will be reinvested in the fund. The hope is that the society's network of grantees, as well as 1400 elected fellows, will be a profitable source of ideas for start-up companies. An advisory board of fellows and some well-known venture capitalists will oversee the fund.

    Medical start-ups in the United Kingdom are frequently given help by organizations such as the Wellcome Trust or cancer research charities, but nonmedical research is more difficult. There's a severe shortage of early stage venture capital, says Roger Brooke, a venture capitalist with the IP Group and one of the fund's early benefactors.

    Bold venture?

    The venerable Royal Society wants to help scientists with good ideas turn them into commercial reality.

    CREDIT: THE ROYAL SOCIETY

    Mathematician Michael Atiyah, a former president of the Royal Society, says this is a good thing for the Royal Society to be doing, well within the scope of an academic body. The Royal Society of Edinburgh, a separate Scottish body of which Atiyah is now president, has had a similar scheme in place for 10 years using government money, he says, and it's been very successful.

    Not everyone is entirely convinced, however. Littlewood is skeptical that there is a problem finding financing for start-ups with a good idea. This is yet another surge in a direction where we don't need much help, he says. I don't feel it's inappropriate, but is the Royal Society the best vehicle to do it? It's increasingly hard to get money just to do science.

  9. AGRICULTURE

    Dueling Visions for a Hungry World

    1. Erik Stokstad

    Sparks began to fly when scientists and activists against genetically modified crops came together to assess agricultural knowledge and the role of biotech in development.

    Sparks began to fly when scientists and activities against genetically modified crops came together to assess agricultural knowledge and the role of biotech in development

    Green machines.

    Experts debated the role of tools, such as fertilizers, that have boosted yields.

    CREDIT: IAN MURPHY/GETTY IMAGES

    When economist Carl Pray heard about plans for the first international assessment of agricultural research, a gold standard sprang to mind: the Intergovernmental Panel on Climate Change (IPCC). But things didn't turn out the way he expected.

    IPCC has been pivotal in proving that climate change is real and linking it to human activities. As an agricultural economist at Rutgers University who has worked in many poor countries, Pray is convinced that agricultural researchand genetic modification in particularis key to fighting pervasive hunger, which will only worsen as the world's population soars to 9 billion during the next 50 years. He hoped that the new project, like IPCC, might be able to muster top experts and galvanize support for a field that had languished through the 1990s. Most encouraging was the leader: Robert Watson, who had earned high marks as a chair of IPCC.

    By the time Pray had signed up and the International Assessment of Agricultural Science and Technology for Development (IAASTD) got under way in 2005 with funding from the United Nations, the World Bank, and several countries, the purview had broadened far beyond food production to include social justice and the environment. The overarching question, posed on the home page of IAASTD's Web site, is a mouthful: How can we reduce hunger and poverty, improve rural livelihoods, and facilitate equitable, environmentally, socially and economically sustainable development through the generation, access to, and use of agricultural knowledge, science and technology? Critics say this broad mandate made conflict inevitable and stunted the assessment's analytical rigor.

    On several key issues, consensus proved elusive. Industry scientists and some academicsmainly agricultural economists and plant biologistsbelieve the assessment was hijacked by participants who oppose genetically modified (GM) crops and other common tools of industrial agriculture. Tensions peaked in October when Monsanto and Syngenta walked out of the assessment.

    View this table:

    Many other participants, who include activists and social scientists, are pleased with the outcome. They note that the voice and experience of small-scale farmers, particularly women, have finally been brought to the fore by the assessment. It really deals with issues of power, influence, and benefits, says Marcia Ishii-Eiteman of the Pesticide Action Network North America in San Francisco, California. Toby Kiers, who studies sustainable agriculture at Vrije University in Amsterdam, the Netherlands, agrees. For technology to be most effective, farmers must be at the center, influencing how it is developed, delivered, and managed, she says.

    But as the drafts are being readied for a final meeting of governments next month, the camps for and against GM crops remain polarized with no resolution in sight. Industry groups, once considered key stakeholders, are boycotting the meeting, and some participants suspect the dissent will undercut the assessment's impact. Says Piet van der Meer of the Public Research and Regulation Initiative in Delft, Netherlands: There is a sense of having lost a wonderful opportunity.

    Big tent

    The origin of the 12 million IAASTD dates to 2002, when a group of ag biotech companies asked the World Bank whether it recommended GM crops for developing countries. Watson, then the World Bank's chief scientist, suggested that the bank review the entire range of agricultural technologies and policies. Convinced that agricultural research should be considered in the context of the myriad factors that affect farmers, Watson and his team solicited suggestions about what to include in the assessment from some 800 stakeholders representing scientific and agriculture-related organizations around the world. Right from day one, I wanted to make sure there was a wide range of views, Watson says. He formed an advisory bureau of 55 people, comprised of representatives from governments, consumer groups, industry, and nongovernmental organizations such as Greenpeace.

    In theory, such an inclusive approach can be a plus, says William Clark, a science policy expert at Harvard University, conferring political legitimacy on an assessment. In practice, it can lead to logjams. Part of the tension over IAASTD reflects two competing worldviews of agriculture. Hans Herren, one of IAASTD's co-chairs, stresses the importance of recognizing the multifunctionality of agriculture. That is, in addition to producing food, farmers have other important roles, such as maintaining the landscape and cultural heritage. In contrast to this view, Herren says others see agriculture as an industrial process, like making cars. That analogy doesn't offend Jonathan Gressel, a plant scientist with the Weizmann Institute of Science in Rehovot, Israel. Producing food is the primary function of agriculture, says Gressel. It should do it safely and [should be] compatible with the environment, just like GM [General Motors] should produce a safe and nonpolluting carbut they have to produce cars.

    Many of the players weren't used to sitting at the same table with opponents. We constantly had doubts about participating, says Benedikt Haerlin. At the time, he represented Greenpeace, which wants a ban on GM organisms (GMOs) in the environment and a phaseout of pesticides and a reduction of synthetic fertilizers. Greenpeace is not used to compromising, Haerlin concedes.

    Molecular biologists and groups that employ them were also skeptical. Rodney Brown of Brigham Young University in Provo, Utah, who was then deputy undersecretary for research, education, and economics at the U.S. Department of Agriculture, worried that the scientific analyses might be swamped by nonscientific views. Like it or not, not all input is equally valuable, Brown says. But almost all participants and observers interviewed by Science say that they had faith in Watson. He has one of the finest, sharpest minds for assessments, says Walter Reid, now at the David and Lucile Packard Foundation in Los Altos, California, who led the Millennium Ecosystem Assessment that examined the state of the world's ecosystems as of 2000 (Science, 1 April 2005, p. 41).

    Watsonwho is now at the University of East Anglia in Norwich, U.K., and chief science adviser to the U.K.'s Department for Environment, Food and Rural Affairswas involved in several other projects, so much of the supervision of the assessment fell to his two co-chairs. Herren, a longtime advocate for sustainable agriculture, is the president of the Millennium Institute, a think tank in Arlington, Virginia. Adding perspective from a developing nation is energy specialist Judi Wakhungu of the African Centre for Technology Studies in Nairobi, Kenya. The pair convened meetings at which the advisory bureau picked the 400-odd authors and assigned them to groups to tackle the many topics, which included bioenergy and the role of women in agriculture, as well as five geographically focused subassessments.

    A question of balance

    It's perhaps not surprising that this massive effort encountered some snags. Some authors of the eight main chapters say that from the start, the process was disorganized, lacked clear direction, and suffered from turnover of participants and continual rehashing of drafts. It didn't help that the makeup of the teams was fairly rigid. Each chapter had to have the same number of men and women as authors. One of the two lead authors on each chapter had to be a woman, and one had to be from a developing country. We wanted to make sure that everyone was represented equally, says Herren. Pray has a different take: It was excruciatingly politically correct in some ways.

    Some teams bogged down in conflicts about hot-button issues such as GM crops or trade liberalization, with various members charging each other with bias. One chapter, on how to help developing countries generate and adopt agricultural research, was canned entirely. It was clear that the chapter was not going to fly, says Beverly Mcintyre of the World Bank, who was a senior administrator on the project. She says the team did not have the right expertise for the task. And midway through, just before initial results were to be presented, the bureau decided to eliminate a major modeling exercise. The International Food Policy Research Institute had raised about 460,000 for the modeling, which would have provided insights to help policymakers compare the outcomes of four broad policy scenarios, such as futures with more free trade or green technologies. But Greenpeace's Haerlin and others objected that the models were not transparent.

    Conflict erupted in the review process as well, with some scientists and GM advocates complaining that their comments were not incorporated. To a certain degree, they may have been outmaneuvered; environmental groups set up a well-organized Web site to funnel comments to chapter lead authors. They may have been outnumbered as well. Bureau member Emile Frison, director of Biodiversity International, a research organization working to conserve agricultural biodiversity, says it was difficult from the outset to engage the best scientists There are probably multiple reasons, including the fact that they didn't see it as important, he says. One participant who asked not to be named puts some of the blame on Watson for not spending enough effort personally recruiting top scientists, as Reid did with the Millennium Ecosystem Assessment.

    Scrutinized.

    Perhaps the hottest issue was the role of genetically modified crops in helping poor farmers and making agriculture more sustainable.

    CREDIT: ZOMI/GETTY IMAGES

    The text of the ag assessment concedes the difficulty of resolving the differences to everyone's satisfaction: One of the key findings of the IAASTD is that there are diverse and conflicting interpretations of past and current events, which need to be acknowledged and respectednot exactly a helpful insight for policymakers trying to decide whether to approve the planting of GM crops, for example. It devolved into I'm okay; you're okay,' says Andrew McDonald, a crop and soil scientist at Cornell University.

    Critics such as Adrian Dubock, who participated while serving as Sygenta's head of biotech ventures, also complain that the summary and synthesis documentswhich are all most people will read of the 2500-page draft assessmentare biased against GM crops and don't incorporate positive appraisals from some of the underlying chapters. Chapter 5, for example, concludes that both transgenic and conventional breeding will be needed to boost crop productivity during the next 50 years. Eliminate transgenic crops, the chapter notes, and humanity would likely be more vulnerable to climatic and other shocks and to increased natural resource scarcity.

    Backbreaking.

    The assessment concludes that agricultural research needs to do more for poor farmers such as these indigenous wheat growers in Bolivia, by better managing pests and soils, for example.

    CREDIT: GILLES MINGASSON/GETTY IMAGES

    But the Global Summary for Decision Makers puts less emphasis on the potential benefits of GM crops, says Dubock, who resigned in protest, and others. In the synthesis report as well, the section on biotechnology tends to highlight the controversies about GMOs, such as lingering doubts about the adequacy of efficacy and safety testing. The majority of the four authors of this synthesis chapter have experience in risk assessment and sociology but not in the agricultural industry or plant modification. Like all the other authors, they were picked by the bureau, which had relatively few representatives from industry. The whole thing was incredibly stacked against GM crops, claims Gressel. An IAASTD official disputes that charge and notes that Deborah Keith of Sygenta was slated to write the first draft but resigned. I felt it was a hopeless cause, Keith says.

    Pullout

    Last October, the biotech companies voted with their feet and pulled out of the process. Their representatives won't attend the final meeting. We can't endorse something that is fundamentally giving the wrong message, explains Keith Jones, manager of stewardship and sustainable agriculture at CropLife International, an industry trade group. He says that the report tends to overstate the potential of organic and ecological agriculture, which he doesn't think is a viable solution for boosting global agricultural productivity.

    Watson, who says he was extremely disappointed in the companies' decision to withdraw, argues that instead of giving up, industry scientists ought to have played a bigger role. They should have screamed and pushed, he says. But he also accepts some responsibility for not keeping close enough tabs on their concerns. It means I didn't succeed as director at keeping all the players at the table. Herren decries the 11th-hour move as well, pointing out that industry reps sat on the bureau, which vetted all of the authors. You cannot come at the end, after all the meetings setting up the rules of the game, and say, I don't like it. By walking out, industry ended the dialogue, Herren says: You can agree to disagree, but that can't happen when you slam the door.

    Not all who were displeased left. In December, for instance, the Alliance Executive of the Consultative Group on International Agricultural Research (CGIAR)the governing body of 15 publicly funded scientific centers around the worldwrote a private letter to the bureau about its concerns. The reader would get a rather negative view about agricultural research in general, says Frison, the chair of the alliance. In the letter, which Science has obtained, CGIAR notes that the assessment chapters might undermine support for research. But CGIAR has remained in the assessment. It is more constructive to make our points as a participant, says Frison, who also appreciates the assessment's emphasis on the importance of involving farmers in research.

    At a final meeting in April, representatives from about 90 governments will gather in Johannesburg, South Africa, to decide whether to endorse the report. (They can accept, approve, or just note it.) Watson doesn't think that industry's pullout will lessen the impact of the report, which he hopes governments and international donors, for instance, will use to guide their investments in agricultural research.

    Robert Paarlberg of Wellesley College in Massachusetts, author of Starved for Science: How Biotechnology Is Being Kept Out of Africa, is skeptical. It's a document that has much less scientific credibility than does IPCC, he says. By being so inclusive, it ended up more a collection of opinions than an incisive summary of the scientific literature. And because its scope is so broad, the assessment doesn't offer targeted analyses for particular problems. You end up with [platitudes] such as Small farmers need to be supported, says Emmy Simmons, an agricultural development consultant who retired from the U.S. Agency for International Development in 2005.

    Watson remains sanguine. He and others think the assessment will bring more attention to the plight of the rural poor and the chronic underinvestment in agricultural research. If we can stimulate a debate, he saysfor instance, about the degree to which agricultural science is meeting the needs of the poor and whether everyone gains from free tradethen it's a success. Nor does he have any regrets about throwing the doors wide open. I always knew it was a social experiment, he says.

    As for Pray, he has mixed feelings. Halfway through this painful exercise, I thought, If [Watson] can pull this off, it will be great,' he says, but we couldn't come to consensus. Now Greenpeace and Monsanto continue to beat each other up. Meanwhile, he says, neither the environment nor the poor are getting the agricultural research they deserve.

  10. GRADUATE TRAINING

    NSF Fellowships Called Powerful Tool for Building the Pipeline

    1. Jeffrey Mervis

    A prestigious program is slated for a big increase next year thanks in part to recent data showing its ability to draw talented students into science.

    A prestigious program is slated for a big increase next year thanks in part to recent data showing its ability to draw talented students into science

    A fellowship program that has nurtured the early careers of Nobel prizewinners and a co-founder of Google has quietly been gaining political favor in Washington. Last month, the Bush Administration proposed a sharp increase in the number of Graduate Research Fellowships (GRFs) awarded by the U.S. National Science Foundation (NSF). And Democratic presidential hopeful Senator Hillary Clinton (D-NY) has called for its expansion as part of her innovation agenda.

    The GRF's rise to prominence has been propelled in part by the work of Harvard University labor economist Richard Freeman, who calls the fellowship the U.S.'s premier award for science and engineering graduate students. In a 2005 study, Freeman found that the GRFwhich provides a 3-year stipend to U.S. citizens or permanent residents for graduate study at the university of their choiceis a powerful mechanism for luring talented U.S. students into science (http://www.nber.org/; working paper 11623). He argues that NSF should triple the number of GRF awards (from roughly 1000 to 3000 a year) and increase the amount of the scholarship (now 30,000) by 10,000. Although NSF has responded with a more modest proposala 32 budget increase that could mean as many as 700 new awards in 2009agency officials are happy to disseminate Freeman's message to make their case.

    Created in 1952, the merit-based program funds all science and engineering disciplines proportionatelythat is, it selects the same percentage of applicants in each field that NSF supports. In the early years, the physical sciences and engineering accounted for the bulk of the awards. Those fields now make up about half the recipients, with the life sciences comprising another quarter and the social and behavioral scientists about one-sixth.

    The program helped nurture a post-Sputnik generation of researchers. Its 43,000 alumni include more than 20 Nobelists; a more recent recipient is Sergey Brin, a co-founder of Google. But by the 1990s, it had fallen on hard times. Stipend levels had failed to keep up with those of other fellowships, and the number of awards had remained constant for decades despite a steady rise in the number of undergraduates majoring in science and engineering. The shrinking ratio, from 5.4 awards per 1000 science and engineering majors in its first few years to 2.2 earlier this decade (see graph), sent a very bad signal to students that science wasn't important, says Freeman.

    Negative numbers.

    A declining ratio of awards to degrees sends students a bad signal, says Harvard's Richard Freeman.

    SOURCE: R. FREEMAN ET AL., NBER WORKING PAPER NO. 11623, FROM NSF AND DEPARTMENT OF EDUCATION DATA

    Students responded by avoiding the program. Hoping to turn things around, NSF began raising the annual stipend, which stood at 15,000 in 1999, until it reached 30,000 in 2004. (Universities also receive 10,500 as an institutional allowance.) The number of applicants nearly doubled, Freeman found, to almost 9000 in 2004, and the overall quality of the applicant pool also rose. In other words, he says, the fellowship's prestige caused more of the best and brightest seniors to consider graduate degrees in science and engineering.

    It certainly opens doors at Harvard, Freeman explains. My department has a policy that if you get a GRF, you're admitted, he says. Absolutely. Because you're not costing us anything. And we know NSF runs a pretty tight ship.

    Analyzing 50 years of data, Freeman calculated that increasing the number of awards substantially would have only a slight impact on quality while resulting in an influx of students into science and engineering. A survey of 1800 Harvard undergraduates similarly suggested that talented students would be lured into science if NSF gave out more fellowships to support their graduate studies. In particular, some 40 of students said that they would opt for graduate school in science if given a national fellowship; only 18 already had such plans.

    Freeman's analysis soon gained adherents. The Brookings Institution's Hamilton Project to foster economic growth has promoted it (http://www.hamiltonproject.org/; policy brief 200609), and Clinton has embraced the tripling of awards and a 33 boost in the stipend, asserting that the fellowships are the key financial resource for [U.S.] science and engineering graduate students.

    It also struck a chord at NSF. He put the pieces together, says Carol Stoel, acting head of graduate education at NSF. The agency expects to make about 825 awards this year, says program director William Hahn, down from 925 in 2007. (For the past 2 decades, the annual number has fluctuated between 800 and 1000.) Its 2009 budget request of 117 million for the education directorate, up from the current 88 million, would raise the current 10 success rate for applicants. Because the fellowships run for 3 years, however, Congress would need to sustain the increase for several years to avoid sending the program on a roller-coaster ride.

    As the biggest single increase in NSF's education budget, the request for the GRF program will attract close scrutiny from Congress. It must compete against programs serving different populations that enjoy strong legislative support, in particular those for minorities, undergraduates, and precollege science education.

    It deserves serious consideration because NSF feels so strongly about it, Representative Alan Mollohan (D-WV), chair of the House panel that controls NSF's budget, explained after a 27 February hearing in which NSF made its case. Is it the fastest way to fill the pipeline? I don't know. And I don't want to prejudge [the request]. But there are a lot of things we need to do to improve science and math education.

  11. MEDICINE

    Blood-Matching Goes Genetic

    1. Elizabeth Quill

    Hoping to prevent adverse transfusion reactions and save lives, European researchers are lobbying to replace serology-based blood typing with matching based on DNA tests.

    Hoping to prevent adverse transfusion reactions and save lives, European researchers are lobbying to replace serology-based blood typing with matching based on DNA tests

    CREDIT: LESTER LEFKOWITZ/CORBIS

    Two decades ago, a 20-year-old man entered Duke University hospital for a hip replacement. He had sickle cell disease and because he was anemic, he needed a blood transfusion before the operation. As with most sickle cell patients, he had received transfusions before. But on this occasion, his body rejected the blood.

    The doctors tried again and again with different blood, but the man's immune system rebelled against every new transfusion, generating antibodies that killed the new blood cells and some of his own in the process. He reacted to everything, says Wendell Rosse, a hematologist at Duke at the time. The man's anemia continued to worsen, and 2 weeks later he died. There wasn't anything we could do, Rosse says.

    Following previous transfusions, the man had become alloimmunized, meaning that his body made antibodies to donated blood. He had so many transfused cells mingling with his own and had made so many antibodies that physicians could no longer identify his original blood type nor find suitable blood. Although this rare case of fatal alloimmunization happened more than 20 years ago, Rosse says he's not sure whether the man would have survived today, as there have been few advances in blood-matching tests in hospitals.

    Some hematologists believe genetic testing offers a solution. For more than 100 years, blood matching, also known as typing, has relied on serology, the identification of surface proteins and carbohydrates, called antigens, on red blood cells. Genotyping looks at the genes that determine these antigens, and some scientists say genetic techniques can more closely match blood between donors and recipients, preventing alloimmunization and other immune-related blood reactions.

    Now, these claims are being put to the test. France, for one, will begin genotyping a portion of blood donors by the end of April to determine if a switch from serology is scientifically justified and practical. In addition, Canada has begun using genotyping as a screening tool to identify donors with rare blood types that are hard to find in emergency situations.

    Old-fashioned.

    Serology tests like this one have been used to match blood samples for more than a century.

    CREDIT: WIKIPEDIA

    The argument that we will have 100 perfect blood for every patient will never be the case, says Neil Avent of the University of the West of England (UWE) in Bristol, who has led a European research consortium exploring blood genotyping. But when you have all the information available, you can find the best blood.

    Matchmaking

    Finding the best blood seems simple. Two antigens on red blood cells determine the major blood groupA, B, AB, or O. A person with type A naturally harbors antibodies to B antigens and vice versa. Give type-B blood to a patient with type A, and antibody reactions will cause blood cells to clump together, sometimes with fatal results. AB people don't have antibodies to either antigen, making it easier to find blood for them. But O people have antibodies to both A and B, as their blood cells have neither antigen, so they can only receive O blood.

    But there's more to blood than A and B antigens. Physicians also routinely test for D, an antigen in the Rhesus (Rh) blood group that can evoke a strong immune response. They try never to give RhD blood to an RhD- person.

    The possibilities get even more complicated. Avent, who also directs UWE's Centre for Research in Biomedicine, says there are 29 known blood groups, which are determined by about 200 antigens. A person's full blood type might read: AB, D, M, N, K-, Lea, and so on.

    A simple antibody test can identify a donor's or patient's ABO blood type, and in theory, similar tests could detect the other so-called minor blood groups. But the reagents to identify some of these antigens are costly, not reliable, or simply not available. For patients who receive only one or two transfusions during their lifetimes, mismatches in the minor blood groups pose no obvious problems. Yet people who receive multiple transfusionsincluding those with sickle cell disease, hemophilia, or leukemiacan develop antibodies to the minor blood group antigens, which is what happened in the Duke University patient. In some cases, the transfused blood can cause acute or delayed hemolytic reactions. The Public Health Agency of Canada, which keeps statistics on such reactions, estimates that as many as 1 in 12,000 transfusions ends in an acute reaction, with as many as 1 in 600,000 ending in death. Delayed reactions occur in as many as 1 in 5000 transfusions but are less often fatal.

    Traditional blood typing has other limitations. Some people have a weak or partial version of the D antigen that is difficult to detect. Misdiagnosing D donor blood as D- could cause serious problems. A D- person given such mislabeled blood will make antibodies that would react to future transfusions of D blood. Furthermore, it's important for women to accurately know their RhD status: If a D- woman had a D baby, any subsequent D fetus is at risk because the mother will have made antibodies to the D antigen during the first pregnancy. Because serology has trouble deciphering RhD status, says Avent, as many as 40 of pregnant women may receive unnecessary drug treatment, which can have side effects, to limit their antibody production.

    Genotyping offers an alternative. By sequencing the 31 genes that determine the surface antigens, hematologists can classify the blood into the 29 groups. For example, a single gene on chromosome 9 controls the ABO antigens, and the versions inherited from each parent determine a person's type. Other blood groups are determined by a single nucleotide polymorphism (SNP), which changes just one base in an antigen-determining gene. Insertions or deletions of DNA within other blood-group genes lead to different antigens. By identifying these different versions of a gene, or alleles, genotyping can predict a person's blood types in fine detail.

    Advocates of genotyping predict that with better matched blood, they can prevent between 80 and 90 of alloimmunization and also eliminate partial and weak versions of the D antigen from the blood supply. Rosse says such tests might have helped his patient. If we had his genotype, we could have matched it with a donor's genotype, Rosse says. We might have found a match.

    Europe takes the lead

    Researchers have been using polymerase chain reaction (PCR)-based techniques to genotype blood samples in the lab for a decade. But if blood genotyping is extended into widespread clinical use, cheaper and faster methods will be needed.

    In 2002, the European Union gave 2.35 million to BloodGen, a consortium of universities and blood centers across Europe that planned to standardize blood genotyping techniques and prove that they beat serology. The consortium, led by Avent, has since developed the BLOODchip, a gene chip that tests a person's DNA using blood samples. PCR alone would require 60 or more tests to determine the blood type as comprehensively as the chip can with just one test. The current chip, produced by the company Progenika, looks at nine blood groups, including the genes that code for the A, B, and D antigens.

    In initial tests, the BloodGen team genotyped 1000 blood samples and found 42 cases that conflicted with serology, some of which were in the Rhesus blood group. Further analysis revealed that two of these errors were the fault of genotyping and 40 were the fault of serology. Progenika has full clinical approval for seven of the blood groups on its chip and is currently seeking approval for RhD. The next round of tests will look at 3000 samples.

    BioArray Solutions in Warren, New Jersey, has developed another genotyping product called BeadChip that tests for 11 blood groups but not A, B, and D. Although the omission is in part practical, some researchers have said it reflects a larger debate in the scientific community about the potential of genotyping to replace, as opposed to supplement, serology.

    A bloody debate

    Avent is adamant that genotyping will replace serology for most blood groups within the decade and in some cases sooner. He predicts European hospitals will demand blood genotyping of patients expecting to receive a transfusion. For multitransfused patients, I expect a change in policy this year, Avent says. Then I would expect other vulnerable groups [such as pregnant women to be] tested. Then I would like to see blood centers genotyping cohorts of donors.

    Chipping away.

    Two new gene chips (BLOODchip above) can test for many blood groups beyond ABO.

    CREDIT: PROGENIKA

    Researchers in the United States are taking a more cautious approach. They believe genotyping has a way to go for the A, B, and D antigens. Researchers have identified more than 100 alleles for the ABO blood type and more than 200 for the Rhesus system, and new mutations are discovered frequently, which makes some people nervous about relying on current gene chips. I don't think we have found all the alleles, says Marion Reid, an immunohematologist at the New York Blood Center.

    Avent predicts that within the next few years, researchers will have compiled the majority of those alleles, and he adds that genotyping is already superior for identifying the D antigen. Willy Flegel, a transfusion medicine specialist at University Hospital Ulm in Germany, agrees. He has genotyped more than 46,000 blood donations identified as D- based on serology and found that 47 are actually D. The smart serologist will apply molecular techniques now for the benefit of the patient, Flegel says. The scientific arguments are clearly in favor of genotyping.

    Connie Westhoff, scientific director at the American Red Cross, concurs that genotyping is the future, but she doesn't expect that the United States will fully adopt it for another 15 years at least, and even then, she does not expect the country to completely abandon serology. We would never throw out our old toolbox, she says.

    Moving forward

    A few countries are already forging ahead with blood genotyping on a large scale. Canada is among the leaders. In December, for example, Quebec announced plans to genotype 22,000 blood donors. Currently, when a patient with a rare blood group needs a transfusion, practitioners have to blindly order blood from banks based on ABO and D grouping alone and then test it with more detailed serology on site. This trial-and-error approach wastes time and money. The screening should make the process faster by narrowing initial blood selection, but serological testing will still serve as a follow-up.

    Jean-Pierre Cartron, scientific director at France's national institute of blood transfusion, says his blood center will be genotyping using both the BLOODchip and the Bead-Chip by the beginning of April. We want to see them together on the same population of donors and patients, Cartron says.

    Flegel says the ABO group will take time to work out, but for all other groups, genotyping should begin now. Only by using the available genotyping tools can hematologists locate unknown alleles and make future gene chips more accurate. We need to learn what we are missing, he says. He agrees that hematologists need to proceed with caution. But, he says, we don't need to wait.

  12. COMPUTER SCIENCE

    Cryptologists Cook Up Some Hash for New 'Bake-Off'

    1. Dana Mackenzie
    1. Dana Mackenzie is a freelance writer in Santa Cruz, California.

    A worldwide competition aims to keep the algorithms for authenticating electronic documents a jump ahead of forgers' ability to defeat them.

    A worldwide competition aims to keep the algorithms for authenticating electronic documents a jump ahead of forgers' ability to defeat them

    In November, three Dutch cryptologists published on their Web site a digital fingerprint of their prediction of the winner of the United States's 2008 presidential election. According to them, the next commander in chief will be 3D515DEAD7AA16560ABA3E9DF05 CBC80.

    After the election, these modern-day Nostradamuses will use a simple mathematical procedure called a hash function, which is available on nearly all computers, to show that a PDF document created before the election has that hexadecimal number as its digital fingerprint. This will prove that they knew the winner all along, because the PDF document could not have been altered after the election. Any such change would make its fingerprint, known as a hash value, no longer match the one that has been published.

    But it's all a trick. The Nostradamus attack by Marc Stevens, Arjen Lenstra, and Benne de Weger is designed to highlight a serious problem in cryptology: The so-called hash functions that many of the world's computers use for authenticating documents are dangerously out of date. The cryptologists prepared 12 separate documents, one saying that John McCain will win, one naming Hillary Clinton, and one even predicting Paris Hilton. By carefully tweaking the contents of each PDF document, in a way not obviously noticeable, they made it so each one generates the same digital fingerprint, computed by a widely used hash function called MD5. As the Dutch effort shows, the ability to produce multiple documents with the same fingerprint renders MD5 useless for authentication.

    Without the ability to authenticate files, such as passwords and online transactions, Internet commerce would be seriously threatened. Therefore, the U.S. National Institute of Standards and Technology (NIST) in November announced a worldwide competition to select a new standard for hash functions, which is expected to conclude by 2012. The winner will be certified for U.S. government use, and if past history is any guide, that will make it a de facto standard for the rest of the world.

    NIST held a similar bake-off (as some cryptologists called it) from 1997 to 2000 to select a new standard cipher for government use, called the Advanced Encryption Standard (AES). The AES competition was the most fun I've ever had in cryptography, says Bruce Schneier of BT Counterpane in Santa Clara, California, who designed one of the five AES finalists and who plans to enter the hash-function competition as well. Think of it as a giant cryptographic demolition derby: A bunch of us put our best work into the ring, and then we beat on each other until there was only one standing. I personally learned an enormous amount about [cipher design] from the AES competition, and we as a community benefited immeasurably.

    Like the previous competition, the new bake-off offers no financial reward, and the submissions must be unpatented so that they can be incorporated into any software. The real payoff to the winner will be prestige. The AES competition drew 15 entries, and the hash-function competition is expected to attract as many as 50.

    Although the contests will be similar, the products could hardly be more different. A cipher, like AES, encrypts data in such a way that it can be recovered but only by someone with a key. Hash functions, on the other hand, are not meant to be reversible, and they have no secret key. They merely show that a document is what it claims to be. They tend to be much simpler than ciphers and have a much broader range of applicationsso many that they are often called the duct tape or Swiss army knife of cryptology.

    Hash functions work by converting any string or message of 1s and 0s to a new string, usually much shorter. For example, the function might take a gigabyte MPEG movie file and boil it down to anywhere from 128 to 512 bits. In the current government standard, called SHA-1, the output, known as the hash, hash value, or hash sum, is 160 bits, whereas for MD5 it is 128 bits. The hash should look more or less random so that no one can guess what the original message said. On the other hand, it should be generated in a completely deterministic manner so that anybody who knows the hash function used can have a computer verify that the hash value matches the hashed file's contents. In addition, it should be staggeringly unlikely that any other document hashes to the same value. When that happens, cryptographers call it a collision.

    Compressing gigabyte-sized files to 160 bits inevitably results in many collisions. But the key point is that it is virtually impossible to find one by random search. That is because there are so many possible hash values2160 of them for a 160-bit hash sum. For such a hash value, the number of movies you would have to hash before generating the same hash twice would be roughly 280, or a trillion a year for a billion years. Not even Bollywood is that prolific.

    However, a hash function can be defeated if it is possible to deliberately create two colliding documents. If this takes more than 280 attempts, then the hash function is considered secure, because such an attack is no better than random guessing. However, if a collision can be found in less than 264 tries, then a supercomputer, or a very large network of personal computers, might be able to do it in a year. If it takes less than 232 tries, one can do it on a PlayStation in a few minutesas the Dutch Nostradamuses did.

    The current standard, SHA-1, borrows its basic architecture from MD5, which was invented in 1992. You feed your message into a device that compresses and randomizes 512 bits at a time. You add another piece of your file to the first piece and feed it through again, and you repeat this procedure until you run out of message.

    Iterative algorithms, like MD5 and SHA-1, are very easy to program and quick to run. But recently, they have come under heavy attack from cryptologists. In 2004 and 2005, cryptologist Xiaoyun Wang of Shandong University in China showed that MD5 could be cracked in fewer than 240 steps, and SHA-1 in fewer than 264. No one has produced an actual collision in SHA-1, but a search, using the spare time of many personal computers, is under way at Graz University of Technology in Austria.

    If you find a [SHA-1] collision, people in industry will be forced to upgrade their products, says Bart Preneel, a cryptologist at Katholieke Universiteit Leuven in Belgium. Anticipating such a breakdown, Microsoft in 2005 banned both SHA-1 and MD5 from new products and has removed MD5 from all its current products, says Kristin Lauter, head of the Cryptography Group at Microsoft Research in Redmond, Washington. Fortunately, a good backup is already available. In 2004, NIST issued several new standards, collectively called SHA-2, which are more secure than SHA-1 because they produce longer hashes (up to 512 bits instead of 160).

    But NIST worries that SHA-2 could eventually fall, too. Everything that has been attacked is in the same family, says William Burr of NIST's Security Technology Group. It may turn out that they aren't broken or can't be broken, but we didn't want to get caught out on the wrong side.

    After extensive debate, including two international workshops in 2005 and 2006, NIST decided that a new competition could turn up completely new approaches to hash functions. We'll be reluctant to pick something that looks just like SHA-2, says Burr. We want some biodiversity.

    Although no designs have been formally submitted yetthe deadline is in Octoberexperts predict that most entrants will continue to be iterative algorithms subtly retooled to defeat the new kinds of attacks. For instance, Preneel's RIPEMDone of the few first-generation hash functions still standingperforms two parallel iterations, making it difficult for an attacker to figure out which one to attack.

    A second approach, called provably secure hash functions, derives its presumptive security from math problems that are considered to be hard to crack (see sidebar, above). This type of algorithm typically does not require multiple iterations, but it does require cryptologists to put their faith in a mathematical black box. Also, such algorithms tend to be slower than iterative algorithms because they require a more elaborate calculationeven though it is performed only once. Speed is at a premium for hash functions, as they are typically used to tag a document in the split-second it's electronically transmitted.

    Not surprisingly, mathematicians love provably secure systems, whereas cryptologists have little use for them. They are typically only provable with respect to one property but are weak with respect to other properties, says Joan Daemen of STMicroelectronics, co-winner of the AES competition. For instance, a provably secure hash developed by Lenstra and his colleagues, called Very Smooth Hash (VSH), was compromised last year when Markku-Juhani Saarinen at a Spanish company called Kinamik showed that it was easy to find near-collisions in VSH. In practice, engineers often truncate a long hash value to a shorter one, assuming that the truncated hash will inherit the long one's security. Saarinen's result means that they can't count on that with VSH.

    In the final analysis, what makes it so hard to come up with good hash functions and prove they workis that they are expected to do so many things. You expect them to do everything and blame them when they don't work, says Preneel. Perhaps a 4-year bake-off will be just what the chef ordered to make some new hash that will satisfy everybody's tastes.

  13. COMPUTER SCIENCE

    Hash of the Future?

    1. Dana Mackenzie

    By incorporating a tangled, three-dimensional maze the size of the Milky Way into a hash function, a cryptographer is betting that neither you nor anyone else will solve it.

    Have you ever struggled to solve a maze? Then imagine trying to find a path through a tangled, three-dimensional maze as large as the Milky Way. By incorporating such a maze into a hash function, Kristin Lauter of Microsoft Research in Redmond, Washington, is betting that neither you nor anyone else will solve that problem.

    Technically, Lauter's maze is called an expander graph (see figure, right). Nodes in the graph correspond to elliptic curves, or equations of the form y2 = x3 ax b. Each curve leads to three other curves by a mathematical relation, now called isogeny, that Pierre de Fermat discovered while trying to prove his famous Last Theorem.

    CREDIT: MICROSOFT RESEARCH

    To hash a digital file using an expander graph, you would convert the bits of data into directions: 0 would mean turn right, 1 would mean turn left. In the maze illustrated here, after the initial step 12, the blue path encodes the directions 1, 0, 1, 1, 0, 0, 0, 0, 1, ending at point 24, which would be the digital signature of the string 101100001. The red loop shows a collision of two paths, which would be practically impossible to find in the immense maze envisioned by Lauter.

    Although her hash function (developed with colleagues Denis Charles and Eyal Goren) is provably secure, Lauter admits that it is not yet fast enough to compete with iterative hash functions. However, for applications in which speed is less of an issuefor example, where the files to be hashed are relatively smallLauter believes it might be a winner.

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