News this Week

Science  02 Apr 2004:
Vol. 304, Issue 5667, pp. 26
  1. ITER

    Stalemate Casts Pall Over Beleaguered Fusion Project

    1. Daniel Clery*
    1. With reporting by Dennis Normile in Tokyo and Charles Seife in Washington, D.C.

    CAMBRIDGE, U.K.—For building research facilities, just as for buying property, the three most important things are location, location, and location. This issue is proving so thorny for the International Thermonuclear Experimental Reactor (ITER)—an effort to prove that nuclear fusion can generate plentiful and cheap power—that the whole $5 billion enterprise is deadlocked. Since December the six international partners have been split over whether to build ITER at Cadarache in France or Rokkasho in Japan. In a last-ditch attempt to break the impasse, E.U. officials traveled to Japan last week for face-to-face talks. Fusion researchers across the globe are now waiting to see if this dialogue has sown the seeds of compromise. “I don't know what can untie this Gordian knot,” says Alex Bradshaw, director of the Max Planck Institute for Plasma Physics in Garching, Germany.

    After more than 15 years of design work and pilot experiments, the ITER partners—China, the European Union (E.U.), Japan, Russia, South Korea, and the United States—were set to make the crucial site decision at a high-level meeting of ministers on 20 December. But Japanese and E.U. officials dug in their heels over which would be the better site for the tokamak (Science, 2 January, p. 22). European researchers claim that Rokkasho is at a greater risk of earthquake damage than Cadarache and that it is so inhospitable that staff members will balk at moving there. Japanese scientists, meanwhile, argue that Cadarache is too far from the coast for large components to be transported there safely.

    Bargaining chip.

    A compromise deal could bring Japan's JT-60 tokamak into the ITER program.

    CREDIT: JAERI

    ITER delegations again met in Vienna, Austria, on 12 and 13 March to study further technical reports on the two sites but failed to find common ground. In the meantime, ITER researchers have been exploring the idea of broadening the project, adding extra facilities so that both sites get a piece of the pie (Science, 13 February, p. 940). The E.U. and Japan “have come to the negotiating table, and one can't walk away with all the marbles,” says former ITER deputy director Ron Parker of the Massachusetts Institute of Technology in Cambridge. With both sides unwilling to renounce their claim to the tokamak itself, the E.U. delegation in Tokyo last week suggested that the two protagonists put the siting decision to one side for the time being and focus on defining a broad fusion research program “without prerequisites,” says Achilleas Mitsos, E.U. director general of research and chief negotiator. “This is not about winners or losers,” he says, “but it must take place very rapidly. We cannot postpone much longer.” The E.U. is now waiting to hear whether Japan will accept its invitation to continue the dialogue in Brussels in the next few weeks. Says Paul Vandenplas of Belgium's Royal Military Academy, “Everything is hanging in the air now.”

    The continuing uncertainty has left researchers wondering what to do next. Because much of the technical planning for ITER depends on the site—what sort of seismic isolation will be needed, for instance, and where the cooling water will come from—progress is slow, says Yasuo Shimomura, ITER's international director in Garching, Germany. Teams of engineers who worked on the ITER design between 1992 and 2001 have been “idling” for the past 3 years, says Satoru Ohtake, director of Japan's Office of Fusion Energy. The longer the delay, the harder it will be to reassemble the teams, he says. “Without a site, you can't do a cost distribution; without a distribution, you can't make an ITER legal body. Everything hinges on picking a site, and we don't have a site,” says Gerry Navratil of Columbia University in New York City.

    If the latest attempt at dialogue fails, Mitsos says he will go to the E.U. Council of Ministers and put the remaining options, none of which would be pretty, on the table. “One or both parties will have to act unilaterally,” he says. “What other possibilities exist?”

  2. RESEARCH GRANTS

    NSF Gives Smithsonian Researchers a Green Light

    1. Jeffrey Mervis

    The National Science Foundation (NSF) has agreed to level the playing field for scientists at the Smithsonian Institution. Last week the National Science Board, NSF's governing body, decided that all 500 Smithsonian researchers should be able to compete equally with academic scientists for NSF grants.

    A mainstay of support for nonmedical academic scientists, NSF is loath to fund researchers whose paycheck comes from the U.S. government. But the Smithsonian, founded by a 1836 gift from James Smithson, holds an unusual status in the federal bureaucracy. Its governing board is composed of legislators, prominent citizens, the chief justice of the Supreme Court, and the vice president; about one-third of its $840 million budget comes from outside the annual appropriations process. “We're this strange trust instrumentality,” says David Evans, undersecretary for science.

    Some Smithsonian scientists now receive NSF funding through an academic affiliation, and others have been eligible because they are paid through trust funds. But the rest have largely been shut out. “We could apply, but the chances were zero if you were at the Smithsonian,” says James Mead, curator of marine mammals at the National Museum of Natural History, who calls the new policy “great news.”

    Castle rules.

    Smithsonian's unique status earns it a shot at NSF funding.

    CREDIT: HISHAM IBRAHIM/PHOTODISC

    There is some uncertainty about the impact of the policy, which would standardize practices across the entire foundation. NSF officials estimate that out of 300 newly eligible Smithsonian scientists, only “eight to 10” would win NSF grants each year. But Evans says, “I'd be surprised” if the number were that low, and Mead predicts that his colleagues will flock to NSF, especially given a shrinking pot of institutional research funds.

    Before agreeing to the change, science board members warned acting NSF Director Arden Bement not to raise the hopes of other federally funded organizations that might feel entitled to a similar exception. “I think that the slippery slope is the key issue,” said Ray Bowen, president emeritus of Texas A&M University in College Station. “We need to define the Smithsonian as a unique entity.”

  3. INVERTEBRATE CONSERVATION

    Respect for Things That Flutter, Creep, and Crawl

    1. Elizabeth Pennisi

    Bugs get little respect, but a group of biologists and conservationists wants to upgrade their status before it's too late. The public should know that more than just a few butterflies are at risk of extinction, says Sacha Spector, an entomologist at the American Museum of Natural History in New York City. Last week, he and about 25 colleagues formed a working group to begin building a constituency for endangered insects, mollusks, and other invertebrates. In addition to planning a Web site to link pertinent databases and resources, the new group, called the Expanding the Ark Coalition, is preparing a white paper arguing the case for more attention to what Harvard sociobiologist E. O. Wilson calls life's “little things.”

    Although invertebrates make up about 80% of known species, they account for a mere 38% of about 500 species now under the protection of the Endangered Species Act, Gary Frazer of the U.S. Fish and Wildlife Service reported at a meeting of several hundred invertebrate experts held in New York City last week. A conservation group called NatureServe has argued that more than 1800 invertebrate species need protection. Until now, says Spector, “we haven't asked [conservationists] to take care of invertebrates like [they do] vertebrates and plants.”

    Endangered.

    The Delhi Sands flower-loving fly has been protected, despite a lack of popular appeal.

    CREDIT: B. MOOSE PETERSON/U.S. FWS

    Frazer, Spector, and others stressed that invertebrates are vital links in the food chain. They are particularly important for pollination, water quality, and nutrient turnover, but their contributions to the environment are often overlooked. To remedy this neglect, Spector says, researchers need much more knowledge about what species are out there—millions may still be undescribed—and how they interact with local ecosystems. Even more important, says Tim New, an entomologist at La Trobe University in Australia, advocates of particular groups such as butterflies need to work together to save all invertebrates at risk: “We need to start acting with a [cohesive] voice,” he notes.

    The road ahead looks rough. “Many of the people we want to convert know very little about invertebrates and have very little sympathy for them,” says New. For example, Jim Bartel of the U.S. Fish and Wildlife Service in Carlsbad, California, has had a terrible time getting community support to protect the Delhi Sands flower-loving fly, an insect that lives in Southern California. Public officials, community members, and the media belittled the effort; some even brought fly swatters to public meetings.

    But the response isn't always negative, says Bartel. The Riverside County, California, community has adopted the Quino checkerspot butterfly and is working to pull it back from the brink. And Gary Davis, visiting chief scientist at the U.S. National Park Service, and his colleagues have been quite successful setting up marine reserves to protect Florida's spiny lobster. Spector is hopeful that this new coalition will lead to more success stories. Davis agrees: “We're moving the ship in the right direction,” he says. “We may not be moving fast enough, but I am optimistic that we can make a difference.”

  4. BIOMEDICAL RESEARCH

    IG Report Faults Handling of Veterans Affairs Funds

    1. Jennifer Couzin

    A report issued last week by the inspector general's (IG's) office in the Department of Veterans Affairs (VA) charges that the department's former research chief, Nelda Wray, mishandled nearly $1.7 million in funds supplied mainly by pharmaceutical companies for VA research. Wray, who left VA Headquarters in December after 11 tumultuous months, is now back at the Houston, Texas, VA Medical Center, where she spent much of her career. Wray and her attorneys have rejected the allegations, and the report says that the Justice Department reviewed the findings and chose not to file criminal charges.

    The fund that drew the IG's attention contains company donations for research projects and is administered for the VA by the Friends Research Institute, a Baltimore, Maryland-based nonprofit. Like other federal agencies, the VA cannot accept private money; it has relied on the institute for almost 30 years to manage such financial arrangements, although it retains authority over the funds. Critics have long warned that oversight was lax. Indeed, the IG report alleges that in 2002, before Wray arrived, her predecessors misspent $537,000 from the fund.

    The IG notes that neither the Friends Research Institute nor the VA “could locate an agreement … delineating the nature and terms of their relationship,” adding to its concern over how the money—often earmarked for specific clinical trials—is used. More than $20 million has been spent on VA-run trials since the fund's inception.

    Money trail.

    A government report alleges impropriety by the VA's former research chief.

    CREDIT: L. BLIZARD/SCIENCE

    The IG report also cites several management lapses during Wray's tenure, including some unrelated to the Friends fund. For example, it alleges that she exhibited “unlawful preference to individuals she wanted promoted or hired”; improperly billed the agency for four personal trips to Houston; spent $23,000 on T-shirts for VA employees “for the purpose of creating collegiality”; violated ethics codes in approving $900,000 in grants to a close colleague in Houston (most of that money has not been disbursed); spent more than $23,800 on a consulting firm to “review Dr. Wray's presentation style and help her respond to questions”; and improperly spent over $30,000 to have two Houston VA staff members assist in her transition from Houston to Washington, D.C., in early 2003. Had Wray handled the paperwork properly, the IG report says, nearly all of the allegedly misspent $1.7 million might have been paid legitimately from VA sources. But it concludes that $79,650 in expenses should have been paid for personally by Wray and her staff, and it urges the VA to recover its losses.

    The VA asked Wray not to comment on the IG report, according to her attorney, June Kalijarvi of the Washington, D.C., firm Kalijarvi, Chuzi & Newman, PC. But Kalijarvi and a second attorney wrote to VA Secretary Anthony Principi last week disputing many of the allegations in the report, and Wray issued a statement of her own rebutting the IG's assertions. Of the Friends money, Kalijarvi argued that “Dr. Wray used these funds in exactly the same manner as her predecessor” and that her supervisors were aware of how the money was being spent. Kalijarvi also noted that Wray's travel expenditures, which the IG report faulted, were approved by her VA subordinates, particularly her chief finance officer, John Bradley. In a separate statement Wray released through her attorneys, she wrote that many decisions involving travel itineraries and hiring were made by her staff, whom she had instructed to abide by VA regulations—and, she writes, “it was reasonable” for her to presume that they “would comply.”

    The VA is reviewing the IG's findings to determine whether to seek reimbursement or take other action against Wray and whether to shift money out of the Friends Research Institute, as recommended by the IG, to more closely supervised accounts. VA Headquarters intends to respond within 90 days.

  5. TECHNOLOGY TRANSFER

    CIA Looks to Universities for Cutting-Edge Tools

    1. David Malakoff

    The CIA is on the prowl for a few innovative academics. Aiming to accelerate the development of university discoveries that might aid U.S. intelligence efforts, the spy agency's venture capital firm has begun combing campuses for promising science. “We're looking for terrific research that needs some help moving to the next stage,” says Gilman Louie, president of Arlington, Virginia-based In-Q-Tel.

    CIA officials founded In-Q-Tel 5 years ago to obtain cutting-edge technology from small, young firms traditionally reluctant to work with the federal bureaucracy. It has since supported more than 50 companies, typically spending up to $3 million per project. Tapping its roughly $35-million-a-year budget, the company is now reaching into universities, too. And although the products—from data-mining software to nanotechnology devices—are intended to help some of the government's most secretive agencies, In-Q-Tel does its investing in the open.

    Last year Louie hired technology development specialist Catherine Cotell, who holds a doctorate in materials science from the Massachusetts Institute of Technology, to raise In-Q-Tel's profile in academia. The company says it is on the verge of inking four new deals involving universities.

    Paper chase.

    Intelligence officials need better ways to sift through and translate mounds of documents, like these captured in Iraq.

    CREDIT: PAUL HAVEN/AP

    Although she can't discuss details of the pending agreements, Cotell can describe how In-Q-Tel tries to develop technologies on its wish list (see http://www.inqtel.com/). One approach is seed money—essentially grants of up to $300,000—to accelerate on-campus work on ideas that aren't quite ready for commercial development. Another is as a “matchmaker” that helps academics license their discoveries to a company already working with In-Q-Tel. For particularly promising inventions, In-Q-Tel will help create a start-up company to develop the product. Cotell says the goal is to give the government quicker access to new tools, and cash-hungry start-up firms quicker access to a buyer. “I'm basically a matchmaker and a technology scout,” she says.

    Louie says that In-Q-Tel ultimately hopes to devote up to 10% of its annual budget to developing ideas submitted by academics. And Cotell says she has yet to hear any objections from academics worried about the company's links to the CIA. In the age of terrorism, she says, university researchers “seem to be very interested in doing whatever they can to help improve national security.”

  6. CANADIAN BUDGET

    Granting Councils Gain Despite Funding Crunch

    1. Wayne Kondro*
    1. Wayne Kondro writes from Ottawa.

    OTTAWA—The first federal budget from a prime minister described by aides as a “science geek” gives Canadian scientists less than they need—but more than they had expected. Last week's announcement by Paul Martin of a 6.3% boost for each of Canada's three granting councils won't relieve the pent-up demand from programs that are pumping up the country's scientific infrastructure. But the increases are nonetheless being applauded because of an unrelated scandal involving Martin's Liberal Party that is forcing him to pull back on the fiscal reins.

    “If I wasn't disappointed, I wouldn't have been asking for enough,” said Alan Bernstein, president of the Canadian Institutes of Health Research, whose budget will rise to $497 million for the fiscal year that began this week. The president of the Natural Sciences and Engineering Research Council (NSERC), Thomas Brzustowski, calls the boost “a statement of faith in the granting councils.”

    Martin's budget boosts overall spending by 3.8%, to $143 billion. That modest rise was meant to be a sign of fiscal prudence after his party acknowledged funneling $100 million into companies run by political allies under a program intended to defend Canadian nationalism against the Quebec separatist movement. The resulting scandal has limited Martin's ability to take bold budgetary steps, including any demonstration of his professed love for innovation.

    Even so, his new budget adds $15 million to a $171-million-a-year program to pay for the cost to universities of supporting federally funded research (Science, 27 October 2000, p. 687). It also gives $45 million to the final year of the Genome Canada project, while supporters marshal arguments for a 5-year, $570 million allocation (Science, 10 March 2000, p. 1732).

    Stronger links.

    Canada wants to foster university-based technologies such as this software for networking cameras.

    CREDIT: DALSA

    But the only sign of a much-ballyhooed push for greater commercialization of university research is a promise to invest $38 million over 5 years in a program to train academic technology-transfer officers and create business-development offices. A private sector panel will draw up the ground rules.

    The granting councils hope their modest increases will alleviate pressure from skyrocketing demand for grant funding. Social Sciences and Humanities Research Council president Marc Renaud hopes to maintain a 40% success rate for standard research grants in the face of more than 1000 new applicants. “We're just overwhelmed,” he says.

    The strength of that demand is reflected in a plan Bernstein floated earlier this year that called for a 47% spending boost. The actual increase, he said, could be applied to soften a planned 5% cut to existing grants or bolster the 22% success rate for new investigators. The grants pressure stems from generous infrastructure awards by the Canada Foundation for Innovation and faculty hiring under the Canada Research Chairs program. NSERC would like to hike the size of its average $24,320 grant.

    Some observers worry that success rates will plunge despite the new funding. “This will only allow the granting councils to barely maintain what they currently have, not meet new demand,” says Canadian Association of University Teachers executive director James Turk. “I'm glad to see this token, but it's not going to solve the problem.”

  7. MARINE CONSERVATION

    U.S. Asked to Act Immediately to Protect Deep-Sea Corals

    1. David Malakoff

    Marine conservationists are demanding that the U.S. government take emergency action to protect deep-sea corals and sponges from net-dragging trawlers. Arguing that environmental regulations haven't kept pace with new science, the Washington, D.C.-based advocacy group Oceana last week petitioned Secretary of Commerce Donald Evans to find, map, and protect the sea-floor organisms in U.S. waters.

    “It's outrageous that the government's idea of taking care of this problem is to allow continued destructive trawling,” says Michael Hirshfield, the group's chief scientist. Seafood industry groups, however, say Oceana is trying to short-circuit existing efforts to draft new conservation plans.

    The 24 March petition (http://www.oceana.org/) is the latest reflection of growing scientific and public interest in so-called cool corals, which grow very slowly in cold, sunless waters down to 2000 meters deep (Science, 10 January 2003, p. 195). Over the past decade, marine researchers have been delighted by discoveries of deep-water coral gardens—and appalled by damage from trawlers moving into deeper waters.

    Net loss?

    Conservationists say that trawlers threaten habitats of deep-sea coral off Alaska and elsewhere.

    CREDIT: VICTORIA O'CONNELL/ADF&G

    Although some nations have begun to protect the organisms, Oceana says the law requires the United States to do more. In particular, the group argues that the federal Magnuson-Stevens Act compels regulators to protect rare or fragile fish habitats from anything more than “minimal and temporary” disruption. Trawling fits the bill, the petition argues, because a single pass of a net can level habitats that may take centuries to recover. To avoid lasting damage, it says, the Commerce Department should immediately designate nearly a dozen known coral and sponge communities in U.S. waters as “habitats of special concern” that are closed to trawling. It should also survey areas believed to hold new colonies and fund research efforts.

    Fishing industry officials want the government to reject the petition on the grounds that the courts have already ordered regulators to produce comprehensive regional plans for protecting fish habitat. “If Oceana wants effective protection, it should let the current process go forward,” says Rod Moore, head of the West Coast Seafood Processors Association in Portland, Oregon.

    Hirshfield, however, is skeptical. He notes that at least one draft plan has already concluded that although trawling damages deep-water corals, the habitat loss has little adverse impact on fish populations. “It's an absurd position,” he says, noting that studies have shown that sponges and corals provide shelter for some young fish.

    Commerce officials are reviewing the petition. A rejection would set the stage for a lawsuit, which some legal analysts predict the government would win. If so, the issue could wind up in the court of public opinion.

  8. BIOTECHNOLOGY

    Human Genome Sciences Retrenches, Haseltine Moves On

    1. Eliot Marshall

    Biotech leader William Haseltine, who riled the genetics community by aggressively sequencing and patenting genes in the 1990s, announced he will step down from the company he has led for more than a decade, Human Genome Sciences (HGS) in Rockville, Maryland. The reason, he says, is that his approach is “not commercial” enough to guide the company through its next phase. Some observers have speculated that Haseltine was eased out. Not so, he says: “I'd been urging the board for some time to bring on management with sales and marketing experience.”

    A former Harvard University AIDS and cancer researcher, Haseltine has run HGS as board chair and CEO since its inception in 1992. During that time, HGS has raised over $2 billion in cash, filed for patents on tens of thousands of genes, and proposed many candidate drugs. Unlike most gene-sequencing companies in the 1990s, HGS set out to turn genomic information into products, but it failed to come up with an effective drug. Last year, one of its most advanced and promising projects—a wound-healing drug called repifermin—was cancelled when clinical trial results were disappointing. HGS also lost ground in financial markets: The price of its stock has declined from a peak of more than $200 per share in 2000 to under $12 this year. The company plans to focus on five projects in its pipeline—including a new cancer drug and a treatment for lupus—while trimming its staff by 20%.

    Field of dreams.

    Haseltine lends a hand at an HGS groundbreaking event.

    CREDIT: LESLIE E. KOSSOFF/AP

    Financial analyst Viren Mehta of the firm Mehta Partners LLC in New York City praises Haseltine for the “bold financings” he carried out during the genomics “bubble” a few years ago and for elevating HGS above the pack. But Haseltine can be faulted for “believing his own aggressive predictions,” Mehta commented in an e-mail, stubbornly investing in the most “challenging” biomedical targets, and failing to opt for a “diversification of risk.” The firm is a pioneer, Mehta added, and “deserves credit for pushing the science.”

    Haseltine credits himself as a pioneer, too. He says that, at a time “when people thought we were crazy,” HGS proved that “you can take a gene of unknown context, or large collection of genes, and use them successfully” to discover drug targets. He argues that HGS also helped show that genes “are interchangeable” and can be viewed as “human microanatomy.” As for the raging controversies over gene patents, Haseltine says: “They look like a tempest in a teapot today. … We haven't damaged the academic enterprise in any fundamental way.”

    Haseltine says he plans to help HGS recruit new leaders before resigning from the board later this year. But he doesn't know whether he will move on to another business, to academia, or to the nonprofit sector.

  9. RADIATION EFFECTS

    U.S. Could Pull Back on Studies of Atom Bomb Survivors

    1. David Malakoff,
    2. Dennis Normile

    WASHINGTON, D.C., AND TOKYO—The United States is considering major cuts in its support of a 54-year-old study of Japanese survivors of the Hiroshima and Nagasaki atomic bombings. Late last month the Department of Energy (DOE) warned scientists working with the Hiroshima-based Radiation Effects Research Foundation (RERF) about possible funding cuts that could derail ongoing studies and force layoffs in the group of 40 scientists.

    The United States now provides 40% of the $40 million annual budget for the foundation, which was created in 1975 to continue studies of the bombing survivors. Any cuts would take effect just as the two nations prepare to commemorate the 60th anniversary of the attacks. “We would seem to be turning our backs on the survivors,” says radiation researcher Burton Bennett, RERF's top official.

    The foundation runs three major studies of the life span and health of the 280,000 survivors and their children, plus it maintains a tissue bank and other records. RERF findings have played an important role in developing radiation exposure models and setting international standards, says Michael Fry, a retired radiation scientist in Indianapolis, Indiana: “Anyone in the field will tell you that this population has been very important.”

    He and other scientists say it would be premature to halt the studies now when more than 40% of the survivors are still alive. For example, researchers are interested in clarifying recent results that suggest exposure to radiation has led to unexpectedly higher rates of cardiovascular disease as well as increased cancer rates. Bennett says the United States also “has a moral obligation to continue” the work.

    The United States earmarks its funds for several RERF projects, including the longevity study, and pays for roughly one-quarter of the foundation's research staff through an arrangement with the U.S. National Academies. Japanese officials won't say whether their country could make up for any U.S. cuts, but foundation officials warn that any interruption in funding could degrade the quality of the research.

    The size of any U.S. cut is still being negotiated within DOE and the White House budget office. The president's 2005 budget request to Congress calls for a 33% cut—to $45 million—in the DOE health program that funds RERF and other activities. But any deal would have to be acceptable to Congress, which has just begun reviewing every agency's budget request for the fiscal year that begins 1 October. Although RERF is little known among lawmakers, past supporters include Senator Pete Domenici (R-NM), the influential head of the spending panel that oversees much of DOE's budget.

    Meanwhile, the U.S. embassy in Tokyo is “watching the process with interest,” says a spokesperson. Researchers are also waiting for word about an extension of the foundation's current 5-year contract, which expires in June 2005.

  10. FORGETTING AND REMEMBERING

    Learning to Forget

    1. Greg Miller

    When remembering runs amok, past pain can disrupt someone's present. New drugs, psychotherapeutic approaches, and other strategies might temper traumatic memories

    Memory lends our lives a sense of continuity, enabling us to learn from experience, nurture lasting relationships, and keep good times from vanishing into the past. But memory also brings pain. A humiliating failure, a gruesome accident scene, or the death of a parent can torment the mind long after the event. In extreme cases, bad memories unravel lives, as they do for people with posttraumatic stress disorder (PTSD) and other anxiety conditions. Remembering the good times is nice, but forgetting the really awful times—or at least keeping those memories in check—may matter more for quality of life.

    After decades of intense and fruitful research on how the brain encodes new memories, many neurobiologists are now turning their attention to how the brain keeps unwanted memories at bay. Recent work has identified key brain regions involved in suppressing memories and fingered some of the chemical messengers involved. Applying their work to the clinic, some researchers have seen promising preliminary results with drugs that either weaken the emotional hold of traumatic memories or prevent newly formed memories from becoming destructive in the first place. These studies may open the way to treatments that return normalcy to the lives of millions of people hamstrung by anxiety disorders.

    But this work makes some bioethicists—including those on President George W. Bush's Council on Bioethics—squirm. They foresee a not-so-brave new world in which the cares and fears of everyday life can be erased by tossing back a pill—much to society's detriment.

    Persistence of memory

    Memories of traumatic events tend to endure, says Roger Pitman, a psychiatrist at Harvard Medical School in Boston, because “evolution has found a way to make us remember things that are important for our survival.” A caveman who encounters a vicious animal while taking a shortcut to the water hole will likely remember the experience and avoid that route in the future.

    Circuits in the amygdala and other brain regions specialize in cementing associations like the one between the shortcut and the animal, which are bolstered by hormones pumped out in times of stress. “The same adrenaline that's making you run from the animal is working in your brain to strengthen associations between the route and the animal,” says Pitman.

    But traumatic memories that are too powerful can be detrimental. If the caveman lies awake night after night reliving the attack, he may lose his effectiveness as a hunter.

    Nearly a century ago, Sigmund Freud proposed that repression—“turning something away and keeping it at a distance from the conscious”—is a basic psychological defense mechanism. The authors of a recent brain- imaging study claim to have found something like what Freud described (Science, 9 January, p. 232). They identified a network of brain regions that keeps unwanted memories below the surface of consciousness.

    Michael Anderson of the University of Oregon in Eugene and colleagues at Stanford University used functional magnetic resonance imaging (fMRI) to monitor the brain activity of volunteers trained to suppress memories—not bad ones in this case, but bland associations. Volunteers memorized pairs of words, such as “ordeal” and “roach.” Then, inside the scanner, single words flashed on a screen in either green or red letters. If “ordeal” appeared in green, subjects were instructed to recall “roach.” But if “ordeal” was written in red, they were to avoid thinking “roach.”

    Distress control.

    When subjects “reappraise” a disturbing image such as a blood-spattered toilet with a less disconcerting explanation, their amygdala activity is similar to that evoked by a neutral image such as a file cabinet.

    CREDIT: PHOTODISC

    On a paper-and-pencil test taken after the scanning session, subjects were about 10% worse at remembering word pairs they'd suppressed compared to ones they'd recalled. The brain scans hint at why. When subjects suppressed a memory, their dorsolateral prefrontal cortex was active. This area has been linked frequently to what cognitive neuroscientists call executive control; it is active, for example, when subjects consciously suppress a particular movement or emotion. At the same time, activity in the hippocampus—a key memory center—decreased. “What this shows is that when people are trying to suppress a memory, they're doing something very active that involves a distinct network of [brain] regions,” Anderson says.

    “It's a very interesting paper on a really underexplored topic,” says Elizabeth Phelps, a cognitive neuroscientist at New York University. “How we forget, or inhibit, or do away with a memory [has] always been a big part of the story, but it's one we haven't really focused on.”

    Anderson plans to repeat the experiment in people who have trouble forgetting, such as those with PTSD. “We might find that people with PTSD are deficient in their ability to recruit this network,” he hypothesizes.

    There are at least two lines of defense when faced with a traumatic experience, says Kevin Ochsner, now at Columbia University in New York City, who collaborated with Anderson on the Science study: Don't remember it happened, or given that it happened, reinterpret it in a more positive light. Just as the dorsolateral prefrontal cortex may dampen activity in the hippocampus to manage memory, it may play an analogous role in managing emotions. It dampens activity in the amygdala when people try to put a positive spin on a bad situation, Ochsner claims.

    He and colleagues showed volunteers a set of disturbing photos—a burned body, a gunshot wound, a toilet spattered with blood or vomit—and asked them to concoct a story in their mind that made the situation less negative. In fMRI scans, the prefrontal cortex lit up when subjects “reappraised,” and the amygdala grew quieter. In fact, subjects' amygdala activity during reappraisal of negative images was similar to that during passive viewing of neutral images such as a file cabinet.

    Both Anderson and Ochsner see their findings as illustrating everyday cognitive processes. “There's this spin control we're doing all the time,” says Ochsner, whether we're dealing with a bad review on a journal article or rehashing an argument with a friend. But the work may shed light on psychiatric disorders as well.

    “We know a lot about the pathophysiology” of depression, Ochsner says, “but we don't know what the pathophysiology reveals.” For example, some studies have found heightened amygdala activity and decreased prefrontal cortex activity in depressed people. That might mean people with depression are less able to tap into the neural networks for reappraisal, Ochsner speculates.

    Stimulating sluggish frontal regions, perhaps with drugs or transcranial magnetic stimulation (TMS) (Science, 18 May 2001, p. 1284), might improve people's ability to place painful memories in context. A study published in the March issue of the American Journal of Psychiatry found that 10 daily sessions of TMS focused on the right dorsolateral prefrontal cortex had a therapeutic effect on 10 PTSD patients.

    Promoting extinction

    Clinical payoffs might also come from research on the signaling molecules involved in learning—and unlearning—fear. Much of this work involves a behavioral training regime called fear conditioning. Typically, researchers present a lab rat with a flash of light followed by a mild shock. After a few repetitions, the rat exhibits a “fear response,” freezing when it sees a flash. If researchers cease pairing each flash with a shock, the rat eventually stops freezing—a process called extinction.

    Although extinction may seem like a simple matter of forgetting, it is not. In a rat that has seemingly lost its fear of light flashes through extinction, the fear response comes back with a vengeance when the light is once again followed by a shock. Many researchers see in extinction a parallel to psychiatric therapy: Both involve a special kind of learning that is prone to relapse.

    Drugs that hasten or fortify extinction, some researchers reason, might be useful for therapies that help people overcome fearful associations. One compound, D-cycloserine, has already shown promise in a clinical trial. The drug enhances the function of a particular receptor for the neurotransmitter glutamate—the so-called NMDA receptor—that earlier work has shown to be critical for extinction. Michael Davis and colleagues at Emory University in Atlanta, Georgia, found that administering the drug to acrophobic patients during therapy—playing a virtual reality game that simulates riding a glass elevator—helps ease their fear of heights in real life (Science, 21 November 2003, p. 1321).

    Other groups have identified additional candidate extinction promoters. Mark Barad, a psychiatrist at the University of California (UC), Los Angeles, says his team is organizing a clinical trial of yohimbine, a drug that stimulates activity of the neurotransmitter norepinephrine and provides an “enormous boost” to extinction in rats. Cannabinoids—the psychoactive ingredients in marijuana—may also have potential. In 2002, Beat Lutz and colleagues at the Max Planck Institute of Psychiatry in Munich, Germany, reported in Nature Neuroscience that mice lacking cannabinoid receptors are impaired in extinction but not other types of learning. Since then his group has been screening cannabinoids and related compounds for ones that aid extinction. The list of candidates also includes drugs that enhance the activity of certain calcium channels or the inhibitory neurotransmitter GABA. Researchers have yet to form a clear picture of how all these signaling molecules fit together.

    Suppress that thought.

    Activity in the dorsolateral prefrontal cortex (arrows) puts a damper on unwanted memories.

    CREDIT: M. C. ANDERSON ET AL., SCIENCE 303, 234 (2004)

    It may also be possible to make extinction—and potentially therapy—more effective without drugs. Barad's group reported in the Journal of Experimental Psychology: Animal Behavior Processes last October that the timing of extinction training has a big influence on its effectiveness. Rats get over their trained fear of light flashes more quickly when exposure to the flash alone is delivered in clusters than when the flashes are evenly spread out.

    Subsequent experiments hint that continuous exposure to the feared stimulus is even better than clusters, Barad says. He sees parallels in his psychiatric practice. One patient with obsessive-compulsive disorder had an irrational fear of catching cancer from people who have cancer, including her mother. Barad convinced her to wear a scarf that belonged to her mother continuously, and over time her fear disappeared.

    “We learn fear very easily,” Barad says, and extinction is the brain's way of weeding out maladaptive associations. Tapping into this natural learning process—whether through drugs or therapy or both—could help patients with a variety of disorders conquer bad associations. Extinction experiments can teach therapists how to expose people more effectively to feared cues and prevent them from expressing inappropriate behaviors in response, Barad says.

    It never happened

    While some researchers work on aids to unlearning, another set of recent studies suggests that it may be possible to prevent newly formed memories of traumatic events from becoming disruptive. Techniques could weaken both the memories themselves and their emotional associations.

    Memories of emotionally significant events are strengthened by stress hormones such as adrenaline. A classic study by Larry Cahill and James McGaugh of UC Irvine published a decade ago showed that blunting the effects of stress hormones in the brain can negate this strengthening effect. Volunteers viewed a slide show and listened to a narrative about the slides—either a tame one about a boy visiting his father at work or a tragic version of the same story. A week later, subjects remembered the emotional story much better. But subjects who received propranolol—a beta-blocker drug, named for the subtype of adrenergic receptor it blocks—remembered the emotional story no better than the neutral one. Propranolol blocks the effects of the neurotransmitter norepinephrine, levels of which rise in the brain in response to adrenaline. The researchers concluded that adrenergic activity—brain signals transmitted by members of the adrenaline family—is essential for the enhancement of emotional memories.

    Problematic.

    The President's Council on Bioethics warns against manipulating memories.

    Subsequent research has hinted that adrenergic activation plays a role in the development of PTSD. People who show greater signs of adrenergic activation, such as a racing heart rate and panicky behavior, immediately after a traumatic event are more likely to exhibit symptoms of PTSD later, says Charles Marmar, a psychiatrist at UC San Francisco.

    Together with colleagues in France, Marmar recently gave propranolol to 11 people admitted to French hospitals following a motor vehicle accident or physical assault. The patients, who did not have serious physical injuries, took the drug within a few hours of the incident in most cases and continued to take it for 2 to 3 weeks. Two months later, this group had fewer symptoms of posttraumatic stress than a similar group of patients that didn't take the drug. A previous pilot study by Pitman and colleagues, published in 2002, found similar results.

    Both Pitman and Marmar say the findings are encouraging but preliminary. “You can't take this to the bank,” Marmar says of the combined results, “but I think it's enough to justify a large-scale trial.” Indeed, both groups learned late last year that they will receive funding for larger, blinded, placebo-controlled trials. “If this is all correct, it means that PTSD, which affects close to 8% of the American population at some point in their life, might be predictable at the time of the event and may even be preventable … with a course of medication that costs $15,” Marmar says.

    Medicating away morality?

    But that doesn't sound like a bargain to the President's Council on Bioethics. In a report* released last October, the panel opined that “the prospect of preventing (even) PTSD with beta-blockers or other memory-blunting agents seems to be, for several reasons, problematic.”

    Among practical problems, the report says, is knowing whom to treat. Victims don't exhibit symptoms of PTSD, by definition, at the time of the event. Accident witnesses might start demanding prescriptions, imperiling their future testimony. In the future foreseen by the council, doctors could “give beta-blockers liberally to soldiers on the eve of combat, to emergency workers en route to a disaster site, or even to individuals requesting prophylaxis against the shame or guilt they might incur from future misdeeds.” The potential for misuse, they claim, abounds.

    Moreover, the report continues, bearing traumatic memories is the moral obligation of those who witness atrocities. Even if individual Holocaust survivors were to benefit from treatments that weakened the memories of their experiences, the council writes, society as a whole might be badly served by having no witnesses whose memories are unadulterated. “Our memory is not merely our own; it is part of the fabric of the society in which we live.”

    The council's report largely misses the mark, says Arthur Caplan, a bioethicist at the University of Pennsylvania in Philadelphia. Certainly society must preserve the record of atrocities such as the Holocaust, he says, but doing so doesn't require denying individuals the benefits of therapeutic drugs: “The notion that we need to have suffering martyrs among us is cruel and exploitative.”

    The subtext of the council's argument, says Caplan, seems to be that using drugs to manipulate memories—whatever the content of the memories—is unnatural and therefore morally suspect. “I don't accept that at all,” he says. For one, it obliterates the line between treating memory and mood disorders and using drugs for the selfish pursuit of self-improvement. And if treating an infection with antibiotics is OK, he asks rhetorically, why shouldn't it be OK to use drugs to correct a problem with memory or cognition? “It's a moral argument that, if turned in in my undergraduate bioethics class, would pull a C.”

    Selectively erasing memories does indeed raise ethical questions, says Joseph LeDoux, director of the Center for the Neuroscience of Fear and Anxiety in New York City. But that's always true of science that pushes the bounds, he says: “If we're successful in doing these sorts of things, it will raise a societal debate about how far we want to go.”

    • *Beyond Therapy: Biotechnology and the Pursuit of Happiness

  11. FORGETTING AND REMEMBERING

    A Star-Studded Search for Memory-Enhancing Drugs

    1. Eliot Marshall

    An eager market—from Alzheimer's patients to aging overachievers—awaits the first memory-enhancing drugs. High-profile neuroscientists are racing to provide the goods

    Forgetfulness is a common failing of old age that patent medicines once promised to cure. But rescuing memory has now moved from snake oils and placebo effects into the scientific mainstream. There's been an explosion of new drug candidates designed to boost memory in recent years, and many are entering clinical trials. Although a few elixirs have already fallen by the wayside, observers see encouraging signs in the breadth and depth of clinical experimentation.

    Although big pharmaceutical firms are heavily involved, some of the most ambitious efforts are led by small companies, each tied to a prominent academic scientist and backed by a famous institution. And star scientists are drawing media attention and giving the enterprise a dash of glamour.

    The commercial potential for memory enhancers is immense. Some drugs in development are designed to help people with Alzheimer's disease or other brain disorders, whose number is increasing rapidly as the population ages. But most would equally well treat mild cognitive impairment, a subclinical condition that often progresses to Alzheimer's, or the kinds of age-related memory declines that are common even in healthy people. Some companies are planning to treat memory problems associated with mental illness and mental retardation. Even the “worried well”—and there are many among the aging baby boomers—could eventually be customers, seeking to medicate perceived memory lapses. This group overlaps with the potentially huge and ethically troublesome market for “off-label” uses—people who simply want to enhance their powers of memory rather than treat memory loss (see Editorial, p. 17).

    Early start.

    Gary Lynch of UC Irvine helped launch Cortex more than a decade ago; in the 1990s the firm began to develop drugs called ampakines to boost memory.

    CREDIT: UNIVERSITY OF CALIFORNIA, IRVINE

    “There's a lot of enthusiasm” about new therapies, says biochemist Tom Dietz, co-CEO of Pacific Growth Equities, an investment firm in San Francisco that follows this field. “We have an aging population, and it's growing. So these companies have a ready market” and not much competition from other approved drugs. “We're seeing the culmination of many years of work,” Dietz says, adding, “that doesn't happen often.” A sample of these companies reveals that they are moving toward the same goals but have different styles and strategies.

    Take a memo

    Gary Lynch was one of the first to explore this territory. A researcher in psychiatry and human behavior at the University of California (UC), Irvine, he helped guide a small company called Cortex Pharmaceuticals during its start-up years in Irvine in the 1980s, when it was concerned with treating stroke and neurodegenerative diseases with growth factors. At his urging, Lynch says, in the 1990s the company began to focus on molecules dubbed ampakines. They modulate so-called AMPA receptors, which respond to the neurotransmitter glutamate. Given the right kind of neural stimulation, AMPA receptors strengthen synapses, the contact points between neurons at which they exchange information. New or more sensitive synapses, according to theory, write experiences into memory.

    Lynch began this work after learning about a potential memory-boosting ampakine compound in a preprint from Isao Ito of Chugai Pharmaceuticals in Japan. Soon after that, a “fortuitous encounter,” Lynch says, brought him together with medicinal chemist Gary Rogers, then at UC Santa Barbara, who quickly concluded that he could make a “more potent, more persistent” version. Rogers and Lynch teamed up to create an ampakine drug now being tested by Cortex as compound CX516. Its safety and proof of principle have been established in phase I and phase II clinical trials, according to Cortex. But it's not likely to become a prescription drug, Lynch notes, because its potency is low. Hopes are now riding on successor compounds, including CX717, which will soon enter clinical testing.

    Counterpoint.

    Eric Kandel of Columbia (left) and Tim Tully of Cold Spring Harbor Laboratory are founders of competing companies, Memory Pharmaceuticals and Helicon Therapeutics, respectively, both seeking to improve memory by raising levels of CREB.

    CREDITS: (LEFT TO RIGHT) SPENCER PLATT/NEWSMAKERS/GETTY IMAGES; MIRIAM CHUA

    “We and everybody else who are using ampakines are trying to make it easier to encode memory,” that is, create a neural trace of an experience, says Lynch. In contrast, several other new companies are emphasizing a slightly different step, targeting the protein machinery that stabilizes memory. “It's going to be entertaining” to watch the competition, says Lynch.

    Nobel spinoff

    Memory Pharmaceuticals Corp., a small company in Montvale, New Jersey, has been featured in journals such as Forbes and Business Week, benefiting from the celebrity of its scientific guru, Eric Kandel, a Howard Hughes neurobiologist at Columbia University in New York City. A co-recipient of the Nobel Prize in physiology or medicine in 2000 for work on the biochemistry of neuron signaling, Kandel has been showered with many awards during a long academic career devoted to the study of how memories are formed and stored at the molecular level.

    Kandel says the idea for Memory Pharmaceuticals took shape over dinner one night with Walter Gilbert, the Harvard biochemist who won a Nobel Prize in chemistry in 1980. The two had been involved with another firm and were discussing memory research. Kandel recalls that his wife Denise “suggested that we start a company.” They did, bringing in venture capitalist Jonathan Fleming and scientific director Axel Unterbeck from the German drug firm Bayer to found Memory Pharmaceuticals in 1998.

    The company, which counted Columbia University among its first backers, has used Kandel's model of long-term memory consolidation to search for potential memory-boosting molecules in animal models. Its initial target is Alzheimer's disease, but it also aims to treat vascular dementia, schizophrenia, depression, and common age-related memory loss.

    At present, Memory Pharmaceuticals has identified four drugs in development. The furthest along in testing (MEM1003) was licensed from Bayer. It's designed to protect neurons against excess calcium inflows, a common defect of the aging brain that damages neurons and eventually impairs cognitive function.

    Next in the pipeline are two drugs derived from Kandel's work (MEM1414 and MEM1917). They are designed to enhance memory by sustaining levels of a critical neurotransmitter called cyclic AMP and a protein it modulates, CREB, which has the power to turn genes on and off. Fluctuations of CREB levels can reshape synapses and are thought to help cement memories. The fourth candidate (MEM3454) is an antischizophrenia compound aimed at a different target, the nicotinic alpha-7 receptor; nicotine eases some symptoms of the disease, and researchers suggest that this may explain the high rate of smoking among people with schizophrenia.

    Only MEM1003 has completed an initial safety trial (phase I), in 185 people. A similar trial of the cyclic AMP booster MEM1414 is under way, and phase II trials are being planned. The Swiss pharmaceutical firm Roche has invested $37 million so far and has promised $248 million if researchers achieve specified milestones. The race to be the first with a memory-enhancing product is intense.

    Competition is much on the minds of folks at Memory Pharma this spring, as they prepare to convert from a private to a public company. They have filed a federal registration proposing to sell 5 million shares in the initial offering, at about $14 a share. The sale will begin after the Securities and Exchange Commission approves. But company leaders can't say much about it, a spokesperson explains. They're in a “quiet period” mandated by U.S. securities laws. This is a new experience for Kandel, an ebullient talker and teacher. He can't comment on the company's prospects, but he says he's enjoying the ride.

    Stealth flier.

    With colleagues at Brown, MIT's Mark Bear founded Sention, a quiet memory drug company that has tried to stay below the media radar.

    CREDIT: DONNA COVENEY/MIT

    Rivalry

    Similar targets are being pursued by a smaller company built around the research of Timothy Tully and Jerry Yin of Cold Spring Harbor Laboratory, called Helicon Therapeutics, in Farmingdale, New York. Like Kandel, Tully has specialized in studies of the molecular basis of memory, also focusing on the role of cyclic AMP and CREB. Tully achieved fame when he published reports in 1994 and 1995 on fruit flies genetically engineered to express high levels of CREB. The insects performed astonishing memory feats, learning a new path to food in a single pass, much faster than normal flies.

    Tully's company, like Memory Pharma, is investigating molecules that can sustain or boost CREB levels in neurons, in the hope that doing so will improve memory function in aging patients. A key element in both cases is to identify specific enzymes (called phosphodiesterases) that degrade CREB and block their action. Helicon and Memory Pharma have patents and interests that could clash.

    Tully says he was spurred to start Helicon by a report on CREB unrelated to his work, published in Nature in 1995. The study identified a defect in a human CREB-binding protein associated with a type of mental retardation, Rubinstein-Taybi syndrome. The only way to test the possibility that this condition might be treatable, he argued to Cold Spring Harbor Lab president James Watson, would be to start a company and make drugs that influence CREB. Watson was persuaded, Tully says, and the lab became a prime investor in Helicon.

    Seven years later, says CEO John Tallman, Helicon has one candidate drug ready for human trials, a phosphodiesterase inhibitor. It might be used to treat early Alzheimer's disease and mild cognitive impairment. Animal testing has gone well so far, Tallman reports, and a phase I clinical trial is set to start “in the second half of 2004.” It is “too early” to talk about other projects, he says. Unlike its rival, Memory Pharma, Helicon isn't selling public stock. “We're happy to be private,” Tallman says; the lack of big company partnership is fine, too, because it gives the company founders “more control.”

    View this table:

    Dark horses

    Less attention has been paid to Sention Inc., a spinoff from Brown University in Providence, Rhode Island. It is the “stealth bomber” of memory-enhancement firms, says Harry M. Tracy, editor of NeuroInvestment, a newsletter in Rye, New Hampshire, that follows the business. He says the company is “very circumspect,” although it has put two candidate compounds through phase I clinical trials and one through phase II. Company co-founder Mark Bear, a Howard Hughes investigator in neuroscience now at the Massachusetts Institute of Technology, admits that he wants to keep it low-key: “We try to be quiet … and let Helicon and Memory have the limelight.” Bear formed the company in 1999 with two colleagues at Brown: Leon Cooper, a theoretical neuroscientist who won a Nobel Prize in physics in 1972, and Mel Epstein, then head of clinical neuroscience at Brown. A distinct aspect of Sention's approach, Bear says, is a broader focus—one that centers on functions “that are well upstream of CREB that regulate the strength of memory consolidation.” But he isn't ready to disclose details.

    Asked about the rumor that they are specifically focusing on glutamate receptors, CEO Randall Carpenter says: “We're receptor agnostic. … We're trying to turn up the gene expression” of proteins that are used as “the universal building blocks for memory storage.” Results should be available “by the end of the year,” Bear promises.

    Many other small firms are contending for a profitable niche, with varying results. Daniel Alkon, a neuroscientist at West Virginia University in Morgantown, has patents on another string of neural receptors. The company he was once allied with, NeuroLogic in Rockville, Maryland, sponsored phase I and II clinical trials, but recently, Alkon says, it “has become less active.” A company official says they and Alkon have parted ways. Meanwhile, other companies are advancing rapidly—most with less direct academic ties—such as AGY Therapeutics in South San Francisco and Saegis Pharmaceuticals in Half Moon Bay, California.

    These are just a handful of the biotech ventures that may have a shot at delivering a first generation of memory-enhancement drugs. Each is trying to chart its own path through the science; each holds a set of patents; and each is trying to pull together funds needed to commercialize its discoveries. It's shaping up to be a memorable race.

  12. NATIONAL SCIENCE FOUNDATION

    On-the-Job Training Slots Open Doors, Lighten the Load

    1. Jeffrey Mervis

    Science assistants aren't program officers—yet. But they have become essential to the way NSF manages its grants portfolio

    It's Jeannine Cody's job to take the call when an environmental biologist contacts the National Science Foundation (NSF) about a grant proposal. Her master's degree in the field has taught her the lingo, and she helps find reviewers as well as writing up the minutes of panel meetings where the proposals are discussed. But Cody isn't the typical NSF research administrator. She's a science assistant, a relatively new breed of professional that has quickly become essential to the smooth operations of the $5.5 billion agency.

    “They're incredibly talented and energetic,” says Joanne Roskoski, executive officer for the $600-million-a-year biology directorate, which has led the way in creating these slots. “They've proved so popular that every cluster in Bio has at least one.”

    The positions are designed to be temporary, typically for 2 or 3 years, although a few have been converted into permanent slots. But what makes the assistants so valuable, say senior managers, is the speed with which they absorb all aspects of NSF's merit-review system. “They take some of the load off program directors, giving them time to think strategically,” says Joseph Burt, acting head of the division of human resource management. “What they do isn't clerical, but it's also not strictly scientific.”

    In return, the assistants, who are often right out of graduate school and typically have a master's degree in a relevant field, get an insider's view of federal support for academic science and a springboard for their careers. Some decide to return for a doctoral degree; others parlay their NSF experience into a permanent job in research administration, often at another federal agency.

    Their numbers are still small, just 30 or so in a professional workforce that tops 600. But NSF hopes to expand their ranks as part of a $75 million management initiative in the agency's 2005 budget request to Congress. And so far NSF stands alone among science agencies in employing such temporary, yet professional, helpers. “I'm not aware of another federal agency that has such a position,” says Burt.

    The science assistants come from backgrounds as varied as the programs that NSF runs, and their career aspirations are equally diverse. “It's opened the door for everything I've done in science,” says Elizabeth Martin, a former NSF science assistant in population biology and systematics who now works for the U.S. Geological Survey in Gainesville, Florida, in its bird conservation network. “I wanted to do something more applied [than what I was doing at NSF], but having NSF on your résumé certainly impresses employers.” Martin, who is also pursuing a Ph.D. at the University of Florida in wildlife ecology and conservation, says she still draws on contacts from her NSF days in both her work and her studies.

    Essential aides.

    Science assistants Brett Mervis and Jeannine Cody help NSF program officers handle a growing workload.

    CREDIT: PETER WEST/NSF

    Leila Harris was one of NSF's first science assistants when she joined the geosciences directorate in 1994. Her work for the interagency global change program was a real-life application of her bachelor's degree in environmental policy and political economy from the University of California, Berkeley. But although she enjoyed interacting with some 30 program managers across five research directorates during her 3-year stint, she decided that teaching and research were more appealing than policy. So she returned to school for a Ph.D., and in January she began a tenure-track position as an assistant professor in the geography department at the University of Wisconsin, Madison. “I got great mentoring at NSF,” she says. “They strongly encouraged me to get my doctorate.”

    Part of NSF's management initiative would increase in-house training, with the goal of making employees more proficient in electronic grants processing. Nat Pitts, who heads NSF's Office of Integrative Activities and oversees its merit-review system, sees science assistants as a key part of this process. They are usually ahead of the curve, he says. “They are sharp, with great computer and communications skills. They are also incredibly quick at manipulating data sets.” Their role as an intermediary with NSF's outside clients can be invaluable, he adds. “We all used to answer those questions,” says Pitts. “Now Brett does it.”

    That would be Brett Mervis, a science assistant who came to NSF as a student intern during his undergraduate years and who returned in May 2002 after earning a master's degree in criminology. But he's already got one foot out the door, with plans to earn a Ph.D. and then work for the Justice Department's Bureau of Alcohol, Tobacco, and Firearms. That's fine with Pitts. “If they're good, we want them to go back to school,” he says. “We don't want to abuse them.”

    That doesn't appear to be a problem. “It's like being a fly on the wall,” says Cody of her vantage point during panel meetings of reviewers or during discussions about program initiatives. “You might think you know how NSF operates, but seeing it in action is totally different.” Their relative youth also injects a refreshing naiveté into the culture of an agency that, like any federal bureaucracy, tends toward stodginess and self- importance. “Imagine working with someone who you've cited in your thesis,” she says. “You get to read proposals, and you learn by osmosis. It's definitely cool.”

    But no matter how many science assistants they employ, NSF officials have no intention of undermining the system that is seen as the gold standard for competitively awarded basic research. In particular, insider status doesn't necessarily translate into greater success in negotiating NSF's stringent merit-review system. “I've applied for NSF funding twice,” confesses Harris, describing her unsuccessful bids for a graduate research fellowship and for dissertation support. “And having worked there didn't win me any extra points. But I certainly know what needs to be in a proposal. And I hope to someday get an NSF grant.”

  13. JAPAN

    New Law Frees Up Universities to Innovate--at Their Own Risk

    1. Dennis Normile

    University presidents in Japan now have more control over their institutions, but they are also more accountable

    TOKYO—Japanese universities entered uncharted waters this week thanks to a new law that turns them into independent public corporations. For the presidents of the 89 national universities, the change is both blessing and burden.

    Although cynics say the law is simply a way for the government to shed some 115,000 civil servants, it gives administrators more freedom to run their own campuses. They can now set tuition fees, hire lab technicians and other workers as needed, implement U.S.-style tenure systems, and carry funds over from one year to another. But that freedom comes with additional responsibilities, notably the need to raise more money from nongovernmental sources and to show that public funds are contributing to better education and research. The law also permits faculty members and employees to form labor unions and bargain collectively.

    Hiroyuki Yoshikawa, former president of the University of Tokyo (Todai), predicts that these changes will produce “an increasing gap between well-managed and poorly managed universities.” University presidents, he adds, will shoulder much of the responsibility for an institution's success or failure, including the ability to maintain market share in a shrinking pool of college-aged students.

    In the past, the president of a national university was elected by, and reported to, the faculty council of professors and associate professors. Consequently, presidents focused more on protecting the interests of faculty members than on leading their institution. Key administrative staff members were seconded from the Ministry of Education, which exercised final control over budgets, the number of faculty positions, new programs, and tuition.

    Yoshikawa, now president of the National Institute of Advanced Industrial Science and Technology in Tokyo, says that the previous system “left a university president with almost no power.” As an example, Yoshikawa recalls having to “borrow” vacancies at Todai left by retirements from existing departments so that he could create a department of environmental studies. The process took 3 years, he says, and “it was not really following the rules.”

    Food for thought.

    University of Tokushima President Toshihiro Aono wants the school to put more effort into winning big grants like this one to study nutrition and stress.

    CREDITS: UNIVERSITY OF TOKUSHIMA

    Toshihiro Aono isn't so patient. Since taking over 15 months ago as president of the University of Tokushima, a small school on the remote island of Shikoku, Aono made a concerted bid for the increasingly important major research grants offered by the Ministry of Education. He pored over the solicitations, handpicked the research teams that applied, and rehearsed the oral presentations required of every finalist in the competition. The strategy worked: Tokushima has been successful in every competition it has entered since Aono arrived. More important, it demonstrated the power of a university president to influence an institution's performance.

    That ability will be put to the test in the years ahead as each university implements a strategic plan drawn up last fall. It's not just a paper exercise, either. The new law says that future funding will be tied to a university's progress toward achieving its goals, and presidents who are unable to nudge their schools along the desired path may see their government funding trimmed. That would come on top of what many fear will be a stagnant or shrinking overall pot of money.

    The most immediate impact of the new law may be in how presidents are chosen. Faculty councils tended to choose presidents from within the school's own engineering or medical departments, which are typically the largest programs at most universities. But future presidents will be picked by a 14-member selection board whose membership is divided between faculty and local business and civic leaders. That mix is expected to produce a different type of president, possibly even someone from outside the university, says Shinichi Yamamoto, director of the Research Center for University Studies at the University of Tsukuba and a member of one of the Ministry of Education advisory committees that forged the new policies.

    The next generation of university presidents will have to redefine their relationships with faculty members, notes Reiko Kuroda, a chemistry professor at Todai and special adviser to its president on research affairs. More assertive presidents may wind up battling faculty members not accustomed to any interference in what they regard as their own affairs, she says.

    Kuroda expects more rapid change at smaller universities, noting that “a small plane can take off more quickly than a 747.” Aono's University of Tokushima is certainly an example of that. In contrast, Kuroda predicts that Japan's leading universities will have a harder time setting priorities. “At Tokyo and Kyoto, every department thinks it is among the best in the world and won't want to give anything up” to other departments, she says.

    Beyond improving their powers of persuasion, Japan's new crop of university presidents will also need to be adept at raising money. “Japan really underfunds tertiary education,” Yoshikawa says, “and the Ministry of Finance wants to squeeze funding even more.” Although the new corporatization law frees up presidents to find new academic sponsors, it's a task that Yoshikawa is grateful was not part of his job description.

  14. AMERICAN PHYSICAL SOCIETY MEETING

    Carbon Foam Reveals a Fleeting Magnetic Personality

    1. Robert F. Service

    MONTREAL, CANADA—More than 6000 physicists braved an early spring freeze here from 22 to 26 March for the American Physical Society's largest-ever March Meeting.

    Hold a magnet up to a piece of graphite or a diamond and not much happens. But researchers from Greece and Australia reported here last week that they've created a spongy, ultralightweight form of carbon that for a few brief hours is strongly magnetic. If they can make the magnetism stick around, the material could prove useful in everything from medical imaging and cancer therapy to exotic electronic circuitry based on the magnetic behavior of electrons rather than their charge.

    “It's a very intriguing material,” says Mildred Dresselhaus, a physicist at the Massachusetts Institute of Technology in Cambridge. David Tomanek, a physicist at Michigan State University in East Lansing who collaborated with the Greek and Australian team on the magnetic theory of the nanofoam, adds that the work underscores how nanotechnology can change long-held understandings of which materials can be magnetic. “It shows that we need to revisit the magnetic prejudice of the periodic table,” Tomanek says.

    The new form of carbon was discovered 5 years ago by a group led by physicist Andrei Rode of the Australian National University in Canberra. Looking for a new way to synthesize straw-shaped carbon molecules called nanotubes, Rode and colleagues fired a high-power, fast-pulsed laser at amorphous carbon in a chamber filled with argon gas. Instead of nanotubes, they got a frothy surprise: a material made up of nanosized carbon clusters connected in a weblike foam. After spotting hints of magnetic behavior, Rode teamed up with magnetic specialists led by John Giapintzakis of the University of Crete in Greece to study the foam in depth.

    Attractive.

    One of the lightest substances ever made, nanoscale froth condensed from superheated carbon atoms is also magnetic at room temperature for a few hours.

    CREDIT: A. RODE/AUSTRALIAN NATIONAL UNIVERSITY, CANBERRA

    Giapintzakis's group confirmed that the carbon foam is initially ferromagnetic. Such materials, which are commonly used for items such as refrigerator magnets, are easily magnetized by even a weak magnetic field and often retain that magnetization after the field is removed. Other common forms of carbon, such as graphite and diamond, by contrast, naturally oppose a magnetic field. The carbon foam's ferromagnetic behavior disappears after a few hours at room temperature but lasts much longer at ultralow temperatures.

    Earlier “discoveries” of magnetic carbon by other groups fizzled after magnetic impurities in the sample were found to be the culprit. But Giapintzakis says extensive tests on the nanofoam show that impurities could account for at most 20% of the magnetism present. “We are sure we do not have an impurity effect,” he says. Bolstering the case, Giapintzakis adds, the team has found that other normally nonmagnetic materials such as boron nitride show similar properties when subjected to the same laser treatment.

    Giapintzakis and Tomanek say modeling studies suggest that carbon atoms turn magnetic when they cool out of the superhot plasma generated by the laser and condense into tiny four-armed cagelike structures that resemble hollowed-out nanoscale versions of a child's toy jacks. Where the arms meet, several carbon atoms are forced to bind to just three neighbors rather than the usual four, leaving them with free electrons that are magnetically active, Tomanek says. Over time, the structures likely break down, reducing the material's ferromagnetism.

    The new carbon nanofoam is also a semiconductor. That means it has the potential to manipulate both an electron's charge and its spin, a property related to its magnetic behavior. That ability could make it and similar materials attractive building blocks for proposed spintronic devices, which compute by manipulating electron spins.

  15. AMERICAN PHYSICAL SOCIETY MEETING

    A Positive Spin on Semiconductors

    1. Robert F. Service

    MONTREAL, CANADA—More than 6000 physicists braved an early spring freeze here from 22 to 26 March for the American Physical Society's largest-ever March Meeting.

    Researchers are working to supplant traditional computer chip technology, which relies on the charge of electrons, with devices that exploit a more ephemeral property of electrons: their spin. Such “spintronic” systems promise to operate at blinding speeds and low power, and they may even work the moment they're turned on. Numerous teams have used lasers to create and manipulate spins. But laser-based systems are impractical for standard computing technology, and groups around the globe have struggled to create and manipulate spins using purely electronic systems. Now, in a pair of reports—one at the APS meeting and another posted on the arXiv preprint server (http://www.arxiv.org/)—a team of California-based researchers announces significant progress in that effort.

    At the meeting, Jason Stephens, a graduate student in physicist David Awschalom's group at the University of California, Santa Barbara, reported creating spins by sending an electrical current from a semiconductor toward a thin ferromagnetic layer. Meanwhile, in the online paper, Awschalom's group reports similar effects simply by engineering the atomic lattices of semiconductors to contain strain, a standard industrial technique. Daniel Loss, a spintronics expert at the University of Basel in Switzerland, calls both of the new observations “very interesting.” Together they hold the promise of creating all-electronic systems for creating and manipulating spins. “They could open the door, definitely,” to new progress in the area, Loss says.

    The first success was a lucky accident: Stephens was preparing to test a new way to create spins optically when he found he didn't need the optics at all. He created a standard electronic device called a Schottky diode, consisting of two connected layers of electronic materials: a semiconductor alloy of gallium arsenide topped with a magnetic metal alloy of manganese arsenide. For spintronic devices to work, researchers must coax the spins of electrons to point more or less in the same direction. Flipping spins from pointing up to down, for example, then allows researchers to change a digital 0 to a 1.

    However, orienting spins isn't easy. In conventional metals and semiconductors, they point in random directions. One way of lining them up is to use magnetic materials called ferromagnets, such as manganese arsenide. In these materials, electron spins point primarily in one direction—which gives the material its magnetism. Electron spins pointing a different direction can't easily enter the material, making it an excellent filter. So a magnetic Schottky diode is just a way to send aligned—or polarized—spins into a semiconductor. Unfortunately, the method doesn't work very well. Atomic-level disorder at the interface between ferromagnets and semiconductors typically scatters electrons, and as a result, few polarized spins ever make it into the semiconductor.

    In preparation for his optical test, Stephens ran his diode in reverse, applying a voltage between the two electrodes that attempted to push electrons first through the semiconductor and then into the metal before exiting the second electrode. In this case, the spins start out unpolarized in the semiconductor. But when Stephens and his colleagues used a laser detection technique to look at the orientation of the spins in their devices, they found that a large number of spins in the semiconductor just below the metal wound up oriented in the same direction. Awschalom believes that the ferromagnetic filter allows electrons with a preferred spin to travel through the ferromagnet, leaving those with the opposite spin to accumulate in the semiconductor. “This is a fundamentally new way to generate spin polarization in a semiconductor,” Awschalom says.

    And it's not the only new way. Awschalom's group also scored a big hit generating spins without using any magnetic material at all, by simply engineering successive layers of semiconductor materials to harbor a type of bending or “strain” in their atomic lattices. Electric fields in strained semiconductors vary across the material, Awschalom explains, so as electrons move through the lattice, they “feel” the magnetic field changing, which in turn influences their spins.

    It remains to be seen whether such novel techniques will finally give spintronics the push it needs to succeed as a working technology. But Awschalom says that theorists have already begun proposing novel types of spintronic architectures to take advantage of the effects.

  16. AMERICAN PHYSICAL SOCIETY MEETING

    Lightning Strikes and Gammas Follow?

    1. Kim Krieger

    MONTREAL, CANADA—More than 6000 physicists braved an early spring freeze here from 22 to 26 March for the American Physical Society's largest-ever March Meeting.

    The next time an electrical storm lights up a summer night, be aware—the sky's glowing in the dark for longer than you might imagine. Gamma rays shoot out of the sky minutes to hours after lightning strikes. Nuclear reactions fizzing in the atmosphere may be the source, and lightning could be the trigger, researchers reported at the meeting. The late-blooming rays, discovered by Mark Greenfield and colleagues at the International Christian University in Tokyo, Japan, could point to an unsuspected source of nuclear processes in the atmosphere and may give physicists new insights into how lightning forms.

    “[Greenfield] seems to be on to something very intriguing,” says Joseph Dwyer, a physicist at Florida Institute of Technology in Melbourne. “The implications are big.”

    Greenfield's group began chasing lightning in 1999, after gamma ray detectors atop the university's physics building recorded radioactive rain—a documented result of radon gas in the atmosphere, but one the physicists had never heard of. Their interest piqued, they started to pay closer attention to the weather. Another surprise came after a lightning storm. Immediately after lightning crackled through the atmosphere, the detectors would register a burst of gamma rays, followed about 15 minutes later by an extended shower of gamma rays that peaked after about 70 minutes and then tapered off with a distinctive 50-minute half-life.

    Lightning packs a 10-million-volt punch, rending the sky with massive electric fields. Physicists know that the fields accelerate electrons, which streak upward and release gamma rays as they decelerate. These gamma rays burst just microseconds after the lightning irradiates the sky. Delayed gamma rays, though, had never been reported before. The timing of the gamma rays—the delay of a few tens of minutes, and the characteristic 50-minute half-life—suggests that they come from nuclear reactions in the atmosphere, Greenfield says. But it would take millions of electron volts of energy to spark such reactions—an amount some physicists think could be supplied only by lightning-triggering cosmic rays, so for now the ultimate source of the reactions is anybody's guess.

    Shocking discovery. In the aftermath of a lightning flash, nuclear reactions in the atmosphere create gamma ray showers that last for minutes or hours.

    CREDIT: C. CLARK/NOAA

    Whatever the cause, Greenfield and colleagues suspect that the lightning's electric field sends positive particles, perhaps ionized hydrogen atoms, careening into other atoms in Earth's atmosphere powerfully enough to cause nuclear reactions. The researchers suggest that accelerated protons slam into argon-40, a common isotope in the atmosphere, and transform it into chlorine-39. The chlorine then decays into excited argon-39, immediately giving off a gamma ray as it relaxes. Chlorine-39 has a 56-minute half-life, which fits nicely with the observed gamma rays. But Greenfield says the gamma rays could also come from many different reactions with an average half-life that just happens to match the observed 50-minute half-life.

    To determine which atoms are giving off gamma rays, the group has set up a high-resolution detector to measure the energies of the rays and see whether they match the signature of argon-39. To make such sensitive measurements, the detectors must be within a few hundred meters of the source of the gamma rays. For now, they're sitting on a rooftop, waiting for lightning to strike.

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