News this Week

Science  25 Jun 2004:
Vol. 304, Issue 5679, pp. 1884
  1. NONPROLIFERATION

    Coalition Throws 11th-Hour Lifeline to Iraqi Weaponeers

    1. Richard Stone

    LONDON—Every day is a survival test for Amna,* a physicist at Al-Nahrain University in Baghdad. “When I get into my car to leave for work, I don't know if I'll make it there alive,” she says. “And I don't know if I'll make it home in the evening. We just pray and hope for the best.”

    With the Coalition Provisional Authority about to hand over power to the interim Iraqi government amid a stepped-up terror campaign, Amna and other scientists have at least two new reasons to look to the future with guarded optimism. On 19 June, L. Paul Bremer, administrator of the provisional authority, signed an order to create the Iraqi Nonproliferation Programs Foundation (INPF), endowed with $37.5 million, to enlist former weapons scientists to work on reconstruction projects. The new Iraqi government will assume responsibility for the effort. A separate U.S. State Department project, the Iraq International Center for Science and Industry (IICSI), with a broad mandate to improve Iraq's scientific infrastructure, also got under way earlier this month. It will continue as a U.S.-run operation after the handover of power, at least until an agreement is negotiated with an Iraqi government to transform it into an intergovernmental organization. “We're not going to allow ourselves to be deterred by what's going on in Iraq now,” says Alex Dehgan, who until last week ran the provisional authority's redirection program for former weapons scientists.

    The efforts are being rolled out not a moment too soon. Coalition officials have a roster of 400 to 500 scientists, technicians, and engineers who were involved in weapons programs under Saddam Hussein and whose flight from Iraq would be considered a proliferation threat. Many former weaponeers, like the rest of the scientific community, have been largely out of work since the Iraq war. “You don't want these people just sitting at home with the knowledge that they have,” says Dehgan, an AAAS diplomacy fellow at the State Department (AAAS publishes Science). Former weaponeers “have been approached by agents and by insurgents,” says a coalition nonproliferation adviser, who knows one top scientist who spurned an offer from Iran.

    Less disconcerting to U.S. officials, but a potential loss to Iraq, is the possibility of a brain drain to the West. For example, Science has learned that Jafar Dhia Jafar, a highly regarded physicist who ran the nuclear program under Saddam and is now in the United Arab Emirates, has been offered a position at a U.S. national laboratory.

    Previous work experience.

    This mural at Baghdad's convention center depicts a soldier using the power of the atom to defend Iraq against Western aggressors.

    CREDIT: A. DEHGAN

    INPF's initial endowment comes from funds left over from the Oil-for-Food Program that were earmarked for nonproliferation. According to C. Tom Owens, chief executive officer of the U.S. Civilian Research and Development Foundation, which has a pilot project for engaging Iraqi scientists, “INPF can be an important anchor for reviving the scientific community.” In the long term, says Carleton Phillips, special adviser on nonproliferation coordination for the coalition, the foundation is meant to “mature into something like the U.S. National Science Foundation and serve Iraqi science and engineering in the broad sense.” Phillips, a mammalian biologist at Texas Tech University in Lubbock who's on loan to the State Department, will wrap up his tour of duty next month. “It's about time to stow the Beretta,” he says. “I'm looking forward to getting into the lab and writing scientific papers again.”

    Several dozen elite scientists who remain in Baghdad are already working for IICSI. In the coming months, the center, with a budget of $2 million a year for the next 2 years, plans to rebuild labs, train scientists in basics such as ethics and proposal writing, fund travel grants for meetings, set up a venture capital fund, and hire more former weaponeers to work on reconstruction projects. Rebuilding infrastructure is expected to be a slog. Most labs have deteriorated badly since the Iran-Iraq War, and even basics such as recent scientific literature are lacking.

    IICSI's debut caps a 6-month setup sprint before the transfer of power next week. Its mission is so sensitive, and the security situation so shaky, that its precise location in Baghdad cannot be published. But Dehgan, who spoke with Science last week in London, emphasizes that it is outside the so-called Green Zone, the coalition's heavily guarded headquarters. “The only way to get scientists to trust you is to meet them and experience the same risks that they are experiencing every day,” says Dehgan, who earlier this year had passed through a checkpoint 20 minutes before it was bombed. As he was leaving Baghdad for London last week, the C-130 transport plane he was on came under attack and had to take evasive maneuvers and throw off chaff.

    A second order signed by Bremer this month creates an Iraq Radiological Source Regulatory Authority. Half of its $7.5 million budget will be devoted to securing radiological sources such as yellow cake at the Tuwaitha Nuclear Research Center, which suffered extensive looting last year. Some staff will be former weapons personnel.

    Amna says the flurry of activity is encouraging. Safety issues aside, she says, doing research in Iraq is nearly impossible now, with 8 hours of electricity a day, at best, in temperatures exceeding 40°C. “Scientists are eager to see something done,” she says.

    • *Her name has been changed.

  2. ITER

    Crunch Time, Again, on Fusion Project

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

    CAMBRIDGE, U.K.—A $10 billion effort to harness energy from nuclear fusion was teetering on a knife edge earlier this week after another deadlocked meeting of its six international partners. Since last December, the six—China, the European Union, Japan, South Korea, Russia, and the United States—have been split over whether to build the International Thermonuclear Experimental Reactor (ITER) at Rokkasho in Japan or Cadarache in France. A meeting on 18 June threatened to turn into a bidding war as both Japan and the E.U. offered to up their contribution if they were to host the ITER tokamak. But European sources fear that Japan and the United States are on the verge of turning their backs on the partnership to build the tokamak themselves at Rokkasho.

    After 2 decades of preparation for the grand experiment, which aims to reproduce the sun's furnace here on Earth, a decision on the site was expected by the end of 2003. But with the E.U. and Japan equally determined to play host, more technical studies were carried out, followed by a series of meetings exploring a “broader” fusion research program with other facilities that would speed the move to commercial reactors and could be sited in the nation that does not get to host the tokamak (Science, 2 April, p. 26).

    Fission over fusion.

    Both Europe and Japan have increased their offers to host ITER.

    CREDIT: ITER

    Although the broad approach proved popular, neither the E.U. nor Japan wants to play second fiddle. Each has already promised to pay up to 48% of ITER's costs in return for the tokamak. In Vienna last week, both raised their bids to 50% and offered to pay up to half the cost—$540 million—of a broadened program. “We still have mirror-image proposals,” says Bernard Bigot, France's high commissioner for atomic energy, who attended the meeting.

    A day of reckoning may be looming. After the Vienna meeting, European sources told Science that Japan, with U.S. support, appears to be preparing to forge ahead without the backing of all the ITER partners. The U.S. delegation expressed at the meeting that one partner should be able to contribute more than half the project's costs; the E.U. delegates responded that ITER would then cease to be a true international collaboration. And the United States is said to have asked if money committed to the broader program could be diverted to ITER itself. Japanese delegates backed this idea, which suggests to some in Europe that Japan would use that money to push ahead on ITER with fewer partners.

    An official at Japan's education ministry, which is responsible for fusion research, denied that Japan is considering unilateral action. “The basic policy is still to make ITER a six-country collaboration,” he says. But Achilleas Mitsos, E.U.'s research chief, has his doubts. “The Japanese didn't say they would go it alone, but I wouldn't be surprised.” The issue may soon come to a head. The U.S. delegation is said to be pressing for a decision by the end of June.

  3. EUROPEAN FUNDING

    E.U. Proposes Bigger Framework Plus a Bonus for Researchers

    1. Gretchen Vogel

    BERLIN—Researchers got some good news from the European Union last week, but with a sting in the tail. The European Commission (EC), the E.U.'s executive body, committed itself on 16 June to creating a new funding body that will support fundamental research based on quality alone, something researchers have wanted for several years (Science, 2 January, p. 23). But the EC intends to bankroll this European Research Council (ERC) by doubling the budget of its vast and unwieldy Framework program from its current $6 billion to an average of $12 billion per year from 2007 to 2013.

    In its current form, Framework concentrates on applied research and will only fund collaborations between labs in more than one member state. It has been roundly criticized by researchers for being a bureaucratic nightmare. A campaign has been building for an ERC more sympathetic to the needs of basic researchers and separate from the E.U. bureaucracy. One group of scientists called on the E.U. to cut the Framework budget in half and divert the extra money to launching an ERC.

    The EC's latest proposal, however, points in the opposite direction. It has called for the budget of the next multiyear program, Framework 7, to double that of Framework 6—with part of the increase going to launch an ERC within the program. The expanded budget would also include new funding for space science and security research. “This is what we've been fighting for,” says Erwin Neher of the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany, and a member of the EC's European Research Advisory Board (EURAB). “That the commission has grabbed on to this idea is a very good sign.”

    Supporters of the ERC have worried that any program administered by the E.U. would have the same headaches as Framework, but Mogens Flensted-Jensen of the Royal Veterinary and Agricultural University in Frederiksberg, Denmark, who helped organize one of the first meetings calling for an ERC, says he is optimistic. “If they decide to spend more money, I think we will see a semi-independent ERC” funded by Framework 7.

    Any funding increase has to be approved by the Member States' finance ministers and the newly elected European Parliament. But the political momentum is behind the EC's proposal, says Helga Nowotny of the Swiss Federal Institute of Technology in Zurich and president of EURAB. Recently, a panel of economists advising EC President Romano Prodi recommended increasing funds for science, she notes. And the Netherlands, whose science minister, Maria van der Hoeven, is a strong supporter of an ERC, takes over the rotating E.U. presidency in July.

    The next concrete step should come when science ministers from Member States meet on 2 July to discuss the EC's proposal, Nowotny says: “If nothing moves there, it would be a big step backwards.”

  4. OCEAN RESEARCH

    Tight NSF Budget Means Less Time at Sea for University Fleet

    1. Jeffrey Mervis

    U.S. marine scientists are facing a 10% cut in the number of days they can spend at sea, as the National Science Foundation (NSF) struggles with a flat budget for ocean science.

    Satisfying every oceangoing scientist with a U.S. government grant is no picnic under the best of circumstances. But when money's tight, it's a nightmare. In January, researchers who use the 27-vessel fleet of the University-National Oceanographic Laboratory System (UNOLS) got a taste of the future when NSF came up $12 million short of what it hoped to spend on ship time this year. UNOLS was forced to defer 13 cruises. This month, NSF and Navy officials told scientists to pare 30 to 40 days from the operating time for the fleet's four biggest ships during the upcoming 2004–05 season. The effect of that reduction—to about 270 days a year—will become clearer next month when UNOLS holds its annual scheduling exercise at NSF.

    With the biggest ships costing roughly $22,000 a day to operate, “that reduction in ship days will save some money, but it will also have an impact on the amount of science that gets done,” says UNOLS chair Timothy Cowles of Oregon State University in Corvallis. “NSF is not the bad guy here; they can do only as much as their budget allows. But funding for ocean science just isn't keeping up with the opportunities out there.”

    Homebodies.

    Big ships like the Roger Revelle are likely to operate for fewer days next year.

    CREDIT: SCRIPPS INSTITUTION OF OCEANOGRAPHY

    NSF funds about 65% of the annual ship days for the UNOLS fleet. (The Office of Naval Research and the National Oceanic and Atmospheric Administration together fund another 25%, with the remainder coming from a variety of other sources.) A 15% jump in 2003 research funding created increased demand for 2004 ship time. But an unexpectedly flat 2004 budget didn't allow NSF to accommodate that “bow wave,” explains Michael Reeve of NSF's Division of Ocean Sciences. Division Director James Yoder says he made up half of this year's shortfall by borrowing from elsewhere in his $320 million budget, but there's still a backlog. And 2005 doesn't look any better: NSF requested only 2% more for its ocean research and facilities programs, and observers say Congress is more likely to trim than boost the agency's overall request for a 3% hike.

    Meanwhile, the costs of operating the UNOLS fleet keep climbing. Reeve estimates that NSF has spent $1 million to meet mandated security upgrades since the September 2001 terrorist attacks. And fuel, traditionally about a quarter of a ship's operating costs, is taking a bigger share as energy prices rise.

    Getting scientists aboard the right ship in the right place at the right time requires intricate planning. And sometimes an investigator doesn't mind being bumped, says Alan Chave of the Woods Hole Oceanographic Institution in Massachusetts, whose cruise this fall to redeploy equipment attached to a deep-sea cable in the Pacific has been delayed a year. “Having more time is actually a good thing,” says Chave, who next month will haul up the faulty equipment. “We need to find out what went wrong and then fix it.” For most scientists, however, delays mean a slower pace of discovery.

    “We'll try to defer as few cruises as possible,” says Cowles about next month's scheduling meeting. “But we know that we'll make people unhappy.”

  5. NEUROSCIENCE

    The Mice That Don't Miss Mom: Love and the μ-Opioid Receptor

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

    Blind, deaf, and hungry, a newborn mouse can't take care of itself. Take away its mother, and a pup will scream bloody murder for someone to come help it. But take away, along with mom, the neuronal receptors that respond to morphine, and the pup just doesn't seem to care.

    This finding in a study led by Francesca D'Amato of the CNR Institute of Neuroscience, Psychobiology, and Psychopharmacology in Rome, Italy, reported on page 1983, supports pharmacological evidence from a variety of animals that the opioid reward system helps wee ones bond with others. The mutant pups behave typically in other ways—they can smell threatening males and whine uncontrollably when cold, indicating that opioids affect social bonding specifically.

    This is the “most robust” evidence to date showing that “a pup needs opiate activation in order to find its mother rewarding,” says neuroscientist Jaak Panksepp of Bowling Green State University in Ohio. “Endogenous opioid activity is a very important player in social feelings, especially of very young and helpless animals.”

    Opioids are best known as painkillers. But give morphine to, say, lonely baby guinea pigs crying for mom, and their shrieks turn into whimpers. “There's an intuitive appeal to the idea that the emotional pain of separation uses the same factors that mediate physical pain,” says behavioral neuroscientist Thomas Insel of the National Institute of Mental Health (NIMH) in Bethesda, Maryland. Pharmacological agents that block or activate morphine receptors in animals from sheep to monkeys support the idea that opioids and their dopamine reward system give baby animals pleasure from nuzzling mom and vice versa, forming a lasting bond—some say it's love—between them. But four different receptors can interact with opioids, and some believe the cleanest way to test a receptor's function is to remove it from the organism.

    No fuzzy feeling.

    Mouse pups lacking a specific opioid receptor don't cry when separated from their mother.

    CREDIT: F. D'AMATO

    So D'Amato and colleagues tested infant attachment in mouse pups born to parents genetically designed to lack both copies of the μ-opioid receptor gene. The team looked at two different measures of behavior: ultrasonic vocalizations, akin to baby wails, and the pups' preferences for nesting beds. First, the researchers removed mom from the living quarters and, 5 minutes later, subjected the pups to a new environment. Normal 8-day-old pups screamed incessantly when placed into a beaker with clean bedding; they screamed about half as much when the beaker contained old, mom-smelling fluff. The mutant mice, though, hardly screamed at all. The lack of screeching was not due to an inability to smell or react to adverse circumstances: When threatening males were near, the mutant pups squealed even more than the normal pups, and all pups freaked comparably when placed in a frigid beaker.

    The researchers then tested whether the pups showed any preferences for familiar smells by allowing them access to two different cages. When given the choice between their home and fresh bedding, both normal and mutant babes waddled to their old abode. When the mice could choose between their own place or a strange mom's nest, all of the normal pups chose their own place. But only a third of the pups lacking the μ-opioid receptor went home. “The pups weren't able to discriminate between moms,” says D'Amato.

    Although the work is “compelling evidence” that opioids play a role in maternal reward, Panksepp points out that by no means are they the whole story. On the research front, opioids have taken a back seat to many other neurochemical components being investigated, says NIMH psychologist Eric Nelson. “Oxytocin has been in the forefront of maternal attachment research recently. This work brings opioids back into focus,” Eric Nelson says.

    Some are more skeptical about the work's significance. That mutant mice aren't bothered by being alone is “a fascinating piece of behavior,” says Insel, but the kinds of attachments that humans have aren't seen in mouse families, which are like communes. “You can think of [human] attachment as love,” he says. “It's selective and enduring. Mice don't have selective attachments.”

    The authors suggest extending this research to look at whether opioids contribute to attachment disorders such as autism. But Panksepp says the work confirms what the “war on drugs” already tells us. “The biggest societal bottom line of this research is not autism, as the authors conclude,” says Panksepp, “but the fact that our young people can feel the warmth of human love pharmacologically, if they are not getting enough of it from their social networks.” That thought may leave you crying for mom.

  6. 2004 ELECTION

    Kerry Blasts Bush Over U.S. Science

    1. Andrew Lawler

    Science has never been a major issue in U.S. presidential campaigns. But this week John Kerry, the presumptive Democratic nominee, made the state of America's research enterprise a part of his effort to unseat President George W. Bush.

    Speaking in Denver, Colorado, on 21 June, Kerry harshly criticized the president for leading “one of the most antiscience Administrations in history.” The Massachusetts senator also pledged to lift the ban on stem cell research and remove ideology from scientific decisionmaking if he wins in November.

    Kerry's talk during a Colorado campaign swing came the same day that four dozen Nobel Prize winners released a letter supporting his candidacy. The laureates, including biologist and California Institute of Technology President David Baltimore, Harvard University chemist Walter Gilbert, and retired Department of Energy lab chief Burton Richter, accused Bush of “undermining the foundation of America's future” by reducing research funding, scaring away foreign talent, and ignoring scientific consensus on the dangers of global warming.

    Science lesson.

    John Kerry claims that ideology rules the Bush Administration's policies.

    CREDIT: DAVID ZALUBOWSKI/AP PHOTO

    In a fact sheet put out the same day, Kerry's campaign blasted the Bush Administration for putting “politics over science to please their right-wing constituency.” Kerry, who supports overturning the ban on federal funding for stem cell lines developed after 9 August 2001, said, “If we pursue the limitless potential of our science and … use it wisely, we will save millions of lives and earn the gratitude of future generations.”

    The Bush campaign wasted no time responding to the attacks. “Only John Kerry would declare the country to be in scientific decline on a day when the country's first privately funded space trip is successfully completed,” says spokesperson Steve Schmidt. “America is the world leader in patents, research and development, and Nobel prizes, and the president's 2005 budget [would] raise federal research and development funding to $132 billion, a 44% increase since taking office.”

  7. ARCHAEOLOGY

    Putting the Stone in Stonehenge

    1. Richard Stone

    CAMBRIDGE, U.K.—Medieval Britons thought that only the magic of Merlin could have erected the massive stones at Stonehenge, one of the world's most famous prehistoric monuments. But now some of Stonehenge's builders may have come to light. Earlier this week, archaeologists announced that they had unearthed a grave of three men who appear to have grown up in Wales—the presumed source of the monument's bluestones—and were buried near Stonehenge some 4300 years ago, around the time it was being built.

    There is no direct evidence linking the remains and the monument, whose purpose—temple, observatory, or status symbol—is an enduring mystery. Rather, it boils down to a case of being in the right place at the right time. “It's an intriguing hypothesis,” says archaeologist Alison Sheridan of the National Museums of Scotland in Edinburgh.

    The grave came to light in May 2003, when a construction crew was digging a trench for a water pipe at Boscombe Down near Stonehenge. They called in Wessex Archaeology, a firm in Salisbury, to continue the excavations. The Wessex team unearthed the remains of three men, a teenager, and three children. The similarity of the skulls of the men and the teenager suggest they are related, says archaeologist Andrew Fitzpatrick of Wessex Archaeology. Burial goods such as Beaker pots suggest that the grave dates from 4200 to 4400 years ago, during the Early Bronze Age. Radiocarbon dates of the bones are not yet in.

    The find complements the firm's discovery in 2002 of the Amesbury Archer, whose grave near Stonehenge is the richest found in Britain from the Early Bronze Age. Analysis of the archer's tooth enamel showed that he grew up in the Alps before emigrating to Britain—also around 4300 years ago. The high status that the archer clearly enjoyed has prompted some archaeologists to speculate that he may have catalyzed or overseen the vast construction effort that erected the Stonehenge stones.

    Grave giveaway.

    This and other Beaker pots pegged the burial near Stonehenge to the Early Bronze Age.

    CREDIT: TOM GOSKAR/WESSEX ARCHAEOLOGY

    Like the archer's, it is the teeth of the three Boscombe Bowmen—called such because of the arrowheads in their grave—that are doing most of the talking. As teeth form, enamel soaks up oxygen, primarily from drinking water, along with other elements. Scientists with the British Geological Survey (BGS) found that the bowmen's enamel has a high proportion of strontium. Coupled with analysis of oxygen isotope ratios, which depend on local environmental conditions such as temperature and distance from the coast, the team determined that the bowmen lived until age 6 in Wales or the nearby Lake District. “This provides a remarkable picture of prehistoric migration,” says the BGS's Jane Evans.

    The connection with Stonehenge, though, is circumstantial. The monument's outer ring is made of huge sandstones believed to have been quarried from the Marlborough Downs, 30 kilometers to the north. The smaller bluestones in the inner ring are thought to have been hauled from the Preseli Hills, 250 kilometers away in southwest Wales, and arranged at Stonehenge between 4000 and 4400 years ago. Fitzpatrick says the association between the bones and the stones is irresistible. Other archaeologists are looking forward to probing that tantalizing hypothesis further.

  8. NATIONAL INSTITUTES OF HEALTH

    Panel Weighs Starter R01 Grants

    1. Jocelyn Kaiser

    For years, the biomedical community has worried about the graying of the average investigator supported by the National Institutes of Health (NIH). A National Academy of Sciences (NAS) panel tackling this stubborn problem has revived an old idea: a special grant tailored to young researchers with bright ideas but little or no preliminary data. At a workshop last week, participants were mostly positive but noted problems that would need to be overcome.

    Experts have watched with alarm as the proportion of researchers under 35 receiving grants from NIH has slipped from 23% in 1980 to below 4% in 2001 (Science, 4 October 2002, p. 40). As possible reasons, they point to fewer new tenure-track positions and more complex biology, among others. NIH Director Elias Zerhouni, who asked for the NAS study, told the committee that he wants “specific action steps” and “testable pilots” rather than more handwringing.

    NIH had such a pilot once, called the R29. But it was phased out 6 years ago after the agency concluded that it was too small (at $70,000 a year compared with more than $160,000 at the time for the standard R01 grant) and that it was not valued by universities. Instead, NIH added a checkbox for new investigators on the R01 application and asked reviewers to put less emphasis on preliminary data. But the checkbox hasn't made any difference, notes the NAS committee's chair, Thomas Cech, who is also president of the Howard Hughes Medical Institute in Chevy Chase, Maryland.

    Aging youngsters.

    The average age of new investigators receiving the two main NIH research grant types rose by about 5 years in the past 2 decades.

    CREDIT: NIH

    Instead, Cech and his co-members are contemplating a different kind of R01. By keeping the name, Cech says, the 5-year grant would give investigators as much money as a regular R01 and wouldn't “carry a stigma” with tenure committees. NIH would drop the section for preliminary data and judge applicants on the methods they propose and previous experience, such as papers and patents. Study sections would review these grants separately from regular R01s.

    NIH program staff expressed a few concerns. “If somebody has preliminary data, they will try to tuck it in,” and study sections may favor those grants, predicted Brent Stanfield, acting director of the NIH Center for Scientific Review. And with the flattening of NIH's budget, finding money for the new program might require rebalancing the grants portfolio or capping large R01 grants, other participants noted.

    But the special R01 sounds like a good idea to Howard Garrison, public affairs director for the Federation of American Societies for Experimental Biology. “Most people I know are very supportive of doing something like this,” he says. And one young investigator at the workshop, University of Maryland cell biologist Iqbal Hamza, 36, says, “I love it.” Hamza was told not to apply for an R01 because his idea was too radical. And the size of the awards from the NIH program that eventually funded his proposal are much smaller.

    Cech's committee is also examining how to help postdocs gain independence and whether more non-tenure-track faculty members should be eligible for R01 grants. He says the panel expects to issue its report later this year.

  9. OCCUPATIONAL HEALTH

    Authors Turn Up Heat Over Disputed Paper

    1. Dan Ferber

    The furor continues over a legally embattled study of cancer risk among former IBM workers. Last week, 13 authors withdrew nine articles from a special issue of a journal on workers' health, with the support of the guest editor, to protest the publisher's rejection of the paper.

    The controversial study, by epidemiologists Richard Clapp of Boston University and Rebecca Johnson of Epicenter in Circle Pines, Minnesota, suggests that some IBM computer-chip workers were more likely than members of the general population to die of certain cancers. IBM has dismissed the analysis, noting that the research was paid for by attorneys for former IBM workers who are suing IBM, and that Clapp was a potential witness for the plaintiffs. (A judge ruled that the study could not be admitted as evidence in one case because it did not establish a link between workplace exposure and increased cancer risk.)

    In March, IBM lawyers warned Clapp that publishing the paper would violate a court order specifying that the internal IBM data be used only in litigation (Science, 14 May, p. 937). In response, Clapp withdrew the paper from a special issue of Clinics in Occupational and Environmental Medicine, published by Elsevier.

    Clapp resubmitted the article in May, however, after receiving legal advice that the study was in the public domain. The journal's guest editor, toxicologist Joseph LaDou of the University of California, San Francisco, who was also listed as a potential witness for plaintiffs suing IBM, accepted it a second time. (It had already cleared peer review.) But Elsevier overruled LaDou, turning the article away, according to Elsevier, because the Clinics journals publish review articles, not original research.

    Nothing in Elsevier's instructions to him precluded articles with original research, LaDou says, adding, “They don't want it because it's a hot potato.” In an e-mail sent on 17 June, LaDou and 11 of the 12 other authors pulled their papers from the journal not long before it was to go to press; the last author has since joined the boycott.

    Elsevier spokesperson Eric Merkel-Sobotta said, “Hostage-taking is not an effective way of getting your point across.” Asked whether IBM had contacted Elsevier about the study, Merkel-Sobotta said, “there's been no coercion and no threats.” IBM spokesperson Chris Andrews says that IBM “has not contacted anyone with regards to [Clapp's] intent to publish.”

  10. BIOMONITORING

    Pollution Gets Personal

    1. Erik Stokstad

    Biomonitoring is charting the public's exposure to many chemicals, but often the health effects are unclear

    After the World Trade Center towers collapsed on 11 September 2001, the world was gripped by the search for survivors. Researchers at the Centers for Disease Control and Prevention (CDC) raced to address an additional concern: the exposure of rescuers to potentially toxic smoke from the rubble. They took blood and urine samples from 370 firefighters, including those digging through the rubble at Ground Zero and those putting out nearby blazes. After examining the samples for dioxins, cyanide, and 100 other chemicals associated with burning buildings, they determined that the rescuers had not been exposed to dangerous levels. Although the team couldn't rule out all possible health effects, James Pirkle, deputy director for science at CDC's Environmental Health Laboratory, says the fast tests were “a huge help,” eliminating the need for a lot of further studies.

    What made the rapid findings possible were tremendous advances in methods of sampling human tissue for chemicals, called biomonitoring. Over the past decade, analytical techniques have improved so much that researchers can detect ever smaller concentrations of chemicals in a single blood sample. The largest effort is CDC's National Report on Human Exposure to Environmental Chemicals, an ongoing $6.5 million survey that is now measuring about 145 chemicals in some 2500 people across the United States every 2 years. “It's critically important early intelligence about compounds that are getting into people,” says Philip Landrigan of Mount Sinai School of Medicine in New York City.

    Biomonitoring is hot. With lab costs down, environmental groups are commissioning their own analyses of chemical exposures. Last year, the Environmental Working Group (EWG) in Washington, D.C., released a report entitled Body Burden: The Pollution in People that examined the levels of 210 chemicals in nine people. In April, the World Wildlife Federation tested for 101 compounds in 39 members of the European Parliament. The impetus is clear: Such studies can generate headlines and political leverage. As a result of biomonitoring data, “we'll see sweeping changes in our system of public health safeguards,” predicts Jane Houlihan, EWG's vice president of research.

    But although biomonitoring can provide reams of statistics about the chemicals people are exposed to, it can't necessarily indicate whether such exposures are likely to make them sick. So while environmentalists herald biomonitoring as a valuable tool for precautionary action, chemical manufacturers worry that it will spark unjustified alarm and costly regulations that may not provide much real benefit to public health. “Industry sees a movement toward collecting a lot of biomonitoring data prematurely, before we know what to do with it,” says Nancy Doerrer, scientific program manager at ILSI Health and Environmental Sciences Institute, an industry-funded group in Washington, D.C. What's becoming ever more obvious, researchers say, is a growing data gap: Although testing for a chemical can take just a few days, discerning its impact on health takes years, says Landrigan. “It's a real conundrum.”

    Clearing the smoke.

    Rapid sampling of rescuers alleviated some health concerns.

    CREDIT: MARK PETERSON/CORBIS

    Going public

    Public health researchers have long studied worker exposure to chemicals. Such testing was key in figuring out the toxicity of PCBs and dioxins, for example. But measurements of actual exposures among, say, chemical plant workers don't translate easily to the average person, who encounters small concentrations through food, air, or skin.

    Enter CDC, which in 1976 first looked at blood and urine samples of the general population and checked for environmental chemicals, including lead and a handful of pesticides. Examining the public for chemical exposure was “a fundamental change in mindset,” says Joseph Thornton, a molecular biologist at the University of Oregon, Eugene. The same point is hammered by environmental groups: Everyone is exposed to chemicals.

    CDC's small testing program was massively expanded in the late 1990s to become the world's largest survey of chemical exposure among the general public. As part of the National Health and Nutrition Examination Survey (NHANES), CDC's biomonitoring results provide a guide to typical exposure to chemicals that pose a known or possible threat to health. Many are pesticides; others are ingredients in cosmetics, plastics, and other components of everyday life. Says Arnold Schecter of the University of Texas School of Public Health in Dallas: “CDC is providing a very careful look at the U.S., a nice snapshot.”

    Biomonitoring's strong suit is that it directly measures the amount of a chemical in bodily fluids or tissues. Those exposure data are much more relevant for risk assessments than are extrapolations from chemical concentrations in soil, air, or water. What you really want to know is not whether asbestos is in the walls but whether it's in your lungs, says Schecter: “If you didn't get it in your body, you don't need to worry about health effects.”

    Ideally, biomonitoring can help public health officials figure out what to worry about—and what not to worry about. But a caveat is that high levels aren't necessarily dangerous, and typical levels aren't necessarily safe. Other major factors relevant to health are how long the compounds persist in the body and the degree to which various groups are exposed. The large sample size of NHANES helps average out these variations.

    What's normal?

    Early surveys were at irregular intervals, but CDC decided in the late 1990s to conduct an ongoing sample of the U.S. population every 2 years. All year long, CDC teams are taking four tractor-trailers to neighborhoods in 30 locations across the country, interviewing residents, performing exams, and sampling blood and urine.

    The number of chemicals tested has jumped from 27 in 2001 to 116 in the most recent survey, released last year. Next year's edition will include about 145. Costs of testing have dropped and speed has shot up, thanks to improvements in mass spectroscopy and other techniques, many of which were pioneered at CDC. “The analytical science has advanced just astronomically,” says Landrigan. Since the 1970s, the precision of lead measurements has increased dramatically, and instead of needing 10 milliliters of blood, only a drop is required. That means researchers can test for many dozens of chemicals in a single 10-milliliter blood sample. More chemicals and more frequent testing mean they can spot trends sooner.

    Biomonitoring showed its mettle early on when it tracked the success of a major public health intervention: the reduction of blood lead levels. When the United States and other countries set out to reduce automobile emissions, models had suggested that lead levels in children would decrease slightly as gas lead levels declined. Beginning in 1976, CDC began checking lead levels in children and adults. Although some questioned the expense of biomonitoring, recalls Landrigan, “the payoff was almost instantaneous,” by showing that the lowered lead level in gasoline was having a dramatic effect. In fact, biomonitoring revealed that blood lead levels declined about 10-fold more than expected between 1976 and 1980. These data were instrumental in the Environmental Protection Agency's (EPA's) decision to remove lead from gasoline more rapidly.

    Worry?

    EWG found, on average, 91 chemicals in people. For many, health effects are unknown.

    CREDIT: ROYALTY-FREE/CORBIS

    By determining typical exposures in the general population—called a reference range—researchers can better investigate concerns about cancer clusters or other apparently heightened disease rates. In 2001, for example, the state of Nevada asked CDC to help study leukemia rates in Fallon, Nevada. Of the 110 chemicals measured, they identified two, tungsten and arsenic, that were found in much higher concentrations among all residents—healthy and sick—than in the rest of the population. As a result, the National Institutes of Health's National Toxicology Program put tungsten on its priority test list and is now pushing to determine whether the metal increases cancer rates in animals.

    CDC's data also highlight national concerns. Its first National Report on Human Exposure to Environmental Chemicals, released in 2001, revealed, for instance, that about 8% of all women of childbearing age—more than expected—have levels of mercury, a potent neurotoxin, higher than the level EPA generally regards as safe. The biomonitoring also showed that the average level in this group is four times higher than that in children—suggesting that regulators can't extrapolate between the two groups. CDC is now measuring various kinds of mercury in people, to determine how much comes from fish, drinking water, or other sources. Researchers are also eager to see whether a revised Food and Drug Administration (FDA) advisory on fish consumption is making a difference.

    What does it mean?

    Biomonitoring doesn't always clear the air, though. CDC tends to pick chemicals for which toxicity data indicate a human health effect. But it also chooses chemicals that are of potential concern because of animal studies that suggest a danger and the number of people of likely exposed. And when toxicity is not clear-cut, it becomes difficult to know what to make of the findings.

    Take phthalates, chemicals found in a wide range of consumer products. In 2000, CDC published a paper on a subset of 289 adults from NHANES, the largest look at these chemicals at that time. Metabolites of several phthalates were higher in women aged 20 to 40 than in other groups. These are ingredients used in nail polish, cosmetics, and other personal-care products such as soap and shampoo, particularly those with fragrances added. Some evidence from animals indicates that the compounds can be estrogenic and could lead to reproductive toxicity. “CDC and NHANES data … made people sit up and pay attention to phthalates,” says Gina Solomon of the University of California, San Francisco, and the Natural Resources Defense Council.

    EWG launched a campaign to remove these compounds from cosmetics and last week petitioned FDA to put warning labels about phthalates and other chemicals on personal care products. But an industry group fired back that the statements of possible danger to fetuses were “alarmist,” and it pointed out that the second national report of 2003 (see sidebar on p. 1893), which includes many more people than the initial study, didn't find elevated levels among 20- and 30-year-old women. CDC cautions, however, that there aren't any guidelines yet on what levels might cause health effects.

    Polybrominated diphenyl ethers (PBDEs) are another case in point. The European Union and California have banned the compounds, widely used as flame retardants, after researchers discovered that levels in breast milk had shot up—even though nobody knows for sure whether these compounds are toxic to humans. Levels are still rising in the United States (Science, 18 June, p. 1730). Last year, the main U.S. manufacturer voluntarily began to phase out two PBDEs, but EPA hasn't regulated any. CDC is now measuring PBDEs.

    For EPA, the problem is that the pace of biomonitoring has eclipsed that of the basic epidemiology and toxicology needed to reveal whether a chemical causes harm. A big step forward, researchers say, would be the multi-agency National Children's Study (Science, 11 July 2003, p. 162), a $2.7 billion health survey intended to follow 100,000 children as they grow up, monitoring levels of environmental chemicals and looking for any associations with disease. It's ready to start in late 2005 if it can get $27 million in funding. Such a prospective study is needed to answer the questions raised by biomonitoring, says Landrigan, a project booster. But it could be years if not decades before those answers are in. “There's no easy way to foreshorten that,” Landrigan says.

  11. BIOMONITORING

    A Snapshot of the U.S. Chemical Burden

    1. Erik Stokstad

    Highlights from the Centers for Disease Control and Prevention's (CDC's) 2003 report:

    Lead. Blood lead levels continue to fall; 2.2% of children ages 1 to 5 had blood lead levels above 10 micrograms per deciliter, the amount set by the CDC as an unacceptable health risk, down from 4.4% in the early 1990s.

    Environmental tobacco smoke. Measured by cotinine—a metabolite of nicotine—blood levels of secondhand tobacco smoke were down 75% in adults over the 1990s, due to workplace and other restrictions on public smoking. Levels in children declined by 58% but are still twice as high as in adults—which points out that new efforts need to be made to reduce children's exposure to secondhand smoke, says CDC's James Pirkle.

    DDT. Although DDT levels have continued to decline since the 1980s, the compound shows up in people born after 1973—the year DDT was banned. Clearly, DDT persists in the environment, and it may be coming into the country in imported food, says Pirkle. Blood levels of DDE, a metabolite of DDT, were three times higher in Mexican Americans than in other groups, raising the question of where they are being exposed—while growing up in or visiting Mexico, or while living in the United States?

    Organophosphate pesticides. Urine levels of these pesticides, including the insecticides chlorpyrifos and diazinon, turned out to be higher in children than in adults, perhaps because their metabolism is different from adults'. Researchers are watching closely to see if the levels go down nationwide, now that the compound has been banned for household use.

  12. MICHAEL MAJERUS PROFILE

    In Defense of Darwin and a Former Icon of Evolution

    1. Fiona Proffitt

    After a severe drubbing, the famous example of the peppered moth is getting refurbished

    CAMBRIDGE, U.K.—Michael Majerus's fascination for “bugs,” as he calls all insects, was ignited at the tender age of 4. His mother can recall the exact moment: It was late summer, and he caught his first butterfly—a red admiral resting on a white chrysanthemum—with his bare hands. From that point on, he was hooked. At night when other children were in bed, the young Majerus roamed the English countryside tending his moth traps. Now 50 and in his 25th year of teaching evolutionary genetics at the University of Cambridge, Majerus still runs his moth traps most nights.

    Majerus's research has focused on sexual selection, sex-ratio manipulation, and the evolution of melanism (the darkening of body color) in various moths, butterflies, and ladybirds. But over the past few years, half of his working life has been occupied by one controversial species, the peppered moth, Biston betularia, and an infamous study that's been attacked by both evolutionary biologists and anti-evolutionists.

    Through his research, Majerus found himself embroiled in the scientific debate over the evolutionary forces behind melanism in the peppered moth. Experiments by British lepidopterist Bernard Kettlewell in the 1950s claimed to show that bird predation, coupled with pollution, was responsible for a color shift in the moth population. But problems with Kettlewell's methodology led some scientists to doubt his conclusions. Majerus was not the first to point out the flaws, but by doing so, he inadvertently set off a wave of anti-evolutionist attacks. While acknowledging that Kettlewell made mistakes, Majerus believes Kettlewell was right in his conclusions and has taken it upon himself to prove it.

    Easy prey?

    Critics challenged the view that the moth population grew darker because birds were more likely to see and devour light individuals.

    CREDITS: M. MAJERUS

    As Majerus shows off some of the roughly 100,000 peppered moth pupae he'll rear for his latest experiment, it's clear that he's prepared to go to great lengths to make his case. Once the moths begin to emerge in May, Majerus begins a daily grind. He releases them at dusk and gets up at dawn to observe their fate: counting how many are plucked from their resting places by birds, and how many survive to see another night. He will continue this routine into August, as he has done for the past three summers. All he needs, he reckons, is another 2 years' worth of data—a total of some 4000 moth observations—to settle the controversy over whether bird predation is the major selective force in favoring one color form of the peppered moth over another.

    Small and unobtrusive, the peppered moth doesn't look like the star in an evolutionary drama. But the rise and fall of the almost-black melanic form (carbonaria) in tandem with changing pollution levels has become the most famous example of evolution in action. Through his pioneering experiments, Kettlewell claimed to have demonstrated that melanic peppered moths were more common in industrialized areas because they escaped the attention of predatory birds when resting against soot-blackened, lichen-free bark. Because more of the darker ones survived to produce the next generation, he argued, entire populations grew darker.

    But doubts emerged over Kettlewell's methodology in recent decades as researchers failed to replicate some of his results. His predation experiments were chiefly criticized for their artificiality: He placed the moths on exposed parts of trees in broad daylight, when they don't normally fly, rather than allowing them to settle naturally; he released them in large numbers, thereby inflating moth densities and possibly creating a magnet for predatory birds; and he used a mixture of lab-reared and wild-caught moths without checking to see whether they behaved the same way. Majerus summarized these criticisms in a book on the evolution of melanism in 1998 and stated that the simplified textbook story of the peppered moth was inaccurate, while asserting that Kettlewell's conclusions were qualitatively sound. Majerus had no idea at the time what a furor his book would cause.

    Jerry Coyne—a highly respected evolutionary geneticist at the University of Chicago—concluded in his review of Majerus's book in the 5 November 1998 issue of Nature that “for the time being, we must discard Biston as a well-understood example of natural selection in action, although it is clearly a case of evolution.” Coyne's words carried weight, and the anti-evolutionists were quick to twist them into an argument against natural selection itself. “Coyne might have just thought he was stirring things up. … As it happened, he was the lightning conductor,” observes Mark Ridley, an evolutionary biologist at the University of Oxford. Coyne thought the flaws in Kettlewell's experiments were sufficient to cast doubt on the idea that bird predation was the agent of natural selection in this case, although he says his “biological intuition is that predation is probably a major cause.”

    Majerus dismisses most critics of the bird predation hypothesis as being people who write about the peppered moth without having a “feel for the organism.” Many biologists start with theories and then test them in the field. Majerus takes the opposite and less fashionable approach: “There's another way of doing science, which is first find your organism and look at it incredibly closely, for a long time, in great detail and see what questions it asks you,” he says.

    Colleagues describe Majerus as a brilliant natural historian and a great communicator. He's made numerous appearances on radio, on television, and in the popular press, and he's on the circuit as an after-dinner speaker. “He doesn't have to try very hard to get a lot of people interested in what he's saying,” says former graduate student Matt Tinsley. “Mike likes having a small crowd of students around him and telling stories.”

    Moth man.

    Majerus, consorting here with hawk moths, has dedicated himself to improving upon Kettlewell's research of the 1950s on bird predation and insect body color.

    CREDIT: F. PROFFITT/SCIENCE

    It's a talent Majerus hopes to put to good use in defending the reputation of Kettlewell and the peppered moth in a road show, which he aims to take around Britain—and possibly the United States—later this year. He is motivated by growing concern over attacks on Kettlewell's character, most notably writer Judith Hooper's scathing account of the men behind the peppered moth story in her 2002 book Of Moths and Men: The Untold Story of Science and the Peppered Moth, which helped fuel an anti-evolutionist campaign to remove Biston from school textbooks. “A lot of [the campaign] is pointed at the peppered moth as being the example that Darwinism is debunked,” says Majerus, who wants to make a public stand against teaching creationism and “intelligent design” in biology classes. “To have people believe the biology of the planet is controlled by a Creator, I think that's dangerous.”

    After decades of moth-watching, Majerus is convinced that Kettlewell was right and that bird predation is the primary agent of natural selection on the peppered moth. “But that can never be enough,” he says, “because I'm also a scientist. … We're miles beyond reasonable doubt, but it's not scientific proof.”

    Majerus's experiment is designed to avoid the mistakes Kettlewell made when comparing the proportion of typical and melanic peppered moths that escape the attention of predatory birds. He's releasing a small number of moths, at night, and letting them choose their own hiding places within specially designed mesh sleeves, which he removes at dawn. Like Kettlewell, he's using a mixture of lab-reared and wild-caught moths, but his design allows him to test for potential differences between the two. Majerus is determined to get “a definite answer” on the bird predation issue.

    Although Majerus expects to confirm Kettlewell's conclusions, he claims not to care which way the results go: Any findings, he thinks, would make a splash by settling the controversy. But peppered moth expert and evolutionary geneticist Bruce Grant of the College of William and Mary in Williamsburg, Virginia, doubts that Majerus will silence the critics. “To do the job the right way is going to be too labor-intensive and it's just not worth it. … Right now, I think there are other things that need doing more.”

    Time is running out for studying the melanic peppered moth, which, with declining pollution levels, is expected to make up only 1% of the British peppered moth population by 2019. And for Majerus, there are other fish to fry: “I don't want to get stuck with peppered moths for the rest of my career,” he says, but he doesn't see his bug obsession waning anytime soon.

  13. QUANTUM PHYSICS

    Elite Retreat Takes the Measure of a Weirdly Ordinary World

    1. Adrian Cho

    At a remote lodge in the rural Midwest, physicists, philosophers, and historians confront the stubborn mysteries of quantum mechanics

    STILLWATER, MINNESOTA—Two men sit at a long table, oblivious to the breakfast-time commotion. One moves a coffee cup from one side of a water glass to the other. “If I look here and don't see the cup,” he says to the other, “then I know it must be there.”

    It sounds like a “deep” exchange between swotty young philosophy majors. But the fellow moving the cup has gray hair—and a Nobel Prize in physics. Sliding the porcelain, Anthony Leggett of the University of Illinois, Urbana-Champaign, explains how scientists might try to see past the strictures of quantum mechanics, the bizarre theory that governs the behavior of tiny objects and clashes with our everyday notions of reality. “None of the existing interpretations of quantum mechanics as a theory of the entire world is satisfactory,” Leggett says to John Preskill, a physicist at the California Institute of Technology in Pasadena.

    Leggett, Preskill, and 22 other physicists, philosophers, and historians have gathered here for the Seven Pines Symposium.* Packed into a slightly ramshackle lodge in a wooded state park, the scholars—all of them men—will share their insights, suites of rooms without telephones, and meals of roast quail and pheasant at a long communal table. Perhaps not since the famous Solvay Conferences of the early 20th century, at which Niels Bohr and Albert Einstein debated the meaning of quantum theory in their free time, has physics seemed so genteel.

    Each year, the symposium tackles another of physics' enduring puzzles: the nature of the vacuum, the concept of a field, the meaning of time. The aim is not to resolve the mysteries but to seed new lines of inquiry, says Roger Stuewer, a historian at the University of Minnesota, Twin Cities, and chair of the symposium's advisory board. “When we get the best people together,” he says, “ideas are planted that in some intangible way will influence what they do in the future.” Those germinating ideas are watered with a mellow Zinfandel and nourished with succulent steak.

    This year, attendees spent 5 days grappling with the implications of quantum mechanics, which have perplexed physicists and philosophers since the theory was invented in the 1920s. The theory explains phenomena ranging from chemical bonding to the structure of neutron stars, and it may open the way to uncrackable quantum communications and superefficient quantum computers. Yet the strange quantum rules clash with our most basic experience of reality. In fact, no one knows how our boring old “classical world,” in which a thing can be in only one place at a time, arises from the weirdness of quantum theory, says Gerard Milburn, a physicist at the University of Queensland in St. Lucia, Australia: “The fundamental question remains, Why do we have classical behavior in a quantum world?”

    Fast cars and philosophy

    Once home to the county poor farm, the two-story Outing Lodge at Pine Point reflects the eclectic character of owner and symposium patron Lee Gohlike. None of the rooms have Internet access, but one provides a manual typewriter in good repair. In another, six portraits of Marilyn Monroe hang in two neat ranks. On the shelves of the expansive second-floor library, the Proceedings of the Royal Society of London and The Philosophical Magazine mingle with Oscar Wilde's comedies, Einstein's letters, and a book entitled The Mysteries of Pittsburgh.

    An amateur philosopher of science, Gohlike made his money restoring classic Mercedes-Benz racing cars. He befriended historian Stuewer 20 years ago and several years later proposed—and offered to pay for—the symposium. The invitation-only affair provides “a kind of demilitarized zone where people are allowed to get into more fundamental issues without being embarrassed,” Gohlike says. Nonetheless, scholars must brace themselves for dizzying discussion and some spirited ribbing when they gather in the cool quiet of the library.

    “Would you call that wave-function collapse?” asks one physicist as he explains how he and colleagues apply quantum theory to the state of the entire universe at once.

    “You don't call that wave-function collapse,” says a historian.

    “Then we don't have wave-function collapse.”

    “They probably do,” another physicist chimes in.

    He said they didn't,” says a philosopher, gesturing toward the historian.

    “I know, but I think he's in error about what he would say.”

    The scholars are debating a deceptively simple question: What does it mean to make a measurement?

    According to quantum mechanics, a tiny object does not follow a continuous trajectory. Instead, it must be described by oscillating quantum waves that reveal only the probability of finding it here or there. An object such as an electron may also be in two different places at once or spin in opposite directions at the same time, a condition known as a superposition. But when measuring an electron, an observer always finds it spinning one way or the other. Even stranger, two separated electrons can be “entangled” so that both spin both ways at once, but in opposite directions from each other. If a measurement shows that one electron is spinning clockwise, the observer instantly knows that the other is spinning counterclockwise, even if it is a world away.

    All this suggests that measurement makes the quantum “wave function” collapse into one possible outcome or another. Yet that view—the so-called Copenhagen interpretation of quantum mechanics —has troubled physicists for nearly 80 years. It assumes that between the bizarre realm of tiny objects and the commonsense world of everyday things lies a fuzzy border. Measurement and wave-function collapse somehow bridge the divide. But why, researchers wonder, should measurement have such unique power? The Copenhagen interpretation also tacks the classical world onto the quantum realm like a sundeck on a submarine, without explaining why it even exists. If quantum mechanics governs everything, then why don't voltmeters and people behave as oddly as atoms and photons?

    Information rules

    Like theologians reinterpreting scripture, physicists and philosophers have sought to resolve their quandaries by reading mind-bending new meanings into the rules of quantum mechanics. Some favor a “many worlds” interpretation, in which the wave function never collapses but merely splits into branches at each potential measurement, leading to multiple realities of which we experience only one. Other prefer so-called modal interpretations that rely on undetectable “partial hidden variables” to ensure, for example, that a voltmeter never reads 0 volts and 5 volts at the same time.

    Whatever their philosophical leanings, physicists now generally agree that quantum mechanics itself makes it extremely difficult to spot really big things in superpositions. Large objects quickly entangle themselves with their surroundings, and such “decoherence” obscures a superposition in somewhat the same way that interference from a vacuum cleaner scrambles the image on a television screen. Strictly speaking, however, decoherence leaves superpositions intact, says historian Michel Janssen of the University of Minnesota. And even if they're hidden, he says, two-places-at-once coffee cups defy our sense of a single definite reality and leave us mired in “an ontology of possibilia and an epistemology of radical deceit.”

    To avoid that dreary fate, participants at this year's Seven Pines Symposium are taking a different tack entirely. Spurred by recent efforts to develop quantum information technologies, thinkers such as Jeffrey Bub, a philosopher at the University of Maryland, College Park, hope to prove that quantum mechanics grows naturally out of the principles of information theory.

    Last year Bub and colleagues showed that three restrictions on how information can be transmitted and copied can reproduce from scratch the basic features of quantum mechanics. They assume that the world can be described by a type of mathematics known as a C* (pronounced C-star) algebra. Then they lay down the laws: no instantaneous transmission of information, no perfect copying of information, and no sharing of information in a particular way called “unconditional bit commitment.” Those restrictions produce a mathematical formalism that looks like quantum mechanics, Bub says. The result suggests that the basic stuff of the universe is information, he says.

    Trying to comprehend quantum mechanics is like grasping at minnows in a stream, however, and information is a particularly slippery concept. “What's it mean to say that the universe is just information?” says Philip Stamp, a physicist at the University of British Columbia in Vancouver. “To me information has to be information about something.”

    Mens sana.

    Fortified by country air, gourmet meals, and an occasional nip, scholars at the Seven Pines Symposium debate why physics seems so strange—and daily reality doesn't.

    CREDITS: PAUL PETERSON

    Physicist Christopher Fuchs of Lucent Technologies in Murray Hill, New Jersey, has an answer: The wave function is an observer's information about the objective world. A measurement instantly refines that information, which is all in the observer's head, giving the illusion that the wave function collapses. In Fuchs's view, the instantaneous collapse is no more mysterious than the clarity that suddenly emerges when you remember that you left your checkbook beside the toaster. “Quantum measurement is the refinement of expectations, period,” Fuchs says. “The only mystery in quantum mechanics is why there is a restriction” on the completeness of knowledge.

    James Hartle, a physicist at the University of California, Santa Barbara, says he likes the spirit of Fuchs's approach. But there may be a hitch, he says. Contemplating the period just after the big bang, quantum cosmologists routinely talk about the wave function of the entire universe. “If the wave function of the universe is only a characterization of somebody's information, then whose is it?” he asks.

    With such questions unanswered and dinnertime approaching, the scholars opt for a stopgap solution: They head for the bar.

    More craziness ahead?

    Yet, with martinis in hand, many continue to talk quantum mechanics. Such is the pull of the riddles of quantum theory—especially now, as new experiments may allow physicists to probe the limits of the theory.

    Driven in part by the need to make reliable “qubits”—bits that can be 0, 1, or 0 and 1 at the same time—for quantum computers, researchers are striving to put ever larger objects and systems into quantum superpositions. In 2000 two teams independently coaxed billions of electrons to flow simultaneously in opposite directions around tiny rings of a superconductor (Science, 31 March 2000, p. 2395). Two years ago another team proposed a scheme to place a tiny mirror in two places at once (Science, 11 October 2002, p. 342). Eventually, says the University of Illinois's Leggett, such experiments might reveal that laws and forces beyond quantum mechanics intervene to prevent truly macroscopic objects from being in superpositions —a notion known as macrorealism.

    The trick is to thoroughly isolate a sizable thing and push back the curtain of decoherence far enough to put the object in two places at once—or fail in a way that reveals a new phenomenon. A coffee cup will likely always remain too large for such experiments, but researchers are marching toward the macro realm. “Ideas that weren't taken seriously 25 years ago are taken quite seriously now,” Leggett says.

    Even if some new theory lurks just over the quantum horizon, don't expect it to restore sanity and comprehensibility to physics. Any subsequent theory will still have to explain all the bizarre phenomena that quantum mechanics already does, says Robert Wald, a theoretical physicist at the University of Chicago, so it, too, will be a strange beast. “What's going to come next is going to be just as crazy or crazier,” he says. “You can count on that.”

    Perhaps that's a good thing. A theory more comprehensible than quantum mechanics wouldn't require such a symposium. And that would spoil the fun.

    • *The Seven Pines Symposium VIII, 5 to 9 May.

  14. ASTRONOMY

    Ultraviolet Astronomers Face Loss of Vision

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

    Blinded by the atmosphere, ultraviolet astronomers rely on orbiting observatories. But with no new satellites on the drawing board, they face dark times ahead

    BERLIN—Astronomers are getting worried that they may soon be cut off from the vast majority of normal matter in the universe: diffuse clouds of gas in the immense spaces between galaxies. These gases—the stuff that all stars were originally made of—can't be seen by ground-based telescopes because they are visible only in the ultraviolet (UV) part of the spectrum, which is blocked by Earth's atmosphere. Astronomers got their first glimpse of the UV universe from orbiting observatories launched in the 1960s, and they have continued to gaze at it ever since. But all the observatories with UV capability currently in orbit are now nearing retirement, and no new ones are in the pipeline. “After 2008, there's nothing,” laments Ana Gómez de Castro of the Universidad Complutense de Madrid in Spain.

    It's not only intergalactic gas that could suddenly become invisible. At UV wavelengths—roughly between 10 and 400 nanometers—astronomers study the hotter objects in the universe, those with temperatures between 10,000 and 100,000°C. They include the atmospheres of hot young stars, protoplanetary disks, and gas that is being sucked up by black holes in active galactic nuclei. The UV spectra of distant quasars are also helping cosmologists answer the question of whether the fundamental constants of physics might have had different values earlier in the history of the universe.

    Borrowed time.

    FUSE, here being readied for launch, has outlived its designed life.

    CREDIT: NASA

    What UV astronomy doesn't do, however, is produce glorious images of the universe's more photogenic locations or address some of the hottest topics in astronomy, such as extrasolar planets. This low profile, UV proponents fear, is causing space agencies to lose sight of the importance of the ultraviolet. Steven Beckwith, director of the Space Telescope Science Institute in Baltimore, Maryland, says that UV astronomy is “just not quite as sexy” as other fields. “We need it badly,” he says. “It's an essential tool, like a hammer, but it's difficult to identify one killer application.”

    Right now, two small NASA satellites are scanning the skies at UV wavelengths. The Far Ultraviolet Spectroscopic Explorer (FUSE), launched 5 years ago this week, is recording high-resolution spectra of selected objects, while the Galaxy Evolution Explorer (GALEX), launched in April 2003, is carrying out an all-sky imaging survey to shed light on the evolution of galaxies and the history of star formation in the universe. The only other space observatory capable of taking UV measurements is the Hubble Space Telescope, whose future hangs in the balance.

    Unfortunately, FUSE is already past the nominal end of its mission and is expected to last a few more years at most; GALEX will finish its work in the fall of 2005; and unless a robotic servicing mission can be mounted in time, Hubble is not expected to survive beyond 2008. And that's it. At a recent symposium in Berlin,* astronomers discussed the next generation of both ground-based and space-based instruments, but among the steady stream of upcoming big, new infrared, x-ray, and gamma ray satellites, UV astronomers had nothing on their slate. “I'm concerned,” says FUSE principal investigator Warren Moos of Johns Hopkins University. Part of the problem, says Moos, is technology. “To have a new space mission, you must have a large increase in capability,” he says. “There just haven't been any recent major advances in technology that would justify the launch of a new, big ultraviolet space observatory.”

    Wide-eyed.

    GALEX is scanning the UV sky, but not for much longer.

    CREDIT: NASA

    To try to focus attention on the coming hiatus, Gómez de Castro, together with other European UV astronomers, has set up a Network for Ultraviolet Astrophysics to plan a road map for the field. “We're not asking for huge things,” she says. “We're modest.” The network, which is funded by the European Union, will assess the future needs of UV astronomy on a European scale and produce a report and road map in June 2005. European UV astronomers are already discussing the design of an ultraviolet World Space Observatory (WSO/UV). Based on existing Russian hardware, the WSO/UV would boast a 1.7-meter mirror and a suite of high-resolution imaging and spectroscopic instruments and, if approved, could launch in 2007.

    According to Beckwith, the Cosmic Origins Spectrograph (COS), a new instrument for the Hubble Space Telescope built by the University of Colorado, Boulder, but grounded since the Columbia disaster, could give a much-needed boost to UV astronomy. “In my view, maintaining Hubble and installing COS is the best hope” for the field, he says. Meanwhile, COS principal investigator James Green is studying plans for an ambitious UV space telescope with a 4- to 6-meter mirror, which could be launched between 2015 and 2020. UV astronomers still have their dreams, but dreams take a long time to come to fruition. Gómez de Castro, for one, doesn't want to wait that long: “In 2020, I'll be retired.”

    • *“Exploring the Cosmic Frontier—Astrophysical Instruments for the 21st Century,” 18 to 21 May.

  15. Asia and Africa: On Different Trajectories?

    1. Jon Cohen

    Asia soon could have more HIV-infected people than sub-Saharan Africa. But that doesn't mean it will have African-scale epidemics

    From the western deserts of India to the eastern ports of China, HIV has raced through the same high-risk group: injecting drug users (IDUs). There is no better way to spread the virus than sharing contaminated needles, and one IDU community after another in Asia has seen prevalence rates rocket from zero to 50% in as short as 6 months. Add high rates of infection among IDUs to a booming sex industry and huge populations of migrant workers, and you have the ingredients for a potential disaster: Some AIDS experts even predict that Asia will have more HIV-infected people in 2010 than the 30 million or so in sub-Saharan Africa today.

    Enlightened care.

    “Anita,” a native of Nepal, says she was sold to a brothel in India when she was 14. She receives free health care and HIV prevention services at a nearby clinic for sex workers run by the National AIDS Research Institute in Pune.

    But there's an asterisk to this grim scenario: The scale of Asia's epidemic has more to do with the size of the continent's population than the explosive spread of the virus. In the past few years, it has become clear that the epidemics in Asia and Africa are surprisingly different. HIV has not spread rapidly by heterosexual sex to cause an African-styled “generalized” epidemic anywhere in Asia, and many epidemiologists now believe it is unlikely to do so in most parts of the continent.

    Yes, HIV has spread quickly in high-risk groups and made inroads into the population at large, infecting an estimated 7 million Asians in all. But no Asian country has reported a prevalence rate in adults higher than 4% (Cambodia, 1999), and relatively few prenatal clinics have found prevalence rates above 1%—the standard measure for a generalized epidemic. In contrast, 12 African countries now have prevalence rates in adults of 10% or more; South Africa reported that 26.5% of pregnant women in 2002 were infected with HIV.

    Could that happen in Asia? “Much of Asia has the potential for an epidemic where 2% to 3% of adults become infected, and by my standards, that's an extremely serious epidemic,” says Tim Brown, a physicist by training who lives in Bangkok and does HIV modeling for the East-West Center. “But will we see 10% to 15% prevalence in Asia outside of a few isolated areas? Absolutely not.”

    Like Brown, Christopher Beyrer, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, stresses that a low prevalence rate in a large country can spell disaster. “One or two percent of the Indian or Chinese populations is an enormous number of people,” says Beyrer. But he also shares the emerging perspective that Asia will not go the way of sub-Saharan Africa. “We've been looking, waiting for evidence of that for a number of years, but—happily—it's not panning out,” says Beyrer, who has closely studied HIV's spread in Thailand, Myanmar (formerly Burma), China, and Malaysia.

    To many who combat epidemics, this means there is a tremendous opportunity to derail the virus by aggressively targeting high-risk groups—IDUs, sex workers, and gay men, who often are ostracized by societies for legal and moral reasons. “If we focus our attention there, we can really do a lot of good work,” says Elizabeth Pisani, an epidemiologist with Family Health International (FHI) based in Jakarta, Indonesia.

    Pisani decries the hype that has surrounded projections of rampant viral spread through general populations in Asia. “With HIV,” she says, “the facts speak for themselves.” And she says that the “obsession with generalized epidemics” has clouded attempts to discern the actual epidemiological patterns. “In the early to mid-1990s, we didn't really understand the shape that epidemics were taking in Asia,” she says.

    The spread of HIV of course differs dramatically from country to country in Asia, as well as within different regions of specific countries. “It's very difficult to speak about ‘the Asian epidemic,’” says Peter Piot, head of the Joint United Nations Programme on HIV/AIDS (UNAIDS). “Whatever we come up with, we always find a big exception in Asia.”

    Yet in the past few years, epidemiologists have stepped up attempts to characterize HIV's spread across Asia as a whole, forcing many to rethink how the virus moves around the continent and, ultimately, how to design targeted prevention programs. Beyrer and his co-workers used molecular biology to track how various HIV subtypes spread out from heroin-producing Myanmar and Laos along drug-trafficking routes in India, China, and Vietnam. Brown spearheaded the development of a fascinating computer model that analyzes the specific characteristics of Asian epidemics. And Pisani and two dozen colleagues in an informal network called Monitoring the AIDS Pandemic have just completed a detailed report on AIDS in Asia that incorporates this new understanding of the epidemic across the continent. They plan to release it in July at the XV International AIDS Conference in Bangkok. Its title: “Face the Facts!”

    Misleading generalizations?

    By 1998, James Chin, an epidemiologist at the University of California, Berkeley, had become a thorn in the side of many colleagues who accused him of downplaying the potential of HIV to spread in Asia. That year, Chin, who started the global HIV/AIDS surveillance program at what's now UNAIDS, co-authored a paper that said, “HIV prevalence rates in the total sexually active population of most Asian-Pacific countries will not, in our opinion, ever reach 0.5%.”

    Chin had long questioned the potential of HIV to spread by heterosexual sex everywhere outside Africa. “I don't think most of the world's heterosexual population has sufficient sexual risk behaviors in terms of networks to drive any type of epidemic of sexual transmission,” says Chin, now a consultant to the World Health Organization and other groups. “You get pockets here and there in the sex workers, and that obviously has to be looked at. And you get epidemics in injecting drug users who share blood where HIV has penetrated into IDU networks. That will continue. But generalized transmission of HIV is a very inappropriate epidemiologic term.”

    Seeing red?

    As the spread of HIV has turned Africa more red (adult prevalence >20%), Asia has become darker blue (2% to 5% adult prevalence). The scales, at least for now, remain dramatically different.

    MAP SOURCE: UNAIDS

    In contrast to Chin's analyses, the U.S. National Intelligence Council published a report in September 2002 that roiled health officials in China and India. The report predicted that by 2010, HIV infections in China could total up to 15 million. India, the report warned, could have 4% of its population infected—a staggering 25 million people. “Those numbers were plucked out of the air,” charges Chin.

    Richard Feachem, an epidemiologist who heads the Global Fund to Fight AIDS, Tuberculosis, and Malaria, says he views those gloomy forecasts in precisely the opposite way from Chin. “It's a huge mistake to say that this can't happen,” says Feachem. “You have to do a heck of a lot to attenuate this epidemic. It would be wise to assume the worst rather than best. I see 15 years of optimistic assumptions about Asia that have turned out not to be true. So I say let's make more pessimistic assumptions, and if we're proved to be wrong, everyone will be very happy.”

    Low-risk high.

    This heroin user in Manipur, India, has a clean syringe and needle provided by a needle-exchange program that former users run.

    Piot of UNAIDS, who played a pioneering role in characterizing the African epidemic, further cautions people not to jump to conclusions about the potential spread in Asia. “The major difference when you compare the African and Asian epidemic is the speed,” says Piot. “It still can go to double-digit prevalence in some countries, and certainly some of the Indian states,” he warns. And Swarup Sarkar, a UNAIDS epidemiologist based in Bangkok, worries, too, about what he calls “subnational” epidemics. “There are subnational epidemics at 5% prevalence or more going on, and we're ignoring this because of low national prevalence overall,” says Sarkar, who has worked extensively in India and several other Asian countries.

    Whether the epidemic in Asia follows the path Chin predicts or one that more closely resembles an African epidemic rests largely on the rate of spread in the general population by heterosexual sex. Although epidemiologists wish they had more data, many now say that marked distinctions characterize sexual behavior patterns in Asia and Africa. “From all behavioral studies, there's a big difference in the number of partners that men and women in Asia report having, and that's not true in Africa,” says Piot. In other words, relatively few females in Asia, other than sex workers, have multiple partners. As Beyrer puts it, “For the great majority of women in Asia, it's still virginity until marriage and monogamy afterward.”

    Piot also notes that in some hard-hit countries in Africa, studies have reported that many HIV-infected older men have sex with younger women, who become infected themselves and then spread the virus to men their own age. “The more we look at it, intergenerational sex is a big, big driver,” says Piot. “If everybody would have sex with someone from their own age group, the epidemic would die out.” In Asia, says FHI's Pisani, “when women do have nonmarital sex, it tends to be with people of their own age.”

    In addition to sexual practices, circumcision plays a role in the spread of HIV, says medical anthropologist Daniel Halperin, who works on HIV/AIDS at the U.S. Agency for International Development. He points to several studies that link the lack of circumcision to Africa's worst HIV epidemics. “Every country in the world that's even getting very close to double-digit prevalence has lack of male circumcision and multiple-sexual- partner patterns among both genders,” says Halperin. He notes that the four countries in Asia that have high circumcision rates—the Philippines, Pakistan, Bangladesh, and Indonesia—have among the lowest HIV prevalence rates in the region.

    Fast tracks.

    HIV races through communities of injecting drug users (right), and a molecular analysis of the virus reveals that subtypes—the strains, designated alphabetically—travel from heroin-producing Myanmar and Laos along drug-trafficking routes.

    CREDITS: (MAP) ADAPTED FROM Y. LU AND M. ESSEX, AIDS IN ASIA (2004); (BAR CHART) CHRISTOPHER BEYRER
    Risk reduction.

    This free needle program run by Daytop in Kunming, China, remains a rarity in its home country—and throughout Asia.

    A model epidemic

    East-West's Brown and co-worker Wiwat Peerapatanapokin decided to investigate the dynamics of HIV's spread in Asia and to test Chin's theory. This mathematical exercise, called the Asian Epidemic Model, charts how various behaviors alter the movement of the virus as it crisscrosses between the general population, IDUs, sex workers, and their clients.

    Brown cautions that “modeling is still more art than science, especially given the huge data gaps in the region.” Still, by adjusting various parameters, they have arrived at several provocative conclusions that many colleagues have studied closely (see page 1934). UNAIDS's Piot goes so far as to say that when it comes to describing the forces that spread HIV in Asia, “the person [who] I believe has the best vision on this is Tim Brown.”

    IDUs play a starring role in the model. Thailand, China, Myanmar, India, Vietnam, Nepal, Indonesia, and Malaysia all have seen the rapid spread of HIV through their IDU populations. “The nidus of the epidemic in mainland Asia are the IDUs,” says Roger Detels, an epidemiologist at the University of California, Los Angeles (UCLA), who works in several Asian countries and has trained dozens of scientists from the region. “The only countries where the first major epidemic was not in IDUs were Laos and Cambodia.”

    The model shows how IDUs dramatically speed an epidemic. “It really can accelerate things by 20 to 30 years,” says Brown. Typically, the IDU population “seeds” sex workers, the other main high-risk group, who provide a “bridge” into the general population. “Sex workers and clients really form a feedback loop,” explains Brown. “It's the rate at which you get feedback between those two populations that determines how quickly the epidemic rises.”

    This dynamic also explains one of the more curious aspects of the Asian AIDS epidemic: Cambodia has the highest documented adult prevalence rate (2.7% in 2001), but hardly any IDUs. Brown explains this by comparing Cambodia to its next-door neighbor, Thailand. In the early 1990s, about 20% of men in both countries reported hiring sex workers. “In Thailand and Cambodia the epidemic was kind of a foregone conclusion because the level of risk was so high,” says Brown. While IDUs fueled the epidemic in Thailand, their role became overwhelmed because sex workers had so many clients. “Clients and sex workers drive the epidemics in Asia,” says Brown, and ultimately, it's the total number of men who visit sex workers that determines how quickly HIV spreads. “If you double the number of clients, you have a larger number of men who are exposed to HIV,” says Brown. “So it builds larger epidemics.”

    Reaching out.

    Billboard in Taunggyi, Myanmar, mixes sex, drugs, and rock ‘n’ roll to spread the AIDS prevention message.

    In one particularly vivid simulation, Pisani used the Asian Epidemic Model to analyze Jakarta with and without IDUs. Jakarta did not detect an HIV-infected IDU until 1998, and the prevalence rate in that community by 2001 had jumped to 48%. Despite consistently low condom use, the HIV prevalence rate among sex workers in Jakarta stayed low for years. But studies show that as the prevalence rate rose in IDUs—one in five of whom report paying for sex—it bridged into the sex worker population, which had a 7% prevalence rate in one 2003 survey. Pisani says this has created “a critical mass of infections” in the sex industry that now will spread more widely. If risk behaviors do not change, she estimates that Jakarta will have 110,000 infections by 2010, one-third of those in IDUs. But without any IDUs, the model suggests that Jakarta would have had only 3000 infections in 2010. “If we had prevented the epidemic among drug users, we would have prevented the whole epidemic,” says Pisani. “It should wake us up to the prevention opportunities where HIV among drug users is still low. Bangladesh, Pakistan, the Philippines—they don't have to go the way of Jakarta.”

    Impassioned debates surround several of the assumptions in Brown's model. The Global Fund's Feachem questions the generalization that Asian women have fewer multiple partners. “I wish it were true,” he says. Epidemiologist Wu Zunyou of China's Center for Disease Control and Prevention in Beijing notes that one study of sexual behavior in China, India, Russia, Zimbabwe, and Peru found that the Chinese reported lower rates of extramarital sex—but their rates of sexually transmitted diseases were the same or higher. “Chinese enjoy the doing, not the talking,” says Wu. UNAIDS's Piot questions whether circumcision has much power. “If lack of circumcision would be a big driver, Asia should have a big, big epidemic,” he says. And Pisani says the Asian Epidemic Model is “not stable enough to run over long periods.”

    Writing on the wall.

    Prevention messages such as this one at an AIDS clinic in Kolkata, India, aim to derail HIV with knowledge of how it is transmitted.

    But there is wide consensus on one prediction that Brown makes: HIV potentially could establish a severe epidemic on the island of New Guinea, which is half Papua and half Indonesia. “If there's one place in Asia and the Pacific that has the potential for a more African-style epidemic, that's it,” says Brown.

    Like countries in sub-Saharan Africa that have substantial HIV epidemics, both men and women in New Guinea report having multiple sexual partners, and the island has virtually no IDUs. “It's probably the hottest epidemic in the whole region,” says Carol Jenkins, a medical anthropologist who lived in Papua New Guinea for 15 years and conducted HIV and behavioral surveys. “Premarital sex has no negative connotation whatsoever.” According to one study of unmarried women between 15 and 24, 41% were sexually active and 30% of that group had sex with men 10 years older than themselves. Although the most recent adult prevalence rate in Papua New Guinea remains a relatively low 0.7%, one prenatal clinic last year reported an HIV prevalence rate of 2.5%. “It may look like Africa in 5 years,” says Jenkins.

    Roadblocks

    In 1997, Beyrer and Yu Xiao-Fang of Hopkins made a startling discovery with their Chinese colleagues Chen Jie and Lui Wei of the Guangxi Provincial Health and Anti-Epidemic Station. A molecular analysis of HIV-infected blood samples from IDUs in Guangxi revealed that two cities located only a few hundred kilometers apart—as the crow flies—had completely different strains, or subtypes, of the virus. Over the next year Beyrer and Yu traveled extensively through Guangxi, and the perplexing discovery soon made perfect sense: One city had a north-south highway running through it, while the other had an east-west highway—and no road directly connected the two locations. “It was really clear that these viruses were following these highways that were distinct,” says Beyrer. “It appeared that the viruses were spreading along heroin trafficking routes through chains of injectors.”

    The researchers expanded their collaboration to look at HIV subtypes found in IDUs from other areas of China and from Myanmar, India, and Vietnam. As they explained in a paper published in AIDS in January 2000, the analysis indicated that specific subtypes moved from heroin-producing Myanmar and Laos to other countries along trafficking routes. “Heroin routes end up being routes for spread and diversification of the virus, which is bad news for the populations along them,” says Beyrer.

    To Beyrer and other epidemiologists, such studies hold a key to preventing the spread of HIV in Asia, which requires an intimate understanding of high-risk groups. “It doesn't matter what your culture is—whether it's Uygur, Muslim, Burmese tribal, or Chinese hipster—if you're on this heroin route, you need to implement prevention,” says Beyrer. “And along these heroin routes, there was a glaring absence of prevention and treatment.” Similarly, studies in Indonesia and Thailand both have shown that many IDUs become infected by sharing needles in prisons, where precious little HIV prevention work takes place. “Too many policymakers operate under the view that injecting epidemics don't have anything to do with anything else,” says Brown.

    As research clearly has shown in Europe, Australia, and the United States, a “harm- reduction package” that offers clean needles, substitution drugs such as methadone, health care, and counseling can powerfully thwart HIV. But prevention campaigns in Asian countries largely have steered clear of IDUs and other high-risk populations, including clients of sex workers, gay and transgendered men (many of whom are bisexual), and female sex workers who inject drugs. Outside Hong Kong, no locality has a wide-scale, comprehensive harm-reduction program for IDUs: Thailand recently targeted users in its stepped-up war on drugs, China still sends them to compulsory treatment centers, and one treatment camp in India even chains them to their beds (Science, 23 April, p. 509). Government health workers in China and Myanmar shy away from distributing condoms to sex workers. Out of nearly 400 sites that tracked HIV's spread around India in 2002, only three explicitly measured the prevalence rate in gay men, and China had none.

    But as Thailand and Cambodia have shown, Asian countries can stage effective prevention campaigns. Both Cambodia and Thailand famously succeeded at slowing their epidemics by launching massive education and condom campaigns targeted at sex workers and their clients (Science, 19 September 2003, p. 1658). Without those campaigns, Brown's model suggests that these two countries may well have Africa-scaled epidemics today. “Thailand and Cambodia without interventions would have reached 10% to 15% adult prevalence by now,” says Brown. “And the reasons they didn't is because condom use went up to 80% to 90%, and men using sex workers dropped in half.”

    Staging effective prevention campaigns requires constant reevaluation, too, as many Asian countries are undergoing momentous transitions. “With a large middle class coming up in India, China, and Indonesia, it's difficult to believe that sexual behavior is not changing,” says UNAIDS's Sarkar.

    Already, studies in both Japan and Thailand have found significant increases in the number of women who report having premarital sex and multiple partners. Masahiro Kihara of the Kyoto University School of Public Health and co-workers wrote in the February 2003 issue of the Journal of the Acquired Immune Deficiency Syndromes that over the past decade, multiple partnerships were “dramatically elevated in young women.” In the March 2003 issue of AIDS and Behavior, a group led by Fritz van Griensven, an epidemiologist at the U.S. Centers for Disease Control and Prevention branch in Thailand, describes a survey in which 43% of unmarried female vocational students in northern Thailand between 15 and 21 reported having had sexual intercourse.

    FHI's Pisani urges people to interpret these trends with caution. An increase in the number of young women who have sex with men their own age could prevent the spread of HIV. Pisani well realizes that this is a discomfiting message. “We're hamstrung by our own touchy-feely rhetoric, and we sacrifice public health,” she says. “The guys are going to have sex anyway. If there are no ‘nice girls’ to have sex with, they're going to have sex with prostitutes.”

    Balancing the scientific findings with the public health needs presents a terrifically tricky equation that no computer model can solve. “You don't want to underestimate the threat,” says UCLA's Detels. “When you're doing public health and you want to introduce interventions, you want to introduce anxiety so the public will do something. But you don't want too much anxiety or they'll say, ‘Hell, I'm already infected.’”

    Pisani says she's “greatly concerned” that an exaggerated emphasis on the threat of generalized epidemics in Asia has taken people's eyes off the target. “It makes it harder for us to do the job that we need to do,” she says. “We've painted it as though it only counts if it's a generalized epidemic. In Asia we can save tens of thousands of lives and a lot of misery if we have the courage to focus our interventions where they need to be focused. And in general, we know where the risk is concentrated in Asia.”

  16. The Asian Epidemic Model's Provocative Curves

    1. Jon Cohen

    Tim Brown and Wiwat Peerapatanapokin of the East-West Center in Bangkok developed the Asian Epidemic Model to better understand the unique forces that propel HIV's spread through countries that typically have many injecting drug users (IDUs), large numbers of sex workers and clients, gay men, and relatively few women with multiple partners.

    Brown and Wiwat created a baseline scenario for “an average risk” Asian country.

    SOURCE: T. BROWN/EAST-WEST CENTER

    In their richly detailed model—which relies on real data from several Asian countries—0.4% are female sex workers (FSW), who see an average of one client a day and do not use condoms about 75% of the time. Clients of sex workers include 10% of adult males. The IDUs, 0.5% of males, share needles two-thirds of the time and inject 2.5 times each day. The model also accounts for men who have sex with men (MSM) and gay male sex workers, and it factors in other sexually transmitted diseases and the lack of circumcision. It even distinguishes among “relationship” sex, “casual encounter” sex, and “sex work” sex. Brown and Wiwat then validated the model by comparing its predictions to specific epidemiological findings in Thailand and Cambodia over the last decade. By 2030, this population, without interventions, would have a 5% prevalence rate in men and 2% in women.

    Condom use in sex workers alone can dramatically reduce a country's adult prevalence rate, but coverage is key.

    SOURCE: T. BROWN/EAST-WEST CENTER

    If Thailand had seen condom use drop from 85% to 60% in 1998, its epidemic would have taken off again.

    SOURCE: T. BROWN/EAST-WEST CENTER

    The model finds that doubling the number of female sex workers and clients drives Asian epidemics more powerfully than any other forces. In this scenario, 23% of men and 8.6% of women become infected by 2030.

    SOURCE: T. BROWN/EAST-WEST CENTER

    Elizabeth Pisani of Family Health International in Jakarta, Indonesia, used the model to determine that if no IDU epidemics occurred there, the epidemic now spreading through sex workers and clients would not have caught fire.

    SOURCE: E. PISANI/FAMILY HEALTH INTERNATIONAL
  17. Monitoring Treatment: At What Cost?

    1. Jon Cohen

    In the past year, China, India, and Thailand each announced ambitious national programs to provide free anti-HIV drugs to people who need them most. Pharmaceutical companies in all three countries have followed Brazil's lead in producing generic versions of brand-name drugs, at a fraction of the cost. Now comes the hard part: figuring out how best to use the drugs.

    Simply identifying patients and getting drugs to them will tax the resources of many countries. And it's no small task to educate patients about the side effects and the importance of taking all of their pills, notes Joep Lange, an AIDS researcher at the University of Amsterdam, the Netherlands, who will co-chair the upcoming international conference in Bangkok. But for clinicians, there's an additional hurdle: how to perform tests that are essential for effective treatment but are now prohibitively expensive.

    In wealthy countries, AIDS clinicians monitor an infected person's number of CD4 white blood cells—the critical lymphocytes that HIV slowly obliterates—and blood levels of the virus itself. Both measures help determine when to start treatment and indicate when treatment has failed. “The diagnostics are the major expense now,” says Bruce Walker, director of the Partners AIDS Research Center in Charlestown, Massachusetts. So several investigators, Walker included, are developing cheap, easy-to-use diagnostics.

    The most common CD4 test relies on flow cytometry, a technology that labels CD4 cells with fluorescent antibodies, shines a laser on the fluid, and counts the number of cells that light up. “It's just a fancy, advanced microscope with a fluid path,” says Walker's co-worker William Rodriguez, who heads their project to develop a cheaper device. Popular flow cytometers made by Becton Dickinson and Beckman Coulter occupy the better part of a standard office-sized room and sell for $65,000 and up. Each test costs up to $40—and that's excluding labor and maintenance expenses.

    Cash flow.

    The U.S. CDC lab in Bangkok has standard flow cytometers that many Asian labs cannot afford.

    With a grant from the Doris Duke Charitable Foundation, Rodriguez and Walker teamed up with chemist John McDevitt of the University of Texas, Austin, to develop a new, portable device that can measure CD4 counts for no more than $3 per test. They expect the machine itself will sell for about $2000. “It's really unbelievably cool,” says Walker, who has projects in both China and South Africa (and does not intend to profit from the device). It blends digital camera technology with “the brains of a palm pilot,” he says. Tests in Botswana have found that the machine's results match those from a flow cytometer 95% of the time.

    The battery-powered device resembles a glucometer that measures blood sugar levels. Patients put a drop of blood on a stick that then slides into the machine. Reagents, kept inside a disposable cartridge the size of a credit card, tag CD4 cells with fluorescently labeled antibodies, and a cheap light-emitting diode takes the place of a laser. The machine then shoots a digital snapshot, and software does an inventory of the lit-up pixels, determining the CD4 count. Over the next 6 months, Rodriguez and Walker hope to shrink the device to the size of a small toaster weighing less than 4 kilos. “We set the specs so it had to work in a shantytown or a rural village,” says Rodriguez. “And you can transport it on a jeep, a donkey, or whatever.”

    Labs in Indonesia and India have started trying out an even simpler CD4 test developed by Suzanne Crowe of the Macfarlane Burnet Centre for Medical Research and Public Health in Melbourne, Australia. “There's no equipment cost,” says Crowe. The assay uses commercially available antibody-coated magnetic beads (“Dynabeads”) to separate out CD4 lymphocytes, which a reagent then stains. A technician looks through a standard microscope and counts the cells. “It's only suitable for places where the volume of work is fairly low,” cautions Crowe, who says each test costs about $5.

    At YRG CARE in Chennai, India, researchers are studying Crowe's test and a system made by Guava Technologies in Hayward, California. The Guava EasyCD4 machine, which sells for $35,000, is a miniaturized flow cytometer that uses vastly less reagent. YRG CARE's clinic director Suniti Solomon says it costs about $2 to run a test, and she rates the system as “highly encouraging.”

    View this table:

    Many other academic labs and companies have entered the race with Beckman Coulter and Becton Dickinson to develop cheaper CD4 tests (see table). The Clinton Presidential Foundation, Médecins Sans Frontières, the Forum for Collaborative AIDS Research, Gay Men's Health Crisis, and the Bill and Melinda Gates Foundation all have become involved in pushing these cheaper technologies forward.

    Several groups similarly want to develop less expensive viral load tests. At the moment, all are based on amplifying HIV's genetic material and typically cost $50 to $80 a test. Cheaper tests ($5 to $20) now being studied measure the HIV protein p24 or the reverse transcriptase enzyme that the virus uses to copy itself.

    Clinicians primarily use viral load tests to determine whether a drug treatment has failed. If so, they switch patients to other drugs. But Walker and other researchers note that switching drugs won't be an option in many poor countries. For now, they argue, cheaper CD4 tests would pay bigger dividends. “In terms of global health,” says Walker, “this is the one thing that can make the biggest difference.”

  18. TREAT Asia Spans the Continental Divide

    1. Jon Cohen

    Over the past 4 years, Kevin Frost of the New York City-based American Foundation for AIDS Research (amfAR) has made more than three dozen trips to Asia in an attempt to organize a unique program that brings together clinicians across the continent. “In Asia, we may draw geographic borders, but the epidemics are interdependent and interlinked,” says Frost, who once played a prominent role in ACT UP, the AIDS activist group.

    The Therapeutics Research, Education, and AIDS Training program that Frost launched, called TREAT Asia for short, has at its center an observational database that includes information on 1200 HIV- infected people in China, India, Indonesia, Thailand, Malaysia, Taiwan, Hong Kong, the Philippines, and Singapore. About half of the patients, who are being followed anonymously at 11 participating centers, are receiving anti-HIV drugs. Clinicians in the network compare the outcomes of different treatment regimens. Including patients who have not begun treatment allows the investigators to chart the progression from initial HIV infection to AIDS, which some data suggest occurs more rapidly in Asia.

    Common cause.

    Ruby Hall Clinic in Pune, India, is one of 11 sites across Asia that are pooling data from HIV-infected patients.

    All of the participants send data every 6 months to computers at the University of New South Wales (UNSW) in Sydney, Australia. “It's an extraordinary range of investigators,” says David Cooper, who heads UNSW's AIDS center and sits on TREAT Asia's steering committee. “I hope we'll get some good ideas about what's going on with treatment and outcomes. We'd really like to take some leadership in monitoring development of resistance in the Asian setting.” Adeeba Kamarulzaman, a steering committee member who runs a TREAT Asia site at the University of Malaya Medical Center in Malaysia, says she also hopes the network will collaborate on clinical trials and other research projects.

    AmfAR contributes $1 million a year to TREAT Asia, but Frost says the project needs a budget five times as large—and he's had trouble raising more funds. “The main obstacle I've heard over and over and over: ‘We fund locally in-country,’” says Frost. “There's nobody who's thinking regionally.”

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