News this Week

Science  19 Sep 2003:
Vol. 301, Issue 5640, pp. 988
  1. INFECTIOUS DISEASES: Early Indications Point to Lab Infection in New SARS Case

    1. Dennis Normile,
    2. Gretchen Vogel

    A puzzling case of infection with the SARS coronavirus has public health officials scrambling to trace its source but breathing a sigh of relief that it seems to be an isolated event. The Singapore patient, a 27-year-old virologist, has the first confirmed infection with severe acute respiratory syndrome since the worldwide outbreak of the new disease was declared contained last July. He was released from the hospital on 16 September, having fully recovered from his dry cough and persistent fever.

    “We don't know how he was infected, but at this stage the most likely source is the laboratory,” says Hitoshi Oshitani, head of the regional SARS response team of the World Health Organization (WHO) in Manila. Klaus Stöhr, a virologist who coordinated WHO's SARS research efforts, calls such a scenario “reassuring.” But even if the infection is traced to a lab accident, the patient's very mild symptoms and the lack of any evident respiratory illness are a reminder, say officials, that SARS could be circulating undetected. “Infectious diseases have a spectrum of clinical symptoms,” Oshitani says. “And we don't know how many people could have mild [SARS] infections” that have escaped detection.

    The new patient is an ethnic Chinese Singaporean postdoc who studies the West Nile virus. He had not traveled outside Singapore recently and had no known contact with any SARS patients. However, he regularly uses a microbiology lab at the National University of Singapore (NUS) and a biosafety level 3 (BSL-3) lab at the Environmental Health Institute (EHI) of the National Environment Agency, both of which have SARS programs. EHI scientists have worked with live samples of the SARS virus in the same BSL-3 lab the patient used for his West Nile studies. The university, by contrast, works with killed virus samples.

    The patient's symptoms were so mild they almost escaped detection. On 27 August, a general practitioner prescribed antibiotics for a fever. When the fever persisted, the patient went to Singapore General Hospital on 29 August. He was sent home after x-rays showed his lungs to be normal. On 3 September, still suffering from a fever, he returned to the hospital and was admitted. This time, doctors detected the genetic fingerprint of the SARS virus when they ran a polymerase chain reaction test. Mindful of a recent false alarm in Canada, WHO was skeptical until the results of a second test, an ELISA test, showed that the patient did not have antibodies to the SARS virus at the beginning of his illness but developed them several days later. At WHO's suggestion, samples were sent to the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, where the positive results of both tests were confirmed.

    Taking no chances.

    Masks were back at Singapore General Hospital, where a SARS case was confirmed this month.

    CREDIT: ED WRAY/AP

    Because none of the patient's two dozen known contacts, now all under home quarantine, has shown any symptoms of the disease, suspicion has focused on the labs. But even there the exact source is not obvious. The entire EHI staff is also under home quarantine, and individuals could not be reached for comment. But a statement posted on the National Environment Agency's Web page claims that “it is unlikely” the student was infected there because he worked in the biosafety lab 6 days after the SARS virus was last studied there—longer than the virus is thought to survive outside the body. NUS also dismisses the likelihood of infection occurring in its labs.

    At the request of the Singapore government, WHO dispatched two biosafety experts, and the U.S. CDC sent one lab safety expert and one epidemiologist to join local scientists and officials in an 11-member panel to investigate equipment and procedures at the two labs. They started work on 15 September and were expected to finish within the week.

    If lab infection is ruled out, says Stöhr, then “other scenarios we consider remote will come into play,” including the possibility that undetected mild cases of SARS are circulating. However, he notes, the apparent failure of the patient to pass on the virus suggests that it does not spread easily via hosts who have such mild symptoms—perhaps due to a low infecting dose of the virus. More worrying, says Stöhr, is the possibility that the virus is circulating in an animal host and could again emerge to cause more severe cases. “Whatever measures are being taken, it is not unlikely that the first SARS case [of a new outbreak] will slip through,” he warns.

  2. NEUROSCIENCE

    Mapping the Brain's Genes: A Microsoft Dividend

    1. Elizabeth Pennisi

    The co-founder of Microsoft and owner of two professional sports teams, Paul G. Allen, is launching a massive project to determine how genes shape brain development and function. He is promising to spend $100 million over the next 5 years on what one researcher calls “a genomelike” effort for neuroscience based at the Paul G. Allen Institute for Brain Science, a new research center that will be based in Seattle, Washington. Its first goal is to create an atlas of where specific genes are expressed in the brain. It “will be a landmark in understanding how genes are expressed,” predicts Tom Insel, director of the National Institute of Mental Health in Bethesda, Maryland, who was involved in some of the planning discussions. “We have become really enthusiastic about this effort.”

    The institute will use nucleotide sequences first to probe the mouse brain and later the human brain, organizers announced on 16 September. The probes will enable them to track the expression of individual genes, says Mark Boguski, senior director of the new institute. Eventually, he and his colleagues plan to merge genomic, brain circuitry, and anatomical data to make a three-dimensional map that researchers can navigate through, cell by cell.

    This comprehensive picture will be publicly accessible at no cost through the World Wide Web. “We would like the atlas to have the kind of impact on the neuroscience community that the genome project has had,” says Boguski, formerly of the Seattle biotech firm Rosetta Inpharmatics Inc.

    As in the genome project, success will depend on computers. For one, the gene studies could yield petabytes (millions of gigabytes) of data, enough to strain even the best high-performance machines. For another, the images will be quite complex. “It's not clear how to put this into digital form,” says Catherine Dulac, a Harvard University neuroscientist.

    The challenges are formidable, says Dulac. The National Institute of Neurological Disorders and Stroke began a similar effort 3 years ago, but it receives less than $5 million per year—not enough to make speedy headway. Dulac says: “It's only when you have enough money and technology development that you can foresee that someday the project will really be done.”

  3. INTELLECTUAL PROPERTY: U.S. Court Opens Door to Free Trade in Ideas

    1. David Malakoff

    Is imported scientific knowledge a manufactured product? A U.S. appeals court recently answered a resounding “no” to that question, making it easier for U.S. scientists to import information crucial to everything from basic research to development of new drugs. The decision “makes it clear that [inventors] can't claim control of useful scientific information just because they have a patent on the process used to produce it,” says John Barton, an intellectual property specialist at Stanford University Law School in Palo Alto, California.

    Last month's decision* arises from a dispute between Housey Pharmaceuticals of Southfield, Michigan, and European drug giant Bayer AG. Housey has a U.S. patent on a protein-screening process that it claims Bayer scientists in Europe used to identify a compound that Bayer's U.S.-based scientists later developed into a promising drug. In a 2001 suit, Housey demanded royalties under a 1988 U.S. law that bars companies from freely importing products “made by a process patented in the United States.” Congress passed the law to discourage firms from sidestepping royalty payments by moving manufacturing operations to nations that don't recognize U.S. patents. Housey does not have a European patent on the process.

    ILLUSTRATION: TIM SMITH

    Joining Housey in a friend-of-the-court brief was Affymetrix, a Santa Clara, California, biotech company. It argued that “information is often more valuable than a physical product and should be protected,” says the firm's attorney, Morgan Chu of Irell & Manella in Los Angeles.

    Bayer disputed such claims, in particular arguing that the information obtained from the overseas screening process wasn't a physical “product.” In addition, it argued that Housey's patent could not “reach through” to the final products, because the screening results weren't essential to actually making the drug. A victory by Housey, Bayer added, could lead to an absurd situation in which scientists entering the U.S. could be sued for patent infringement for simply recalling results obtained using patented research tools abroad.

    Some academic scientists, meanwhile, worried that Housey's argument, if upheld by the court, could force them to determine which results sent in by foreign collaborators were produced with patented tools and then pay royalties. “The implications were pretty interesting and sometimes very strange,” says Michelle LeCointe, a patent attorney at Baker Botts in Austin, Texas.

    Bayer won the first round of the legal fight, but Housey appealed to the U.S. Court of Appeals for the Federal Circuit, a specialized panel that hears major patent disputes. The three-judge panel dismissed Housey's claim, explaining that the 1988 law “is limited to physical goods that were manufactured and does not include information.”

    Neither side could be reached for comment. But Stanford's Barton says that the decision should cheer up academic researchers who worry about the effect of proliferating patents on research tools. “It affirms the idea that [patent protections] can go too far,” he says.

    Another consequence, however, may be to encourage some firms to move even more research offshore to avoid royalties. Firms doing diagnostic testing, for instance, “could send [biological] samples offshore and then import the results,” he notes—even if the results were just in a researcher's head.

    • *Bayer AG v. Housey Pharmaceuticals, 02-1598, U.S. Court of Appeals for the Federal Circuit, 22 August 2003.

  4. AMAZON ARCHAEOLOGY: 'Pristine' Forest Teemed With People

    1. Erik Stokstad

    It's not easy for humans to survive in the Amazon, where floods and barren soils take a heavy toll on crops. Many modern attempts to farm have failed miserably, and the most remote tracts harbor just a few scattered villages. Scientists had thought it was ever so. Yet in the past 2 decades, archaeologists have amassed evidence that parts of the Amazon were more densely populated before Europeans arrived in the 15th century than they are now and that much of the forest has been deeply affected by humans.

    On page 1710, a detailed regional study concludes that pre-Columbian people shaped one of the least known parts of the Amazon basin. Studying tropical forest and savanna around the headwaters of a tributary called the Xingu, a team led by archaeologist Michael Heckenberger of the University of Florida, Gainesville, found that the area was widely transformed over the past 1000 years by a dense population of farmers living in a highly planned network of villages. “This is an incredibly important indicator of a complex society,” says Susanna Hecht, a geographer at Stanford University's Center for Advanced Study in the Behavioral Sciences. “The extent of population density and landscape domestication is extraordinary.”

    For more than 20 years, researchers have been building the case that prehistoric peoples had a significant impact on much of the Amazon. There were many hints: large mounds near the mouth of the river, sophisticated dikes and fish weirs in Bolivia (Science, 4 February 2000, p. 786), forests planted with palms and fruit trees, and patches of soils enriched by humans (Science, 9 August 2002, p. 920). But many experts assumed that bigger, more complex societies were restricted to the larger and relatively fertile floodplains in the region's lowest lying lands.

    Well connected.

    Wide roads (red) linked ancient towns more populous than modern Kuikuro villages (top).

    CREDITS: (TOP TO BOTTOM) M. HECKENBERGER; SCIENCE SUPPLEMENTAL ONLINE MATERIAL

    That's not the picture emerging from the highlands of the Upper Xingu, where Heckenberger has spent more than a decade mapping earthworks and villages within a 1000-square-kilometer study area. Working first with machetes and surveyor's transits and later with Global Positioning System receivers, the team came across overgrown canals, ponds, and roads up to 50 meters wide built with meter-high curbs. Some villages were surrounded by a defensive ring of moats up to 5 meters deep and 2.5 kilometers around.

    The newest work has revealed an astonishing plan: 19 pre-Columbian villages linked to surrounding, smaller settlements. The villages were always 3 to 5 kilometers apart and connected by remarkably straight roads. Shorter avenues headed out from the villages toward the same points of the compass, as if the villages had all been built from a similar blueprint. “This really blew us away,” Heckenberger says, for it implied a society much larger and more complex than any in the Amazon today.

    Exactly how big, however, is hard to say. By sampling ceramic fragments to plot village limits and estimating the density of houses from those in recent villages, Heckenberger's team estimates that each prehistoric cluster supported between 2500 and 5000 people—a much higher figure than usually imagined for upland sites. The roads imply that all these villages were occupied simultaneously. “Why would they build these roads if it were not to move between villages?” asks team member Carlos Fausto, an ethnologist at the Museu Nacional in Rio de Janeiro, Brazil.

    These ancient farmers also left their mark on the land, Heckenberger argues. “Today, you have to go miles to see anything like untouched forest. And that's with just small villages.” Instead of virgin forest, the team found large patches of secondary regrowth. Village plazas, for example, are overgrown with grasses, and certain kinds of trees grow on the ancient roads or abandoned farms. “The point is that in 1492, human influence had spread to essentially the entire area,” Heckenberger says. “None of the area was natural.”

    Not all researchers agree. Archaeologist Betty Meggers of the Smithsonian Institution's National Museum of Natural History in Washington, D.C., who has studied the Amazon for more than 50 years, doubts that prehistoric populations were large or exerted a widespread impact on the environment. “It contradicts everything that we know about limitations to intensive agriculture,” she says. Meggers says there's no hard archaeological evidence that the sites were densely packed and permanently inhabited; perhaps smaller groups moved from one site to another. But the vast majority of experts say Heckenberger's interpretation makes sense, although assumptions and details still need to be nailed down.

    Understanding past human impacts on the Amazon could help predict the results of current changes, says Eduardo Sonnewend Brondízio, an anthropologist at Indiana University, Bloomington. The research could also provide insights into how to farm sustainably in the Amazon, he and Heckenberger say, because the large populations described by early explorers declined from introduced disease, not agricultural failures. “These people were doing something we don't seem very successful at: sustaining populations without destroying biodiversity,” says Clark Erickson of the University of Pennsylvania in Philadelphia.

  5. SCIENTIFIC SOCIETIES

    IEEE Under Fire for Withdrawing Iranian Members' Benefits

    1. Owen Gaffney*
    1. Owen Gaffney was an intern in Science's Cambridge, U.K., office.

    CAMBRIDGE, U.K.—One of the world's largest scientific societies has barred researchers in certain countries from publishing in its journals and receiving member benefits. The Institute of Electrical and Electronics Engineers says it has taken these steps against scientists in Iran and four other so-called rogue nations subject to U.S. trade sanctions to ensure that IEEE staff stay on the right side of U.S. law.

    But other scientific organizations do not discriminate against scientists from these countries, leaving some observers to accuse IEEE of playing the rogue. “The IEEE's treatment of its members living in Iran and other embargoed countries has been a disgrace,” says Ken Foster, a bioengineering professor at the University of Pennsylvania in Philadelphia and a former president of an IEEE chapter. “I see a shocking lack of transparency and ethical timidity on the part of the IEEE.” IEEE President Michael Adler argues that his association's actions are prudent. “We must … do what is necessary to protect the organization and its volunteers,” he writes in an open letter to IEEE members to appear in next month's issue of IEEE Spectrum.

    IEEE publishes 30% of the world's literature on computing, electronics, and electrical engineering and has 380,000 members in 150 nations. In January 2002, IEEE stripped members in Iran, Cuba, Iraq, Libya, and Sudan of certain benefits, including the use of the IEEE logo to promote activities, electronic access to publications, and access to job listings. (They still can receive print subscriptions.) Members from the five proscribed countries can attend IEEE conferences but only at a nonmember rate, IEEE says.

    In September 2002–9 months after it imposed the restrictions—IEEE petitioned the U.S. Office of Foreign Assets Control (OFAC), which set the embargo policy, to confirm its stance “or at least issue us a license to permit these activities as an exception,” Adler says. IEEE had not received a reply as Science went to press.

    With 1700 IEEE members, Iran by far suffered the most. According to Fredun Hojabri, president of Sharif University of Technology Association, a nonprofit that represents alumni, faculty, and students of Iran's premier engineering university, the saga began when IEEE officials determined that they would violate OFAC sanctions if they proceeded with a conference in Iran. In a 14 January 2002 letter to IEEE members at the University of Tehran, then-president Joel Snyder wrote that “the IEEE can no longer offer full membership privileges or support activities” in Iran. Then, without notice, IEEE blocked Iranian members from accessing their e-mail accounts through IEEE.org, asserts Hojabri, a chemist.

    Months of protest letters from Iran's engineering community have failed to sway IEEE. The institute declined to respond to questions from Science.

    The issue boils down to the interpretation of the term “service” in the OFAC regulations. In an undated internal memo, Michael Lightner, IEEE's vice president of publications, states: “OFAC's position is that publication and formatting for publication is allowable but editing is not allowed. OFAC does not precisely define ‘editing’ so it is possible to prohibit much of our peer review and article preparation process.” IEEE resisted this interpretation, according to Adler: “IEEE firmly believes that the peer review and editing of technical journal articles should be permissible under the current regulations.” However, because failure to comply with OFAC regulations could trigger fines of up to $500,000 and up to 10 years in jail, IEEE opted to continue its restrictive policy to protect its staff.

    Other scientific societies see things differently. A spokesperson for the American Geophysical Union, which has a dozen members in Iran, says AGU does not consider publishing to be a trade issue and “accepts paper submissions from anywhere in the world.” The American Society of Mechanical Engineers echoes that view, as does AAAS, Science's publisher. “We do not put any restrictions on submission or publication of papers based on economic or other sanctions,” says Monica Bradford, executive editor of Science.

    IEEE's singular position is causing headaches for its leadership. In a 9 September letter to Hojabri, Gerald Alphonse, a candidate for IEEE-USA president, states: “I suspect that the IEEE could have better served its members by adopting a wait-and-see attitude instead of being proactive about those restrictive laws. This would have avoided the disenfranchising of many of our overseas members.”

    Lightner appears to have anticipated the furor. “Improperly understood or presented, [the policy] could cause … concern,” he wrote in the memo. “We are asking that distribution be limited to those with a direct need to know.” With the containment strategy having gone bust, it will be up to IEEE's rank-and-file members to decide whether to support the policy itself.

  6. PLANETARY SCIENCE

    The Small Ones Can Kill You, Too

    1. Richard A. Kerr

    When scouting possible disasters from space, size isn't everything. That's the message from a NASA panel* that wants the government to spend more to quantify the risk from near-Earth objects (NEOs)—mostly asteroids—too small to wipe out civilization but big enough to destroy a major city or trigger a deadly tidal wave. Such a program would cost three to five times the current modestly funded effort, the panel says, but the knowledge gained would be more than worth the price.

    In 1998, Congress pressured NASA to find 90% of the estimated 1100 NEOs 1 kilometer and larger in diameter, a size big enough to devastate humanity. The agency is spending almost $4 million a year toward meeting that goal by the 2008 deadline. But there are an estimated 120,000 or so smaller impactors—140 meters to 1 kilometer in diameter— in orbits that pass near Earth's. They hit on average every 10,000 years or so and could wipe out a major city or hit the ocean and generate a deadly tsunami. There's also substantial risk from the 10% of larger NEOs that would still be unaccounted for after 2008.

    The use of ground-or space-based telescopes or both could identify an estimated 90% of the remaining risk, says the 12-member expert panel, at a cost of $236 million to $397 million over 20 years or less. That's about the price of a modest spacecraft mission to another planet. And NASA isn't likely to bear the entire burden. “Who nominated NASA to be the only one to protect the home planet?” NASA associate administrator for space science Edward Weiler asked an impact-hazard workshop last year. The impact threat “deserves more funding at the federal level,” Weiler said, a thinly veiled invitation for the National Science Foundation to take on the job.

    Small but destructive.

    A new report wants the government to target objects as small as the rock that devastated 1600 square kilometers of Siberian forest in 1908.

    CREDITS: WWW-TH.BO.INFN.IT/TUNGUSKA

    “We've been doing the less expensive [searches] first,” says team vice chair Donald Yeomans of NASA's Jet Propulsion Laboratory in Pasadena, California. But the cost-benefit ratio of looking for smaller objects is still so large, he says, that “you pay for any one of these search systems in the first year” of operation. And planetary scientist Clark Chapman of the Southwest Research Institute in Boulder, Colorado, adds that “there'd be a scientific bonanza from this, no doubt.” Knowing the orbits, compositions, and physical makeup of small NEOs would allow planetary scientists to better understand where meteorites come from in the asteroid belt and what gets them from there to here.

    An improved ability to spot potentially deadly asteroids won't automatically save lives, panel members acknowledge. It could, however, provide enough warning for engineers to work out a way to nudge the threatening object away from its encounter with Earth. Everything from a nuclear blast to a dusting with highly reflective powder to let sunlight do the work has been suggested. A warning time of years or even decades would let researchers fit the method to the particular body (Science, 13 September 2002, p. 1785).

    Whatever the calculated benefits, NASA isn't likely to rush into the next-generation search for NEOs, says Yeomans. The report's cover page notes that “NASA considers the … findings to be preliminary,” meaning that more study is needed before setting a course beyond 2008.

  7. WORLD TRADE CENTER

    Chemical Studies of 9/11 Disaster Tell Complex Tale of 'Bad Stuff'

    1. Robert F. Service

    NEW YORK CITY—The destruction of the World Trade Center (WTC) towers 2 years ago spewed toxic gases into the air like a “chemical factory,” says a new analysis of the environmental effects of the 11 September terrorist attacks. But the good news is that Manhattanites largely escaped serious exposure to most of the toxic substances, as heat from the fires quickly carried most of the material far above the city. The data, presented here last week at a meeting of the American Chemical Society (ACS),* buttress a new internal report that criticizes the Environmental Protection Agency (EPA) for being too reassuring to the public in the days after the towers collapsed.

    The data represent the most comprehensive accounting of environmental conditions at and around Ground Zero in the aftermath of the attacks. More than a dozen research teams used a wide range of instruments to identify and quantify the amount of particulate matter, trace metals, and combustion byproducts that wafted over lower Manhattan. “It was bad stuff, and lots of it,” says Thomas Cahill, a professor emeritus of physics and engineering at the University of California, Davis, who led a group studying ultrafine particles in smoke.

    In the hours after the disaster, thousands of office workers, police, and firefighters were exposed to very high levels of pollutants from pulverized concrete, wallboard, ceiling tiles, computers, electrical equipment, and office furniture. Because no air-quality monitors were set up then, researchers have little precise knowledge of the contents of the initial cloud. Instead, many early studies have analyzed the dust that blanketed lower Manhattan immediately after the collapse and the smoke that continued to rise from the buildings' remains.

    Aftermath.

    Airborne spectrometers mapped the spread of debris and chemicals from the collapsed WTC towers.

    CREDIT: ROGER N. CLARK ET AL./USGS (SPECLAB.CR.USGS.GOV/WTC)

    Those reports tell a mixed story. Last year, for example, a team led by New York University environmental scientist George Thurston found that the WTC dust contained only a small fraction of hazardous metals, asbestos, and organic compounds. Moreover, most of the dust particles—a combination of concrete, gypsum from wallboard, and glass fibers—were too large to be inhaled deep into the lungs. Later work fingered the highly alkaline dust as the chief culprit behind the “WTC cough” that plagued many Ground Zero workers and lower Manhattan residents, and other studies last year flagged more serious health concerns. One, for example, revealed that 75% of the first wave of Ground Zero workers studied in a federal screening program suffered from ear, nose, or throat problems 10 months after the attack, and 50% still suffered lung problems.

    At the ACS meeting, most of the concern focused on the noxious fumes spewed by debris fires that burned until 20 December 2001. Paul Lioy, an environmental scientist at Rutgers University in Piscataway, New Jersey, says that his team recorded over 400 different compounds in the WTC smoke, many of which they had never seen before. Cahill says he believes that anoxic conditions underneath the debris pile allowed chlorine to oxidize a wide variety of metals and organic compounds, creating a chemical stew normally seen only coming from municipal incinerators.

    A series of studies found that the plume contained high levels of polycyclic aromatic hydrocarbons (PAHs), many of which are considered toxic. Cahill found that levels of these compounds 1.8 kilometers northeast of Ground Zero spiked several times in September and October and peaked on 3 October, a day when a regional inversion plunged much of the smoke down to ground level. Although he has sampled sites around the globe, including the persistent haze in Beijing, China, and the Kuwaiti oil fires that raged during the 1991 Persian Gulf War, “October 3rd was the worst,” Cahill says.

    From the ashes.

    Rising smoke carried deadly substances away from Manhattan but exposed workers at Ground Zero.

    CREDIT: GREGG SWAYZE AND TODD HOEFEN/USGS

    Fortunately for residents, Cahill and others agree that the heat from the flames carried most of the smoke aloft. “The concerns have become more and more focused on Ground Zero,” Cahill says. No pollution-tracking equipment was set up at the recovery site. But nearby readings suggest that workers without respirators were likely exposed to high levels of toxic substances. A team led by EPA analytical chemist Erick Swartz noted PAH levels six times as high as those found during dangerous Los Angeles smogs. Those smog events usually last 2 to 3 days, Swartz says, “but the exposures at Ground Zero lasted for months.” “The measurements we have seen are certainly worthy of the most serious kind of concern,” Cahill says.

    The good news was that beyond Ground Zero, few people likely received dangerous long-term exposures to this witch's brew. “There was a very quick decrease in concentration [of hazardous compounds] from inside Ground Zero to outside,” says Lioy. Levels dropped off quickly over time, too. Measurements taken five blocks from Ground Zero by Thurston's team showed that trace elements such as lead, vanadium, and chlorine spiked in September and early October 2001, but nearly all returned to background levels by late October.

    Still, lower Manhattan residents aren't in the clear yet. The collapse of the towers filled nearby buildings with a fine coating of dust. At least three of those buildings remain too contaminated to reopen. And one of EPA's own scientists has cautioned that the agency's efforts to oversee cleanup of dust in one building have left behind possibly dangerous levels of asbestos, lead, and other potentially toxic substances. How those chemicals will affect New Yorkers likely won't be apparent for many years.

    • *226th ACS National Meeting, 7–11 September 2003, New York City.

  8. NEWS FOCUS SPECIAL REPORT

    The Next Frontier for HIV/AIDS: Myanmar

    1. Jon Cohen

    Each country, let alone each continent, faces unique problems when confronting HIV and AIDS. Myanmar, Thailand, and Cambodia have the highest rates of HIV infection anywhere outside Africa. Nearby Vietnam has a lower HIV prevalence than the United States. Yet Vietnam has a raging problem with HIV and injecting drug use, and Cambodia does not. Myanmar and Thailand have much more similar epidemics, fueled by a potent mix of injecting drug use and commercial sex work, yet the governments that run these neighboring countries could hardly have reacted more differently. This collection of articles focuses on these four countries to spotlight both successes and worrisome trends in Asia, a continent that, without significant new prevention efforts, will have more HIV infections by 2010 than sub-Saharan Africa does today, some modelers predict. It is the first in an occasional series on HIV/AIDS in Asia, leading up to the XV International AIDS Conference in Thailand in July 2004.

    Reporting for this series was supported in part by a fellowship to Jon Cohen from the Kaiser Family Foundation. Photographs are by Malcolm Linton.

    PHOTO BY MALCOLM LINTON

    HLAING THAYAR, MYANMAR (BURMA)—San San Min strolls through a cluster of wooden shacks perched on stilts above former rice paddies. In one shack, which serves as a daycare and feeding center, dozens of rail-thin children mill about or rest on the bamboo-slatted floor. A clinician in her 50s who has a knowing smile, San San Min crosses a footbridge to another shack in which a few dozen men and women who also have frighteningly skinny limbs and necks lie on wooden beds. Unlike the children, they need more than hearty meals and a place to spend the day: They have AIDS, and these shacks are their home. This collection of huts is one of three clinics that San San Min runs for the Dutch branch of Médecins Sans Frontières (MSF) in this ramshackle town less than an hour from Yangon (Rangoon),* Myanmar's once glorious and wealthy capital city.

    San San Min pauses to speak to a 33-year-old man sitting on a bed next to a prostrate, 28-year-old woman. A tank top hangs on the man's skeletal torso, revealing the bones of his rib cage and the scorpion tattoo that adorns his chest, a symbol of his stronger days when he worked in criminal intelligence. The woman keeps her eyes shut and clasps her hands over her stomach, tensing rigid with pain and then softly moaning. In an adjacent bed lies a 36-year-old woman, whose mother kneels on the floor, alternately fanning and feeding her ailing daughter. As the mother scoops spoonfuls of soup into her daughter's mouth, her gums badly swollen from candidiasis, she thanks San San Min: “If my daughter wasn't here, she would die.”

    Myanmar has one of the worst HIV problems in Asia. According to one controversial estimate, 3.46% of the adult population—some 687,000 people—is infected with HIV, a figure the government hotly disputes (see sidebar, p. 1652). The virus is spreading largely through injecting drug use and prostitution. And, as in many other poor countries, migrant workers—gem miners and loggers in Myanmar's case—are a major conduit into the general population. The staggering obstacles that those doing battle against AIDS face here are abundantly apparent at San San Min's clinic, which is poorly equipped and began treating a few patients with antiretroviral drugs only this spring—the first clinic in the country to do so. Yet, there are some modest successes: When the clinic opened 3 years ago, “there was a mean survival here of 6 months,” says San San Min. “Now people are living about 2 years.”

    One difficult obstacle is the government. Myanmar is run by a military dictatorship that infamously crushed a democracy movement in 1988—and then changed the country's name from Burma. Its government has alienated much of the world, devastating this one-time Asian economic tiger. Not only does the military's iron-fisted rule isolate Myanmar and limit the willingness of wealthy countries to invest or offer assistance, it also tightly controls how its doctors both portray and respond to the country's HIV/AIDS epidemic. Many physicians and scientists fled the country following the 1988 crackdown (San San Min left before the turmoil and returned in 1993), all but destroying the research community. What's more, the government wraps itself in moral rhetoric that makes it difficult to acknowledge, let alone effectively help, those at the focal point of the epidemic: commercial sex workers and people who inject heroin. (Only Afghanistan grows more opium.)

    Hand in hand.

    Heroin injection and HIV infection unfortunately have afflicted many gem miners, such as this man.

    PHOTO BY MALCOLM LINTON

    Severe poverty compounds the problems. The cash-strapped government offers the barest of health care: A World Health Organization report in 2000 concluded that, of all its member states, only Sierra Leone had a health system that functioned worse than Myanmar's. “They've gutted their public health system,” says Chris Beyrer, an HIV/AIDS epidemiologist at Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, who has been a vocal critic of the government.

    Myanmar rarely issues visas to foreign journalists, but after receiving several requests over 3 months, the Ministry of Health invited Science to enter and—accompanied by a government AIDS epidemiologist—tour the country to meet with public health officials, clinicians, scientists, and HIV-infected people. Scant resources exist at every level, and as with poor countries elsewhere, Myanmar relies heavily on various United Nations branches and international nongovernmental organizations such as MSF to help slow HIV's spread and care for those who have become infected.

    Hot spot.

    San San Min runs the Médecins Sans Frontières AIDS clinics in hard-hit Hlaing Thayar.

    PHOTO BY MALCOLM LINTON

    Although many people in the country speak critically of the government, no one Science met with did so openly. Several also stressed that the leaders have stepped up their resolve to deal with HIV/AIDS. “The government policy has changed significantly, and our people will find more and more services available,” assures Hla Htut Lwin, head of the National AIDS Program. A new fund, supported by three European countries and organized by the Joint United Nations Programme on HIV/AIDS (UNAIDS), also promises to pump $21 million into battling the disease over the next 3 years, effectively tripling the amount now available. “This is the first time the AIDS effort here has had serious funds,” says Eamonn Murphy, the UNAIDS country coordinator. That said, Murphy, Hla Htut Lwin, and others at the front still face an uphill battle.

    Bare necessities

    Nearly 90 years ago in Rangoon, the Pasteur Institute built a replica of its Paris headquarters, a French colonial edifice with grand arches and high-ceilinged, vast rooms. Today, the building houses Myanmar's National Health Laboratory, a bare-bones operation. The bacteriology lab grows samples in a wood-cased incubator that the Pasteur might have purchased not long after setting up shop. A huge cast-iron centrifuge, rubber belts dangling from it, lies broken in a hallway. In the virology lab, which is sweltering because the air conditioner broke, technicians hunt for HIV in blood donor samples sent in by hospitals. The samples arrive in old penicillin vials.

    Khin Yi Oo, who heads the virology lab, acknowledges that it would be safer to transport blood in vacuum-sealed test tubes. “At present, we can't provide for all of the hospitals to use the test tubes,” Khin Yi Oo explains. Although the lab has three machines that can test the samples for HIV antibodies, one sits on the floor, unplugged. “I can't find people to fix them,” she says.

    The National Health Laboratory does not have a flow cytometer, a machine that can automatically count CD4 cells: the main immune warriors that HIV selectively targets and destroys. Indeed, Khin Yi Oo and the other scientists here do not know of a single flow cytometer in Myanmar. Like most government employees, they have no access to the Internet, which the military monitors and tightly controls.

    Mixed message.

    Avoid sex and drugs, says this AIDS billboard outside Mandalay's general hospital, making no mention of condoms or clean needles.

    PHOTO BY MALCOLM LINTON

    Although the National Health Lab collaborates with a Japanese team that analyzes the genetic signature of the HIV strains circulating in Myanmar, no sequencing machine exists here that would allow the scientists to do the work themselves. They also do not have a machine that can perform the polymerase chain reaction (PCR) assay, a molecular copier of DNA that has become as ubiquitous in modern biology labs as microscopes. A PCR machine would allow them to measure the amount of HIV in an infected person's blood cells, a key test for evaluating health status and responses to treatment.

    Tin Nyunt, director of the National Health Lab, says that although his staff obviously needs equipment, that's not at the top of his wish list. “We need more training, capacity building of our young staff,” he says. And that means more collaborations with foreign scientists. “Leave politics as it is for the politicians,” urges Tin Nyunt. “We are the scientists. The people from the United States and elsewhere should know that we are working for the people, not the government.”

    Clinical tribulations

    Just as the National Health Laboratory stands out for what it does not have, so, too, does the government-run clinic across the country in Mandalay that focuses on HIV and other sexually transmitted diseases (STDs). Kan Oo, who runs the clinic, points to an old centrifuge, similar to the one at the National Health Lab. “It should be kept in the museum,” Kan Oo says. “It's older than me.” The clinic also lacks something even more startling: patients.

    On average, the clinic sees no more than 10 people a day, and at the moment, no one is here but staff. “It's a vicious circle,” explains Min Thwe, an epidemiologist at the National AIDS Program, who served as Science's escort around Myanmar. Because of the limited resources, the clinic doctors must diagnose most STDs by symptoms rather than by tests for specific causative agents. “So it means there's no distinction between you and the private general practitioner, and you have fewer people using your clinic,” says Min Thwe. “And then donors see this. Most STD clinics end up receiving less and less.” Last year, Kan Oo says that the clinic, a part of Mandalay's sprawling general hospital complex, offered HIV tests to only 70 people. “We can't promote them that much because we don't have enough test kits,” says Min Thwe.

    Kan Oo oversees 17 STD clinics in the region, and the one with the most cases— a telltale sign of where the most HIV exists—is in Myitkyina, the city closest to the country's jade mines. Remotely located and extremely difficult to reach during the rainy season, the mines have all the ingredients that HIV loves: large migrant populations, prostitution, and many injecting drug users (IDUs). No government clinic exists at any mine.

    On the street outside the clinic, a large billboard, which shows men shooting up and a male-female couple surrounded by a heart, instructs people how to protect themselves from AIDS. “Avoid Drugs. Avoid Sex. Preserve Your Traditional and Cultural Values.” The billboard avoids promoting the use of condoms and clean needles, two strategies that have proven most effective in derailing HIV.

    Rubber meets road.

    An educator with Population Services International raises the condom consciousness of truck drivers.

    PHOTO BY MALCOLM LINTON

    Mandalay does have a fairly progressive condom education and distribution program. At a truck stop this scorching morning, three dozen drivers gather around a young woman, who sits under a tree holding a wooden phallus and demonstrates to the men how to put on a condom properly. Population Services International (PSI), headquartered in Washington, D.C., dispatches educators such as this woman around the city each day to give demonstrations, answer questions, and distribute condoms and HIV information pamphlets. She hands a man a fresh condom and encourages him to put it on the phallus. The other drivers, many of whom have red-stained teeth from chewing beetle nut, giggle. “Don't be ashamed to go and get a condom,” the woman says, straight-faced. “It's not against the culture.”

    Since 1996, PSI has worked in Myanmar, staging education sessions such as this one and selling condoms at a steep discount to grocery stores, street vendors, and other distributors, who then sell them for a few cents each. Yet political and cultural factors make it difficult for PSI to educate members of high-risk groups such as IDUs and commercial sex workers. Until recently, for example, a woman carrying a condom could be arrested as a prostitute. But Tin Oo, a physician who heads the Mandalay PSI program, says the government has become much more permissive about allowing PSI to promote condoms. The organization is now allowed to advertise condoms in magazines, and “we've just applied for permission to put up a billboard here,” he says.

    Sticking points

    Shan state, a mountainous region bordering on China, Thailand, and Laos, grows more opium than any other region of Myanmar. In its capital, the pine-studded hill town of Taunggyi, psychiatrist Gyaw Htet Doe runs the Drug Dependency Treatment and Rehabilitation Unit. The patients' rooms at the 10-bed center have barred windows and sturdy steel doors that padlock shut. “Since this was constructed in 1975, we had this attitude, ‘He's a drug user, lock him up, he's a bad guy,’” says Gyaw Htet Doe, shaking his head. “So the setting is almost like imprisonment. If I had the funds, I'd like to tear the place down and build something more in keeping with modern practices.”

    Barrier to treatment.

    Gyaw Htet Doe (in doorway) says the prisonlike facility used for their drug rehab program sends the wrong message to patients.

    PHOTO BY MALCOLM LINTON

    Myanmar has a schizophrenic view of IDUs that ignores most of the tenets of what's called harm reduction, a growing movement that treats addiction as a disease rather than a crime and strives to find practical ways to help addicts avoid dangers such as HIV. Although Myanmar offers treatment at centers like this one, anyone caught with drugs or even paraphernalia faces imprisonment. IDUs can purchase needles at drugstores in Taunggyi, but in more remote areas, they are not available. There are no needle distribution or exchange programs, both of which have proven effective at stopping HIV transmission. Gyaw Htet Doe also would like to offer methadone as substitution therapy for heroin. “It would be like a wish come true,” he says. But the government considers methadone an illegal narcotic. Another law says that all drug users must be committed to units like this, meaning that no outpatient treatment technically can take place.

    Gyaw Htet Doe and his staff of four nurses, who run the only drug treatment center for roughly 1.5 million people in southern Shan state, treat about 100 inpatients a year. “We're short in terms of manpower, expertise, funding—a whole lot of things,” he says. Basically, all they can offer—to people who can afford to travel to Taunggyi—is detoxification, counseling for the patient and the family, and education. They don't track the recidivism rate, which he simply describes as “pretty high.”

    One of the inpatients, a 32-year-old HIV-infected man who has two children, has received treatment here 10 times. Like many other patients who come through the center, he started regularly visiting prostitutes when he worked in the nearby ruby mines in Mongshu, where, on a good day, he could earn up to $10. A government physician such as Gyaw Htet Doe earns $10 a month.

    The patient says he smoked heroin for 2 years before injecting. “My friends told me it would be a higher high,” he says, compulsively folding and unfolding a hand towel.

    Forward thinking

    Strong ties connect the fate of HIV/AIDS efforts in Myanmar—and indeed the fate of the country itself—to Aung San Suu Kyi, the leader of the National League for Democracy, the main opposition party. For much of the past 15 years, the government has kept Suu Kyi under house arrest, even after her party's landslide victory (never observed by the military) in the 1990 parliamentary elections and her award the following year of the Nobel Peace Prize. Suu Kyi long has discouraged tourism and cautioned foreign governments not to aid the country that she and her supporters still call Burma, arguing that the outside money helps prop up the regime.

    Following her release from house arrest in 2002 and much talk about reconciliation between the government and the National League for Democracy, Suu Kyi had what many perceived as a change of heart about foreign investments with regard to HIV/AIDS. She met with several outside groups working on the problem, including San San Min and her patients in Hlaing Thayar. She effectively gave her blessing to the two most ambitious aid packages then on the table: the new fund organized by UNAIDS, and an attempt by scientists from the U.S. Centers for Disease Control and Prevention (CDC) to establish a far-reaching collaboration.

    The forward momentum has suffered some serious blows. In December 2002, the U.S. government suddenly and inexplicably put the CDC project in the deep freeze (see sidebar, p. 1654). Then on 30 May, the Myanmar government drew international criticism—and new sanctions—from the United States and many other countries when it put Suu Kyi under “protective custody.” Her detainment came after a deadly incident that the government described as a brawl between Suu Kyi's supporters and a mob that had gathered to demonstrate against a rally she planned to hold; the U.S. State Department, which investigated the incident, described it as a “premeditated ambush” on Suu Kyi's motorcade by “government-affiliated thugs.” Politically, the incident and Suu Kyi's arrest “crushed everything moving forward,” says Beyrer of Johns Hopkins.

    Mapping a strategy.

    National AIDS Program director Hla Htut Lwin says Myanmar badly needs more collaboration with scientists from other countries.

    PHOTO BY MALCOLM LINTON

    Still, groups that determinedly separate politics from health promise to continue their efforts to improve the country's feeble and woefully insufficient response to HIV/AIDS. The most far-reaching project, the Joint Programme on HIV/AIDS, offers a detailed plan that aims to improve care and treatment for infected people over the next 3 years and to significantly expand campaigns to prevent transmission from sex and injecting drugs. “We're trying to initiate a coordinated program in a country that has had a piecemeal approach,” says Murphy of UNAIDS.

    The plan, which includes research to evaluate the impact of specific interventions, addresses several touchy issues head-on. Harm-reduction programs for IDUs, it says, should include substitution drugs such as methadone and easy availability of clean injecting equipment. Condoms should become more widely available to sex workers, youth, and even prisoners. Voluntary counseling and testing for HIV—a key prevention strategy that the government now allows only at its clinics—should become widely available in both public and private clinics. “It could be a great change,” says Hla Htut Lwin.

    UNAIDS has organized a fund to support the $51 million project, which to date has raised $21 million, the bulk of it coming from the United Kingdom. Other donor money already committed to HIV/AIDS projects in Myanmar totals about $10 million. But even “combining all the available resources, the gap is still huge,” cautions Hla Htut Lwin. “And even if we have more money, we can't move forward fast enough without more collaboration.”

    A number of people working in the country stress that Myanmar must act now, because the older generation of scientists and doctors such as Hla Htut Lwin had better training than their younger colleagues do. The quality of domestic universities has steadily eroded, and opportunities to study abroad have steeply declined. “The country currently has the technical capacity to do the job,” says Murphy. “We have a window of opportunity.” The other, more obvious reason for Myanmar to quickly step up its attack on HIV: The virus is walloping its population. “Time is running out,” says Myat Htoo Razak, an AIDS researcher and clinician who left the country in 1989 and now works in Thailand. “I have tremendous respect for people working inside Burma,” he says, but they “are fighting fire rather than preventing fire.”

    And they are trying to contain the fire with water pistols. Consider that only in September last year did MSF receive the government's blessing to begin a pilot study to treat 100 AIDS patients in Hlaing Thayar with antiretroviral drugs, the first such program in the country. The program began treating people this April. In a shack located between the children's feeding center and the room filled with adults who have late-stage AIDS, Nilar, a 31-year-old woman whom MSF has hired as a peer educator, sifts through patient charts, looking for eligible patients. Nilar, the mother of a 12-year-old girl, has AIDS herself and has now started to receive anti-HIV drugs through the MSF pilot study. “I compare it to winning the lottery,” says Nilar.

    As much as this project means to Nilar and a few lucky others, San San Min puts it into stark perspective. “There's some kind of hope here, but we have to be clear,” she says. “This is a pilot program for this township.” Myanmar has tens of thousands of people with AIDS who need treatment now. In May 2003, Nilar was one of only 13 people in the country other than the wealthy few who can afford their own medicine who have begun to receive life-extending anti-HIV drugs.

    That, unfortunately, reflects a tragic reality for HIV-infected people in Myanmar: This resource-rich country, once the envy of its neighbors, has a withered, skeletal medical and research infrastructure that itself appears to have a case of late-stage AIDS. And the prognosis, at least for the near future, remains grim.

    • *Burma's military rulers changed the country's name to Myanmar and changed the names of many cities. The former names of familiar cities—the only names recognized by the military's opponents—are given in parentheses.

  9. NEWS FOCUS SPECIAL REPORT

    The Politics of Prevalence

    1. Jon Cohen

    YANGON, MYANMAR (RANGOON, BURMA)—On 25 June 2001, Chris Beyrer roiled public health officials and the military leaders who run this country with a startling analysis of HIV prevalence here. At a special United Nations meeting on HIV/AIDS in New York City, Beyrer, an epidemiologist at Johns Hopkins Bloomberg School of Public Health in Baltimore, reported that HIV had infected 3.46% of the adults in Myanmar, which translated to 687,000 people. The Joint United Nations Programme on HIV/AIDS (UNAIDS), in contrast, had estimated a prevalence of 1.99%, or 510,000 adults.

    Although the difference might seem academic, it has profound public health implications. And the reaction to Beyrer's analysis indicates how politically sensitive HIV estimates can be.

    Beyrer's conclusions, if correct, would fundamentally recast the scope of the country's epidemic. The numbers suggested that HIV had spread further in Myanmar than in any Asian country other than Cambodia, which at the time had an adult prevalence of 4%. It also implied that Myanmar had a “generalized” rather than a “focal” epidemic, which means that the virus had spread well beyond high-risk populations. “That drove them into a frenzy, because that's not what they wanted to hear,” says Beyrer, who worked for many years in neighboring Thailand.

    Beyrer based his analysis largely on unpublished documents from Myanmar's Ministry of Health that reported 1999 HIV-infection rates in so-called sentinel groups, such as pregnant women and military recruits. As is standard practice, he and his co-workers extrapolated from those data to arrive at an estimate of HIV prevalence for the nation as a whole.

    Both the military government and scientists here reacted strongly. In September 2001, Major General Ket Sein, then Myanmar's health minister, assured delegates at a regional meeting of the World Health Organization that “contrary to the gloomy picture presented in some reports, especially those of the Western media, HIV/AIDS is not rampant in Myanmar.” He further contended that “data from these sentinel sites cannot be generalized to represent the whole country,” because they came mainly from urban settings and border areas that have higher risks.

    Hla Htut Lwin, who heads Myanmar's National AIDS Program, also cautions against extrapolating from the sentinel data, which the country routinely has collected since 1992. “It's not scientifically valid,” says Hla Htut Lwin, who trained in epidemiology at the University of California, Los Angeles. He adds that Beyrer “hasn't done any scientific research in our country.”

    Double trouble.

    The most conservative estimates suggest that more than 20% of both female sex workers and injecting drug users have become infected with HIV.

    GRAPH SOURCE: MYANMAR'S NATIONAL AIDS PROGRAM

    Beyrer counters that if anything, he and his colleagues underestimated the prevalence because they explicitly excluded sentinel data from commercial sex workers and injecting drug users, two groups that have much higher prevalence than the general population and thus would have skewed the analysis. “The bottom line is what we did is an unbiased, simple, critical analysis of existing data,” says Beyrer. “Anybody reasonable would come up with those numbers.” Beyrer and co-workers published a detailed description of their methodology and findings in the 1 March issue of the Journal of Acquired Immune Deficiency Syndromes.

    Beyrer adds that the country has gone to great extremes to deny that it has a generalized epidemic, which is defined as a prevalence of 2% in adults. In 1999, UNAIDS, working with Myanmar public health officials, arrived at a prevalence of 1.99% (510,000 out of 25.7 million adults). “It's a joke,” says Beyrer. “They asked, ‘How close can we go [to being accurate] without crossing that threshold?’” The latest Myanmar figures from UNAIDS, based on 2001 data and an extensive consultation with Myanmar, report a range of 180,000 to 420,000 HIV-infected adults and children.

    Timothy Mastro, an HIV/AIDS epidemiologist at the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, says that Beyrer's estimate is “quite reasonable with the data at hand.” But Mastro, a member of a CDC team that assessed the HIV/AIDS situation in Myanmar last year, says his organization has attempted to stay clear of the debate over whether the epidemic is focal or generalized. “The data are so thin that it leaves it open to debate, and existing data can't resolve it,” says Mastro.

    Myanmar this summer launched a new and improved HIV surveillance project, notes Hla Htut Lwin, emphasizing that the government acknowledges its HIV problem. “Whether it's 200,000 infected people or 400,000, we already assume we have a great potential of this HIV outbreak in different parts of the community.”

  10. NEWS FOCUS SPECIAL REPORT

    Myanmar: The Collaboration That Almost Was

    1. Jon Cohen

    YANGON, MYANMAR (RANGOON, BURMA)—In mid-June 2002, six scientists from the U.S. Centers for Disease Control and Prevention (CDC) arrived here on a sensitive mission. With the approval of the U.S. government and the military leaders who run this country—as well as the opposition party headed by Nobel Peace Prize winner Aung San Suu Kyi—the scientists hoped to forge a plan to tackle HIV/AIDS in this badly ailing and politically shunned nation.

    For 2 weeks, the team, led by CDC epidemiologist Carmine Bozzi, traveled widely, meeting with more than 150 clinicians, scientists, politicians (including Suu Kyi), United Nations representatives, local police, and HIV/AIDS workers from nongovernmental organizations (NGOs). “We did get a unique perspective that I don't believe other expatriates have had,” says CDC epidemiologist Tim Mastro, who ran CDC's extensive HIV/AIDS program in neighboring Thailand for 7 years.

    After leaving the country, the team proposed a collaboration between CDC and many NGOs—and, more surprisingly, Myanmar's Ministry of Health. This would mark a dramatic shift for the U.S. government, which under President Bill Clinton in 1997 banned U.S. companies from making new investments here because of what he called “large-scale repression of the democratic opposition.” It also meant a terrific amount to Myanmar's public health workers, who have the barest of resources. “Doctors and technical people here have such strong respect for the CDC, they would have been really keen to have the help,” says Eamonn Murphy, the country coordinator for the Joint United Nations Programme on HIV/AIDS.

    The CDC scientists formally spelled out their vision in a frank report that ran nearly 50 pages. “Our observations, together with a review of the available data, indicate that there is a serious, widespread epidemic of HIV and AIDS in Burma and that the response to date has not been adequate to stem its tide,” the CDC team noted. They urged the government to change its policy and allow NGOs to conduct voluntary HIV testing and counseling, a cornerstone to prevention and treatment programs. They knocked the government for the way it deals with injecting drug users (IDUs), including its severe criminal penalties—70% of the prison population, they estimated, were drug offenders—and its dearth of treatment facilities. “[I]t appears that little or no interventions for IDUs have been supported officially,” they noted. Although programs exist that promote condoms to sex workers, treat tuberculosis, and attempt to prevent transmission of HIV from infected mother to child, the CDC researchers found all of them wanting.

    The often thin-skinned Myanmar government did not pull the plug on the project after CDC completed its blunt critique. But CDC's parent organization, the Department of Health and Human Services (HHS), did. It abruptly canceled the team's follow-up trip in December 2002.

    The order came from William Steiger, head of HHS's Office of Global Health Affairs. Steiger says the decision—which caught many inside and outside the country off guard—came from the “whole apparatus,” including the U.S. Embassy in Rangoon, the State Department, HHS, and CDC. He says it hinged on the country's failure to allow NGOs to perform voluntary counseling and testing. Steiger acknowledges that withholding HIV/AIDS assistance could punish the very population that most needs help. “It's a fine line,” he says. “We have to be certain the regime itself is supporting politics for public health. Right now it's not.”

    On 29 May, Hla Htut Lwin, the head of Myanmar's National AIDS Program, spoke with Science about the potential CDC collaboration, which he thought had a detectable pulse. “I'm still hoping we can work with the CDC and that the U.S. government will understand that HIV prevention can't wait for political solutions,” said Hla Htut Lwin. The next day, the government again cracked down on the democracy movement, detaining Suu Kyi. Whatever slight pulse remained became weaker still. “If Aung San Suu Kyi is in detention, the State Department is not going to let us do anything,” says Steiger.

  11. NEWS FOCUS SPECIAL REPORT

    HIV and Heroin: A Deadly International Affair: Vietnam

    1. Jon Cohen

    HIV is largely confined to injecting drug users in Vietnam, but it is crossing into China. A novel project is tackling the drug route

    LANG SON, VIETNAM—As though navigating through a minefield, Doan Ngu steps gingerly through an abandoned dirt lot near the center of this small, northern city. Once an elementary school, the lot now has become a popular place to inject heroin; hundreds of used syringes and their plastic wrappers litter the ground. Ngu, wearing open-toed sandals, points his toe at the tip of one syringe. “This is a new one,” says Ngu. “It still has fresh blood.”

    Ngu, an official at the National AIDS Standing Bureau in Hanoi, a 3-hour drive south, looks up at the majestic, striated mountains in the distance. “It makes me very sad,” says Ngu, who grew up a few kilometers away from the old schoolyard. “There are plenty of places like this.”

    Vietnam, a long, narrow country with 80 million people, has relatively little HIV: At the end of 2001, the Joint United Nations Programme on HIV/AIDS estimated that 130,000 of its adults, or 0.3%, had become infected—fewer per capita than in the United States. But as this dirt lot in Lang Son suggests, Vietnam has a serious problem with injecting drug users (IDUs). HIV is spreading in this group, and the effects are spilling over into neighboring China. According to official estimates, IDUs account for 65% of Vietnam's HIV infections.

    A novel, intriguing intervention study run by Ngu and a team of distinguished international researchers aims to slow the spread of HIV in both Lang Son Province and across the border in China's Guangxi Province. “We can save many human lives and the economy,” says Ngu of the project, which met much resistance. “But only a few people understand that.”

    Political pressures

    In 1991, Vietnam tested the blood of 70,000 IDUs, patients who had sexually transmitted diseases, sex workers, and blood donors. Only one case of HIV surfaced. By 1994, the country had begun to see an exponential spread of the virus in IDUs, and international alarm bells began to sound. It was feared that Vietnam, like its neighbors, would soon see HIV rampantly spreading through sex workers, migrants, and the heterosexual population. “It's especially developed very fast in the recent few years,” says A Chung, who heads the National AIDS Standing Bureau.

    Testing ground.

    A needle-exchange program in Lang Son samples blood from residents (top) to monitor HIV prevalence, which continues to rise countrywide in injecting drug users.

    GRAPH SOURCE: VIETNAM'S MINISTRY OF HEALTH; PHOTO BY MALCOLM LINTON

    But the domino effect from IDUs to other groups has yet to happen on a dramatic scale. “Vietnam is not Cambodia or Thailand,” says Jamie Uhrig, a Canadian public health physician who has worked in Vietnam for the past 10 years, including a 2-year stint with the United Nations Development Programme. Uhrig contends that the spread of HIV in Vietnam likely will remain primarily in IDUs. “There is no heterosexual epidemic in Vietnam, and there won't be,” he predicts. “Most of the factors that produce a generalized epidemic in Asia aren't there.” Led by an authoritarian regime that opened to outsiders only in the 1990s, Vietnam does not have brothel-based sex workers, Uhrig points out, and the sex trade that does exist is “among the quietest in the world.” Truck drivers, police, and military men do not often frequent sex workers. Gonorrhea, one of the sexually transmitted diseases that helps spread HIV, “has all but disappeared.” Condom use, he says, is common. “They don't want other people's fluids touching them.”

    Vietnam has, however, had little success in slowing the spread of HIV among IDUs. The country has “cold-turkey” rehabilitation centers—methadone is considered an illegal drug—and some in-home treatment. Chung, a sociologist by training, says they have failed. “It's not showing any success, because relapse is about 90% after detoxification,” says Chung. Convincing the government to embrace harm-reduction strategies that treat drug addiction as a disease rather than a crime also has presented serious challenges. “Working with the police and other agencies is more difficult than working with IDUs,” he says.

    Field of nightmares.

    Peer educators working with Doan Ngu regularly remove needles from this open-air shooting gallery.

    PHOTOS BY MALCOLM LINTON

    The virus may not yet be spreading much from IDUs into Vietnam's general population, but it is crossing the border with China. Epidemiologists who study molecular changes in the virus have found evidence that much of the HIV infecting IDUs in southern China comes from northern Vietnam, where heroin is purer and cheaper.

    Against this backdrop, Abt Associates, a research consulting firm based in Boston, Massachusetts, organized a meeting in Kunming, China, in 1997 on the regional spread of HIV. The meeting, sponsored by the Ford Foundation, led three of the attendees to hatch the idea for what became the Cross-Border HIV Prevention Intervention project. “We thought if we have momentum for this regional conference, why don't we see if we can get international cooperation?” recalls one of the trio, Don Des Jarlais, a renowned researcher on IDUs and HIV based at the Beth Israel Medical Center in New York City. Des Jarlais, the Ford Foundation's Joan Kaufman (a reproductive health specialist who now heads Harvard University's AIDS Public Policy Program), and Abt's Ted Hammett decided to try to organize syringe-exchange programs in both countries.

    They soon recruited Wei Lu, director of HIV/AIDS Prevention and Control in Nanning, China, and other leading AIDS officials from both regions. But several hurdles quickly appeared. China and Vietnam have had many conflicts in the past, resulting in a touchy atmosphere, exacerbated by the fact that drug use is considered a “social evil” in both cultures. They had also hoped that the U.S. National Institutes of Health (NIH) would be the main source of support for the project, but the U.S. government forbids needle-exchange programs. In the end, the Ford Foundation agreed to pay for the needle-exchange aspect of the project and hire the peer educators. NIH awarded the group a grant that will provide nearly $2 million over 4 years. China also did not permit syringe exchange, so Des Jarlais suggested that they use a “social marketing” scheme that allows IDUs to exchange used syringes for a voucher that they can turn in at local pharmacies to receive clean syringes.

    The project began in 2002, with teams of (supposedly) former IDUs hired at each of the project's 10 sites to serve as peer educators who distribute vouchers or even clean syringes. The researchers also established baseline HIV prevalence among IDUs in each locale: 47% in Lang Son Province and 18% in Guangxi. “In the absence of intervention, 18% could go to 40% in a year,” says Des Jarlais, who notes that this is the first research project attempting to stop HIV's spread across international borders.

    Open borders

    Walking up to a broken wall from the old schoolhouse, Ngu points out evidence of the project's impact. A dirty Styrofoam container and a wicker basket each hold mountains of used syringes that the peer educators have collected from the abandoned lot, to prevent both their reuse and accidental needle sticks. “That's just from 1 week at this site,” Ngu says.

    Before burning these syringes, the project workers count them: From January through December 2002 alone, they totaled 163,827 in Lang Son Province. The Vietnam arm of the project also distributed more than 25,000 new syringes in that period. Preliminary data show that the prevalence of HIV has not increased in Lang Son in more than a year, further evidence that the program has made some headway.

    Ngu well recognizes the limits of the project and would much like to see Vietnam embrace a more comprehensive harm-reduction program, including offering methadone. “We need to work harder to explain things to our policymakers,” says Ngu. “They're still mixing up and confusing the political with the HIV/AIDS problem. Now's the time for action. I say this not because I'm a fortuneteller. It's because we have learned from other countries.”

  12. ASIA--THE NEXT FRONTIER FOR HIV/AIDS

    Two Hard-Hit Countries Offer Rare Success Stories: Thailand & Cambodia

    1. Jon Cohen

    By heavily promoting condom use, Cambodia and Thailand have blunted their epidemics, but the virus continues to make headway in some populations

    CHIANG RAI AND BANGKOK, THAILAND, AND PHNOM PENH, CAMBODIA—On a moonless evening, a group of female and transgendered sex workers wearing identification cards around their necks strolls through a park that abuts a Buddhist temple in downtown Phnom Penh. The dark park has a wide variety of sex for hire. Men seeking men head for the fountain. Straight women sit on the grass with small piles of oranges in front of them, a thinly veiled cover for negotiating a later sexual rendezvous. Men dressed as women, some of whom have breasts from taking steroids, hang out near the restrooms. The people with the identification cards have worked this park themselves many a night, but this evening they have a different mission: Oxfam Hong Kong has hired them to distribute condoms.

    Like neighboring Thailand, Cambodia has mounted a “100% condom program” that, with help from sex workers themselves, aims to persuade everyone selling or paying for sex to use a condom with each encounter. Supported by government and nongovernmental organizations, the campaigns have yielded measurable successes. In Cambodia, HIV prevalence among all adults fell from 4% in 1999 to 2.6% by the end of 2002, by which point the Ministry of Health estimated that a total of 259,000 Cambodians had become infected since the first case surfaced in 1991. A recent study by the Cambodian Ministry of Health projected that without increased condom use and other behavior changes, Cambodia would have had about three times as many HIV infections.

    Grassroots prevention.

    A member of the Women's Network for Unity (in green) promotes condom use in a Phnom Penh park that has a flourishing sex trade.

    PHOTO BY MALCOLM LINTON

    Thailand, which recorded its first HIV case in 1984, by 1991 had already launched a nationwide 100% condom campaign. Although national figures do not exist for the early years of the epidemic, prevalence has stabilized at around 2%. “Most of the data confirm that prevalence declines after 1993, 1994,” says Sombat Thanprasertsuk, who directs the Ministry of Public Health's AIDS branch. A recent model by his office similar to the Cambodian one suggests that if the country had not attempted to thwart HIV, 10% of the population would have become infected by 2000. “The condom program really worked,” says Jordan Tappero, head of the large HIV/AIDS program in Thailand run by the U.S. Centers for Disease Control and Prevention (CDC). “It's very unusual that a woman in a brothel would accept a client without a condom.”

    Both the Thai and Cambodian programs have achieved even more impressive results among specific high-risk groups. “Consistent condom use” by Cambodia's brothel-based sex workers increased from 51.3% to 89.8% between 1998 and 2002, and HIV prevalence in that group plummeted from 42.6% to 28.8%. Another study conducted by Cambodia's national HIV/AIDS program shows that 75.8% of urban police reported having paid for sex in 1997, but that number had dropped to 32% by 2001.

    In Thailand, that same population's prevalence dropped from 28.2% in 1996 to 12.27% in 2002. Timothy Mastro, Tappero's predecessor at CDC's Thailand program, says he well remembers the “tremendous excitement” when evidence first surfaced in 1995 that the prevalence in new military recruits had begun to drop in lockstep with increased condom use. “The Thai success was extremely heartening for everyone doing HIV prevention on a national level,” says Mastro. “There really had not been a demonstration that a heterosexual epidemic could be changed by behavioral interventions and condom campaigns.”

    Turning the tide.

    Thailand's aggressive condom campaign receives much credit for dramatic drops in prevalence in military recruits (top). A model (bottom) shows how stabilizing the epidemic has likely averted millions of infections.

    GRAPH SOURCE: THAILAND'S MINISTRY OF PUBLIC HEALTH

    Today, leading AIDS epidemiologists routinely cite Cambodia and Thailand as examples of how aggressive prevention campaigns championed by enlightened governments can dramatically slow the spread of HIV. True enough. But the accolades tend to blur the fact that these two countries have extraordinarily different AIDS epidemics. And in spite of the successes, HIV, abetted by government policies that are far from progressive, continues to gain ground in some populations.

    Thai troubles

    At Saen Sok village in the lush mountains that surround the northern Thai city of Chiang Rai, four HIV-infected men and women from the Akha hill tribe sit at their chief's house under the shade of a sala, an open-air hut. Mingaw Huyi, who has one of her five children lying in her lap, became infected by her husband, a heroin addict who died from AIDS 3 years ago. The other three adults became infected because they shared needles themselves, and each has spent time in prison for heroin possession. One, Sompong Joebaw, 34, started injecting heroin 17 years ago, along with all of his closest friends. “I'm the only one left,” he says. “They've all died from AIDS.” Myat Htoo Razak, who heads a project for Family Health International that aims to lower the spread of HIV in the Akha, says that “hill tribes disproportionately have been affected by HIV/AIDS, and a lot of them have died already.”

    As the Akha see it, HIV continues to thrive in their community because of government discrimination. “There's an obvious prejudice against hill tribe people,” says Micu Joebaw, 45, who says she began injecting more than 20 years ago and has lost one husband to AIDS, another to a bullet, and a son to suicide. Hill tribes speak their own languages, and many people here understand little Thai, which means that the bulk of HIV/AIDS education campaigns in Thailand have no impact on them. Many Akha—some of whom are refugees from Myanmar —do not have Thai citizenship, severely limiting their access to government services. Sompong had Thai papers, but they were revoked because of his drug use. They say the discrimination pervades the services that they do receive, too. Mingaw, who learned she was infected with HIV from a routine blood test during her last pregnancy, says the Thai nurses at the hospital where she gave birth publicly chided her for being infected. “I was very angry.” Mingaw starts to cry. “But I couldn't say anything or it would get worse.”

    GRAPH SOURCE: CAMBODIA'S MINISTRY OF HEALTH

    The chief, Teerawat Pitakpraisri, worries greatly about the future of his villagers. “In the past, drugs have been the number one problem,” says Teerawat. “From now on, HIV will be the number one problem for their health, the burden to their family, and the community. The young especially will have no future and, in time, they'll get into this vicious circle.”

    HIV in injecting drug users (IDUs) among the Akha and other hill tribes represents a dramatic example of a problem that extends throughout Thailand. Since researchers started routinely assessing HIV infections at drug-treatment clinics in 1989, the HIV prevalence in IDUs of all ethnicities has remained steady at about 40%. A report issued by the World Bank in November 2000, Thailand's Response to AIDS: Building on Success, Confronting the Future, bluntly spelled out the situation. Written by World Bank economists Martha Ainsworth and Agnes Soucat in collaboration with epidemiologist Chris Beyrer of Johns Hopkins University's Bloomberg School of Public Health in Baltimore, Maryland, the report noted that “the pragmatic approach followed in preventing HIV transmission in commercial sex, which is also illegal, has not been followed for IDUs, who remain highly stigmatized, and frequently incarcerated.”

    IDUs fight back.

    Activist Paisan Tan-Ud advocates for drug users' rights.

    PHOTO BY MALCOLM LINTON

    Recently, 70 current and former IDUs formed an activist group, the Thai Drug Users Network. “Our message is ‘Treat us like human beings; provide us with services like everyone else,’” says Paisan Tan-Ud, who helped organize the group. The network sharply criticizes the services that do exist. Methadone maintenance programs, it says, are restricted to Bangkok, and even those limit dosing to 45 days. “Methadone maintenance should give you methadone as long as you want it,” contends Paisan. The clinics also taper doses, which he says leads many people to start using heroin again while receiving methadone. No needle-sharing programs exist, either, and regulations currently prohibit users of illegal drugs from receiving anti-HIV drugs. The World Bank report, which explored these shortcomings in detail, urged Thailand to launch “a major new effort” to prevent infection and transmission of HIV among IDUs. Otherwise, the report warned, “IDUs will continue to be a reservoir of infection and will pass HIV not only to other IDUs, but their sexual partners and children.”

    Sombat of the Ministry of Public Health's AIDS branch readily addresses the limitations to Thailand's success story. As for the hill tribes and discrimination, “we know there's a problem there,” says Sombat, stressing that both the government and nongovernmental organizations are attempting to improve the situation. “We must do something fast, as quickly as possible.” For IDUs, Sombat says he supports harm-reduction principles, which aim to treat addiction as a disease rather than a crime. “The behavior of sharing needles and equipment among IDUs is hard to change,” says Sombat. And he acknowledges the shortcomings of their current treatment programs. “We know from the past that treatment for heroin users has a limited effect,” he says. “The percent who are cured is quite low.”

    Cambodia's conundrum

    Oddly, considering the plight of Cambodia's neighbors, injecting drug use has played no measurable role to date in the epidemic in Cambodia. No one has a convincing explanation for this—some suggest that poverty or the strict rule of the past kept drugs out of reach—but Hor Bun Leng, deputy director of the AIDS program run by Cambodia's Ministry of Health, worries that the situation might change. “You can see rising drug use here with smoking and sniffing, and that later could become injecting,” he says. “And if we have IDUs, the outbreak will be more serious than ever before.”

    But there is another, immediate concern: HIV continues to spread through Cambodia's thriving sex industry, in spite of successful efforts to increase condom use. Rosanna Barbero, a coordinator for Oxfam Hong Kong, and many others note that the number of sex workers—and the spread of HIV— exploded in 1993 when the United Nations sent more than 20,000 troops to the country to help restore order.

    Hill tribe hardship.

    HIV-infected Akha say government discrimination fuels epidemic.

    PHOTO BY MALCOLM LINTON

    On a lazy Saturday morning in Phnom Penh, a group of sex workers who have gathered at the old Kong Kea Restaurant, a barge parked on the banks of the Tonle Sap River that serves as headquarters for Oxfam Hong Kong, highlights the stark limitations of condom campaigns and guffaws at the notion that the government has an enlightened position toward sex work. Indeed, frustrated by their government, sex workers formed the Women's Network for Unity 3 years ago, which has its office at the barge.

    Although Cambodia, like Thailand, outlaws sex work, the government registers brothels and requires the women who work in them to visit clinics once a month for checkups to see whether they have any sexually transmitted diseases. But Barbero, who since 1999 has helped sex workers “empower” themselves, says that “ordinary people” do not like brothels. “Even men who regularly use brothels think it's against the culture,” Barbero says.

    The clash between Cambodia's cultural mores and the thriving sex work industry came to a head on 21 November 2001, when Prime Minister Hun Sen suddenly ordered all brothels shuttered. “It was very irresponsible for the prime minister to wake up one morning and say ‘Close the brothels’ without looking at the consequences,” says Mu Soc Hua, minister for women's and veterans’ affairs, who dressed up as a sex worker 2 days after the raids to see their effects firsthand. “The crackdown led girls onto the street, which led to more rape. And no one uses a condom during a rape, so it led to more spread of HIV. It also gave the police more freedom to raid brothels.”

    Hor Bun Leng readily acknowledges the government's murky policy toward sex workers but says that from the perspective of the Ministry of Health, the policymakers also deserve credit for helping slow the spread of HIV in this most vulnerable group. “Part of the success story is that the government allows us to work with high-risk populations,” says Hor Bun Leng. “They open the door.”

    Hor Bun Leng stresses that residue from the country's politics of the past confronts him more profoundly than any current political obstacles. The Khmer Rouge-led genocide in the 1970s that killed nearly 2 million Cambodians—including his parents and siblings—left a severely impoverished population, and not just financially. “Because they survived this event, they have had limited information and education,” he explains. This, in turn, makes it more difficult to compel them to change high-risk behaviors.

    Hor Bun Leng says that in spite of the real decreases in prevalence and dramatic increases in the use of condoms, this is no time for Cambodia to drop its guard. “Cambodia looks like a patient who has recovered from a disease,” he says, “but it's very easy to go back.” Indeed, he adds: “We still have the highest prevalence of HIV in the world outside of Africa.”

  13. NEWS FOCUS SPECIAL REPORT

    Can a Drug Provide Some Protection?

    1. Jon Cohen

    PHNOM PENH, CAMBODIA—Carpet-bombed by the United States during the Vietnam War, devastated by Khmer Rouge genocide that killed nearly 2 million people, and then occupied by the Vietnamese until United Nations soldiers restored order in 1993, this country has had to build a functioning public health system from the ground up. Little wonder, then, that scant biomedical research occurs here. But now, a collaboration has begun between Cambodian scientists and an international team of researchers on a cutting-edge HIV prevention study that raises eye-popping possibilities—and profound ethical dilemmas. “If this project works, it's going to be groundbreaking,” says Kimberly Page-Shafer, an epidemiologist at the University of California, San Francisco, and one of the three principal investigators.

    The study builds on intriguing monkey research, first published in Science 8 years ago (17 November 1995, p. 1197), indicating that the anti-HIV drug tenofovir can prevent monkeys from becoming infected with SIV, HIV's simian cousin. Page-Shafer's team and its Cambodian and Australian co-investigators plan to test whether a daily dose of tenofovir can similarly block HIV in uninfected people. In all, the 2-year, placebo-controlled trial hopes to enroll 860 sex workers who are at high risk of becoming infected. “It's a prevention study that has a very high chance of providing a positive result quite quickly,” says co-principal investigator John Kaldor, an epidemiologist at the University of New South Wales in Sydney, Australia, who is working for the U.S.-based Family Health International.

    The team hopes to start recruiting for the trial in January 2004. Kaldor and Page-Shafer, along with co-principal investigator Ly Penh Sun of the Cambodian National Center for HIV/AIDS, Dermatology, and STDs, have received approval from the Cambodian government and secured funding from both the U.S. National Institutes of Health and the Bill & Melinda Gates Foundation. Expectations are high: “It's one of the few things I have heard about that might work as a preventive,” says AIDS vaccine researcher Ronald Desrosiers, head of Harvard's New England Regional Primate Research Center in Southborough, Massachusetts.

    Not surprisingly, the study—similar versions of which will take place in Cameroon, Ghana, Nigeria, and the United States—has attracted intense scrutiny. “Many people are concerned,” says Phillipe Glaziou, an epidemiologist at the Pasteur Institute here. Not only will the study give people who do not have HIV a potentially toxic drug, but it could backfire, says Glaziou. “Obviously, if you tell prostitutes they might get some protection from drugs, they'll tend to think that they can have sex without condoms and make more money,” he cautions. “On the other hand, it's quite interesting to know whether tenofovir would be effective.”

    The tenofovir researchers have thought long and hard about these issues. They selected tenofovir because it requires only one pill a day (it has a long half-life) and has fewer side effects than any anti-HIV drug available. “It's a very benign drug,” says Kaldor. And although the researchers have serious concerns about “behavioral disinhibition,” they will try to counter it with intensive counseling, condoms, and tests and treatments for other sexually transmitted diseases. Page-Shafer notes that preliminary data from an AIDS vaccine efficacy trial just being completed in Thailand (see p. 1663) has found that the injecting drug users who participated in the trial reduced their high-risk behavior.

    The research that paved the way for this trial was a 1995 monkey study, in which an injectable form of tenofovir given daily completely protected monkeys intentionally given SIV. Gilead Sciences in Foster City, California, subsequently made a pill form of tenofovir for infected patients to use in combination with other anti-HIV drugs. The U.S. Food and Drug Administration approved it in October 2001.

    In November 2001, researchers published another monkey study that raised a mind-bending possibility: Tenofovir might indirectly affect the animals' immune systems and might even help them contain newly acquired infections. A research team led by virologist Jeffrey Lifson, a contractor at the U.S. National Cancer Institute, in November 2001 reported that it infected five animals with a highly lethal strain of SIV and the next day began a 28-day course of treatment with tenofovir (Science, 28 June 2002, p. 2325). The animals' immune systems completely controlled the infection and then by some as-yet-undefined mechanism defeated a subsequent “challenge” with a different strain of SIV.

    Desrosiers, who collaborated on the study with Lifson, says that the Cambodian study in humans—although it is intended to prevent people from becoming infected—may inadvertently shed light on Lifson's still-confusing results. “I'm more excited about this than anything I've heard about in a while,” says Desrosiers.

  14. NEWS FOCUS SPECIAL REPORT

    Thailand's Do-It-Yourself Therapy

    1. Jon Cohen

    BANGKOK, THAILAND—Eight people dressed in matching blue protective gear, wearing face masks or complete oxygen hoods, sit together at a long table, looking for all the world like disease detectives preparing to attack an outbreak of a rare virus ravaging the local population. Indeed, that's their mission, but they're not bug detectives. These workers are in the vanguard of a movement to bring anti-HIV drugs to patients in poor countries at affordable prices: They spend their days filling bottles with anti-HIV pills (the masks prevent inhalation of the medicine) that the Thai government is manufacturing and plans soon to make widely available here.

    In April 2002, the Government Pharmaceutical Organization (GPO), which employs these workers, began producing a generic version of three anti-HIV drugs—d4T, 3TC, and nevirapine—mixed together into one pill called GPO-VIR. Treatment requires only two pills a day, each of which costs a mere 50 cents. About 5000 Thais now receive GPO-VIR, but by the time Thailand hosts the XV International AIDS Conference in July 2004, the country plans to offer GPO-VIR to 60,000 of its 600,000 HIV-infected people. “This means a lot for Thailand,” says Thongchai Thavichachart, a clinician who runs GPO. “It is the time for us to help our people.”

    Quality control.

    Workers hand-inspect freshly made GPO-VIR.

    PHOTO BY MALCOLM LINTON

    It also means a lot to some pharmaceutical companies, which have fought to prevent the manufacture of generic versions of their patented drugs. The World Trade Organization explicitly underscored in 2001 that countries had a right to “protect public health” and “promote access to medicines for all.” But Thailand and other generic manufacturers still face challenges from the pharmaceutical industry, which now focuses on some finer points of the law. “We're not going to compete with any big company,” says Thongchai. “We're a small plant only for serving our country policy.”

    At the moment, the company can produce only about half the GPO-VIR that Thailand will need to treat 60,000 people, the number that officials estimate most badly need this cocktail of drugs. Thongchai has every confidence that GPO will meet the challenge of ramping up production, which leaves Thailand with a more profound challenge still: how to deliver the drugs to its HIV-infected people. Taweesap Siraprapasiri of Thailand's Ministry of Health emphasizes that far more obstacles exist than simply providing GPO-VIR. “It's lifelong care,” says Taweesap, adjunct director of an HIV/AIDS collaboration with the U.S. Centers for Disease Control and Prevention. “We need a lot of training and partnerships; we need infrastructure and cooperation with nongovernmental organizations. And we're really concerned about the budget.” Praphan Phanuphak, who heads the HIV Netherlands, Australia, Thailand Research Collaboration, also urges his government to start negotiating with other generic manufacturers now to buy more anti-HIV drugs to help people who fail on GPO-VIR. “It will take years for GPO to produce other drugs,” says Praphan. “There are many more drugs from India that are cheap.”

    Opening doors.

    GPO's Thongchai Thavichachart.

    PHOTO BY MALCOLM LINTON

    A Belgian branch of Médecins Sans Frontières (MSF) already has begun training Thai clinicians in the best use of GPO-VIR, but some of the most basic tools remain in short supply. Paul Cawthorne, who heads the MSF program, says it “is a nightmare” to get a person's CD4 count, a relatively expensive measurement of a key white blood cell that indicates the stage of a person's illness and is used to monitor the effectiveness of treatment.

    Yet Cawthorne takes heart from Thailand's recent push with GPO-VIR and bristles when outsiders caution that the drugs in this cocktail have serious limitations. True, they have less than optimal potency, and d4T in particular can cause serious side effects. “People in the West keep saying it's not the best,” says Cawthorne. “OK, d4T is not a brilliant drug. We have to accept that Thailand, even though it seems to be wealthy, it's not wealthy in its ability to afford all the drugs it needs.”

    Cawthorne notes that when he started working in Thailand 6 years ago, he had to fight to find a hospital bed so that someone dying from AIDS could receive the most basic medical care. “GPO-VIR is a major, major step,” says Cawthorne. “The thought that as of now you would have people on triple therapy was beyond our wildest dreams.”

  15. NEWS FOCUS SPECIAL REPORT

    Thailand Beats the Odds in Completing Vaccine Test

    1. Jon Cohen

    A just-completed efficacy trial in injecting drug users is a major accomplishment. Even the company behind the trial wondered if it could be done

    BANGKOK, THAILAND—Gulping down a tin cup full of yellow syrup, a 32-year-old man visiting this clinic at Taksin Hospital for his daily dose of methadone explains that after 14 years of injecting heroin, he recently became infected with HIV. “I had a wife, but she left me when I told her about my blood results,” says the man, who ekes out an existence as a day laborer and lives with his father. “I knew that HIV was transmitted by sharing needles, but I had a craving.”

    His tragic circumstance is, unfortunately, not unusual: A catastrophic 40% of injecting drug users (IDUs) in Thailand are infected with HIV. But his infection is particularly noteworthy because it occurred while he was participating in a landmark AIDS vaccine study, just now coming to a close. In the painful calculus of a placebo-controlled vaccine efficacy trial, some people must become infected for researchers to determine whether a preparation has any worth. (Until the data are unblinded, it will not be known whether he was given a placebo or the vaccine.)

    Regardless of the ultimate results, just completing the study—the first AIDS vaccine efficacy trial ever held in a developing country—marks a significant achievement. “It took one-and-a-half years for us to get this study past six committees,” says the project's director, Kachit Choopanya, a pediatrician who shifted into treating IDUs in the 1970s. “This has been very hard for us.” The researchers screened 4944 IDUs who volunteered for the study, a collaboration between the Thai Ministry of Public Health, the U.S. Centers for Disease Control and Prevention, the Bangkok Metropolitan Administration, and the vaccine's manufacturer, VaxGen of Brisbane, California. From that initial group, the researchers selected 2545 uninfected people to receive either a placebo or the vaccine, a genetically engineered version of HIV's surface protein, gp120, made from HIV strains circulating in Thailand. By the time the study formally came to a close this June, the 380 staff members working in Taksin and the other 16 clinics involved in the study had given more than 17,000 injections, drawn more than 40,000 blood samples, and processed a half-million forms charting the results.

    Thai PI.

    Kachit Choopanya ran the 2500-person study.

    PHOTO BY MALCOLM LINTON

    VaxGen co-founder Donald Francis says that when a colleague first suggested conducting this efficacy study in Thai IDUs, he was highly skeptical. “I said, ‘Oh my god, we can't follow them for anything.’” Yet fully 95.6% of the participants showed up for all three injections given during the first 6 months, and by mid-May 2003, 84.4% had received four more booster shots. Francis attributes the high retention rate to the deep trust that the IDU community has for Kachit, mixed with pride that participants felt in joining the study. “There aren't many opportunities for drug users to feel that way,” he says.

    The high retention rate is especially remarkable because at each study visit, 30% of the participants reported having spent time in jail or prison during the preceding 6 months. “We didn't really expect that when we started,” says Francis. The researchers conducted more than 2000 visits to incarcerated trial participants, collecting blood samples and giving the vaccine.

    Before they began the trial, the researchers had to confront a sticky ethical question: Could participants be placed at greater risk of becoming infected? The concern does not center on the vaccine itself, which contains a harmless piece of HIV that cannot cause an infection, but on the possibility that participants might indulge in riskier behavior if they assumed that they had received the vaccine and that it offered some protection. However, a 1-year analysis of participants—who all received risk-reduction counseling at each study visit—showed that injecting drug use declined from 93.8% to 66.6%, and needle sharing dropped from 33% to 17.5%.

    Strong medicine?

    Data from this methadone clinic at Taksin Hospital will help assess whether the vaccine works.

    PHOTO BY MALCOLM LINTON

    The decision made by the 32-year-old man at Taksin Hospital to share a needle pinpoints one reason why someone who understood this risk would take it. “We didn't have enough money to buy heroin for each one of us, so we pooled our bhat,” he explains, describing an incident with friends that he thinks led to his infection. “We shared the same syringe so that each one of us received our fair share.” A syringe provides an ideal calibration device, as it has lines that precisely demarcate one cubic centimeter of liquefied heroin from another. Risk-reduction strategies typically ignore this vexing reality.

    The much-anticipated results from the study are likely to receive exceptional scrutiny. VaxGen sparked a red-hot controversy last February when it announced the results of a separate efficacy study conducted in North America, the Netherlands, and Puerto Rico. That trial, which mainly enrolled gay men at high risk of sexual transmission, found that the vaccine offered no more protection from HIV infection than did the placebo. But the company claimed that the vaccine inexplicably seemed to work remarkably well in a small subset of black participants and possibly Asians, too—a subset analysis that came under harsh criticism (Science, 7 March, p. 1495).

    Although researchers roundly dismissed the notion that race would affect how well a vaccine worked, many remain open to the idea that the different route of transmission in this trial could lead to a different outcome. The Thai study group plans to reveal its results before the end of the year.

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