News this Week

Science  04 Jun 2004:
Vol. 304, Issue 5676, pp. 1422

    U.S. Trade Policy Creates Confusion Over Co-Authorship

    1. Yudhijit Bhattacharjee

    Farzad Naeim anticipated plenty of logistical challenges in his latest endeavor, but he didn't expect to run into problems with U.S. trade laws. The structural engineer at John Martin & Associates in Los Angeles led a scientific team that visited Bam soon after a devastating earthquake leveled the ancient Iranian city last December. The team linked up with Iranian colleagues to assess the damage and loss of life, observe emergency-response operations, apply and test new methods of collecting perishable data, and recommend measures to reduce destruction the next time around. Publishing the findings in the journal he edits, Earthquake Spectra, seemed like the least of Naeim's worries.

    Not anymore. A single sentence in a five-page statement by an obscure U.S. government agency—barely noticed when the statement was issued 2 months ago—has thrown Naeim for a loop and jeopardized his plans to disseminate the results of that reconnaissance mission in an upcoming issue. And he's not alone. Scientists of all stripes are now wondering if work done in collaboration with scholars in Iran, Cuba, and Sudan—countries under a U.S. trade embargo—will ever see the light of day.

    Ironically, the 2 April statement from the Treasury Department's Office of Foreign Assets Control (OFAC) was initially seen as a favorable solution to another thorny problem of whether U.S. journals would risk breaking the law if they edit manuscripts from those sanctioned countries (Science, 9 April, p. 187). In a five-page letter to the Institute of Electrical and Electronics Engineers, OFAC reversed its 30 September 2003 decision requiring journals to obtain a license to edit manuscripts from Iran and other sanctioned countries. But although the letter appeared to endorse normal publishing procedures, it noted in passing that “a collaborative interaction … between an author in a sanctioned country and one or more U.S. scholars resulting in co-authorship” would be considered “a prohibited exportation of services.”

    Devastation in Bam.

    Papers by U.S. and Iranian authors on last December's earthquake may run afoul of U.S. laws.


    That comment has since triggered confusion and concern among scientific societies and publishers, who say they've never heard of such a restriction. “If it's true that U.S. seismologists might be liable for criminal prosecution for co-authoring a paper on the earthquake, it is a policy that makes no sense,” says Susan Newman, executive director of the Seismological Society of America.

    OFAC's views on publishing have already led to the shelving of some projects. A coalition including the Association of American University Presses, the Association of American Publishers, and the American Institute of Physics (AIP) is weighing a suit that would argue that such a policy violates their First Amendment rights. “This affects a range of activities integral to publishing—from codevelopment of material with authors in sanctioned countries to translations,” says Larry Siems, director of international programs for PEN, an authors' group that is part of the coalition.

    The core of the problem, Siems says, is OFAC's claim to exercise oversight of any U.S. publishing activity. A 1977 law authorizing economic sanctions was amended in 1988 to exempt “information” and “informational materials” from restrictions on trade with sanctioned countries. But OFAC says the exemption does not apply to “transactions with respect to information materials not fully created and in existence at the date of the transactions.” OFAC spokesperson Molly Millerwise says that the 2 April statement on co-authorship is part of a “standing policy” at the agency. At the same time, she notes, the policy could be reconsidered “should someone come forward and ask OFAC to review the co-authorship or collaborative process.”

    Harold Jaffe of the Department of Energy's (DOE's) Office of Science thinks that OFAC is waiting for the chance to do exactly that. He says OFAC officials responded favorably when asked about the legality of DOE scientists producing papers with Iranian researchers from collaborative work on the Large Hadron Collider being built at CERN, the European particle physics laboratory near Geneva. “They made it clear that their objective was not to make the joint publication of papers illegal, per se,” he says. On this basis, Jaffe says DOE doesn't intend to apply for a license or place any co-authorship restrictions on its scientists.

    OFAC's willingness to license co- authorship on a case-by-case basis is no consolation for Marc Brodsky, AIP's executive director. Brodsky says the policy will simply discourage U.S. researchers from collaborating with scholars in sanctioned countries. “If this isn't prior restraint, what is?” he asks.


    Youngest Extrasolar Planet Reported

    1. Richard A. Kerr

    WASHINGTON, D.C.—Astronomers announced at a NASA press conference here last week that they have found strong evidence for the youngest known planet circling another star. The putative planet is so young, its discoverers say, that it may have formed by runaway collapse of the star's disk of orbiting debris. If so—and there are plenty of skeptics—the discovery would support a controversial new instability mechanism of planet formation.

    At the press conference, astronomer Dan M. Watson of the University of Rochester, New York, showed how infrared spectra recorded by the Spitzer Space Telescope, launched last August, have revealed a central hole in the disk of debris circling the nearby star CoKu Tau 4. When Watson and his colleagues compared the behavior of shorter-wavelength infrared radiation coming predominantly from the star to that at longer wavelengths mainly from the dusty disk, they concluded that the debris has been cleared out near the star to form a gap. Such gaps have been found around other stars, Watson noted, but the Spitzer observations show an exceptionally clear and sharp-edged gap. The most likely explanation, said Watson, is that a planet formed there and swept up the debris. And whereas other examples of disk gaps are millions of years old, he said, this star “is only 1 million years old. That really causes problems for the standard model of planetary formation.”


    The gap in a star's debris disk is real, but whether a new planet cleared it is contentious.


    According to the conventional view, a planet like Jupiter forms by the slow accumulation of icy and rocky bits until the nascent planetary core generates enough gravity to pull in a planet's worth of gas. That process is probably too slow to explain the CoKu Tau 4 planet, astronomer Alan Boss of the Carnegie Institution of Washington (CIW) told the press conference. He favors the view that the disk destabilized and its gas and dust rapidly collapsed into clumps that went on to form planets (Science, 6 June 2003, p. 1498). That would allow formation of a planet around a star as young as CoKu Tau 4. It would also let planets form from even the shortest-lived disks, upping the number of planetary systems in the galaxy.

    However, other researchers are not convinced there's a planet there. “They certainly haven't detected a planet directly,” says astrophysicist Richard Durisen of Indiana University, Bloomington. A small, undetected companion star might have cleared the gap instead, for example. And “we don't know these ages very well,” he adds. The star could actually be old enough that a somewhat improved version of the gradual accumulation mechanism could work.

    Astronomers are also uneasy because they've been burned before. Provocative claims of discovery made at previous NASA press conferences have proved groundless, notes astronomer Paul Butler of CIW. A planet reportedly wandering free between the stars was one notable example. But in this case, he says, it will be 10 years before new space missions can confirm or refute this planet claim.


    Side Effects Sideline Hemophilia Trial

    1. Jocelyn Kaiser

    One of the most promising gene therapy trials to date has been halted because two patients developed mild side effects. Over the past 3 years, the biotech company Avigen of Alameda, California, had been conducting clinical safety tests with a therapy shown to partially cure hemophilia in dogs. But after the latest of seven patients developed minor signs of toxicity, Avigen last week stopped the trial.

    The study built on the work of Stanford's Mark Kay and the University of Pennsylvania's Katherine High, who showed in 1999 that dogs with hemophilia B that were injected with an adeno-associated virus (AAV) vector carrying a gene for Factor IX, a blood-clotting protein, improved significantly (Science, 2 March 2001, p. 1692). Since 2001, Avigen has been conducting safety tests on people in which the vector carrying Factor IX is injected into a liver artery.

    But in October 2002, a patient given a higher dose of vector construct developed slightly elevated levels of liver enzymes, while the patient's Factor IX levels went down. Liver enzymes also rose in another patient this spring, suggesting that their bodies were mounting an immune response to the vector. “It really didn't make sense to pursue it” further, says Avigen research vice president Glenn Pierce.

    Kay and High hope they can modify the trial and continue testing the therapy, which they and others believe shows promise. “In terms of the science, I think things are going pretty well,” says High. The first step, Kay says, is to confirm with ongoing tests that the AAV vector triggered the immune response. Then, they would like to conduct a trial that briefly treats patients with immunosuppressive drugs at the same time as the gene therapy. Avigen and co-sponsor Bayer are testing this approach in animals and haven't ruled out another human trial in the future, says Pierce. But if they can't come up with the funding, another possibility is a trial with academic support, High says.

    Avigen's decision isn't a major setback to the field, researchers say, because the safety problem was minor and seems to be specific to this trial. This is in contrast to the death of a patient in Pennsylvania in 1999, apparently caused by reaction to a vector, and two cases of leukemia that developed in children in a trial in France, most likely because a vector inserted near an oncogene. Some other gene therapy trials are using the AAV vector, and more plan to do so. But most are injecting small doses locally into tissues, not the liver artery—into the eye or brain, for example —a practice that is less likely to provoke side effects, notes gene therapy expert Savio Woo of Mount Sinai Medical Center in New York City. Also, “there are improved [AAV] vectors on the horizon” that are more efficient and can likely be used in smaller doses, says Woo.

    But there is one broader lesson from the hemophilia trial, Kay says: “Until you go into humans, you just don't know” if it will work.


    Controversial Fossil Could Shed Light on Early Animals' Blueprint

    1. Erik Stokstad

    For decades, paleontologists have been eagerly looking for the roots of the so-called Cambrian Explosion—an apparent eruption of many-celled animals about 540 million years ago in which all the major animal body plans appeared. One key question: When did animals first develop mirror- image symmetry and other features (such as a digestive tract) that go with it? Now, researchers claim to have found the oldest known fossil of a “bilaterian” animal. But other experts suspect that the microscopic specimens might not be fossils at all.

    The new animal, described online this week in Science (, was an oval blob less than a fifth of a millimeter long. The authors say it shows that key features of bilaterians are preserved in rocks some 580 million to 600 million years old—and thus that the genetic tool kit used to assemble more sophisticated body plans was present long before the Cambrian. “If these are bilaterian fossils, they would help tone down the suddenness of that ‘explosion,’” says Jere Lipps of the University of California, Berkeley.

    Two sides.

    Fossil “bilaterian” or natural mineral formation? Experts disagree.


    The fossils come from the Doushantuo Formation in southwestern China, rocks famous for well-preserved fossils of microscopic sponges and embryos. One group including Jun-Yuan Chen of the Nanjing Institute of Geology and Palaeontology in China has collected thousands of specimens from the deposit. To examine them, Chen teamed up with paleontologist David Bottjer of the University of Southern California in Los Angeles and Eric Davidson of the California Institute of Technology in Pasadena. In 10 cross sections of similar specimens, they identified several key features of bilaterians. These include what appear to be a mouth, pharynx, and gut; layers of mesodermal, endodermal, and ectodermal tissue; body cavities, called coeloms, on either side of the gut; and pits in the soft outer surface that might have contained sensory organs. The researchers dubbed the creature Vern- animalcula guizhouena, or “Small Spring Animal,” because the Doushantuo Formation was deposited after a glacial period.

    Skeptics see it differently. “These may well have started out as fossils, but we can't say much about their morphology,” says Stefan Bengtson of the Swedish Museum of Natural History in Stockholm. For example, Bengtson suspects that the presumed tissue layers are really thin, banded mineral crusts. In these rocks, such crusts commonly line the walls of cavities left from decayed organisms, he says. Chen's team says that the fossils can't be artifacts because many specimens show the same structures and are the same size.

    If Vernanimalcula is real, it could force some researchers to rethink what ancestral bilaterians should look like. Many had pictured a larger, more complicated beast, says Doug Erwin of the National Museum of Natural History in Washington, D.C. Partly, that's because analyses of modern animals imply that these ancestors had genes that could make complex patterns. Vernanimalcula “suggests that you don't have to have a complicated animal as a primitive bilaterian,” Erwin says.


    TIGR Escapes Venter's Plan for Consolidation

    1. Eliot Marshall*
    1. With reporting by Jocelyn Kaiser.

    Scientists at TIGR—The Institute for Genomic Research, established 12 years ago by J. Craig Venter in Rockville, Maryland—hunkered down for a stressful reorganization last week. But it never happened.

    Board chair Venter and his advisers had proposed a cost-saving move to fold TIGR in with three other research outfits Venter created in 2002 under the umbrella of the J. Craig Venter Science Foundation. But when TIGR's board met on 24 May, it decided to let TIGR stay free. The result: TIGR will retain its independent status under director Claire Fraser.

    The proposal to merge TIGR with the other outfits came about, according to Venter and others, because TIGR's board was interested in streamlining the administration. “It seemed too complex” to have duplicate human-resources and grants-management staffs, says board member Gerald Rubin, a fruit fly geneticist and vice president of the Howard Hughes Medical Institute in Chevy Chase, Maryland. Venter says he favored some consolidation, including an effort to bring the scientists together. The combined scientific staff amounts to 136: 109 at TIGR and the rest at the Venter foundation's Joint Technology Center (JTC), the Institute for Biological Energy Alternatives (IBEA), and The Center for the Advancement of Genomics (TCAG). JTC is primarily a sequencing center, IBEA explores microbial routes to energy production and carbon storage, and TCAG focuses on ethics and education.


    J. Craig Venter proposed streamlining TIGR.


    But the proposal brought out tensions. Some TIGR scientists urged the board not to alter a system that seemed to be working well. TIGR, which is more investigator-driven than the other three organizations, has won many grants from the Department of Energy and the National Institutes of Health, and it has sequenced the genomes of many microbes, including the one that causes anthrax. TIGR staff members worried about a more top-down management style if Venter were in charge, a source there says.

    The internal protest may have had an impact. Venter's reaction to the internal debate is that some people “panic” when change looms. He says he likes a research organization to be able to reorient itself quickly and use a “cross-disciplinary approach” to focus on problems. In contrast, he suggests, “TIGR has evolved into a standard academic model” under which people get funded by seeking and winning focused grants. “The two cultures are different,” agrees Rubin. The board decided “everyone would be happy” if TIGR were left to remain independent.

    TIGR's board will still be chaired by Venter, and its relationship with the other institutes—including the sequencing center—will stay the same. “Nothing has changed,” Venter says. Fraser says that TIGR is moving ahead with plans to create a cancer genomics group, add work on viral genomes, and expand plant genomics.

    There's still one matter to be decided, though: The three non-TIGR centers will still be combined, but the merged outfit doesn't yet have a name. Several possibilities, including the J. Craig Venter Institute, are being considered. Venter says the choice will not be made by him.


    Syngenta Donates 48,000 Mutant Arabidopsis Plants

    1. Elizabeth Pennisi

    For plant biologists, the search for gene functions just got a lot easier. Last week, the agribusiness giant Syngenta International in Basel, Switzerland, released 48,000 mutant strains of Arabidopsis, the first plant with a sequenced genome, to a stock center for distribution the world over—with no fees and no strings attached.

    Arabidopsis is the species of choice for biologists interested in plant development and function. With the sequence in hand, researchers set out to learn what every gene in the Arabidopsis genome does. Teams in Germany, the United States, Japan, the United Kingdom, and elsewhere have been scrambling to insert DNA into all the genes, one by one, to disrupt each gene's function and make mutant seeds. With the addition of the Syngenta seeds, “we are over 90% of our way to the goal of identifying mutations in all plant genes,” says Joseph Ecker, a plant geneticist at the Salk Institute in La Jolla, California.

    Rich harvest.

    Newly donated mutant Arabidopsis strains will boost plant genomics.


    Syngenta began stockpiling mutants in 1999, using them to study resistance to drought and disease. When the collection outlived its usefulness, Syngenta decided to pass it on rather than destroy it. “We know how important these lines could be,” says Allen Sessions, a Syngenta plant geneticist in Research Triangle Park, North Carolina.

    Especially notable, says Ecker, is that Syngenta released these seeds and the genomic data without requiring anything in return. “It's a significant gift and at the same time, an embarrassment for the ‘academic’ labs that are still trying to benefit financially,” he notes. For example, the Arabidopsis Biological Resource Center (ABRC) in Columbus, Ohio, charges $4 for each mutant provided, but another public distribution center called GABI—run out of the Max Planck Institute for Plant Breeding Research in Köln, Germany—charges about $600 for a single mutant. And GABI and others require materials transfer agreements to control how the data are used and distributed. Ecker hopes that situation will soon change.

    Meanwhile, researchers have already lined up to take advantage of what Syngenta has provided. “We got 50 e-mails this week,” says ABRC Director Randy Scholl. And he expects many more in the near future.


    NIH Weighs Demand to Force Sharing of AIDS Drug Patents

    1. David Malakoff

    The government's interpretation of a 25-year-old law giving federally funded researchers the right to patent and commercialize their discoveries was put to the test last week. AIDS activists want the National Institutes of Health (NIH) to use its legal muscle to rein in the spiraling domestic cost of an important AIDS drug. But major research universities and former government officials who wrote the law say that if the activists got their way, it would damage efforts to commercialize academic discoveries.

    At the heart of the conflict are two provisions of the 1980 Bayh-Dole Act. One says that government-funded inventions should be “available to the public on reasonable terms.” The other gives funding agencies the right to “march in” and force a patent holder to license its inventions to other companies if the existing license holder isn't taking “reasonable” steps to develop the invention or if change is needed to “alleviate health or safety needs.”

    But balancing health and safety needs with the larger goal of turning research into products can get tricky. “Is it fair for U.S. taxpayers who paid for the development of these drugs to pay five to 10 times more than [patients] in other countries?” asks James Love of Essential Inventions, a Washington, D.C.-based advocacy group. He says NIH should act to “protect the notion that [the law] is a fair bargain [and not] an unmitigated giveaway.” Opponents agree—to a point. “While I'm sympathetic to the effort, … twisting intellectual-property law to control drug prices would be intolerable,” said Norman Latker, a retired NIH general counsel.

    Bye-bye Bayh-Dole?

    Former Senator Birch Bayh (right) says NIH would undermine innovation policy if it intervened on Abbott patents, as James Love's Essential Inventions group has requested.


    The battle was joined in January when Essential Inventions asked NIH to march in on four patents held by Abbott Laboratories of Chicago, Illinois. It claimed that the firm was profiteering on a widely used AIDS drug called Norvir ( A 25 May hearing at NIH heard comments on the petition.

    Norvir is used to boost the effectiveness of other anti-HIV medications. It was developed in the early 1990s by Abbott researchers supported by a 5-year, $3.5 million NIH grant awarded in 1988, and the government has a stake in four of the six patents covering the drug. Norvir has been on the market since 1996, but last year Abbott increased U.S. retail prices for some formulations by up to 400%.

    Health care activists want the government to force Abbott to roll back prices. The Essential Inventions petition, for instance, asks NIH to require the company to license the four patents to competing manufacturers and to compel all producers to deposit small royalty payments into an R&D fund. “This is precisely the type of abusive pricing problem that Bayh-Dole's march-in clauses were meant to remedy,” says Sean Flynn, a lawyer for the group, arguing that the law's “reasonable terms” provision applies to drug pricing.

    That view, however, was disputed by a string of witnesses—including the law's co-author. “We never intended for [Bayh-Dole] to be used to control prices. We stayed away from that on purpose,” said former Indiana senator Birch Bayh (D), who sponsored the legislation with former Kansas senator Bob Dole (R). Essential Inventions “flagrantly misrepresent[ed]” the law's legislative history and intent in its petition, he added.

    Two university groups—the Association of American Universities (AAU) and the Council on Governmental Relations (COGR)—agree with Bayh and predicted that companies would refuse to invest in taxpayer-funded inventions if NIH granted the petition. “It's a misapplication of the statute … [that] would likely have serious unintended and adverse consequences,” said AAU representative Theodore Poehler, vice provost for research at Johns Hopkins University in Baltimore, Maryland. “It would be a major deterrent to licensing inventions … if potential licensees believe the government has authority” to control prices, added COGR representative Andrew Neighbour, a law professor at the University of California, Los Angeles.

    NIH officials gave little hint after the hearing of how they will rule. Mark Rohrbaugh, head of the agency's technology-transfer office, said he plans to “move expeditiously” to make a recommendation to NIH Director Elias Zerhouni, who will make the final decision. Although many legal observers predict that NIH will reject the petition, Love is hoping for a boost from election-year politics. “Drug pricing is a big political issue” that President George W. Bush won't want to hand to his opponent, he says. Love has also asked NIH to exercise march-in rights on another drug, Pfizer's Xalatan glaucoma treatment, which he says costs up to five times more in the United States than abroad.


    Economists Rate Greenhouse Gas Curbs a Poor Investment

    1. John Bohannon*
    1. John Bohannon is a writer based in Berlin.

    COPENHAGEN—Feel like throwing your tax money away? Invest in measures to rein in global warming. That's the controversial conclusion, at least, of a workshop here last week that brought together a varied group of economists, including three Nobel laureates, to analyze spending on global problems.

    Participants of the “Copenhagen Consensus” weren't purely naysayers: They lauded, as money well spent, initiatives proposed to combat AIDS, malaria, and malnutrition, for example. “This will help us focus on the more important problems,” says workshop organizer Bjørn Lomborg, director of the Environmental Assessment Institute in Copenhagen.

    Many scientists don't buy that argument, however. “We shouldn't be spending less on climate change so we can spend more on sanitation. The problems are interrelated,” says Stephen Schneider, a climatologist at Stanford University, who labels the workshop's premise “phony and a distortion.”

    The stated premise was that the industrialized world has limited funds—about $50 billion a year—for aid to developing countries and no objective way to set priorities. According to Lomborg, author of The Skeptical Environmentalist—a 2001 book that sought to discredit a host of environmental concerns (Science, 2 January, p. 28)—“eco-myths” such as global warming “prevent us from acting rationally” when committing resources to improving the world. It would be better, he argues, to base spending on cost-benefit ratios. Measures to stem climate change should compete for development aid, Lomborg suggests, because according to predictions “the developing world will suffer most of the damage from climate change.”

    With backing from the prime minister of the right-leaning Danish government, Lomborg invited the nine economists who attended —including Nobelists Robert Fogel of the University of Chicago, Douglas North of Washington University in St. Louis, Misouri, and Vernon Smith of George Mason University in Fairfax, Virginia—to rank solutions to pressing problems according to their likely return on investment. Experts, chosen by Lomborg, argued for and against each of 10 “challenges” (see table).

    View this table:

    Laying out the case for climate change was William Cline, an environmental economist at the Center for Global Development in Washington, D.C. His primary evidence was the 2001 report of the Intergovernmental Panel on Climate Change (IPCC), which predicts an increase in average global temperatures of between 1.4° and 5.8°C by the year 2100. Lomborg acknowledged that the report is “the best of our knowledge on climate change.” The economic benefits of stemming global warming include protecting the lives of income-generating human beings as well as arable land. Steps to limit warming center on reducing emissions of greenhouse gases such as carbon dioxide, a tenet of the Kyoto Protocol. The most cost-effective strategy, Cline argued, would be a global carbon tax, more aggressive than the one called for under Kyoto, that would halve greenhouse emissions by the end of the century.

    Stacked deck?

    Bjørn Lomborg (right) with Danish Prime Minister Anders Fogh Rasmussen.


    The panel rejected that line of argument, concluding that Cline's proposals would be “very bad” investments. Panelist Nancy Stokey, an economist at the University of Chicago, explains that the solutions would require “large expenditures for benefits that would come far in the future.” Even with a less limited budget, the Kyoto Protocol, in the panel's view, is not worthwhile.

    That leaves scientists such as Schneider, a lead author of the IPCC report, fuming. “Climate change is not an economics problem. It's an ethics problem,” he says. Adds John Holdren, an environmental policy expert at Harvard University, “One can't help suspecting … that Lomborg has stacked both the participants list and the framing of the questions to achieve this result.”

    Lomborg rejects that charge, arguing that the workshop's organization was “unbiased.” He acknowledges, though, that the panel was short on environmental expertise. “I invited other economists,” who declined to come, he says, dismissing his critics as “conspiracy theorists.” Lomborg plans to distribute the panel's conclusions to governments and to the United Nations.

    Illustrating how influential Lomborg is perceived to have become, environmental economists convened an alternative conference, “Global Conscience,” in Copenhagen last week to discuss sustainable development. “We shouldn't choose between poverty eradication and prevention of climate change,” says co-organizer Christian Jørgensen, chair of the nonprofit Danish Ecological Council. “Prevention of climate change will pay off; it will reduce our dependence on Middle East oil, and it will create a new industrial sector for renewable energy and energy conservation.” Clearly, economics alone won't reconcile these sharply divergent world views.


    Poised for Takeoff?

    1. Jon Cohen

    This is the third in a series on HIV/AIDS in Asia, leading up to the XV International AIDS Conference to be held in Bangkok, Thailand, in July. The first two parts, on Southeast Asia and India, were published in the 19 September 2003 and 23 April 2004 issues (

    BEIJING—Last year, a simple handshake sent a message that reverberated across China. On 1 December, World AIDS Day, every major media outlet in the country carried pictures of Premier Wen Jiabao greeting Sun Fuli, an AIDS patient at Ditan Hospital here. Sun, a former taxi driver from Shanxi Province, was one of three HIV-infected patients who met with Premier Wen. In this country, where symbolism is paramount, the message was unmistakable.

    The visit by Premier Wen and Health Minister Wu Yi to Ditan Hospital sent a signal that HIV/AIDS had finally moved to the top of the central government's agenda. “There were still some people within the State Council who said, ‘How dare they go see these AIDS patients,’” says Wang Longde, vice minister of health. But at the highest levels of the central government, Wang says, there has been a “huge change.” Equally important, it was the first time that anybody from China's top leadership had reached out to confront the fear and discrimination that HIV-infected people frequently face in China.

    During the past year, China has launched a program that promises free anti-HIV drugs to all poor people who need them. The central government has budgeted some $60 million this year for AIDS prevention and control, more than three times the amount spent in 2002. It has also eased the stern stance toward injecting drug users (IDUs)—who account for two-thirds of the country's estimated 840,000 HIV infections —and is sponsoring pilot projects in “harm reduction,” such as offering clean needles and methadone treatment (see p. 1434). “Today, what the government is doing is probably more than 500% what it was doing a year ago,” says epidemiologist Ray Yip, country director for the Global AIDS Program of the U.S. Centers for Disease Control and Prevention (CDC).

    Peer prevention.

    Nong Yanling (standing) and other heroin users in Ningming help run a novel needle-exchange program.


    Several forces compelled the government to revamp its HIV/AIDS strategy. The first is that China's epidemic is at a critical juncture. It is still at an early stage, with a relatively low prevalence in the general population of 1.3 billion people, but some outside assessments have warned that it is poised for takeoff and has all the ingredients for a major disaster. Although officials dismiss the warnings as alarmist, they work with a new sense of urgency—sharpened by the recognition that China badly mishandled last year's outbreak of severe acute respiratory syndrome (SARS). “We have to thank the SARS epidemic, which gave a wake-up call for the whole country,” says Shao Yiming, an AIDS vaccine developer (see p. 1437) at China's CDC who heads the China Integrated Programs for Research on AIDS (CIPRA), an ambitious $14.8 million project funded by the U.S. National Institutes of Health.

    A second health fiasco pushed the government to intensify its AIDS efforts: Thousands of poor people became infected with HIV after selling blood to commercial outfits that used unhygienic procedures (see p. 1438). That tragedy may have accelerated the country's response to HIV/AIDS by 5 or 10 years, says Yip.

    China still faces staggering problems. Take Sun Fuli's case. Anti-HIV drugs rescued him from death in 2003: “I thought I only had 2 days to live,” he says. But he received a contaminated blood transfusion in 1998, long after most countries had cleaned their blood supplies. Now the government provides him drugs, but they're far from optimal (see p. 1433), and he must travel hundreds of kilometers to have his treatment properly monitored. Clinicians who want to improve HIV prevention and treatment efforts also must contend with a government that harshly punishes critics—it detained physician Wan Yanhai for 1 month because of details he exposed about the blood donor calamity—and remains wary of nongovernmental organizations and other outsiders offering help.

    In April, Science visited Beijing, villages in Henan Province hard-hit by infections of blood donors, and two areas with large numbers of IDUs and sex workers, Yunnan Province and Guangxi Zhuang Autonomous Region. Despite the denial of some interview requests, many scientists, officials, and people directly affected by the epidemic spoke with surprising candor. And many stressed how much they believe their government's response has improved over the past year. “I never say anything as praise to government officials, but this time I can't help myself,” says Zhou Zengquan, an AIDS clinician in Kunming. “The things they've done, I'm really grateful.”

    More than a handshake.

    Sun Fuli smiles at the famous photo of Premier Wen Jiabao greeting him and other AIDS patients.


    Today, says Shen Jie, deputy director of China's CDC, “the biggest challenge doesn't lie in the government policy.”

    Young epidemic

    Wu Hao, head of infectious diseases at Beijing's You'an Hospital, leads a tour of the modern, well-kept AIDS ward, which has 50 beds, all but 10 of which are empty. You'an, which specializes in infectious diseases and sees more AIDS patients than any hospital in the city, treated its first case in 1990. Until 1999, explains Wu, they saw as few as 10 AIDS patients a year. But each year since 1999, You'an has cared for about 200. “Most people who come here for AIDS were infected in 1994, 1995, so they started to feel ill about 1999 or 2000,” says Wu.

    For the largest AIDS hospital in the capital city of the world's most populous nation, 200 AIDS patients a year is a remarkably small number. But AIDS cases present a crude barometer because, as Wu indicates, several years separate HIV infection and symptomatic disease. Further complicating matters, the epidemic has profound regional differences: Beijing, which treats many former blood donors from neighboring provinces, does not reflect the situation in the rest of the country. Fear of discrimination, poverty, and a lack of education about the disease also keep some ailing patients from seeking help. Still, the sharp increase in AIDS cases at You'an does reflect a national phenomenon: HIV did not make much headway in China until the 1990s. “Generally speaking, it's still an immature epidemic,” says CDC's Shao.

    Fewer than 4000 AIDS cases have been reported from 1985 to December 2003, says the Ministry of Health. But the ministry recognizes that the reported figure grossly underestimates the number of AIDS cases, most of which go unreported, and says the true total is about 80,000. Similarly, the 62,159 cumulative HIV infections reported to the health ministry by last December is a small fraction of the actual number, which they put at about 840,000.

    Epidemiologists divide China's AIDS epidemic into three phases. During the entry phase, from 1985 to 1988, the country recorded only 22 HIV infections, and officials viewed the disease as a foreign problem. China's health minister declared in 1987 that the disease could be kept at bay because homosexuality and promiscuity were limited. The government banned the import of blood products and barred HIV- infected foreigners from living in China, and an article in the state-controlled Beijing Review the same year noted that it was illegal for Chinese citizens to have sex with foreigners or to import secondhand clothing.

    In 1989, nearly 150 IDUs in Yunnan Province in China's southwest corner, which borders Myanmar (Burma), tested positive, initiating the “spreading phase” of the epidemic. During the early 1990s, many commercial outfits pooled blood from paid donors, separated out the plasma, and then returned the red blood cells to the donors so that they could sell blood more frequently; as many as 250,000 blood donors became infected with HIV by this process, according to estimates in China's recent application to the Global Fund to Fight AIDS, Tuberculosis, and Malaria. To this day, IDUs and blood donors account for more than two-thirds of China's infections (see pie chart, p. 1432).

    Focal and local.

    Reported HIV cases vastly understate the actual number, but they reveal that most infections have occurred in IDUs and plasma donors who primarily live in distinct regions.

    The current “expansion phase” that started in 1995 has seen rapid spread from IDUs and blood donors to their partners and children, as well as the steady rise of infections in sex workers. Gay men, who are ignored by official surveillance, are an emerging high-risk group, too. “China is experiencing one of the most rapidly expanding HIV epidemics in the world,” the country's application to the Global Fund declares. Part of the expansion may simply reflect China's more forthright attitude about the scope of its epidemic: Official estimates of the number of infected people more than doubled between 1999 and 2002.

    Just how far HIV will spread into the general population has triggered much speculation—and blistering discourse.

    Reading tea leaves

    From HIV's point of view, China certainly has many attractive features.

    Aside from the boom in heroin use and the thriving sex industry, the country has a “floating population” of more than 100 million migrant workers; these predominantly young, male laborers—prime customers for sex workers—typically travel between their rural homes and cities, offering HIV extensive transportation routes to remote areas. Knowledge about the disease and condom use remains low in many populations. Other sexually transmitted diseases, which can facilitate the spread of HIV, have steeply increased over the past 2 decades.

    Myron Cohen, an AIDS researcher at the University of North Carolina (UNC), Chapel Hill, who chairs CIPRA's scientific advisory board, says the “surplus” of men that has resulted from the country's one-child-per- family policy may also spur the epidemic. In a paper in press at Sexually Transmitted Diseases, Cohen, UNC sinologist Gail Henderson (his wife), and their Chinese colleagues explain that many unmarried men possibly “will find no sexual outlet over the course of their lives other than commercial sex, and this may lead to even greater demand for sexual services in the future.”

    In a particularly dire assessment of China's future, a United Nations-sponsored group issued a report in June 2002 called HIV/AIDS: China's Titanic Peril that warned: “A potential HIV/AIDS disaster of unimaginable proportion now lies in wait to rattle the country, and it can be feared that in the near future, China might count more HIV infections than any other country in the world.” A U.S. National Intelligence Council report issued a few months later projected that by 2010, China could have up to 15 million HIV-infected people.

    Health Vice Minister Wang dismisses these gloomy forecasts, noting that many predictions rest on the assumption that China would not dramatically alter course: “With so much support and collaboration from the international community and our own efforts, it's clear that China will have a very bright, rosy future for AIDS control.”

    Experts inside and outside China agree that Titanic Peril exaggerated the threat. “I really don't think we're looking at that gloomy of a picture,” says demographer Simona Bignami-Van Assche, a Ph.D. candidate at the University of Pennsylvania in Philadelphia who did a detailed study of HIV/AIDS in China. As Bignami-Van Assche explains, forecasters base their predictions on estimates of HIV prevalence in China that come from “sentinel” sites around the country. China has only about 200 such sites nationally—Thailand, by comparison, has 500 for a population 5% the size of China's—which creates much of the confusion. When Bignami-Van Assche analyzed data for Yunnan Province, which has about one-fourth of the national sites, and extrapolated to the rest of the country, she concluded that China will have no more than 6 million infections by 2010.

    Longde's journey.

    Health Vice Minister Wang Longde says he's seen a “huge change” in the central government's AIDS policy.


    “It's understandable that the outside world has developed a misunderstanding about China's attitude toward AIDS statistics,” says Vice Minister Wang. In part, the problem mirrors one seen with SARS: There is no national system for collecting all available data, and local officials “were not so open,” says Wang. “They fear if they make it public how many people are infected with AIDS it will affect their economic development.”

    CDC's Shao bristles at the notion that the national government wants to downplay the epidemic. “Nobody has tried to hide any figures,” says Shao. (A recent Time magazine article that outraged many Chinese scientists had the headline “China's Secret Plague.”) He is now advocating that China establish a database to mesh data from national and provincial testing sites, blood-screening efforts, and hospitals.

    China's crossroads

    As the government expands HIV/AIDS testing, along with counseling and education, epidemiologists should gain a better handle on the scope of the epidemic. Just as importantly, the attitudes of health care workers and the public toward the disease should also change.

    Counterintuitive countermeasures.

    Ray Yip of the U.S. CDC says prevention should target the already infected.


    You'an Hospital's Wu Hao says widespread fear still exists among many doctors and nurses. And he unabashedly shows photos of how his colleagues first reacted to AIDS patients in the early 1990s. The doctors wore boots and gloves, and after the patients died, they slid huge ice blocks under their beds to avoid moving their bodies to the morgue. “They lied to funeral homes that otherwise would not take the patients,” says Wu. And they hauled the dead patients' furniture outside and burned it. Today, Wu says he and his staff train health care workers from across the nation to help avoid the mistakes that You'an made.

    Changing public attitudes will be a lot easier now that China's leadership has acknowledged the problem. But major challenges remain. Trained AIDS clinicians and the equipment needed to monitor treated patients remain scarce. Few anti-HIV drugs are on the market. And campaigns to promote condom use, needle exchange, and HIV education will test the ability of the country to move from words to actions.

    Because China's epidemic has yet to explode, a window of opportunity exists today that soon will close, says Chung To, whose Hong Kong-based Chi Heng Foundation (which means “bring wisdom into action”) helps AIDS orphans in China and educates gay men about the disease. “China is at a crossroads, and whether it will become South Africa or Thailand depends on how the government reacts in the next 2 years,” says Chung, referring to Thailand's widely lauded success at slowing HIV's spread.

    The U.S. CDC's Yip notes that most of the infections to date have occurred in discrete locations in two specific populations: IDUs and blood donors. This means that China could target “the source of the future infections” as the cornerstone of its prevention campaign.

    UNC's Cohen says that China's large number of IDUs, sex workers, migrants, and surplus men means “mega-dangers” still lie ahead. But he urges outsiders to appreciate the dynamic nature of the country, which can mobilize public health troops with unparalleled speed and efficiency—as SARS last year proved. “If success is what they want,” says Cohen, “this can-do culture is unlikely to accept failure.”


    A New Treatment Campaign, But With Limited Weapons

    1. Jon Cohen

    The government has promised free AIDS drugs, but the available therapies have serious limitations, and identifying and monitoring patients pose fundamental challenges

    RUILI, YUNNAN PROVINCE—As a user of opium and heroin for nearly 2 decades, Da Zhan Sha speaks with great authority about the drugs' pleasures and dangers. Da, a 45-year-old truck driver, learned in 1999 that he had become infected with HIV. A heroin-using son is infected, too. Here at the Jile Township Clinic, the doctors taught Da to use condoms to avoid transmitting the virus to his wife, who remains uninfected, and offered to help him quit using drugs. But they cannot offer treatment for his HIV infection. Indeed, when asked whether he has heard that anti-HIV drugs exist, Da looks puzzled. “I'm not sure,” he says. “I'm not clear about that.”

    None of the many AIDS posters and graphics that decorate the walls of the Jile Township Clinic offers any information about anti-HIV drugs, and Rui Ying, a savvy doctor who comes from the predominant Dai ethnic group in the region and works with the many injecting drug users here, says she has yet to receive training about how best to use them. “I only do HIV/AIDS education,” Rui says.

    Yunnan, which borders heroin-producing Myanmar (formerly Burma), has more HIV-infected people than any other Chinese province. Until a few months ago, the lack of knowledge and medical training here about anti-HIV drugs made little practical difference: Few people could afford the drugs anyway. Last fall, however, the central government promised free anti-HIV drugs to all poor people in need. The dearth of information at the epicenter of China's epidemic shows that health officials here and across the country have a lot to do just to get this ambitious and much-welcomed program off the ground. They also have to contend with a paucity of drug choices and a dearth of equipment to monitor the immune systems and HIV levels of those being treated.

    “In all treatment programs there are a lot of issues, but the first priority is we have to urgently respond to save patients,” says Zhang Fujie, a clinician at China's Center for Disease Control and Prevention (CDC) in Beijing who heads the national effort. “This is just the beginning.”

    Given the widespread lack of knowledge about the disease, identifying the people who most need treatment presents a major hurdle. An estimated 80,000 Chinese already have symptomatic AIDS, but China has identified less than 5% of them. “It's very difficult in China to find the patients,” says Zhang. But he thinks as word spreads that AIDS drugs exist and are freely available, it will trip a critical switch: More people will volunteer for testing, and if they learn they're positive, they're more likely to take precautions to prevent transmitting the virus. “We can't separate prevention from treatment and testing,” says Zhang. “We have to organize the whole program.” The program, he says, hopes to treat as many as 15,000 people by December and up to 50,000 by the end of 2005.

    Drug dilemmas.

    Drug treatment had not yet reached Da Zhan Sha, an HIV-infected heroin user in Dehong Prefecture in hard-hit Yunnan Province.


    Training issues loom especially large. Zhang says perhaps 10 hospitals and fewer than 200 clinicians in the country have experience with anti-HIV drugs. “Training a doctor takes time,” Zhang says. “Not just 2 days or 2 weeks. We need 3 months.”

    The four AIDS drugs now available in the program—ddI, d4T, AZT, and nevirapine—also leave much to be desired. Not only do they have serious toxicities, but “the four drugs we're now using can easily develop resistance among HIV patients if they're not doing good adherence,” says Wang Zhe, deputy director of the CDC in Henan Province, which started its treatment program last year (see p. 1438). Shao Yiming of the CDC in Beijing says they have analyzed 500 blood donors receiving treatment: After only 9 months, 20% to 30% indeed had become resistant to nevirapine. David Ho, head of the Aaron Diamond AIDS Research Center (ADARC) in New York City, says he'd be hard pressed to pick a worse combination. “It's awful,” says Ho, who organized a treatment program here that uses drugs donated by GlaxoSmithKline (GSK). “My biggest complaint to the Ministry of Health is that no one in China is as well treated as some of the African patients.”

    Throughout China, AIDS clinicians bemoan the fact that most patients cannot access GSK's drug 3TC, which remains far too expensive. It is a key component of the cheapest, most effective cocktails used in Africa, India, Thailand, and Brazil. “We would like our HIV patients to have 3TC as early as possible,” says Wang.

    The problem is that GSK holds the patent on 3TC. Countries that make generic versions of it either have licensing arrangements with GSK or exemptions from World Trade Organization rules. But GSK has been reluctant to make such arrangements with China; critics say the company wants to protect its 3TC market, as a lower dose of the drug treats hepatitis B, a significant problem in China.

    Ellen t'Hoen, a lawyer who runs Médecins Sans Frontières' (MSF's) Campaign for Access to Essential Medicines, argues that the Chinese government should invoke what's called a compulsory license, which would legally allow it to make the drug generically. “It's perfectly within the existing system,” says t'Hoen, who was in Nanning, the capital of Guangxi Zhuang Autonomous Region, as a part of a visit to help China solve the problem.

    Ideally, China's generic manufacturers would like to combine 3TC with other drugs to make a “fixed dose combination” that would require only two pills a day. “This is very key if we want to avoid resistance,” says Yves Marchandy, who runs an MSF treatment project in Nanning. What's more, he says, China has a better capacity than any country to make and export a cheaper fixed-dose combination, which he says could be “a major change for the world.”

    Top doc.

    Zhang Fujie heads China's new drug treatment program.


    GSK says it is just about to ink a deal that will offer the Chinese government 3TC at “preferential prices.” If the negotiations fail, Zhang says, China knows that it can invoke a compulsory license. “We have to get 3TC in the very near future,” says Zhang. “We have no time to wait.”

    3TC isn't the only anti-HIV drug China lacks, however. Similar problems have prevented it from importing or manufacturing several drugs available as generics elsewhere. China also has no formulations available for HIV-infected children. Says MSF's Marchandy: “We really are David facing Goliath, and we don't have a lot of stones.”

    More stones may come from the China AIDS Initiative, a project announced in November 2003 by ADARC's Ho and former U.S. President Bill Clinton. The initiative joins ADARC with the Clinton Presidential Foundation, leading Chinese universities, Yale University, and the Brookings Institution. The initiative hopes to help with AIDS advocacy, education, and treatment, with the Clinton Foundation now attempting to negotiate the purchase of low-priced AIDS drugs and monitoring tests.

    China's new treatment program not only has few stones; the training and monitoring shortcomings mean it also has one hand tied behind its back. But in the next few months, the few anti-HIV drugs they do have should arrive at clinics across the country, including the one at Jile Township. And for HIV- infected people like Da, news of the existence of these drugs surely will overshadow concerns about their limitations.


    Changing Course to Break the HIV-Heroin Connection

    1. Jon Cohen

    Injecting drug users account for more than half of China's HIV infections. Authorities are now tentatively launching “harm-reduction” programs in hard-hit provinces

    YUNNAN PROVINCE AND GUANGXI ZHUANG AUTONOMOUS REGION—When people cross the short bridge from Myanmar to China at the tiny city of Wanding, a quaint billboard greets them. It shows a couple supping on a beach as the sun sets. “Preserve your purity, keep off drugs, prevent AIDS,” the billboard advises in the language of the Dai and Jingpo ethnic minorities, Mandarin, and even English. The billboard's flip side has a similar multilingual message but a less genteel image that reflects China's new resolve against the burgeoning HIV/AIDS problem in this region: It shows a fist.

    HIV has established a beachhead here among injecting drug users (IDUs). Myanmar (formerly Burma) is the world's second largest heroin producer, and the border in this area is so porous that the Dai and Jingpo in many places freely cross the shallow stream that separates the two countries. “We don't have any natural or cultural border,” says Li Fanyou, deputy director of Dehong Prefecture's Center for Disease Control and Prevention (CDC). Not surprisingly, pure Burmese heroin has become plentiful, and HIV has traveled with it.

    In 1989, tests of Dehong IDUs found 146 infections—75% of the reported cases in all of China at the time. HIV raced through Dehong, infecting more than 80% of one IDU group tested in 1992. By 1996, HIV had spread to IDUs beyond Yunnan's borders, with Guangxi to the south and Xinjiang to the north especially hard hit. Today, Yunnan still has more HIV-infected people than anywhere in China, accounting for one-fourth of the reported cases, and in Dehong the virus infects more than 1% of pregnant women, an indicator that the epidemic has spread to the general population. It is in these border regions that China's most crucial HIV/AIDS battles now are being fought.

    Free trade.

    A needle-exchange program in Ningming tracks syringes by printing an AIDS ribbon on them.


    Encouraged by political changes that give them new freedoms, AIDS workers finally can attack the problem head-on. “In the past 10 years, the central government has not provided enough policy support for needle exchange and methadone substitution programs,” says Chen Jie, deputy director of the Guangxi CDC. Now, Chen and other health officials are scrambling to determine how best to scale up their efforts. And each locale has unique visions of how to proceed.

    Eyes wide shut

    Ruili, a bustling city 20 kilometers from Wanding, is widely known as a place where cheap heroin and an abundance of sex workers can be found at “barber shops,” massage parlors, and hotels. But it has another, less obvious, feature: “We have many people who have died from AIDS,” says an HIV-infected IDU attending a seminar at the CDC in Ruili.

    On 1 March, Yunnan Province issued Regulation 121, which calls for aggressively expanding education efforts. Freshly minted HIV/AIDS prevention banners already decorate the streets of Ruili and other cities. And, to the astonishment of many, the regulation explicitly promotes the distribution of clean needles, methadone, and condoms. Posters of Regulation 121 appear in the lobbies of hotels—which the government now says must offer condoms in the rooms—and in the infamous barber shops. It represents a radical turnaround.

    For all the urgency, however, the provincial health bureau is moving cautiously on some fronts. It will soon start several pilot projects for both needle exchange and methadone substitution, which Wang Yunsheng, deputy director of the HIV/AIDS office for the Yunnan Provincial Bureau of Health, says will run for 3 years. “We cannot be in too much of a rush, but we also cannot wait too long,” he says. With needle exchange, they have to overcome the widely held perception that distributing needles will increase drug use, he says. Methadone remains expensive and tightly controlled by the central government.

    Outreach to sex workers—who in Yunnan still have an HIV prevalence below 3%—is limited to the training of peer educators and brothel managers. “We're not distributing condoms to sex workers because prostitution is illegal in China,” says Wang. As one Yunnan sex worker says, “The government keeps one eye open and one eye shut.”

    Guangxi's garrote

    Driving through the craggy mountain range of Guangxi that borders Vietnam, Chen Jie of the provincial CDC explains why it's necessary to move carefully before launching wide-scale programs for IDUs and sex workers. But like his counterparts in Yunnan, he feels the pressure mounting.

    Guangxi did not diagnose a case of HIV in an IDU until 1996. But for the past 3 years, says Chen, the number of HIV infections has risen faster in Guangxi than in any other province. Chen's incidence data are among the best in China: In collaboration with Johns Hopkins University, which hopes to stage AIDS vaccine tests here, they have followed a cohort of more than 400 uninfected IDUs for 5 years and seen an annual new infection rate of 5%.

    Cut above.

    Residents at Daytop's progressive drug treatment program in Kunming move through a hierarchy of jobs as part of the rehab program.


    Given Guangxi's large number of IDUs, Chen questions whether the province could ever afford to supply free needles to all of them. And he says the harsh laws against drug users make their job more difficult.

    In Pingxiang, a town a few kilometers from the Vietnamese border that also has a flourishing sex trade, the local CDC has cut a deal with police not to harass IDUs who seek help. That in itself is a remarkable change: Li Ronghe, a 25-year-old IDU the CDC works with, says police have put him in a compulsory rehabilitation camp nine times.

    Li, a user for 10 years who imports Vietnamese goods to China, speaks frankly about the limits of AIDS education. Most IDUs have learned that sharing needles can spread HIV, he says. But late at night or in a rural area where clean needles don't exist, things change. “We have to share,” says Li.

    In Ningming, an hour's drive from Pingxiang, the local health bureau since October 2002 has run a massive needle exchange with the cooperation of local police. Supported by the Ford Foundation and Abt Associates in Boston, Massachusetts, local CDC officials have hired IDUs as peer educators to collect used needles and distribute new ones. A sister program operates just across the border in Vietnam (Science, 19 September 2003, p. 1657). So far, the Ningming project has handed out 200,000 needles. According to local CDC surveys of 300 IDUs, the percentage who report sharing needles has dropped from 70% to less than 10%. “My biggest hope now is that they'll provide methadone maintenance,” says IDU Nong Yanling, a peer educator with the program.

    Future is now

    Methadone and needle exchange play central roles in “harm reduction,” which treats addiction as a disease and makes preventing HIV's spread the goal. China, to date, has hardly embraced the strategy: It has more than 700 “compulsory rehabilitation centers,” which incarcerate IDUs “without trial or any other semblance of due process,” said Human Rights Watch in a September 2003 report. Li, speaking from personal experience, says the camps are of “no use.”

    At the Pingxiang camp, IDUs go through detoxification and then a rigorous program of outdoor activity and education, says Zhuang Huande, director of the center. Zhuang has no problem with methadone, but needle exchange contradicts drug laws, he says. “After so many lessons we've received from the CDC, I'm confused myself,” says Zhuang. He also subscribes to the oft-repeated national goal of eradicating drugs. “To eliminate drug use is a much more effective way to eliminate HIV spreading than needle exchange,” he says. “It's a fundamental solution.”

    Harm reduction has, however, secured a foothold in Kunming, Yunnan's capital. Psychiatrist Yang Maobin started a voluntary treatment program called Daytop in 1996 that relies on methadone, needle exchange, and other harm-reduction tools. “At that time, the doctors here knew nothing about drug addiction,” says Yang, who had become frustrated working in government-run detoxification centers. Today, Daytop, which is modeled on a program in New York, houses 100 people, 20% of whom are infected with HIV. The China-UK AIDS Prevention and Care Project—a $28 million effort by the U.K. Department for International Development—funds Daytop, but it also charges residents nominal fees.

    Little distinguishes Daytop from similar programs in more developed countries—which is why it's so remarkable in China. Daytop has a hierarchy of jobs from cooking and cutting hair to running the organization. Graduates move to a reentry center, where they wash and repair cars to learn basic work skills before leaving. Some 2000 people have passed through, and although 70% start using again, Yang says only 40% of those who complete the 18-month program relapse.

    Wang Xiaoguan, Daytop's vice director, is one of the success stories. After graduating from university in 1989, Wang found an accounting job and opened a restaurant. He soon started using heroin and, after a few years, lost both jobs. Wang, 34, sometimes shared needles, only learning of the dangers in 1998 at Daytop. “There was really a lack of education then,” says Wang, who remains HIV-negative.

    Wang urges his government to do away with compulsory camps. “They're like jails,” he says. “They are jails.” He also thinks the Daytop model already has proven that harm reduction works in China and questions the need for so many pilot programs. And although he appreciates the government's rapid changes, he says, “it's not fast enough.”


    Vaccine Development With a Distinctly Chinese Flavor

    1. Jon Cohen

    Shao Yiming is heading efforts to develop HIV vaccines, and he's considering one approach that the West has all but abandoned

    KUNMING—An unusual gray stone on the front lawn of the primate research center here is the first hint that the facility is not simply a clone of its Western counterparts. Carved with Chinese characters, the stone is a memorial to the center's monkeys, which serve as surrogate humans in biomedical research. Other centers may respect their experimental animals, but rarely with a memorial. And the difference is more than superficial: Even the AIDS vaccine work taking place in the center's laboratories has a uniquely Chinese cast.

    For more than 2 decades, AIDS researchers have tested candidate vaccines on Indian rhesus macaques. But India, for political and religious reasons, banned their export in 1978, and many AIDS investigators today delay experiments because of acute shortages of the species. Researchers at the Chinese Academy of Medical Sciences' primate center here, however, face no such roadblock because they work with Chinese macaques, which they think may even prove a better model. And among the vaccine strategies they are pursuing is one that Western researchers have all but written off as too risky.

    Like Indian rhesus macaques, Chinese macaques succumb to SIV, a simian cousin of HIV, but the human AIDS virus cannot copy itself inside their cells. To overcome this problem, researchers have combined genes from HIV and SIV to construct a hybrid virus known as SHIV, which causes an AIDS-like disease in Indian rhesus macaques. Now, a team led by Shao Yiming, a virologist based at China's Center for Disease Control and Prevention (CDC) in Beijing, is tailoring a similar hybrid virus for Chinese macaques. As part of a larger project backed by a grant from the U.S. National Institutes of Health, the researchers have just begun to test whether this virus reliably causes disease in animals in the primate center's shiny new biosafety labs.

    Primate boost?

    AIDS vaccine developer Shao Yiming hopes to develop a new animal model with the Chinese macaque.


    Many researchers look askance at results from SHIV tests in Indian macaques, arguing that the hybrid virus doesn't mimic HIV in humans closely enough. But Shao hopes to avoid at least one critical drawback. HIV exploits a unique cellular receptor to establish an infection and then typically switches to a different one. Unlike other SHIV makers, Shao relied on a recently infected person for an HIV strain and confirmed that it used the proper receptor. Ronald Desrosiers, head of the New England Regional Primate Research Center in Southborough, Massachusetts, says if Shao makes a better SHIV model, “that would be tremendously useful.”

    In addition to his SHIV work, Shao is constructing AIDS vaccines for human tests. Furthest along is one designed to deliver a one-two punch to the immune system. After priming the immune system with a vaccine made from HIV genes stitched into a ring of bacterial DNA, a second shot presents the same genes spliced into vaccinia, the smallpox vaccine virus. Several other teams have developed similar “prime-boost” vaccines, but Shao is customizing his for China with HIV genes from a strain of the virus isolated in Xinjiang Uygur Autonomous Region and a strain of vaccinia called Tiantan (Temple of Heaven) that formed the backbone of China's smallpox vaccination program. He hopes to begin human tests early next year.

    In a more radical venture, Shao has teamed up with virologist Shen Rongxian of the Harbin Veterinary Research Institute in Heilongjiang Province to study a vaccine Shen developed against equine infectious anemia virus (EIAV). An attenuated form of EIAV is the only effective vaccine ever developed against a lentivirus—the family that includes HIV and SIV. Over the past 30 years, it has protected 75 million horses and donkeys.

    Shao, Shen, and co-workers from three U.S. universities will compare the vaccine virus to the “wild-type” strain to try to tease out which genetic factors make EIAV pathogenic. They will also try to deduce the immune responses that lead to protection, and how EIAV protein structures compare to their HIV counterparts. The goal is to apply the findings to the design of HIV vaccines. “It's an extremely important model to understand the mechanism of protective vaccine immunity,” says collaborator Ronald Montelaro, an EIAV expert at the University of Pittsburgh in Pennsylvania. “It's an experiment we all should learn something from.”

    Ideally, Shao says he hopes the result will be a vaccine that uses only the HIV parts needed for protection. But if that strategy fails, he says they plan to move forward with a live, weakened HIV vaccine. This approach is highly controversial, in part because Desrosiers made attenuated SIV vaccines that seemed safe but then reverted to virulence. Shao says EIAV proves that it is possible to make a safe live lentivirus vaccine. He stresses that they would proceed cautiously, testing the vaccine extensively in monkeys. “It's pretty exciting to think about the possibilities,” says Desrosiers. “It's not an unrealistic scenario.”

    Shao says the sense of urgency about developing an effective AIDS vaccine is far greater in China than in countries with more contained epidemics. “I think the live attenuated approach has been dropped too early in HIV research because of the safety concerns,” says Shao. “In science, nothing should be considered impossible until we try it.”


    An Unsafe Practice Turned Blood Donors Into Victims

    1. Jon Cohen

    As many as 250,000 paid donors may have been infected in the 1990s. The government is now making drugs available, and authorities are trying to make sure people take them

    HENAN PROVINCE—With a morning chill still in the air, Wei Jianli leaves her home in the remote farming village of Donghu for another day of work. Toting a stack of notepads and dressed in a double-breasted pink blazer, Wei, 32, walks to her next-door neighbor's house and a ritual unfolds that she repeats twice a day, 7 days a week, at 10 different homes. As Wei makes a few notes on a pad, her neighbor opens a packet containing the anti-HIV drug ddI and pours the powder into a tin cup. The 36-year-old farmer adds water, and as he waits for the drug to dissolve, he swallows pills that contain two other anti-HIV drugs, d4T and nevirapine. After he gulps down the ddI, Wei says her goodbyes and heads to her next charge.

    The direct observation of treatment (DOTS) program that Wei works with is one of many recent attempts by both the provincial and central government to help people caught in a tragedy that has devastated Donghu and many other villages in Henan Province. Wei, her next-door neighbor, and the nine others she'll visit twice today all became infected with HIV as a result of an unhygienic blood industry, which officials say they shut down in 1995.

    More than 600 villagers in Donghu sold their blood, for about $5 per donation. The blood centers pooled and centrifuged the blood, retained the plasma, and reinfused the donors with red blood cells from the pool, which enabled people to sell their plasma more frequently without developing anemia. The practice turned out to be an efficient way to transmit HIV. In Donghu village alone, 231 donors became infected; one-fourth of them already have died from AIDS. Wei says a total of 27 people are infected in the 53 families in her immediate neighborhood. At least 250,000 people in seven provinces may have been infected through this route, but the catastrophe in Henan is the most famous, in part because it was the first to come to public attention.

    In 2000, enterprising Chinese journalists, in defiance of the Henan government, reported on the “strange illness” that had suddenly surfaced in several of the province's poor farming villages (see sidebar). Chinese and foreign media soon flocked to Donghu and other remote villages, which led Henan officials to bar journalists, scientists, and even international aid workers. But, with Wang Zhe, deputy director of the Henan Center for Disease Control and Prevention (CDC), as a guide, province officials allowed Science to visit Donghu, Guotun, and Wenlou villages, and they led tours of the many new schools, clinics, and orphanages under construction in these areas. “We are clear about the epidemic situation of HIV spreading in Henan, and I don't want to lie about it,” says Liu Xuezhou, deputy director-general of the province's health bureau.

    Liu is sensitive to what he asserts are exaggerated reports, which he says wrongly extrapolate from the hardest hit villages to the entire province. Provincial studies of blood donors, Liu says, show widely varying infection rates in different villages, with a range from 1% to 40%. He says their most recent tests found that Henan has a total of 35,000 infected people.

    Liu also disputes widespread charges in the media that Henan attempted to hide the calamity. “Before the year 2000, there were not so many AIDS patients,” says Liu, referring to the time lag between infection and disease. “We were not fully aware of the problem.” A report issued by Human Rights Watch in September 2003, Locked Doors, faults China for the “lack of any government accountability” in the “Henan blood scandal” and calls on top leaders “to launch a complete, independent, and impartial investigation.” (The provincial government clearly had ties to what it calls the “illegal” industry until shutting it down, but Henan officials referred Science's questions about this matter to the central government, which did not reply.)

    On watch.

    As part of a program in Donghu village to improve adherence, Wei Jianli observes her neighbor drink a dose of the anti-HIV drug ddI.


    In response to the crisis, the central government launched a program in March 2003 called China CARES (Comprehensive AIDS RESponse) that offered infected plasma donors in Henan and other provinces free anti-HIV drugs manufactured in China. Since the drugs arrived, Wenlou, which has 670 HIV-infected people, has seen deaths decline from as many as three a day to one a month.

    But a serious problem soon surfaced: Many people only took the drugs intermittently—which can quickly lead to resistance (see p. 1433)—or stopped taking them altogether. Zhang Fujie, an AIDS clinician at the CDC in Beijing who directs China's treatment program, says that of the 7012 patients in various provinces who joined the treatment program, 19% dropped out. When a small group of infected villagers at the Wenlou clinic were asked about this, one 35-year-old farmer immediately spoke out. He took anti-HIV drugs for 1 month last year and then stopped. A father of two who says he no longer can work, the farmer has no plans to restart the treatment. “My liver didn't function properly,” he says. “I can't stand it.”

    Epidemiologist Ray Yip, head of the U.S. CDC's program in China, says, “People were not getting any adequate information.” It particularly bothered him that patients did not realize the stakes of stopping treatment. “The message that ‘this is your once-in-a-lifetime chance’ did not get across,” he says. Yip stresses that the problem stems from what amounts to an emergency relief program mentality: “The government was under tremendous pressure to get it out.” Wang agrees that the overnight decision to launch the treatment program did not allow for the proper education of patients or local doctors about the importance of sticking with the treatment.

    The DOTS program in Donghu, which Yip helped start, is one of several efforts to reduce the high dropout rate. Since it began, “adherence rates have risen dramatically,” says Wang.

    Side effects.

    Experts worry that misunderstandings about toxicities led many ex-blood donors with AIDS like this Wenlou village farmer to reject the free anti-HIV drugs offered.


    Guotun also launched a DOTS program, with help from the Chi Heng Foundation in Hong Kong. It offers a special incentive for patients who adhere: free eggs every 2 weeks. Wu Zongren, the doctor who runs the program, says that 100 patients now receive treatment, and not one has died since the program began. As Wu speaks in the village clinic, his son and grandson drop by. The son was married to a woman who became infected from selling blood and since died. HIV infected both Wu's grandson and his son, who now helps run the DOTS program. “It's like a war, and we are the commanders,” says the elder Wu.

    The Global Fund to Fight AIDS, Tuberculosis, and Malaria recently approved China's application for $98 million to vastly expand and improve treatment to blood donors. The money also will help monitor CD4 white blood cells in treated people, a critical measure of whether the drugs are working. And it explicitly calls for more DOTS programs.

    If Donghu is an indicator, the DOTS programs ultimately may lead to the type of complaints from patients that caregivers want to hear. After Wei Jianli watches another neighbor, Wang Xiuzhi, swallow her medicine, the 45-year-old mother of three grouses about the need to have someone observe her. “How can I not take my medicine on time?” she protests. “I'm concerned for my life.” Wei patiently listens, and then walks away with a satisfied smile.


    A Scoop of International Proportions

    1. Jon Cohen

    BEIJING—A chance encounter on a train in October 1999 led Zhang Jicheng, then a reporter for Henan Science and Technology Daily, to uncover a huge AIDS scandal that would shake China and attract intense international attention—and cost him his job.

    On a train ride from southern Henan back to his home in the province's capital, Zhengzhou, Zhang met two couples from a remote village called Wenlou who said they were heading to Beijing. Others in Wenlou had tested positive for HIV after selling their blood, and the couples wanted authoritative medical tests for themselves. Zhang decided to visit Wenlou the following day.

    Zhang spoke with several HIV-infected people who had sold blood, and he interviewed teachers at the village school. “Many told me children already had lost parents and didn't know which disease had taken their lives,” says Zhang. He dropped in on the director of health for the county. “The director was drunk at the time I went there, so he was not on guard,” Zhang says. The man showed off pamphlets the health bureau had printed to educate villagers about HIV/AIDS.

    Four years earlier, epidemiologist Wu Zunyou of the Anti- Epidemic Station in neighboring Anhui Province and Roger Detels of the University of California, Los Angeles, had published a paper in The Lancet about a mother and her two daughters who became infected with HIV after selling plasma. Several provinces immediately shut down these businesses (they were formally outlawed the next year but continued operating in many places), and the Anhui cases appeared to be isolated accidents. But now Zhang had stumbled upon strong, if anecdotal, evidence of a much larger problem. In November 1999 his paper submitted a draft of his story to officials at the Henan Provincial Committee of the Communist Party, who blocked its publication. “If I was younger and an activist, I would have gone to the street,” Zhang says.

    Dogged reporter.

    Zhang Jicheng was fired after breaking the Henan blood donor story.


    Zhang did the next best thing: He sent a copy of his story to Huaxi Metropolitan News, a paper across the country in Sichuan Province, which on 18 January 2000 ran “Strange Disease in a Henan Village Shocks Top Officials.” When Henan officials learned of the story, they told Zhang's editors to fire him. But Zhang had always written under a pen name for the Henan paper, and his editors kept him on. He continued to visit Wenlou and other villages hard hit by HIV, but his paper could not publish the stories.

    To Zhang's surprise, his Huaxi story appeared on the U.S. Embassy Web site. Liu Jianqiang, a correspondent with China's bold Southern Weekend, who wrote a chronology of how this story unfolded, says the Chinese mainstream media had “turned a deaf ear to the AIDS reporting in Henan.” That August, China News Weekly published “AIDS National Disaster,” but the Henan story didn't become huge news until October, when The New York Times began in-depth reporting on the problem.

    The debacle, which Southern Weekend soon reported reached far beyond Henan, made minicelebrities—and state pariahs—out of several doctors who helped expose it. It also pushed the government to deal more aggressively with the country's AIDS epidemic. Reporter Zhang Jicheng, however, has received next to no attention for his major scoop, which he shrugs off.

    In the summer of 2001, Henan Province held a meeting called the Marxist Concept of News Reporting at which each journalist received marks from the local propaganda office. “I was given no score,” laughs Zhang, whose pen-name ruse by then had been discovered by the authorities. So Zhang was fired a second time, and he moved to Beijing, where he published several of the stories that he had been forced to withhold. Although he now covers other subjects, he remains keenly interested in his old home. “Henan is a rich mine for reporters,” says Zhang.

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