# News this Week

Science  23 Apr 2004:
Vol. 304, Issue 5670, pp. 496
1. REGULATORY POLICY

# White House Softens Disputed Peer-Review Plan

1. Jocelyn Kaiser

Last year when the White House issued a proposal for improving peer review of federal science documents, scientists and activists denounced it as a heavy-handed attempt to bog down government action. A revised version released last week has eased many concerns. Among other changes, the Office of Management and Budget (OMB) peer-review bulletin would no longer delay the release of time-sensitive data. And it endorses accepted standards for screening reviewers for conflicts of interest.

“They've been very responsive. This document is much, much more flexible,” says David Korn of the Association of American Medical Colleges, which along with the Federation of American Societies for Experimental Biology had criticized the bulletin as “overly prescriptive.” Another former critic, National Academy of Sciences (NAS) president Bruce Alberts, says the revised bulletin “will help to improve the quality of the government's scientific assessments and thereby its decision-making.” Some remain critical, however, and OMB is allowing 30 days for further comment.

The peer-review bulletin is part of an ongoing campaign by John Graham, a former Harvard professor who is now director of OMB's Office of Information and Regulatory Affairs (OIRA), to improve the quality of federal science reports, such as risk assessments. It imposes the first governmentwide standards for peer review, describing which documents require review and detailing procedures for those with significant economic impact (Science, 5 September 2003, p. 1307). Although some agencies already have extensive peer-review policies, actual practice varies, Graham said.

At an NAS workshop convened last November to review the initial draft, experts noted that the rules could slow the release of time-sensitive information, such as results from clinical trials. Also troubling, some said, a potential academic reviewer with funding from the agency organizing the review could be disqualified, whereas industry ties seemed less restricted. The proposal would also have made public individual reviewers' comments, which journals and the NAS review panels don't do. OMB received nearly 200 agency comments, many critical.

In the new version, agencies have more discretion to decide what form of peer review to use, and time-sensitive data are exempt. Having received a peer- reviewed grant from the agency is no longer assumed to pose a conflict of interest (although a contract could). The bulletin recommends that agencies adopt NAS standards for handling conflicts. And reviewers' comments can be anonymous.

The revised bulletin also raises the threshold for the most stringent review: It will apply mainly to “highly influential” assessments with at least $500 million a year in regulatory costs—up from$100 million. OMB expects that this will include one or two dozen documents per year.

“There's a collective sigh of relief,” says epidemiologist David Michaels of George Washington University in Washington, D.C., one of 20 former federal officials who had asked that the initial bulletin be withdrawn. “This is a much better-thought-out proposal.”

But not everyone is satisfied. “This process could still create additional delay,” says Winifred De Palma of the Washington, D.C.-based advocacy group Public Citizen, a view Michaels shares. They and others point out that OIRA has not adequately shown why the new procedures are needed. “Nobody can argue in the abstract with the concept of peer review,” says former U.S. Food and Drug Administration official Michael Taylor, now at Resources for the Future, a Washington, D.C., think tank. But he and others say that the degree of good—or mischief—it does will depend on how agencies implement the new standards.

2. U.S. OCEAN SCIENCE

# Commission Urges Major Boost in Cash and Clout

1. David Malakoff

A blue-ribbon panel that has spent the past 3 years looking at how the nation manages and studies the seas has concluded that “major changes are urgently needed.”

In a preliminary report (oceancommission.gov), the U.S. Commission on Ocean Policy this week called for a powerful new White House oceans council, doubled spending on marine science, and major new ocean observation and exploration programs. The report closely tracks many of the recommendations made last year by a privately funded panel, the Pew Oceans Commission (Science, 6 June 2003, p. 1484). But even though both panels are sending the same message, “it's going to take a monumental political effort to get [them] through Congress and the White House,” predicts one congressional aide.

Congress created the oceans commission to reprise the 1969 Stratton Commission, which helped create the National Oceanic and Atmospheric Administration (NOAA) and a host of new marine policies. Led by retired Adm. James Watkins, the 16-member panel hosted dozens of meetings before sending out a 450-page draft this week to state governors. A final version will go to the White House and Congress later this year.

The commission's central finding is that existing programs are too fragmented, underfunded, and uncoordinated to tackle today's issues, from overfishing and climate change to pollution and coastal erosion. A new National Ocean Council, led by a senior presidential aide and with a high-profile advisory panel, would help the president reorganize and expand key agencies, such as NOAA, and draft long-range plans. It would also establish a set of regional, nonregulatory councils to set a national agenda.

The panel says ocean science spending should double over the next 5 years, to about $1.3 billion, and include funds to build ocean observatories and conduct curiosity-driven exploration. It also wants scientists to have more influence on regional panels that set fishing quotas—an idea certain to be controversial. The panel estimates that it would cost about$4 billion initially to implement its recommendations and $3.2 billion a year to carry them out. 3. SPACE SCIENCE # NASA Backs Two Missions to Spot Promising Planets 1. Andrew Lawler* 1. With reporting by Robert Irion. NASA plans to launch two multibillion-dollar spacecraft in the next decade to search for Earth-sized planets. The decision, which expands the agency's previous plans for a single mission, was prompted by President George W. Bush's new vision for space exploration. NASA is likely to team up on at least one of the missions with the European Space Agency (ESA), which has been planning a similar planet-hunting instrument. Although funding remains uncertain on both sides of the Atlantic, astronomers are pleased that NASA is backing two powerful instruments to seek Earth-like environments—and therefore life—beyond the solar system. Scientists so far have detected more than 120 extrasolar planets. But finding and studying terrestrial-sized spheres requires a major leap in technology (Science, 2 January, p. 30). Astronomers and engineers in the United States and Europe have been competing fiercely in recent years to develop those technologies, and ESA and NASA both hoped to launch their respective missions, called Darwin and Terrestrial Planet Finder (TPF), before 2020. The president's January speech added new impetus to those plans. In addition to proposing human visits to the moon and Mars, Bush called for greater emphasis on the search for Earth-like worlds around other stars. Scientists are glad that NASA decided to strike while the political iron is hot. “I'm delighted,” says Princeton University astrophysicist Marc Kuchner, a member of the TPF science working group. “The only thing I'll miss is all the fun we've had competing [with Europe] to see who will find the most planets.” ESA has focused on free-flying interferometers, in which light collected by several telescope mirrors flying in formation is combined to form a single infrared image. The distance between the mirrors allows astronomers to cancel out the glare from the central star and capture light coming from an angle, which could denote a small planet. NASA, meanwhile, has pursued a variety of options, including free-flying interferometers as well as a single-spacecraft interferometer in which several mirrors would be arrayed along a truss. An alternative is an optical-light coronagraph, in which an extraordinarily smooth mirror is designed to suppress a star's light by a factor of 10 billion and allow astronomers to concentrate on photons from the zone in which planets might exist. NASA's Jet Propulsion Laboratory (JPL) has pursued work on both a medium-sized elliptical mirror of 4 by 6 meters—designed to fit snugly within a rocket housing—as well as a larger 10- to 12-meter segmented mirror. In a 12 April memo to scientists, TPF project scientist Charles Beichman of JPL says the agency wants to build the smaller coronagraph first, for launch around 2014, followed several years later by a free-flying interferometer. The combination of monitoring both visible and infrared wavelengths, he adds, could lead to a “reliable and robust determination of habitability and the presence of life” on planets beyond Earth's system by providing independent confirmation in some cases. Zlatan Tsvetanov, TPF project scientist at NASA Headquarters, says that pursuing both technologies will enable scientists to develop instruments for subsequent missions that are capable of measuring specific spectral lines of gases, such as oxygen and methane, that could denote life. ESA officials are happy with NASA's decision. “It certainly strengthens our position in Europe,” says Malcolm Fridlund, an ESA scientist based in Noordwijk, the Netherlands, who also is on the TPF science working group. Tsvetanov says NASA is interested in supporting a precursor mission by ESA in 2010 or 2011 to test some of the free-flying interferometer technologies. Whether ESA will take part in the NASA coronagraph mission “remains to be seen,” according to Fridlund. Scientists anticipate that the Darwin and TPF efforts will soon be merged, although funding decisions are a long way off. The coronagraph will cost less than the$2 billion James Webb Space Telescope slated for launch early in the next decade, according to NASA officials, whereas the interferometer likely will cost between $3 billion and$4 billion. Webb should be built and in orbit before the bulk of the money is needed for the two new projects, says Tsvetanov.

Tsvetanov insists that other science programs won't suffer because of the new missions. In fact, says Kuchner, the coronagraph could also reap data on supernovae, used to understand the nature and whereabouts of dark energy. And an interferometer might yield important clues to the early stages of solar system development by revealing smaller bodies in younger systems. “We can do groundbreaking cosmology as well as exploration,” he says.

4. AIDS MEETING

# Edict Limits U.S. Speakers at Bangkok Conference

1. Jennifer Couzin

U.S. health agencies are scrambling to comply with a directive from the Department of Health and Human Services (HHS) to scale back the number of government scientists they send to this summer's XV International AIDS Conference in Bangkok, Thailand. Twenty slots each have been allocated to the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC), while HHS is reserving 10 places for members of its staff.

HHS plans to spend no more than $500,000 on the meeting, half to pay for travel scholarships for about 80 African scientists. In comparison, it spent$3.6 million and allowed 236 people from HHS and U.S. health agencies to attend the AIDS meeting in Barcelona 2 years ago. (The limit on attendees does not apply to university scientists.)

Some researchers are dismayed. “It's absolutely ridiculous to micromanage CDC and NIH in this way,” says Neal Nathanson, associate dean for global health programs at the University of Pennsylvania in Philadelphia and director of NIH's Office of AIDS Research from 1998 to 2000. But some legislators may approve. On 7 April, 29 House Republicans sent a letter to HHS Secretary Tommy Thompson asking him to examine how much HHS spends on AIDS meetings and compare it with other health conference costs.

HHS officials handed out the travel quotas at a meeting in March (Science, 19 March, p. 1747). Soon afterward, Jack Whitescarver, director of the Office of AIDS Research, sent a confidential e-mail memo to top NIH officials allocating the 20 slots by institute. The National Institute of Allergy and Infectious Diseases, by far the biggest player in AIDS research, got nine; other institutes received between one and three spots each. Whitescarver's own office, the memo reported, would send no one.

Whitescarver's message also noted that HHS official William Steiger had said that the decision to restrict the number of government travelers to 50 “was as a result of the treatment the Secretary received in Barcelona and HHS opinion that this meeting is of questionable scientific value.” During a talk in Barcelona, Thompson was heckled by hundreds of AIDS activists. Whitescarver declined Science's request for an interview. HHS spokesperson William Pierce had no comment on the memo but said the $500,000 limit on travel to Bangkok seemed “reasonable,” adding, “We don't think this will hamper the communication of scientific information in any way.” Conference organizers, meanwhile, are waiting to learn which of the invited authors will come to present findings. Many U.S. scientists whose papers have been accepted will not be allowed to make the trip. (HHS prohibits its scientists from presenting their work if they're not traveling on the government's dime.) So NIH and CDC research managers now have the unenviable task of selecting attendees, and scientists themselves are looking for stand-ins if they get bumped. CDC spokesperson Kathryn Harben said that the agency would “make decisions on which [talks] are most important.” NIH spokesperson Donald Ralbovsky declined to explain how NIH would select its 20 attendees. In one NIH division, a senior scientist has had four abstracts accepted, while a postdoctoral fellow has had one. “They both can't go,” says an NIH staffer familiar with the case, “so what are they going to do?” Snub the postdoc, or cancel the senior scientist's four talks? A shrunken U.S. contingent could affect other aspects of the meeting, some observers say, such as workshops for international NIH grantees. As is customary, NIH staffers had planned to meet with African, Asian, and other AIDS researchers to discuss how resistance to AIDS drugs in clinical trials might be managed. Now those meetings may not take place. And Mark Feinberg, an AIDS researcher at Emory University in Atlanta who worked at NIH in the 1990s, worries that the reduced contingent could be “disillusioning for people in developing countries.” Some in Congress agree with HHS that conference spending needs to be reined in. “We should first resolve the AIDS treatment gap” in the United States, says Roland Foster, a staffer on the Government Reform Subcommittee on Criminal Justice, Drug Policy, and Human Resources, chaired by Representative Mark Souder (R-IN). In late February, the full committee voted to shift$7 million out of the $40 million HHS conference budget into domestic AIDS treatment. HHS helps fund at least one AIDS meeting every month, says Foster. The international AIDS meeting “is just the tip of the iceberg,” and his office intends to keep asking questions. 5. SCIENCE AND SECURITY # Reports Examine Academe's Role in Keeping Secrets 1. David Malakoff Two new reports have reminded scientists of the fine line between scientific freedom and national security at U.S. universities. The first, from two associations representing top research institutions, documents how some government agencies are routinely including stringent security restrictions in contracts for basic research at universities—in violation of a long-standing White House policy against such restraints. The second, from the Pentagon's in-house watchdog, urges the government to stiffen existing rules because some universities aren't doing enough to keep cutting-edge technology out of the wrong hands. The two reports, although pointing in opposite directions, could influence the scope of pending government rules. Both studies* are a product of the persistent tension between academic scientists and government security officials created by the war on terrorism. Since the 2001 attacks, officials have stepped up security, including efforts to protect “sensitive” findings from government-funded studies. But universities complain that they are seeing a growing number of security requests that violate a 1985 presidential order to either classify sensitive findings or leave them in the public domain (Science, 18 October 2002, p. 529). To get a grip on the issue, the White House Office of Science and Technology Policy (OSTP) last year asked the Association of American Universities and the Council on Governmental Relations to formally track the complaints. The two Washington, D.C.-based groups, which represent top U.S. research institutions, asked 20 universities to report every problematic contract provision they received over a 6-month period in late 2003 and early 2004. The report, which was sent to OSTP on 8 April, identifies 138 “troublesome clauses,” originating mostly from the Department of Defense or DOD contractors (see chart). Three-quarters of them involved language that required the researcher to gain prior approval to publish or share research results. The rest typically required researchers to limit or get prior approval for the involvement of foreign scientists. All of the schools reported receiving at least one troublesome contract, and at least one-fifth of all the contracts received by the schools during the study period contained problematic clauses, estimates Julie Norris, author of the university report and director of the office of sponsored research at the Massachusetts Institute of Technology (MIT) in Cambridge. Nearly half of the contracts were renegotiated, and 15 awards were ultimately rejected, some because signing them would have triggered a range of other regulations, including export-control rules that require campuses to exclude foreign scientists or students from some laboratories. “What we're seeing is a tremendous cost to the research enterprise in trying to deal with these clauses—and these are some very savvy institutions,” Norris says. Her panel recommends that the government do more to remind agencies of the 1985 presidential order and to remind government contractors that they don't have to “pass down” restrictive clauses to universities. That suggestion, however, may be undermined by the findings of a 25 March report on technology-export rules from the DOD's inspector general. Although it gives academic administrators high marks for complying with the rules, it found that at least one university gave a foreign scientist unauthorized access to unclassified technology relating to air-combat logistics. To prevent such problems, the report says DOD contract officers need to become more vigilant and beef up contract language. Some university officials fear that the inspector general's report could lead the Pentagon to adopt a controversial proposal under review for more than 2 years that would extend regulations on research (Science, 3 May 2002, p. 826). In addition, they are concerned about a Department of Commerce report due out shortly that also examines export controls at universities. One administrator predicts that the two reports could “embolden” government officials who want greater controls on basic research results. Meanwhile, Norris says OSTP wants to know more, including how much money is involved in the troublesome contracts. White House science adviser John Marburger says the information will be “very helpful as we work with federal agencies to develop research practices that are also consistent with security needs.” 6. REPRODUCTIVE BIOLOGY # Japanese Scientists Create Fatherless Mouse 1. Gretchen Vogel All Japanese children know the story of Kaguyahime, the moon princess who was born from a bamboo shoot and refused to marry. Now the fairy-tale girl shares her name with a real-life creature of equally strange origin: the first mammal born from two genetic mothers. Scientists in Japan announced this week that they have created an apparently healthy mouse by combining the genetic material from two egg cells. The mouse, named Kaguya, is the first mammal born without contribution from a sperm cell. Men, however, do not need to fear becoming redundant anytime soon; this latest feat in technology-assisted reproduction, which requires a gene knockout and two rounds of nuclear transfer, is more a lab trick than a potential way to make babies. Although insects, reptiles, and other animals can develop from unfertilized eggs—a process called parthenogenesis—mammals require the contribution of both father and mother. Mammal eggs that are pricked with a needle (apparently simulating penetration by sperm) will begin to divide and can form normal-looking embryos. But the fetuses that develop from such parthenogenetic eggs invariably die in the womb. Scientists have long suspected that the deadly defects arise from miscues in the imprinting process, in which certain genes are turned on or off during the development of eggs and sperm. Imprinting seems to be part of the evolutionary battle of the sexes. In sperm cells, for example, genes are marked to encourage the production of fetal growth hormones—presumably because it is to the father's advantage to have robust offspring. The egg, on the other hand, labels genes so that growth hormones are down-regulated—presumably because larger offspring are harder on the mother during pregnancy. Natural selection has ensured that in a normal pregnancy, the competing signals balance each other to create a healthy fetus. But in parthenogenetically developing eggs, the fetus inherits two sets of maternally imprinted chromosomes, getting twice the normal dosage of some genes and lacking others. In mice, parthenogenetic fetuses derived from a single egg cell do not survive past 10 days, half the normal gestation time. Developmental biologist Tomohiro Kono of Tokyo University of Agriculture and his colleagues have been studying imprinting and parthenogenesis for more than a decade. To try to create sperm-free mice, they developed a technique in which they combine the nuclear material from an immature oocyte—which contains a single copy (haploid version) of each chromosome—with that of a mature oocyte that contains its own haploid chromosome set, creating a complete diploid genome. The chromosomes are then transferred to a third oocyte, which has had its nucleus removed. Next, that oocyte is prompted to begin dividing. In 1996, Kono and his colleagues produced fetuses that developed to 13.5 days, a record for female-only development. The team suspected that the immature oocytes used as starting material had erased the imprints inherited at birth but had not yet applied maternal ones. Because sperm imprint fewer genes than eggs, these imprint-free oocytes resemble paternal rather than maternal genomes, perhaps allowing fetuses to develop further than other parthenotes. Two years ago the team showed that these mice could develop to 17.5 days when a mutation in the immature oocyte disabled a gene called H19. In normal sperm, the H19 gene is imprinted, blocking its expression. This allows the expression of a neighboring gene, called Igf2, which produces a protein that encourages fetal growth. In oocytes, H19 is not imprinted; this enables the mother's copy to down-regulate the production of the Igf2 protein and keep the fetus from growing too large. In parthenotes, both copies of H19 are turned on, leading to a fatal lack of Igf2. In the current work, published this week in Nature, the team again used oocytes from newborn mice carrying an H19 mutation. This time, however, the mutation was larger—and apparently more effective at blocking H19 expression. The researchers constructed 598 eggs, each carrying one set of chromosomes from a normal mouse and another from the mutant. They transferred 371 surviving embryos to 26 mice. To their surprise, when they checked the progress of the pregnancies at day 19, they found 28 pups, 10 alive and 18 dead. Two of the 10 seemed relatively normal, and one, Kaguya, survived to adulthood. She has since given birth to a litter of healthy pups. Although they call the work interesting, some scientists such as developmental biologist Azim Surani of the University of Cambridge, U.K., question whether Kaguya can really be called a parthenote, because she has two genetic parents, albeit both female. The experiment is a “proof of principle” that a mammal can be born without contribution from sperm, says Patrick Tam of the Children's Medical Research Institute in Sydney, Australia. But he says lines of female- descended mammals are unlikely to become commonplace. The technique “is amazingly complex,” he says. “There are not more than two or three labs in the world capable of pulling this off.” Indeed, why Kaguya survived is still a mystery. Given that just two of nearly 600 tries succeeded, says Davor Solter of the Max Planck Institute for Immunobiology in Freiburg, Germany, it is possible that Kaguya and the other survivor developed from immature oocytes that carried either an incomplete erasure of the paternal imprints or a lucky combination of genes that allowed them to overcome their imprinting abnormalities. 7. PALEONTOLOGY # New Biomarker Proposed for Earliest Life on Earth 1. Richard A. Kerr Recognizing life's remains becomes increasingly difficult as they shrink in size and increase in age. Little wonder paleontologists and astrobiologists have taken to tussling over what was and wasn't alive billions of years ago on Earth or on Mars. Now, on page 578, a group of geoscientists takes a newly developed marker of recently past life and applies it to some of the oldest rocks on the planet. The researchers report the discovery of microscopic tubules in 3.5-billion-year-old sea-floor rock that strongly resemble microtubules apparently bored in modern sea-floor rock by microorganisms. If the ancient borings indeed had a biological origin, life was firmly established just a few hundred million years after the end of the rain of giant impacts that had repeatedly sterilized the young Earth. But, true to the field's recent history, the first application of the microtubule biomarker to ancient rocks is getting a mixed reception. This new contender for oldest biomarker on Earth comes from South African rock that formed as lava oozed across a sea floor 3.5 billion years ago. Geologists Harald Furnes and Neil Banerjee of the University of Bergen, Norway, and their colleagues have found tubular structures sprouting from mineral-filled fractures in what was once the glassy rind of submarine lavas resembling a pile of pillows. These ancient microtubules, which average 4 micrometers in width and 50 micrometers in length, bear a striking resemblance to microtubules in modern sea-floor pillow basalts. In the past decade, Furnes and other researchers have built a case for modern microtubules, at least, being the tracks of rock-eating microorganisms. These geologically young microtubules have the right size and shape to have been formed by micrometer-scale organisms. They can contain lingering organic remains and nucleic acids or just enhanced amounts of carbon and nitrogen, building blocks of life. The carbon is isotopically lighter, which could be life's doing. And in the lab, particular microbes have been shown to eat their way into rock and glass, taking up essential nutrients stored there such as phosphorus and iron. Still, yearlong experiments produce only shallow pits. Furnes and his colleagues found most of those characteristics—similar size and shape, signs of organic matter, and light carbon isotopes—in the microtubules from the South African rocks, convincing them that that they have found a “3.48-billion-year-old biomarker.” Others agree. “I've looked at hundreds of rocks” while studying modern microtubules, says petrologist Martin Fisk of Oregon State University in Corvallis. “To me, it's unequivocal that the textures they see were created by microorganisms. I think they've got the best evidence I've seen for life at that time.” Other equally ancient signs of life have all come in for criticism lately (Science, 24 May 2002, p. 1384). Others are a bit more cautious. The South African microtubules “do look just like modern analogs in deep-sea glasses,” says microbial geochemist Jennifer Roberts of the University of Kansas in Lawrence. But although compelling, the evidence “isn't a smoking gun,” she adds. Abiotic chemical reactions, she notes, might move a few elements and isotopes around while carving out tubules in glass. Paleontologist Martin Brasier and his colleagues at the University of Oxford, U.K., think they have an example of just such ancient abiotic borings. Unaware of Furnes's latest work, they were pursuing microtubules in Australian sea-floor lavas of the same age. “There's no doubt theirs and ours are the same sort of thing,” says Brasier, but “we have a completely different interpretation of what's going on.” In analogy to examples previously reported by others, Brasier believes that decomposition—possibly of organic matter—produced fluids that drove a mineral grain into the glass as chemical reactions at the grain ate into the glass, sort of like a corrosive-tipped pile driver. “We still do not know whether life is needed,” says Brasier. With the inevitable uncertainties inherent in any one biomarker, “we're really going to need to look at a number of pieces of biological evidence,” says Roberts. That's the approach—still unsuccessful after 8 years—that proponents of biomarkers in martian meteorite ALH84001 have followed. In the meantime, Fisk is upping the ante a tad. At last month's Lunar and Planetary Science Conference in Houston, Texas, he and his colleagues presented examples of microtubules in the mineral olivine that resemble those in volcanic glass. Then he made a planetary connection by showing similar “tubelike alteration” in Nakhla and Lafayette, two martian meteorites. 8. HIV/AIDS IN INDIA # HIV/AIDS: India's Many Epidemics 1. Jon Cohen* 1. Reporting for this series was supported in part by a fellowship to Jon Cohen from the Kaiser Family Foundation. This is the second in a series of articles on HIV/AIDS in Asia, leading up to the XV International AIDS Conference to be held in Bangkok, Thailand, in July. The first part, on southeast Asia, was published in the 19 September 2003 issue (http://www.sciencemag.org/sciext/aidsasia/). ### News Focus: HIV/AIDS in India #### HIV/AIDS: India's Many Epidemics Sonagachi Sex Workers Stymie HIV The National AIDS Research Institute's Long Reach The Needle and the Damage Done Till Death Do Us Part CHENNAI—Pacing restlessly in front of her husband, who lies comatose in a hospital bed here, a 23-year-old woman spills out a tragic story. A bookbinder by trade, her husband, 29, has meningitis, caused by an opportunistic infection that flourishes during late-stage AIDS. She holds an infant in her arms and keeps an eye on their 4-year-old boy, whose birth transformed their lives. During that pregnancy a blood test determined that she was infected with HIV. “The doctor told my husband, not me,” the woman explains. “My husband tore up the results and told me there won't be anything there. Then he quietly went to get tested himself.” She soon learned the truth, and a test of their son revealed that the virus had passed to him, too. The news quickly traveled to their neighbors. “They avoid us,” the woman says. “They are afraid.” So is she. The couple have no income except for money her sister gives them. They live 400 kilometers from here, but in desperation they made the 9-hour train trip to the massive Government Hospital of Thoracic Medicine, the old Tambaram Sanatorium for tuberculosis. Located just outside Chennai (formerly Madras)—the sprawling capital of south India's Tamil Nadu state—Tambaram has developed a reputation over 75 years for rescuing people from death's door. “They come with lots of hope,” says one of the bookbinder's doctors, Satagopa Kumar. “They think coming to Tambaram will be a cure. We have to tell them slowly.” Kumar and his colleagues are delivering their sad message to a staggering number of people these days. Tambaram—which spreads out over 45 hectares and has cows and pigs roaming under the giant banyan trees that shade the grounds—sees more HIV-infected patients than any hospital in India. Last year alone, Tambaram admitted nearly 10,000 HIV-infected people and saw 120,000 more as outpatients—double the load in 2001. Only a tiny percentage of the patients can afford to buy lifesaving anti-HIV drugs, although a government program announced in November promises to provide them for free to the country's neediest. “This institution is not functioning in the ideal situation,” says superintendent P. Paramesh, who welcomes a recent$5 million infusion from the U.S. Centers for Disease Control and Prevention to help upgrade the facility. “We're able to do what we're able to do.”

Each of the five AIDS wards for men, including the one housing the bookbinder, has three dozen beds and few vacancies. Today, the two AIDS wards that care for women and eunuchs have resorted to their overflow strategy: offering new inpatients thin straw mats on the tile floor. Pediatrics has yet another ward devoted to AIDS.

As Kumar walks the wards in his white lab coat, patients and relatives call out, desperately pleading for help. “Most people don't know the incidence of HIV in the community,” says Kumar. “When they come here, they know.”

## Denominator problem

India shares one time zone, but more than 1 billion people live in its vast regions, and they speak different languages, practice different religions and customs—and face different AIDS epidemics. Heterosexual transmission accounts for 85% of the country's estimated 3.8 million to 4.6 million HIV infections, but in some areas, such as Manipur state in the Northeast, injecting drug use (IDU) drives the spread. In the slums of Pune, HIV has made serious inroads, but in similar conditions in Chennai a recent study found few infections. Sex workers in Kolkata have joined a union that promotes condom use and, research shows, has helped keep their HIV prevalence down to 11%, well below the 50% found in the red-light districts of Mumbai and Pune (see sidebar on p. 506).

Since 1992, the federally run National AIDS Control Organisation has coordinated the country's response to the epidemic, yet huge differences in resources exist geographically, and not always for obvious reasons. Pune's National AIDS Research Institute (NARI) and Chennai's Tuberculosis Research Centre have the latest scientific equipment, allowing investigators to characterize everything from HIV strains (mostly the “subtype C” seen in Africa) to individual viral levels and the resultant immune damage.

In contrast, the School of Tropical Medicine in Kolkata, the main government provider of AIDS care in West Bengal state, does not have a polymerase chain reaction machine and thus cannot measure anyone's HIV level, and the institution has just one flow cytometer, the machine used to count CD4 cells, a key indicator of immune function. New Delhi has a state-of-the-art substance abuse treatment center, whereas in Manipur, most of the HIV prevention and care for IDUs comes from nongovernmental organizations run by former users (see p. 509).

In January, Science visited AIDS researchers, caregivers, patients, community workers, and people at high risk of becoming infected in Pune, Kolkata, New Delhi, Manipur, and Chennai. Although the epidemic differs from place to place, similar forces across the country aid and abet the spread of HIV, including strong taboos about discussing sex, the limited power that many women have (see p. 513), and widespread discrimination against the infected. India also has a massive population of mobile workers and the largest number of people living beneath the World Bank poverty line of $1 per day. Many AIDS experts say they're deeply worried about where the Indian epidemic is headed, and a wave of international aid has started to pour in, including a$200 million commitment from the Bill & Melinda Gates Foundation.

Epidemiologist Richard Feachem, head of the Global Fund to Treat AIDS, Tuberculosis and Malaria—which has awarded India $153 million—says the country could become the major epidemic in the world. “If we look at the current response in India, they're much better than 2 or 3 years ago, but it still falls way short of what's necessary to attenuate a looming disaster,” says Feachem. “India is well on the way to a huge and explosive epidemic. It's about 15 years behind Africa, but it's on the same trajectory.” From an official vantage point, HIV has infected roughly 4 million, or only 0.8%, of the adults between 15 and 49 years old—just a smidgen higher than the prevalence in the United States and European countries. But Peter Piot, head of the Joint United Nations Programme on HIV/AIDS (UNAIDS), cautions that the impact of the country's epidemic is obscured by “the denominator problem”: India's huge population. A seemingly low national prevalence can equal a huge number of infected people; India now accounts for at least 10% of the world's HIV infections and is second only to South Africa. Although neither Piot nor Feachem expects that a country of India's size will reach South Africa's 20% adult prevalence rate nationwide, both emphasize that such comparisons make little sense. “Each state in India is bigger than most African countries,” says Piot. (Indeed, 10 have larger populations than South Africa.) Feachem says “there's nothing to prevent 20% prevalence of adults” in particular states. Faced with steadily increasing patient loads, many AIDS clinicians here strongly suspect that the country already has a much higher prevalence than reported. “I'd say there are approximately 5 to 10 million infected people,” asserts Suniti Solomon, one of the clinicians who described India's first AIDS cases in 1986 and now heads YRG CARE, an HIV/AIDS education, care, research, and training nonprofit in Chennai. In 2002, the U.S. National Intelligence Council (NIC) caused an uproar when it issued the dire prediction that by 2010, HIV could infect up to 25 million Indians, or about 5% of the adult population. This would roughly equal the total number of adult infections in all of sub-Saharan Africa today. Shortly after the report came out, then-Health Minister Shatrughan Sinha publicly criticized U.S. Ambassador Robert Blackwill and Microsoft CEO Bill Gates for referencing the figures, saying, “I fail to understand how people holding such important positions can stand on our soil and say that India will have 25 million sufferers of AIDS by 2010.” N. K. Ganguly, an immunologist who heads the Indian Council on Medical Research (ICMR)—the country's counterpart to the U.S. National Institutes of Health (NIH)—thought the NIC report widely missed the mark. “The projections have no basis in fact,” says Ganguly, who is based in New Delhi. Although Ganguly acknowledges his country's initial missteps in combating HIV—“we went through a lot of hiccups,” he says—he also thinks its efforts have made some headway: “The way AIDS should have increased, it has not. We have not become South Africa.” Robert Bollinger, an AIDS epidemiologist at Johns Hopkins University in Baltimore, Maryland, who has worked extensively in the country for the past 12 years, says the prevalence debate reflects the fact that researchers rely on “sentinel” sites in the major cities, which sample groups such as pregnant women, sex workers, and IDUs. “All of the estimates are based on limited information about what's happening in rural areas,” says Bollinger. “Does that mean they're overestimates or underestimates? Until we get data, it's difficult to say.” Solomon, for one, welcomed the NIC report because she believed it helped spur the government to launch its ambitious new program to supply anti-HIV drugs to 100,000 people by the end of 2005. “The whole thing was a big mess,” says Solomon, who thinks the Indian government's reaction to the report was overblown. “But India has to be pushed for everything.” And John Fahey of the University of California, Los Angeles (UCLA)—another AIDS epidemiologist who has a long history of working in India—says the government's new treatment program will help sharpen estimates. “With the availability of antiretrovirals, it will become easier to do surveillance as an HIV test is no longer a death sentence and there's less stigma,” says Fahey. Ramesh Paranjape, director of NARI, echoes the pragmatic perspective heard from many AIDS officials throughout Asia. “Whether HIV has infected 6 million or 8 million people here, our responsibility is not going to change,” Paranjape says. ## Drug dilemmas Around the time the bookbinder was admitted to Tambaram, another AIDS patient in a similar condition entered the upscale Ruby Hall Clinic across the country in Pune. The two cases followed different paths. The second man, the owner of a milk shop, had enough money for his wife to bring him to Ruby Hall, where the experienced AIDS team led by Sanjay Pujari diagnosed progressive multifocal leukoencephalopathy. Caused by an endemic virus that thrives in damaged immune systems, the disease best responds to anti-HIV drugs. One-fourth of the HIV-infected patients who come to Ruby Hall Clinic receive anti-HIV drugs, and the milk seller's family assured the doctors that he had enough money to pay for an initial course of treatment. “They said he won't be able to afford them lifelong, but since the government [drug support] program is around the corner, he can afford to start now,” says Ameet Dravid, a resident who cared for the man. By late January, the milk seller had markedly improved and could even speak a few words—in particular, “I want to go home.” The clinic planned to discharge him later that day. The new government program, which officially begins this month, offers a standard cocktail of free antiretroviral drugs, made by Indian generic manufacturers, to specific groups of infected people around the country. To receive the drugs, people must live in one of six states designated “high prevalence” (see map, p. 505). Only infected people who are under 15, are pregnant, or have full-blown AIDS qualify for the free treatment. The effort, says ICMR's Ganguly, is a “very courageous decision.” But soon after Health and Family Welfare Minister Sushma Swaraj unveiled the program on 30 November last year, clinicians across the country began debating the particulars and the staggering obstacles they face. “I strongly feel that antiretrovirals should be provided to all HIV needy patients in this country, but the process is very awkward,” says Pujari. He particularly worries about the cost of monitoring people under treatment, which ideally requires measuring their levels of CD4 white blood cells and the amount of HIV in their blood. “Monitoring is more expensive than the drugs,” says Pujari. Pujari and others also fear that India cannot train its clinicians quickly enough. “The abuse of these regimens is already happening,” says Vinay Kulkarni, a private practitioner in Pune who runs a busy HIV/AIDS clinic. “Many times, drugs are prescribed by doctors at the wrong dosages and the wrong combinations.” This can quickly lead to drug-resistant strains. Kenneth Mayer, who heads the AIDS program at Brown University in Providence, Rhode Island, and collaborates with Solomon, notes, too, that India's generic manufacturers of anti-HIV drugs have little incentive to train doctors. In contrast, he says U.S. drugmakers, concerned about meeting Food and Drug Administration requirements, “bend over backward” to train clinicians in the proper use of new drugs. Aside from cost and logistical issues, some AIDS clinicians have different ideas about who should receive treatment first. Subhasish Kamal Guha of the School of Tropical Medicine in Kolkata has seen his annual HIV patient load jump from 300 to 500 during the past 2 years, but West Bengal state does not qualify as a high-prevalence region. “Instead of singling out states, the poorest of the poor should be provided ARVs [antiretrovirals], regardless of where they live,” says Guha. At Chennai's Tuberculosis Research Centre, Soumya Swaminathan argues that criteria for eligibility should include whether a person has tuberculosis. In a recent study, Swaminathan and her co-workers found that more than 40% of their HIV-infected patients who develop TB die within 2 years—and two-thirds of them succumb to other AIDS-related diseases. “Even though we do excellent treatment of TB and can cure this, their long-term outcome is very bad,” says Swaminathan. Currently, TB patients who have a diagnosed coinfection with HIV can receive free antiretrovirals through the new program only if their CD4 counts drop below 200, which does not apply to about one-third of the patients Swaminathan sees. As Solomon discusses her own misgivings about the new treatment program, a crow she once fed some biscuits to incessantly taps its beak on her office window. The crow provides an uncanny backdrop to the conversation: More and more HIV-infected people in India now know that drugs can extend their lives, and they desperately want them. “There may be chaos,” says Solomon, who also fears that lack of training, monitoring, and funding will hamper the new program. “But we still need to do it.” ## Contradiction central Three years ago, Niteen, 35, was hospitalized in Pune with pneumonia and tuberculosis. When the doctors diagnosed AIDS and explained that life-extending drugs existed, Niteen and his wife, Kavita, decided he had to have them, no matter the cost. The couple, who had a “love marriage” (as opposed to an arranged one) and have a 9-year-old boy, have had to sell their house to pay for Niteen's anti-HIV drugs. But the treatment, which Niteen receives through a clinic run by NARI, has turned his life around: His CD4 count has jumped from a life-threatening 28 to 325—well above the 200 level that denotes AIDS. When Kavita and Niteen told their families about his infection, they offered both emotional and financial support. She remains uninfected, and unlike most married couples in India, they regularly use condoms. “I'm still scared, but I'm trying to fight with it,” she says. Niteen and Kavita's situation does not reflect the typical dilemma faced by the many HIV-infected people here who have no access to expert care, suffer from stigma, and understand little about the disease. But that's the point: India thrives on contradictions and diversity, mocking any description of its travails that holds too fast to one perception. As Johns Hopkins's Bollinger puts it, “India lives in 5 centuries at the same time.” Not only do Niteen and Kavita challenge the stock image of AIDS in India, they also have joined a cutting-edge clinical trial that demonstrates how research has moved beyond describing the virus and its patterns of spread to more complex analyses. As part of an international study sponsored by NIH, NARI will evaluate whether treatment with antiretrovirals can lower the risk of HIV transmission in “discordant” couples such as Niteen and Kavita. NARI is also conducting one of the world's largest trials to assess whether extended treatment of infants with the anti-HIV drug nevirapine can reduce transmission through breast milk, as well as a trial of a vaginal microbicide. NARI also plans to launch India's first AIDS vaccine trial in collaboration with the International AIDS Vaccine Initiative (IAVI). The small study of a vaccine that stitches HIV genes into a harmless adeno- associated virus should begin in the next few months, says IAVI's Jean-Louis Excler. Outside NARI, both YRG CARE and the Tuberculosis Research Centre in Chennai have intensive hunts under way for cheaper ways to monitor the health of people receiving antiretrovirals. IAVI, which bankrolls another project to develop an Indian-made AIDS vaccine that uses modified vaccinia Ankara to shuttle in the HIV genes, hopes to stage full-scale efficacy trials, too, and Excler already has traveled extensively to evaluate possible sites. More than 100 Indian researchers also have trained at HIV/AIDS programs run by Johns Hopkins and UCLA, and all but a handful have returned home. Looking ahead, forecasters see contradictions aplenty. “Ten years from now, I'm sure India will be at the top in terms of burden of disease and the magnitude of the problem,” says Piot of UNAIDS. “But I'm also quite confident that India, at least in some of the states, will have the best AIDS programs in the world.” The stakes reach far beyond India's borders, contends the Global Fund's Feachem. “India is the single most important country with regard to the history of the global epidemic,” says Feachem. “If we lose the fight in India, we lose the fight globally.” 9. HIV/AIDS IN INDIA # Sonagachi Sex Workers Stymie HIV 1. Jon Cohen ### News Focus: HIV/AIDS in India #### Sonagachi Sex Workers Stymie HIV The National AIDS Research Institute's Long Reach The Needle and the Damage Done KOLKATA—At the edge of the kaleidoscopic outdoor bus depot that occupies several downtown blocks here, dozens of women in multicolored saris, some toting children, step into two well-worn buses this temperate January morning. It seems like a perfectly unremarkable sight, except for one detail: The women are sex workers from the city's Sonagachi red-light district. They belong to the Durbar Mahila Samanwaya Committee (DMSC), a quasi-trade union that today will bus them 200 kilometers for a 4-day retreat. In all, 800 people will attend to review the union's many programs, the most celebrated of which has kept the HIV prevalence in these women down to 11%. “With sex workers everywhere else, within 3 to 4 years, the prevalence has just skyrocketed,” says Smarajit Jana, the epidemiologist who 12 years ago started what's widely known as the Sonagachi Project. Jana, who left the project in 1999 and now works in New Delhi for the relief agency CARE India, holds what DMSC president Debasish Chowdhury Digha calls a “demigod” status among the sex workers. “His idea was totally different,” says Digha. “Dr. Jana realized that sex workers could run the project. No one could accept that. Only Dr. Jana thought about sex workers and their families.” Featured in the international media and celebrated as a “model” effort by the World Health Organization, the Sonagachi Project set up a health clinic and hired sex workers for “peer outreach.” Wearing distinctive coats over their saris, the women gave out free condoms and spread the word about HIV and AIDS. They negotiated with madams, police, and what Jana calls the “local ruffians” who run the sex industry, convincing them that using condoms protected their investments. Tired of dealing with loan sharks, they opened their own bank to lend one another money. Condom use soared and HIV prevalence crept up slowly, whereas the prevalence in the red-light districts of Pune, Mumbai, and Goa has topped 50%. “Sonagachi has not been replicated in many parts of India,” says N. K. Ganguly, who heads the Indian Council of Medical Research. “We need to know why.” Teasing out the answer has become the subject of several investigations—including a$1 million effort under way by DMSC that's funded by the Bill & Melinda Gates Foundation. “We want to break this myth that it's not replicable,” says Jana. “We'll do it in broad daylight.”

There is some scientific evidence that the Sonagachi model can succeed in other Indian settings. Working with Jana and Sonagachi outreach workers, a team led by psychologist Mary Jane Rotheram-Borus of the University of California, Los Angeles, conducted a controlled study for 16 months that compared 100 sex workers from one community in West Bengal state who'd received “enhanced intervention” with 100 sex workers in another. All the women who received the enhanced intervention—which repeated the Sonagachi strategy of having peer outreach workers advocating for sex workers and “empowering” the women—reported using condoms more frequently than those in the control group. (The researchers tested for sexually transmitted diseases to validate this, but too few occurred for a meaningful analysis.)

Rotheram-Borus cautions sex workers who want to replicate Sonagachi that it did not begin as an empowerment movement. “It requires support initially from high-status persons within their culture who have political and social clout,” she says. “Other groups of sex workers would need, I think, the type of supports that the Sonagachi have had: highly educated volunteers mobilized initially by Jana who trained, supported, and shared their social status with the sex workers.”

Sex workers elsewhere in India have taken notice of Sonagachi's success. “They have a great union,” says Mary D'Souza, who runs Saheli, a sex worker group in Pune, and spent time in Sonagachi. “I want to create the Sonagachi Project here.”

10. HIV/AIDS IN INDIA

# The National AIDS Research Institute's Long Reach

1. Jon Cohen

### News Focus: HIV/AIDS in India

HIV/AIDS: India's Many Epidemics

#### The National AIDS Research Institute's Long Reach

PUNE—At Byramjee Jeejeebhoy Medical College, a 25-year-old HIV-infected widow comes in to have her baby's blood tested for the virus, part of a clinical trial she has joined that aims to prevent transmission through breast milk. The blood samples will go across town to the National AIDS Research Institute (NARI) for analysis.

In the city's Yerawada neighborhood of cluttered tenements and wobbly shacks, George Swamy and his staff from the John Paul Slum Development Project provide home care, medicine, counseling, and meals to more than 300 patients with AIDS. NARI trained much of the staff and pays their monthly wage.

At an upstairs flat in Budhwar Peth that looks directly into the brothels across the street, sex workers receive free health care. NARI runs the clinic.

NARI is one of the world's only national research institutions dedicated to HIV/AIDS, and its tentacles reach all over Pune. Its headquarters, on a 3-hectare campus in an industrial neighborhood outside the city, houses a staff of 60 whose labs have a DNA sequencer to hunt for resistance mutations in HIV, polymerase chain reaction machines, flow cytometers, and phalanxes of computers. “NARI is the best equipped and most experienced HIV/AIDS research institute in India,” says epidemiologist Robert Bollinger of Johns Hopkins University in Baltimore, Maryland.

Bollinger had much to do with helping the institution become established. Set up by the Indian Council of Medical Research, NARI came to life in Pune because it could easily poach scientists from the venerable National Institute of Virology located here. In 1992, the nascent institute began a collaboration with Bollinger on a project funded by the U.S. National Institutes of Health (NIH) to prepare sites for AIDS vaccine efficacy trials. The project ultimately fizzled out because NIH became disillusioned with the performance of the lead vaccines in line for these trials, but the NARI researchers got their sea legs and began to develop a detailed understanding of the spread of HIV in Pune. “It was a huge boost for the program,” says epidemiologist Sanjay Mehendale, NARI's deputy director. Bollinger remains tightly linked to many NARI projects. “He has been fantastic to collaborate with,” says NARI's leader, immunologist Ramesh Paranjape. “We call him an honorary citizen of Pune.”

NARI received half its $2.1 million budget this year from foreign grants and contributions, and its work now reaches far beyond epidemiology. A repository of Indian HIV isolates contains 190 strains. One novel study has looked for anti-HIV activity in 143 herbal preparations, which are hugely popular here. (None was found.) In the 27 March issue of The Lancet, a study by NARI and Hopkins researchers reported that circumcision gave men some protection from HIV but not from other sexually transmitted diseases, suggesting that cells in the foreskin may be extra-vulnerable to the AIDS virus. NARI also has plugged into NIH-funded clinical trials that involve discordant couples and vaginal microbicides (see main text). In a few months, NARI plans to launch a study with the International AIDS Vaccine Initiative of the first AIDS vaccine to be tested in India. NARI has one obvious shortcoming: Its tentacles rarely stretch beyond Pune. “As a national institution we should have reached every place,” agrees Paranjape. “And as we get more resources, we would like to do it.” 11. HIV/AIDS IN INDIA # The Needle and the Damage Done 1. Jon Cohen Although many “harm reduction” efforts attempt to slow HIV's swift spread through injecting drug users, critics say it's a scattershot approach that's having limited success ### News Focus: HIV/AIDS in India HIV/AIDS: India's Many Epidemics The National AIDS Research Institute's Long Reach The Needle and the Damage Done Till Death Do Us Part IMPHAL—On 26 January, Republic Day, India celebrates the birth of its constitution in 1950, the final symbol that it was free from the shackles of the British Raj. But this year in the Northeast—a jutting triangle of land that is home to many distinct ethnic groups—insurgents fighting for separation from India called a general strike, forbidding people from leaving their homes until 6 p.m. All day, heavily armed Indian troops filled the streets here in Imphal, the capital of Manipur state. But this evening at Robinson Ningshen's home, a handful of people who gather after the end of the curfew see the events as little more than a nuisance and make no mention of the holiday, the insurgency, or the soldiers. Instead, they speak about a different threat that strikes Manipur day in, day out: HIV and injecting drug users (IDUs). Robinson,* a physician who has a small clinic behind his house, introduces one of his brothers and a cousin. Both now live with him and his wife. Both have had long battles with “number 4”—the potent, cheap, pure heroin that flows across the long border that Manipur shares with Myanmar. Both are HIV-positive. The cousin's wife died last year from AIDS, and one of his children also is infected. Robinson explains that another brother and a sister-in-law overdosed from heroin. HIV infected two other cousins who shot heroin, too. “I never thought HIV would come here,” says Robinson. “And I never imagined that it would come to such a stage like it is now.” Although sharing contaminated needles officially accounts for fewer than 3% of India's HIV transmissions, the prevalence among IDUs in Manipur reached nearly 40% last year—and many suspect that figure is low. Sentinel testing in 2002 reported that the virus had infected only a slightly lower percentage of IDUs in Tamil Nadu state and the city of Mumbai. Although the government has endorsed harm-reduction strategies such as needle exchange, no organized, nationwide effort exists to slow the transmission of HIV in IDUs, who shoot a staggering array of pharmaceutical-grade drugs in addition to heroin. And the epidemic spirals out from networks of IDUs to their communities. “Nowhere in the world are injection drug users living alone and isolated,” says psychiatrist Suresh Kumar, who runs the Sahai Trust, a street outreach program for users in Tamil Nadu's capital, Chennai. “They're always connected to their injection and sexual partners. And so HIV infection is not going to confine itself.” Given the paucity of government support, nongovernmental organizations (NGOs) and AIDS clinicians in Chennai, Manipur, and other locales have patched together unusually tight networks that stage their own harm- reduction programs. They distribute condoms and clean needles, provide health care, run “de-addiction” camps, and promote the view that drug use is a disease rather than a crime. When they can afford it, these networks also provide substitution drugs such as the opiate buprenorphine. (Because India classifies methadone as a narcotic like heroin, no programs use it.) Yet significant limitations confront this patchwork of prevention efforts, which in practice means few people actually receive substitution drugs, few medical specialists work with users, and some clearly outdated—and even inhumane—drug treatment strategies survive. “India is lagging behind with regard to IDUs,” says Kumar. “There's a feeling that it's not a big problem.” ## Number 4 The situation for IDUs in India is especially complex in Manipur, a remote state of 2.4 million people where political tensions are acute. “The whole thing is very difficult in this region, and it's not something we have control of,” says Ronny Waikhom, a former IDU who became infected with HIV and now runs the CARE Foundation, a group of ex-users who buy anti-HIV drugs in bulk and sell them at cost. Many donor organizations stay clear of the Northeast; there is scant AIDS research here; and even the Manipur State AIDS Control Society helps IDUs mainly by funneling funds to the few dozen NGOs that work with them. As with many former users who now run these NGOs, Ronny attended university and started shooting heroin with his friends shortly after it first arrived in Manipur in the early 1980s, carried overland by Burmese traffickers who had found their sea routes blocked by antidrug campaigns. He stopped using in 1990. “It was the peak time that HIV was exploding,” says Ronny, two of whose brothers became IDUs and died from AIDS. Manipur started testing for HIV in 1986 but did not detect its first case until October 1989. Within 6 months, the prevalence in IDUs zoomed to 56%. By 1998, it had climbed as high as 70%, driven in part by the increasing popularity of shooting a painkiller called spasmoproxyvon. “It came up as though the floodgates were lifted,” says Narendra Singh Potsangbam, a leading Manipuri AIDS clinician. For 2002, reflecting the latest data, the three sentinel sites that tested IDUs reported that the prevalence dropped to 39%—but hardly anyone here takes these figures seriously. “It's not even near to reality,” Narendra says. More than half of all infected Manipuris today are male IDUs, and a team led by epidemiologist Roger Detels of the University of California, Los Angeles, reported in the International Journal of STD & AIDS that 45% of the wives of users they tested were HIV-positive, too. Another study by the same group, which included researchers from Imphal and Kolkata, found that the men had a shockingly high prevalence of hepatitis B(100%) and hepatitis C(92%). The aid groups that work with IDUs in Imphal and Churachandpur, a district 60 kilometers to the southwest, offer a wide range of treatment and prevention services. But resources are skimpy. Harsh political realities further complicate their work, such as the zero-tolerance stance that some insurgents take against drug users: They shoot people in the leg for holding drugs or beat them just for carrying needles. Few NGOs have attempted to measure the impact of their harm-reduction programs, says R. K. Raku, who runs the Northeast India Harm Reduction Center: “We need to do a lot of groundwork in practicing science-based programs.” One recent study run by the Social Awareness Service Organisation in Manipur and funded by the European Commission evaluated whether using buprenorphine pills could reduce risky behavior. The 2-year project found that about one-third of the more than 400 users who participated stopped injecting, and another third adopted safer injecting practices. Many hoped that the data would persuade the government to provide buprenorphine, but it costs about$1 per day—roughly the same as anti-HIV treatment—and nothing happened. Now hardly anyone in Manipur receives the drug.

Several NGOs, many with a religious bent, operate de-addiction programs that detoxify users and teach them skills to stay off drugs when they leave. The facilities range from permanent, well-kept homes and school-like dorms to makeshift camps with corrugated tin walls where residents sleep on straw-covered dirt. Gilead's Balm in Churachandpur has one small room of bunk beds that houses 60 men, several of whom have chains and locks on their ankles. “They want to run away during the withdrawal period,” explains Pau Thankam, the director of Gilead's Balm. “We don't have proper medicines.” This practice horrifies many of the NGOs that help IDUs in Manipur. “They're violating their basic human rights,” says Anand Chabungbam, the director of the comparatively upscale Kripa Foundation rehab program, which helped him stop using in 1991 and then hired him.

At the top of the agenda for NGOs and AIDS clinicians alike is the new government program that offers free anti-HIV drugs (see p. 504). Many worry that monitoring people on treatment will prove a nightmare in a region that has just one lab capable of determining critical CD4 white blood cell counts and already requires a 1-month wait. “If the government of India, the United Nations, or the World Health Organization doesn't do something drastic very fast, it's going to be horrible, really horrible,” says Robinson.

## Taking it to the streets

When Suresh Kumar and his outreach workers from the SAHAI Trust arrive at a public toilet in a slum outside the south India metropolis of Chennai, a dozen men—many of them barefoot and wearing plaid lungi skirts—cluster around to receive freshly wrapped needles and syringes. The workers then walk into fetid stalls and pick up a bucket filled with used needles, as well as others lying about. “We can't reach the majority of drug users from hospitals,” explains Kumar, whose staff earlier in the day did similar needle exchanges with IDUs shooting heroin in the bushes near a railway station. “Here, nobody wants to come and disturb them.”

For more than 2 decades, Kumar has focused on helping drug users in Chennai, and he says that drug laws consistently have made the problems worse. In 1983, says Kumar, impure “brown sugar” heroin—number 4 rarely makes it to mainland India—first became popular among university students after the troubles in nearby Sri Lanka led Tamil rebels there to become involved in the drug trade. As addicts ran out of money, they turned from smoking brown sugar to the more cost- efficient injecting. The introduction of tougher drug laws in 1985—including a minimum 10-year sentence of “rigorous imprisonment” for possession of just one-half gram of heroin—and crackdowns on traffickers, says Kumar, led IDUs to start abusing buprenorphine, the sedative diazepam, the antihistamine avil, and other pharmaceuticals. “The war on drugs is not a war on drugs,” he says. “It's a war on drug users.” (In 2001, India amended its drug law, allowing users caught with less than 5 grams of heroin to seek treatment instead of going to prison.)

Unlike in Manipur, in Chennai heterosexual transmission remains the main route of HIV infection. But about 30% of Chennai's IDU population has become infected, and Kumar faces many of the same frustrations that confront people in the Northeast. “The success of drug treatment is so low,” says Kumar. “That's why we've switched to HIV prevention.”

Kumar spends a lot of time battling perceptions. A study he and colleagues published in the March 2000 issue of the International Journal of Drug Policy found that two-thirds of 100 men interviewed still shared needles and fewer than one-third used condoms. “They think they can only acquire HIV through a man who got it through sex,” says Kumar.

Study after study, Kumar notes, has proven that needle exchange, substitution drugs, professional treatment, and other harm-reduction efforts can thwart HIV: “We have more than enough evidence in the world to say that.” Rather than focusing exclusively on changing the behavior of IDUs, he suggests, people should train their sights on policymakers. “They're not responding to scientific findings,” he says. “Given the evidence, why don't they change?”

## New day dawning in Delhi

A guard sits at the gated entrance to the walled-off National Drug Dependence Treatment Centre, which opened last year in Ghaziabad, an industrial city located about an hour's drive from New Delhi. Rajat Ray, a psychiatrist at the All India Institute of Medical Sciences who heads the center, says the guards worry more about who comes in than who leaves. “A lot of unwanted visitors supply people with alcohol and drugs,” says Ray. And he grimaces when he hears that a de-addiction center in Manipur chains patients to prevent escapes. “We have people living in the Dark Ages in this country,” says Ray. This \$2.5 million facility, in contrast, is wholly of the 21st century.

Funded entirely by the Indian government, the center occupies 4 hectares, and its buildings have 8500 square meters of space filled with 50 hospital beds, recreation rooms, outpatient clinics, an animal laboratory, a library, and even a daycare center. The staff of 12 doctors expects to see 25,000 patients each year, some of whom will stay for between 2 days and 3 months. Ray walks through the building's grand atrium to the pharmacy, opens a cabinet, and pulls out a box filled with buprenorphine pills. The center, in short, wants for nothing.

The few sentinel studies of Delhi IDUs suggest that only 5% or so have become infected with HIV. Heroin, surprisingly, has little link to HIV here, as the vast majority of users treated at the center smoke rather than inject brown sugar. In another twist, a favorite drug among Delhi IDUs is buprenorphine. Switching addicts to the pill form, then, does nothing to address their underlying addiction. However, says Ray, that “is a nonissue to me,” as his first goal is to get people off needles.

Ray acknowledges that the resources at his disposal make him the envy of his Indian colleagues. But, he says, “even though we have the knowledge, technical expertise, and know-how, even then, the fact of the matter is that drug abuse is a low priority in India.” He adds that many policymakers who care about infectious diseases fail to see the link to IDUs. “It's irrational.”

N. K. Ganguly, head of the Indian Council of Medical Research, agrees that the country must do more to stop the spread of HIV among IDUs. “Our program on drug abuse is quite rudimentary,” says Ganguly. “Here again comes the priority of what do you do? And now with antiretrovirals, we've jammed all of our people and resources to that.”

Frustrated by their government's lack of a national program to stop the spread of HIV in IDUs, some drug treatment experts still say they're making significant progress. New Delhi's Luke Samson heads SHARAN, an NGO that promotes harm reduction in five cities and successfully lobbied the government in 2001 to reduce penalties for personal drug use. “We have some of the most enlightened laws in the world now,” says Samson. He also applauds the government for endorsing harm reduction. “The only question is how to do it and who's going to do it,” says Samson. “The whole thing with harm reduction is you don't wait for the people to come to the center; you take the center to the streets. Right now, there's a huge gap between the policy and the street.”

• *In this part of India, people are formally known by their first names.

12. HIV/AIDS IN INDIA

# Till Death Do Us Part

1. Jon Cohen

HIV-infected women in India, many of whom had arranged marriages, often find that their in-laws reject them. But some arranged marriages can have decidedly positive outcomes for HIV-positive people

### News Focus: HIV/AIDS in India

The Needle and the Damage Done

Till Death Do Us Part

KOLKATA—Twenty-five days before giving birth, Jhuma Dewali learned that she was infected with HIV. Her husband, a gold artisan who often worked in Mumbai, far from their village in West Bengal state, died from AIDS 3 days later. Like the vast majority of couples in India, theirs was an arranged marriage, and, as is customary, they lived with his parents. “My in-laws said, ‘When our son is lost, what's the use of having you?’” Dewali remembers. They promptly evicted her. Dewali and her son, who is now 2 and is also infected with HIV, live with her parents in Kolkata. Her in-laws, says Dewali, were supposed to give her half of his property. They offered her one-fourth. On top of all these woes, she can afford anti-HIV drugs only for her son, not for herself.

Women now account for about one-fourth of the HIV infections in India, and at ante- natal clinics that screen blood for the virus, nearly 90% of those who test positive report having a monogamous relationship, Indian government researchers have found. “For an average Indian woman, the greatest risk of acquiring HIV is through marriage,” says Sanjay Pujari, a leading AIDS clinician at Ruby Hall Clinic in Pune. And like Dewali, many women who test positive find themselves confronting not only a life-threatening disease, but stigma and shame that they did nothing to bring on.

Nita Mawar, a social anthropologist at Pune's National AIDS Research Institute (NARI) who studies stigma and discrimination, says women often face the added burden of having their in-laws blame them for bringing HIV into their homes. Frequently, she says, the husband is healthy and does not know of his HIV infection. “It's the woman who learns about her HIV status when she's pregnant,” says Mawar. “So throw her out of the house!” Rashmi Jadhau, an AIDS clinician who works at a NARI clinic, says she has even seen cases of discordant couples in which the wives test negative for HIV, yet “they still want to blame the women.”

The intense stigma and discrimination some HIV-infected women face creates tragic dilemmas. HIV- infected mothers who learn that they can transmit the virus through breast milk often opt to use “top milk” (typically from cows or buffalos). “But if they are visiting relatives from the husband's side, they put the child to the breast,” says Gowri Sastry, a clinician at Byramjee Jeejeebhoy Medical College in Pune who is running a study that attempts to prevent breast milk transmission of HIV. Anita, a 20-year-old woman in this study who learned she was infected from a test done when she went into labor 5 weeks earlier, explains that she hasn't yet told her husband. “He's an alcoholic and may blurt it out,” says Anita, who has told him they must use condoms.

Nongovernmental organizations all over India try to help HIV-infected women who have suffered discrimination. Jhuma Dewali now receives assistance from the Society for Positive Atmosphere and Related Support to HIV/AIDS, a group in Kolkata that teaches women to sew and sell handicrafts made from jute. In Manipur, the Social Awareness Service Organisation has a program that assists HIV-infected widows. In Pune, the Institute of Health Management dispatches social workers who sometimes intervene in family conflicts that erupt because of HIV: They recently persuaded one 25-year-old widow's mother-in-law to take the woman and her two children back in.

Having families meet with professional counselors can make a huge difference, says Vinay Kulkarni, who runs an AIDS clinic in Pune and does HIV research, education, and training for a nonprofit organization called Prayas. With his wife Sanjeevani, an HIV/AIDS counselor, Kulkarni's recent studies have focused on stigma and coping strategies for HIV-infected women. “Discrimination against women is a fact,” he says. “But our data show tremendous family support once they are properly counseled.”

Suniti Solomon, an AIDS clinician in Chennai who runs the private YRG CARE clinic, decries the fact that it remains taboo to discuss a prospective groom's HIV status in an arranged marriage. The elaborate ritual requires matching horoscopes, the payment of a dowry to the groom's family, and the prospective bride showing her charms by, say, singing a song. “Instead of all this, can we say, ‘We would like to see the HIV status for the man?’” asks Solomon. “In the house it's just impossible to ask this. The boy's mother will say, ‘Do you think my son would be the type of boy to go outside? How dare you ask! I'll make sure your daughter never gets married!’”

Solomon has nothing against arranged marriages themselves and indeed proudly introduces a couple that she put together. The man, an HIV-infected patient of Solomon's, told her he had no intention of marrying. “I thought I should not spoil another person's life,” the man, a mechanical engineer, explains. But Solomon advised him that he could marry, and she had a plan: She would find him an HIV-infected bride. Soon the man traveled across the country to Maharashta state to meet the woman, and, although they faced concern from their families because of their different cultures, they wed. Against Solomon's advice, they had a child, who, it turns out, did not become infected, possibly because of the preventive steps they took, including giving antiretroviral drugs to both mother and baby, giving birth by cesarean section, and not breastfeeding. “Sometimes,” says the woman, beaming at their 18-month-old son, “I don't even remember I'm infected.”

13. # The Pulsar Menagerie

1. Robert Irion

The lighthouses of the universe take on countless guises, as astronomers have learned to their ongoing delight during the last 4 decades

When pulsars spun their way into astronomical lore in 1967, their debut was hardly glamorous. The radio telescope that found them was not a photogenic dish, but a 4.5-acre British field wired with 2048 gangly aerials. The first signal, spotted in August, was an odd “piece of scruff” embedded within kilometers of chart recordings. Puzzled for months by that flickering light, the University of Cambridge research team called it LGM-1, in case it came from little green men.

By December, it was clear that the pulses—precisely one every 1.33731109 seconds—streamed from an exotic, compact body. The team's first report, led by radio astronomer Antony Hewish, proposed “stable oscillations of white dwarf or neutron stars.” But a blaze of research in 1968 left no doubt that the group had unveiled an object prophesied in the 1930s by astrophysicists Walter Baade, Fritz Zwicky, and Lev Landau: an ultradense neutron star, perhaps 20 kilometers across, left by a massive star's death in a supernova explosion long ago.

Hewish went on to share the 1974 Nobel Prize in physics—an honor that also should have recognized his graduate student Jocelyn Bell Burnell for her central role in the discovery, many astronomers feel. Since then, a stream of findings has made pulsars the darlings of high-energy astrophysics for theorists and observers alike. “Pulsars have blessed us with stunning and unexpected discoveries every few years,” says astrophysicist David Nice of Princeton University in New Jersey.

## The iconic Crab

Among the 1500 pulsars now known, just one has an ironclad link to a fiery birth display witnessed by scientists: the famous pulsar inside the Crab Nebula. Chinese astronomers first recorded the Crab supernova as a “guest star” on 4 July 1054. Today, the pulsar's fierce output of energy lights up the blast's expanding tangle of debris.

Giant radio dishes in Green Bank, West Virginia, and near Arecibo, Puerto Rico, spotted the Crab pulsar in 1968. Astronomers were startled by its rapid-fire blips, 30 each second. Even more thrilling was a perceptible change in its spin rate: The Crab's clock was losing 36.5 billionths of a second per day.

The results vindicated a bold model put forward by theorist Thomas Gold of Cornell University in Ithaca, New York. In Gold's view, pulsars were spinning neutron stars that gradually wound down under the influence of intense magnetic fields. Energy lost by a pulsar's deceleration, he reasoned, would illuminate the nebula. Part of the energy would stream into space within two cylinders of light, sweeping through the cosmos like lighthouse beams as the pulsar spun. The broad details of Gold's model still reign today.

The Crab quickly rose to iconic status. But as it turns out, the pulsar is far from typical. It's unusually bright, spewing a huge portion of its energy into radio waves and x-rays. Moreover, it raised hopes that hordes of pulsars would turn up in other supernova remnants, but most searches have struck out. “There is another branch of compact objects created, and they're definitely different from the canonical pulsars everyone expected,” says astrophysicist Patrick Slane of the Harvard-Smithsonian Center for Astrophysics in Cambridge, Massachusetts.

## Einstein's test bed

Another graduate student was central to the next pulsar triumph. This time, the Nobel committee rewarded both the student and his adviser with the physics prize, in 1993.

The setting was a search for new pulsars in 1974 at Arecibo Observatory. Russell Hulse, working under astronomer Joseph Taylor of the University of Massachusetts, Amherst, devised a computer algorithm that picked out pulsars 10 times more sensitively than did previous efforts. One object, called PSR B1913+16 for its sky coordinates, spun 17 times per second—but its timing pattern kept changing. “My reaction was not ‘Eureka, it's a discovery,’ but ‘Nuts, what's wrong now?’” recalls Hulse, now a fusion scientist at the Princeton Plasma Physics Laboratory. “I was frustrated and annoyed.”

Vexation turned to elation when Hulse divined the truth: The pulsar darted in an 8-hour orbit around another body. Taylor rushed to Arecibo, and the pair confirmed the system that became known as the Hulse-Taylor binary. The pulsar's orbit revealed that its partner was a nonpulsing neutron star. Taylor worked with astrophysicist Joel Weisberg, now at Carleton College in Northfield, Minnesota, and others to show that Einstein's general theory of relativity was needed to describe the strong gravitational embrace of the two objects—the first such test outside our solar system.

Most critically, the team showed that the two bodies inexorably spiral together, at exactly the rate predicted by Einstein 60 years earlier. Gravitational waves carry away the lost orbital energy. “It's indirect, like showing that radio waves exist because you know the radio transmitter uses power,” Hulse says. “But it was the first evidence for the existence of gravitational waves.”

## Outrageous spin

By the late 1970s, research on pulsars had dwindled, says astronomer Donald Backer of the University of California (UC), Berkeley. It was a perfect time for a whopper, and Backer's team found it at Arecibo in 1982: PSR B1937+21, rotating a jaw-dropping 642 times per second. Yet another graduate student, Shrinivas Kulkarni (now at the California Institute of Technology in Pasadena), made the key initial find at the telescope.

This “millisecond pulsar” sparked a theory frenzy. It was nowhere near a supernova remnant, but its rotational speed—exceeding 1/10th the speed of light at its equator—looked like that of a freshly minted neutron star. Astrophysicists Malvin Ruderman, the late Jacob Shaham, and colleagues at Columbia University in New York City suggested that the pulsar was old but got a new lease on life by yanking material from a companion star. Gas plunging onto the greedy neutron star spun it up to outrageous rates, like a merry-go-round getting constant shoves.

Since then, astronomers have found nearly 100 such “recycled” pulsars. Some are isolated, but others have a partner in the process of being eaten or literally blown away by the pulsar's radiation. For instance, the “black widow” pulsar, found in 1988 by astronomer Andrew Fruchter of the Space Telescope Science Institute in Baltimore, Maryland, and co-workers, may evaporate its low-mass companion star within a billion years.

Oddly, searches have yet to expose a faster pulsar than PSR B1937+21. “It seems the spin-up mechanism can't push them much below 1.5 milliseconds,” says astronomer Richard Manchester of the Australia Telescope National Facility in New South Wales. A more frantic spin rate may make neutron stars so unstable that they emit gravitational waves, putting the brakes on their acceleration.

## The planetary surprise

Millisecond pulsars are the best clocks in the universe, slowing down by less than a billionth of a second per year. “They're like perfect flywheels, almost as simple as any of Einstein's Gedanken [thought] experiments,” says astrophysicist Stephen Thorsett of UC Santa Cruz. This precision led to the next pulsar bombshell in 1992: the first planetary system beyond our own.

The “pulsar planets” surfaced when astrophysicist Alexander Wolszczan of Pennsylvania State University, University Park, and radio astronomer Dale Frail of the National Radio Astronomy Observatory in Socorro, New Mexico, saw minuscule fluctuations in the arrival times of pulses from PSR B1257+12. Their model suggested that two planets, a few times larger than Earth, tugged the pulsar to and fro ever so slightly as they orbited.

The claim was controversial, but Wolszczan thinks the impact was worth the early catcalls. “After a relatively short period of disbelief, the average reaction was that the existence of planets around a neutron star must mean that the planet-production process in general was a robust one,” he says. Indeed, more than 100 other planets are now known, although PSR B1257+12 is still the only burned-out corpse of a dead star known to have a planetary system.

The pulsar is special in another way, too: Further analysis of its signals revealed a closely orbiting third planet, much smaller than the other two. The masses and relative positions of the three planets are “shockingly similar to our inner solar system,” Wolszczan notes.

## Double the pleasure

The latest stunner was anticipated for years: two pulsars deadlocked in a tight orbit. The new system, detected by the Parkes Radio Telescope in Australia and announced in January, will likely provide even more stringent tests of general relativity than the Hulse-Taylor binary (Science, 9 January, p. 153).

Already, astrophysicists are mystified by the energetic interplay between the neutron stars. Intense winds from the faster rotating pulsar create a tear-shaped shock wave around the slower pulsar. Teams are probing this process as one pulsar dips behind the other, every 2.4 hours.

In one interpretation of the data, the fast pulsar is churning out 100,000 to 1 million times more charged gas than expected from the seething region above its surface, says theorist Jonathan Arons of UC Berkeley. “The physics is not quite incredible, but it's close,” he says.

As searches for new pulsars continue, astronomers await the next varieties on their wish list. These include a pulsar orbiting a black hole and a submillisecond pulsar, spinning faster than 1000 times per second. “The record of history in this field shows that if we can think about it, we'll find it,” says Backer.

And after 37 years, the remaining questions haven't lost any luster. Why do nearly all pulsars contain about 1.35 times the mass of our sun? How do some supernovas expel pulsars into space at more than 1000 kilometers per second? What controls whether pulsars are born as “magnetars,” with ultrastrong magnetic fields (see p. 534)? Stay tuned; more pulsar programming is heading your way.

14. # Pulsars Surf the Cosmic Waves

1. Robert Irion

Imagine floating in the middle of a large lake, where you can't quite see the shore. If people throw big rocks into the water, you'll feel a riot of ripples. With the right tools, you might be able to tell how many rocks splashed in—and how big they were.

In space, the “rocks” are binary pairs of giant black holes at the cores of galaxies, and the “ripples” are gravitational waves. Long before they crash, the spiraling black holes churn the waters of spacetime. The waves, spanning light-years, traverse the entire universe. As each one passes by, it distorts the apparent distances between objects in a subtle but distinct pattern.

Millisecond pulsars surf those waves. As they bob to and fro, their signals arrive in telescopes on Earth at slightly different times. By timing an array of such pulsars for years, astronomers think they might spot the imprints of gravitational waves in this decade—perhaps beating out several major physics experiments on the ground.

Astronomer Donald Backer of the University of California, Berkeley, thinks his team is “within a factor of 5” of the necessary precision to detect the waves, using about a dozen pulsars in the Northern Hemisphere. And in Australia, a group is using the Parkes Radio Telescope, which has discovered two-thirds of all known pulsars. But the project is no day at the park, notes Richard Manchester of the Australia Telescope National Facility: “You need 20 pulsars in all quadrants of the sky, submicrosecond times of arrival, and weekly or biweekly monitoring. That's hard work.”

15. # Crushed by Magnetism

1. Robert Irion

The strongest—and strangest—magnetic fields in the galaxy stop some pulsars dead in their tracks and literally fracture their surfaces

Mutations are the spice of life, but the most freakish mutants usually die at a tender age. This biological rule holds true in astrophysics: Some of the strangest mutations in space create superenergetic but short-lived cousins of pulsars, called magnetars.

Like a pulsar, a magnetar is a neutron star forged at the center of a supernova when a massive star explodes. But something odd happens during a magnetar's birth. An unknown process—perhaps ultrafast rotation within the dying star's collapsing core—endows each magnetar with a crushing magnetic field. This magnetism, up to 1000 times more intense than that of a typical pulsar, is the strongest known in space.

As the magnetic forces subside, they rupture the brittle crust of the neutron star and drive fierce bursts of gamma rays and x-rays. But the pyrotechnics takes a toll. The magnetism acts as a brake, grinding each magnetar to a near-halt within thousands of years and short-circuiting its spin power. In contrast, an ordinary pulsar can sweep the galaxy with rotation-powered beams of radio waves for millions of years.

Astrophysicists have found just 11 magnetars, but their brief lives and sporadic tantrums point to a far larger population that we can't see. “There probably are hundreds of thousands of these dead relics, undetected and undetectable, now spinning in our galaxy,” says x-ray astronomer Chryssa Kouveliotou of NASA's Marshall Space Flight Center (MSFC) in Huntsville, Alabama. Indeed, some proponents think the objects might not be mutants at all but common offspring of supernovas. “It's quite possible that a majority of neutron stars are magnetars rather than radio pulsars,” says astrophysicist Robert Duncan of the University of Texas, Austin.

## A hundred billion MRI scans

That's a grand claim, but Duncan and fellow theorist Christopher Thompson of the Canadian Institute for Theoretical Astrophysics in Toronto, Ontario, have swayed skeptics before. They first calculated that powerful magnetic fields could lace through newborn neutron stars in 1987, when Duncan was a postdoctoral researcher at Princeton University and Thompson was a graduate student. But their solution for the strengths of such fields—1015 gauss—was so startling that they weren't sure what to make of it for several years.

For perspective, Earth's global magnetic field is about 0.6 gauss. Magnetic resonance imagers for medical scans attain 10,000 gauss. Radio pulsars cluster around 1012 gauss, a deduction based on magnetism's gradual braking effect on their spins. Such fields are impressive, but a radio pulsar's main power comes from its rotation, not its magnetism. The magnetic fields act as conveyor belts to carry radiation spawned as the neutron star slows down and sheds rotational energy. No one expected the fields to soar much higher.

But Thompson and Duncan realized that ultrastrong fields could explain some mysteries. Notably, astrophysicists were puzzled by soft gamma repeaters (SGRs). These unidentified objects emitted erratic flares of soft gamma rays—a notch above the most piercing x-rays—then fell quiet. In 1979, an SGR in a neighboring galaxy unleashed a giant flare that packed as much energy into its first 0.2 seconds as the sun produces in 10,000 years. The source was close to the remains of a recent supernova. However, the flare ebbed and flowed just once every 8 seconds as it gradually subsided, seemingly far too slow to come from a pulsar.

The theorists postulated that the bursts arose from a slow-spinning neutron star that had spun breathtakingly fast at birth. Astrophysicists Adam Burrows of the University of Arizona in Tucson and James Lattimer of the State University of New York, Stony Brook, had shown that during a neutron star's first 10 seconds of existence, its hot nuclear fluid would convect about 100 times every second. If the neutron star whirled between 100 and 1000 times each second during those birth pangs, Thompson and Duncan calculated, it would spark a furious dynamo—a self-sustaining generator of an intense magnetic field, 1015 gauss and beyond.

Once magnetism suffuses the dense superfluid of a neutron star, it's tough to disperse. Still, the magnetic fields and the electric currents that support them try to shift into patterns that are less taut with pent-up energy. “The magnetic field is strongly wound up in a tight spiral inside the star,” Thompson explains. “It is the progressive unwinding of the field that drives the [SGR] flares.” Each shift strains the solid crust of the neutron star. At a critical point the crust snaps, creating faults that may span a kilometer. Once the surface cracks, the magnetic fields above it whip into new positions as well. The violent motions blast particles along the magnetic fields, triggering gamma rays and x-rays.

Duncan and Thompson published this scenario in 1992, discarding their initial “burstar” term for the more descriptive “magnetar.” Three years later, they noted that the magnetic fields should confine a burst's energy in a fireball lasting a few minutes, exactly the pattern observed.

Still, their notions were too fantastic for most colleagues. As recently as January 1998, Duncan was relegated to the last talk of the last session at a meeting of the American Astronomical Society (AAS)—just after a speaker who explored alternatives to Einstein's general theory of relativity.

But later that year, observations won the day. First, a team led by Kouveliotou used NASA's Rossi X-ray Timing Explorer (RXTE) satellite to measure pulsations once every 7.47 seconds in an SGR with frequent outbursts. The periodic fluctuations were visible only during bright bursts; at other times the SGR did not emit ordinary pulsarlike beams. The object's rotational “clock” was slowing down by an astonishing 0.26 seconds per century—an effect that could result only from the strong drag of a magnetic field around 1015 gauss.

Then on 27 August 1998, a wave of gamma rays and x-rays more intense than the 1979 flare swept through the solar system. The source was an SGR across the Milky Way. Despite the distance, the radiation was powerful enough to affect radio transmissions on Earth by strongly ionizing the upper atmosphere. Slow, 5.16-second pulsations modulated the flare. Kouveliotou's team also studied it with RXTE to show that the SGR's spin decelerated at a magnetar-like clip.

With those findings, magnetars passed into mainstream science. Peers honored the work last year when Duncan, Thompson, and Kouveliotou jointly received the 2003 Bruno Rossi Prize, the top research award from the AAS High-Energy Astrophysics Division. It was a stark contrast to the theory's early years, Duncan recalls: “There was resistance, and a whole bunch of people thought it was crazy. But I view it all as a normal part of the scientific process.”

## Transients and nuclear bombs

In recent years, astronomers have broadened the magnetar family. Most now agree that objects called anomalous x-ray pulsars (AXPs), which pulsate slowly in x-rays but not in radio waves, are another flavor of magnetar. Astronomer Victoria Kaspi of McGill University in Montreal, Canada, and her colleagues have shown that AXPs can spew impulsive bursts, although not quite as vehemently as SGRs.

Curiously, the 11 known SGRs and AXPs all spin at nearly the same rate: between 5 and 12 seconds for each rotation. Magnetic fields stifle a young magnetar's spin so severely that its rotation stutters from a few milliseconds down to a few seconds within centuries—such a brief interval that astronomers would have to get lucky to see a furiously spinning magnetar. “And if they were active for more than a few thousand years, we'd expect to see some with periods of tens of seconds, but we don't,” says astronomer Peter Woods of MSFC. “So it appears to be a very short life cycle when they are x-ray bright.”

Two new studies to appear in the Astrophysical Journal suggest that magnetars are more common than their measly statistics indicate. In one report, astronomers led by Woods describe an AXP that flickered intensely for 4 hours in June 2002, then just as quickly faded. Similar outbursts elsewhere in the galaxy might go undetected by current instruments, says Woods, because telescopes that monitor the whole sky aren't yet sensitive enough. In another study, astronomers led by Alaa Ibrahim of NASA's Goddard Space Flight Center in Greenbelt, Maryland, exposed a “transient” magnetar. The object was too faint to attract attention throughout the 1990s, but it suddenly grew 100 times brighter in early 2003.

In their quiet states, these misbehaving magnetars bear some resemblance to faint sources of x-rays in supernova remnants, called central compact objects. They also look similar to another mysterious class of bodies called dim isolated neutron stars. Kaspi, a collaborator on both studies, agrees that the magnetar family tree may include some of these branches. “Dim isolated neutron stars could be dead magnetars with some residual heat,” she says. “I think the numbers are consistent with half the neutron star population being born as magnetars.” But better counts—and a firmer handle on the strengths of magnetic fields—are needed before anyone accepts that logic.

On the theoretical side, several groups are probing possible links between magnetars and gamma ray bursts (GRBs), the most energetic explosions in the cosmos. Many astrophysicists now think the most viable triggers of long- duration GRBs, lasting seconds to minutes, are powerful supernovas that create newborn black holes. However, a magnetically dominated wind from a new magnetar makes more sense as a coherent driving force, says astrophysicist Maxim Lyutikov of McGill University. “The dissipation of magnetic energy can be very efficient,” he notes. In contrast, blasts of matter from close to a black hole might lose too much energy within violent shocks.

In related work, modeling by Hubble postdoctoral fellow Todd Thompson of the University of California, Berkeley, shows that a brand-new magnetar will sling matter into space along stiff magnetic “spokes” at nearly the speed of light. This outpouring of mass expels so much momentum that if the magnetar spins 1000 times per second at birth, it takes merely 10 seconds to slam the brakes down to about 300 spins per second. That deceleration releases a whopping 90% of the object's energy. Thompson thinks all that energy can propel a hyperenergetic supernova or, under the right conditions, a GRB.

The heaviest elements in nature could arise in this turbulent setting as well, Thompson adds. Astrophysicists haven't yet identified a convincing site for the “r-process,” the creation of heavy atomic nuclei by rapid bombardment with a fierce wind of neutrons. Ultrastrong magnetic fields might keep a hot bath of neutrons and protons close enough to a new magnetar to push element synthesis up the periodic table to uranium and beyond.

Duncan, advocate of all things magnetar, loves the idea. “It's possible that all elements heavier than bismuth are synthesized in magnetar winds,” he says. “If that's true, nuclear bombs and reactors are running on magnetar energy.” Since supernovas supply the iron in our blood, it's only fair that magnetars get in on the action as well.