News this Week

Science  25 Jul 2008:
Vol. 321, Issue 5888, pp. 472

    Thumbs Down on Expensive, Hotly Debated Trial of NIH AIDS Vaccine

    1. Jon Cohen

    When he scuttled plans for a huge AIDS vaccine efficacy trial last week, Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases (NIAID), erased any doubts that he is willing to buck his own advisers when necessary. Fauci made his decision even though NIAID's AIDS Vaccine Research Subcommittee (AVRS) voted in May in favor of a study of a candidate designed by scientists at his own institute. “Voting is important provided you have the opportunity to ask people why did you vote that way,” says Fauci, who spoke with several subcommittee members after the meeting. “When you ask [them] for the scientific rationale, they often change their minds.”

    View this table:

    In canceling the Partnership for AIDS Vaccine Evaluation (PAVE) study, which would have cost $63 million, Fauci also challenged researchers to come up with a “lean and mean” alternative. Fauci, who lately has faced intense pressure from AIDS vaccine investigators to put more money into fundamental research (see p. 530), says so much confusion exists about what a vaccine should contain that proceeding with this particular vaccine was simply too dicey. “Given the fuzziness of all this, I'm just not willing to go ahead with such an expensive trial.” Fauci encouraged researchers to design a smaller, cheaper clinical trial that would reveal whether the vaccine has sufficient promise to warrant a larger efficacy study.

    Buck stopper.

    NIAID's Anthony Fauci nixed an expensive study—over-ruling advisers.


    The PAVE trial had already been dramatically scaled back from the initial plans for this vaccine, which is made by NIAID's Vaccine Research Center (VRC). Last fall, NIAID had hoped to start testing the vaccine in 8500 people around the world, for an estimated $140 million. But just when the trial was about to start, evidence surfaced that a similar AIDS vaccine made by Merck & Co. did not work and may even have left some people more vulnerable to HIV infection (Science, 16 November 2007, p. 1048). NIAID promptly canceled that trial and began reassessing plans for the PAVE study.

    Both the Merck and VRC vaccines use adenovirus-5 (Ad5), a type of cold virus, to deliver HIV genes into human cells. In the Merck study, for some unknown reason, the vaccine led to higher infection rates in uncircumcised men who had high antibody levels to Ad5 before the study began. Leaders of the PAVE study redesigned their trial to include only 2400 circumcised men who had low levels of Ad5 antibody. But Fauci said he worried that this study would ultimately not have the power to determine which immune responses correlate with protection, the central mystery in the frustrating search for an AIDS vaccine.

    AVRS member Dennis Burton applauds the decision. “The vaccine was too similar to the failed Merck vaccine to warrant a largescale trial,” says Burton, an immunologist at the Scripps Research Institute in San Diego, California.

    NIAID's Gary Nabel, who designed the VRC vaccine—which contains more genes than the Merck vaccine and uses a priming dose delivered by a naked DNA plasmid—stresses that this is not the end of the project. “What's been proposed is to try and reach a middle ground where we can still move forward and learn,” says Nabel. Fauci says he would like to see a smaller trial evaluate whether people who receive the vaccine and later become infected with HIV better control the virus. “We're not going to blow $63 million right off the bat until we get a signal that it's working,” says Fauci. Two smaller trials of the VRC vaccine currently under way (see table) may also yield some insights.

    Even AVRS members who supported the scaled-back study were relatively sanguine. “I'm a little disappointed,” says Louis Picker, who studies AIDS vaccines at Oregon Health & Science University in Portland. “We could learn an amazing amount by establishing immune responses in people and following them both in terms of if they get infected and if they do not.” Then again, Picker agrees that the VRC vaccine is far from ideal. “Everyone in their hearts is disappointed we don't have something better,” says Picker.

    Fauci says the money not spent on the PAVE study will become available to fund basic research, but he cautions that even a leanand-mean trial of the vaccine could still cost $45 million.


    New Purdue Panel Faults Bubble Fusion Pioneer

    1. Robert F. Service

    The third time was no charm for Rusi Taleyarkhan, the “bubble fusion” pioneer at Purdue University in West Lafayette, Indiana. After two previous investigations looked into alleged scientific misconduct by Taleyarkhan, a third panel has now cited Taleyarkhan for two cases of misconduct. Both cases centered on efforts by Taleyarkhan to make experiments carried out by members of his lab appear as independent verification of his previous work.

    Taleyarkhan first sparked controversy after he and colleagues reported in Science in 2002 that they had generated nuclear fusion with a simple tabletop setup. Fusion, the process that powers the sun, normally takes place at pressures and temperatures intense enough to cause atomic nuclei to combine and give off energy in the process. Decades' worth of efforts to harvest energy from that process in reactors on Earth have failed. In their original Science paper, Taleyarkhan, who was then at Oak Ridge National Laboratory in Tennessee, and his colleagues reported that firing a pulse of ultrasound and neutrons at a cylinder of acetone in which the hydrogen atoms had been replaced by deuterium atoms caused bubbles to form, swell, and collapse. The heat and pressure at the center of the collapsing bubbles reportedly fused deuteriums together, liberating nuclear byproducts and excess energy.

    The work raised the promise of limitless energy and spurred numerous early attempts to replicate it, all of which failed. Taleyarkhan moved to Purdue in 2004 and set about reproducing the original bubble fusion results. That winter and spring, according to the panel's report, Taleyarkhan's postdoctoral assistant Yiban Xu conducted bubble fusion experiments and wrote up the results, which were submitted to Science. The paper was rejected and later resubmitted to Physical Review Letters. PRL too rejected the paper; according to the panel's report, a reviewer commented that it was “unusual” that the experiment was done by one person “so that needed crosschecks and witnessing of results seem lacking.”

    Bubble bursts.

    A new investigation finds that Rusi Taleyarkhan misrepresented work from his lab as independent confirmation of his prior results.


    In early 2005, Taleyarkhan asked Adam Butt, a master's degree candidate in his lab, to proofread the paper and check some of its numbers. After Butt did so, the panel says his name was added as an author of the paper, which was then submitted to Nuclear Engineering and Design (NED) and quickly accepted. “In this context, it is plain that the intent was to create the appearance of a joint author who participated in the experimentation itself,” the panel's report concludes. “This is research misconduct.” The panel flagged Taleyarkhan for a second count of misconduct for a 2006 PRL paper in which Taleyarkhan and colleagues cited the NED paper as proof of independent confirmation of bubble fusion. Although the panel concluded that several other allegations did not constitute scientific misconduct, the report was still deeply critical of Taleyarkhan's behavior and in some cases his scientific procedures.

    In an e-mail to Science, Taleyarkhan says that the new report “is flawed from various perspectives and incorporates factual errors,” though he does not spell them out. He adds: “The current state of matters represents a major setback for university faculty members in general—this sort of selective victimization to meet political-funding priorities of a huge institution (with relatively incomparable resources vs the sole individual) could happen to any other faculty member.”

    Kenneth Suslick, a chemist at the University of Illinois, Urbana-Champaign, and a longtime critic of bubble fusion, calls the report “some kind of vindication.” Suslick says he was disappointed the report didn't more squarely address questions of possible scientific fraud that have been raised about the research (Science, 17 March 2006, p. 1532). The report states that although such allegations were made to a previous panel investigating Taleyarkhan's work, they were not forwarded to be made part of the current panel's investigation—but it does not explain why. The current report also did not attempt to evaluate the original scientific results behind “bubble fusion.”

    The latest panel was set up in March 2007 following complaints to the Inspector General of the Office of Naval Research (ONR), which helped fund some of Taleyarkhan's experiments. The panel was chaired by Purdue biochemist Mark Hermodson, and four of its six members came from outside Purdue University. Although the current panel submitted its report to ONR in April, it was formally accepted and made public only on 18 July.

    Taleyarkhan's lawyer, John Lewis of Lewis and Wilkins LLP in Indianapolis, says Taleyarkhan plans to appeal the report's findings. However, he adds that he is “not optimistic” the appeal will succeed, given that it will be conducted by the university. Purdue spokesperson Joseph Bennett says that Purdue officials will not comment on the report until after any appeal is complete next month. The ONR letter states that the funding agency will keep the case open until Purdue takes corrective action to prevent similar occurrences in the future.


    Paper Retraction Puts Focus on Informed Consent Rules

    1. Dennis Normile

    Stung by a front-page newspaper exposé of an alleged lapse in research ethics, officials at the University of Tokyo's Institute of Medical Science are planning to overhaul efforts to educate researchers on ethics rules and tighten internal review and compliance procedures. At the same time, scientific journals are getting stricter about documenting the fact that human studies have undergone ethics review.

    “What we learned is that periodic educational efforts to raise everyone's awareness of clinical research ethics guidelines were insufficient,” says Motoharu Seiki, the institute's dean.

    The incident centers on a group led by Arinobu Tojo, who works on molecular therapies for leukemia. The group retracted a paper on acute myeloid leukemia by Seiichiro Kobayashi et al. that was published online on 21 May and in the 1 July issue of Haematologica. An investigation determined that a statement the authors made to the journal that the study had been approved by an institutional review board (IRB) was erroneous (Science, 18 July, p. 324).

    Seiki says the group retracted the paper on its own initiative and that, to the best of their knowledge, there is no problem with the data, and patients were not put at risk. He says Tojo may have believed that approval of another aspect of his research covered this study as well. (No one has answered Tojo's office phone, and he did not immediately reply to an e-mail from Science.)

    An outside investigative panel is now looking at other papers from the same lab. But Seiki says a key issue is that the retracted study relied on blood and bone marrow samples collected from six acute leukemia patients before the Ministry of Health issued its first guidelines for informed consent and IRBs in mid-2003. The guidelines allow the use of samples collected without informed consent only if approved by a review committee, but it doesn't clearly state that this requirement applies to old tissue samples or give any guidance on the use of such samples. Seiki says the institute needs to make researchers aware that use of these samples also requires IRB approval.

    Cold case.

    Research on archived human tissue, shown in this stock photo, has created an ethical quandary at the University of Tokyo's Institute of Medical Science and elsewhere.


    A whistleblower first alerted the institute's research compliance office of the Tojo group's alleged infractions. Seiki says the office discussed the issue with Tojo but didn't take the matter any further. The whistleblower later tipped off the Asahi Shimbun, a prominent daily newspaper, which contacted the institute, prompting the formal investigation. Seiki concedes the need “to put in place a system under which such mistakes are avoided.”

    Mario Cazzola, editor-in-chief of Haematologica and a hematologist at the University of Pavia in Italy, says this is the first time a paper has been retracted from the journal for a false or erroneous statement about ethical review. Editors at several other publications also think it is a first.

    Journals appear to be paying more attention, Robert Dellavalle, a dermatologist at the University of Colorado, Denver, and colleagues wrote in an article in the February 2008 issue of Clinical and Investigative Medicine. They reported that 83% of 101 Englishlanguage medical journals surveyed require ethics committee approval of human research in their instructions to authors, up from 47% of 102 journals surveyed in 1995. And among those, 85% ask for a statement from authors attesting to such approval.

    Journal editors' opinions are mixed on the effect iveness of requiring statements from authors, as opposed to the IRBs themselves. In an e-mail to Science, Margaret Winker, president of the World Association of Medical Editors and deputy editor of the Journal of the American Medical Association, said that in a recent forum discussion some members felt that a statement from the IRB is needed to guard against false disclosures. But Dellavalle, on the other hand, believes requiring authors to state that they have complied with ethical reviews is already filtering out improperly conducted studies.

    The Journal of the American Academy of Dermatology has begun requiring a copy of the IRB approval letter. Haematologica now asks authors to include the name and e-mail address of the approving IRB or ethics committee, the date of approval, and the case identification number; it may decide to require a copy of the IRB's letter as well once a paper has been provisionally accepted. And Science is also discussing requiring the IRB approval letter, according to Katrina Kelner, deputy editor for life sciences. Science now requires a statement of compliance with informed consent and IRB approval for human studies, although it is not published.

    Dellavalle thinks journals should require and publish a description of the approved experimental protocols. This would help keep researchers from getting approval for one experiment and doing another—and would protect human subjects and keep scientists honest. The checklist for papers on research involving human subjects is bound to get a bit longer.


    Europe's Science Gathering Draws Crowds and Long-Term Funds

    1. Martin Enserink*
    1. With reporting by John Travis.

    BARCELONA—Judging from the hallway talk, Europe's biennial science festival was a boon for this city's notorious pickpockets; tales abounded about participants who, after a stroll along the fabled Ramblas, spent the afternoon at a police station instead of debating biofuels or brain science. But that was about the only blemish on the EuroScience Open Forum (ESOF) 2008.

    Graphic Read much more about ESOF 2008 at Findings, Science's news blog.

    This year saw twice as many participants as attended the 2006 edition in Munich—some 4500 from 66 countries, including about 400 journalists—more sessions, and a greater variety of big names. Hatched only 4 years ago in Stockholm (Science, 3 September 2004, p. 1387), ESOF is fast becoming a key meeting point for scientists, policymakers, and reporters from around the continent; the meeting has come to embody the integration of dozens of national research cultures into something more European, says Norbert Kroó, vice-president of the Hungarian Academy of Sciences.

    ESOF's format was inspired by the annual meeting of AAAS. (“A smaller AAAS meeting with better food,” one participant quipped.) Both have a very broad scientific program, covering everything from nanotechnology to cosmology, and many public outreach events. ESOF's many policy sessions dealt with distinctly European trends and anxieties, however, such as international mobility or difficulties turning research into economic growth. At a session on innovation, for example, a speaker advocated the “dedemocratization” of R&D by betting more money on fewer groups, because Europe's tradition of spreading funding across countries isn't working.

    Clear sailing.

    Outreach events such as this balloon-launched paper ship are a hallmark of ESOF, which has secured new funding for its future meetings.

    CREDIT: ESOF 2008

    ESOF is held in a different city every other year and, like the Olympics, is largely organized by a local committee and people they recruit from across Europe. The inevitable result has been the occasional reinvention of wheels, says Enric Banda, co-chair of the Barcelona committee. To address that problem, five private foundations—two each from Italy and Germany, and one from Sweden—announced on Monday that they have formed a “Supporters Club” that will pony up €1.6 million over the next 4 years to set up an ESOF secretariat. Right now, Euroscience, ESOF's parent organization, has only one permanent staff member.

    The secretariat will take care of fundraising at the European level and serve as an institutional memory. But ESOF wants to retain the strong local involvement because it generates much more enthusiasm than a central organization, says Swedish physician Carl Johan Sundberg, who dreamed up the concept 10 years ago.

    Making cities vie to host ESOF is also a way to improve future meetings. The northern Italian city of Torino, for instance, won the 2010 edition in part because it promised a very ambitious Web presence. Torino computer scientist Angelo Raffaele Meo has taken up the challenge of webcasting every session live, and remote viewers will be able to interact, for instance, by e-mailing questions for speakers.

    Helga Nowotny, the Austrian chair of the 2010 program committee, said she'd also like to see more participants from Eastern Europe and from private businesses. Sundberg, for his part, says he'll strive for more audience participation. “Too often, it's still a series of talking heads,” he says.

    Dublin and Vienna have thrown their hats in the ring for ESOF 2012 and were lobbying heavily in Barcelona. Other cities that want to cultivate a brainier image have until 1 October to bid.


    Lessons of Disasters Past Could Guide Sichuan's Revival

    1. Richard Stone

    BEIJING—Two months after an earthquake devastated a mountainous swath of Sichuan Province, urban planning experts met* here to take stock of how past disaster responses could guide a massive reconstruction effort about to get under way. One tragic lesson confirmed by structural engineers is the shoddiness of many schools and other buildings that collapsed—and the countless deaths that could have been avoided.

    “This disaster creates an opportunity to rebuild a more resilient community,” says Steven French, an urban planning professor at the Georgia Institute of Technology in Atlanta. As John Holmes, U.N. under-secretary-general for humanitarian affairs, puts it, “now is the moment to appraise, with sober wisdom, how to avoid the mistakes of history.” Questions include where to rebuild communities and whether building codes must be strengthened.

    The 12 May Wenchuan earthquake killed at least 70,000 people and left nearly 5 million homeless. China mobilized an army of soldiers and volunteers to get displaced people into shelters and set up makeshift schools. Last month, the State Council issued a decree ensuring scientific input into the reconstruction of a fractured area encompassing 20,000 square kilometers. “In very few disasters have I seen the consistency and rapidity of China's response,” says Ede Ijjasz, a sustainable development expert in the World Bank's Beijing office.

    But the harsh truth is that many building collapses could have been avoided. Engineers have concluded that scores of structures had poor ductility—the ability to sway with shaking or retain integrity long enough for people to escape. Reinforcement bars (rebars) in concrete beams and columns provide ductility. Observers have decried obvious cases of negligence, such as missing or grossly deficient rebars.

    There were more subtle—but equally fatal—defects as well. A team from the Ministry of Education's Key Laboratory of Building Safety and Efficiency found that many collapsed structures lacked transverse rebars. “From the reconnaissance of the earthquake damage, it is clear that most of the damaged concrete building columns and beam to column joints did not have proper transverse reinforcement,” states a report by lab director Xiao Yan, a civil engineer at the University of Southern California in Los Angeles and Hunan University in Changsha. “Transverse reinforcement is particularly important to confine the concrete.” And in many instances, floors were not tied to support walls, allowing buildings to “split apart and collapse,” says William Holmes of Rutherford & Chekene Consulting Engineers in San Francisco.

    As experts dissect the damage, efforts to shore up buildings are under way. For example, a $58 million effort to reinforce columns and repair masonry is progressing fast at Southwest University of Science and Technology (SWUST) in Mianyang, which lost three students to the earthquake (Science, 30 May, p. 1145). Staff members are pitching in—the university canceled their summer vacations—and the campus is expected to reopen at the end of August, says SWUST mining professor Zhang Zhigui.

    A bigger challenge is to rebuild villages wiped out by landslides and towns such as Beichuan damaged so extensively that they must be reconstituted from scratch. In hard-hit areas, “recovery is complicated, messy, ugly, and painful. It's an insane environment for professional planners,” says Robert Olshansky, a disaster expert at the University of Illinois, Urbana-Champaign. Over the past several weeks, geophysicists have been revising active maps designating areas that are at risk of intense shaking in future quakes or are prone to landslides.

    Major surgery.

    Reconstruction at Southwest University of Science and Technology is in high gear; the campus should reopen next month.


    The Chinese government is now plotting out the details of Sichuan's reconstruction. One basic necessity is to move freely in the damaged region. Last week, Sichuan authorities told urban planners that it will cost $10.6 billion to revamp the province's transportation network. This will be one component of a reconstruction plan that China's National Development and Reform Commission says will be ready by September.

    “The government's role should be to send lots of money and stay out of the way,” says Olshansky. He points to the “remarkable” comeback of Yogyakarta, Indonesia, ravaged by an earthquake in May 2006. “Housing collectives in each village were given money,” he says, and in just 2 years, “virtually all seriously damaged homes have been rebuilt.” One experience that Chinese planners would not wish to repeat is that of Orléansville, Algeria, which was reduced to rubble in a 1954 earthquake. The replacement city—Al Asnam—was poorly built, says Ijjasz, and it too was destroyed in a 1980 quake.

    Economic and emotional recovery in Sichuan could take years, experts say. “It takes a tremendously long time to recover from these kinds of events,” says Lawrence Vale, an urban planning professor at the Massachusetts Institute of Technology in Cambridge. Although infrastructure in Kobe, Japan, was repaired within 2 years after a 1995 earthquake, many small businesses and major industries have not bounced back, says Haruo Hayashi, a disaster-management specialist at Kyoto University. “In Kobe, 20% of people say they feel they are still victims,” he says.

    One question preying on the minds of victims is where they will live when they move out of temporary shelters. Experts advise Chinese authorities to take such decisions with utmost care. “The tension at the core of recovery is speed versus deliberation,” says Olshansky. Another conflict, he says, “is between what planners will be promoting and the plan in the minds of inhabitants: the predisaster city.” Whatever rises from the rubble in Sichuan, it had better be structurally sound.

    • * China Planning Network City Resilience Roundtable: Rebuilding and Restoration After the Sichuan Earthquake, 16 July.


    EPA Calls for More Studies on Health Risks of Climate Change

    1. Eli Kintisch
    Hot topic.

    CDC is mapping areas that are most vulnerable to heat waves.


    Long-term changes in climate can affect human health in myriad ways. Last week, a new report by the U.S. government's climate change science program outlined a research road map to help Americans adapt to a warmer climate.

    “The bottom line is that there are very real health risks associated with climate change,” says Centers for Disease Control and Prevention (CDC) epidemiologist Howard Frumkin, a reviewer of the report, which was written by a team of government and independent scientists under the direction of the Environmental Protection Agency (EPA). The report cites an expected increase in the range of vectors that carry Lyme disease and West Nile virus and a greater risk of diarrheal diseases following more frequent flooding. Experts in the field acknowledge, however, that the science cannot yet help local officials anticipate specific public health crises. “A city health director says to us, ‘What's the infectious disease I need to prepare for given the changing climate?’ That's a question we can't answer right now,” says Frumkin.

    The report calls for health-surveillance systems to include “climate sensitive pathogens and vectors.” It recommends more studies to model the health impacts of climate-related events such as wildfires or floods, as well as regional climate models to provide scientists with higher resolution data regarding local climate forecasts. Most current studies of public health issues don't include a climate component, it notes.

    The report doesn't address whether the federal government is spending enough on climate-related “human dimensions.” But last year, the National Research Council estimated the amount at $30 million, a level it said was woefully inadequate. A House spending panel has proposed giving CDC an additional $7.5 million next year “to prepare and adapt to the potential health effects of climate change.”

    CDC now spends less than $1 million on climate-related programs, including a mapping project combining temperature, census, and public health data to identify the areas within cities where residents are most vulnerable to heat waves. CDC's Frumkin says several important studies remain on the drawing board because of insufficient funding. And the agency's new $27-million-per-year national effort to track health changes related to environmental factors such as allergens excludes waterborne vectors and other factors specifically linked to possible warming.

    The report seems to have escaped the strong political headwinds that previous official efforts on the topic have encountered during the Bush Administration. Last year, the White House censored written congressional testimony by CDC Director Julie Gerberding that made many of the same points contained in the new EPA report (Science, 2 November 2007, p. 726). Former EPA official Jason Burnett said earlier this month that Vice President Dick Cheney's office directed the excisions because he didn't want her testimony to affect EPA's pending rulemaking, ordered by the Supreme Court, on whether greenhouse gases should be regulated due to their effects on human welfare. This month, the agency decided to punt the issue to the next Administration (Science, 18 July, p. 324).

    While that storm was raging, however, drafts of the interagency report were circulating freely on a federal Web site. Several authors, including epidemiologist and health consultant Kristie Ebi, say they experienced no political meddling while preparing the document.


    From Atop a Mountain, A Deeper Look at the Sun

    1. Yudhijit Bhattacharjee

    The world's largest solar telescope could help answer long-standing questions about our nearest star. But with environmental opposition and budgetary challenges, will it get built?

    The world's largest solar telescope could help answer long-standing questions about our nearest star. But with environmental opposition and budgetary challenges, will it get built?

    For the view.

    Some residents of Maui say adding another telescope will spoil the beauty of the Haleakala summit.


    One morning in the ancient past, a Hawaiian legend says, the demigod Maui—after whom the island is named—stood atop the Haleakala shield volcano and lassoed the rising sun. He made the Sun promise to slow its journey, giving Maui's mother longer days to dry her tree-bark cloth.

    Today, astronomers are hoping to use the Haleakala summit for a more scientific tryst with the sun. Supported by funding from the National Science Foundation (NSF), they plan to build the world's largest solar telescope there. The Advanced Technology Solar Telescope (ATST) is proposed to be 43 meters high with a 4-meter-wide mirror that will help researchers image the sun's surface in unprecedented detail. Researchers hope that observations from ATST will confirm theoretical models about the sun and answer fundamental questions such as the origins of sunspots and solar flares.

    But as the project enters its final design stage, some fear that it may never see the light of day. Some local Hawaiians are campaigning to block construction of the observatory, arguing that ATST will ruin the grandeur of a mountaintop already cluttered with a half-dozen smaller telescopes. Meanwhile, a tough funding climate combined with a spiraling cost estimate poses a serious threat to the project.

    Nonetheless, ATST's proponents within NSF and the National Solar Observatory (NSO) in Tucson, Arizona, the principal developer of the project, are pressing ahead with plans to begin construction in 2010. By the end of this year, they hope to reach an agreement with local Hawaiian groups to let the project move forward. And despite the uncertain budgetary picture, they believe ATST has a good chance of being funded, in part because the federal government has not invested in a ground-based solar observatory in decades. “This is transformational science for solar physics,” says NSO's Jeremy Wagner, project manager for ATST. “This facility can answer fundamental questions about the sun that the solar community has been chomping at its bit to answer.”

    To stare at the sun

    If it is built, ATST will be the first new ground-based telescope in a generation dedicated to studying the sun's vast, complex, ever-changing magnetic field. Solar astronomers hope ATST will reveal the contours of this field at a resolution of about 30 kilometers across the sun's surface—about five times the resolution of today's most advanced solar telescopes.

    This level of detail could help astronomers unlock mysteries such as why sunspots occur where they do, why their numbers wax and wane on an 11-year cycle, and what suddenly causes coronal mass ejections—huge outpourings of hot solar gas that can destroy satellites, disrupt power grids, and jeopardize space flights.


    The sun is also the most accessible laboratory for studying astrophysics, solar physicists say. “We have no way of studying other stars in detail,” says Robert Rosner, a solar astronomer at the University of Chicago and a co-principal investigator on the ATST project. “With the sun, we have an opportunity to actually look at fundamental processes such as the generation of magnetic fields.”

    Efforts to build high-resolution solar telescopes run into the distorting effect of air turbulence on light collected by the telescope. ATST's designers counter this problem with a deformable mirror, mounted so that 1000 actuators flexing 1000 times per second can bend it to bounce off the light at the precise angles needed to correct for atmospheric distortion. “It's similar to how noise-cancellation headphones work,” says Robert Hubbard, an engineer with NSO. An ensemble of 12 mirrors, including the deformable one, will ultimately guide the column of light into a charge-coupled device camera. Because magnetic fields polarize light in specific ways depending on their strength and direction, scientists will be able to map the magnetic field of the solar area being imaged.

    By the time NSF officials picked the Haleakala site as their top choice out of six finalists, Haleakala's long sunny days, clear, tranquil skies, and dust-free environment had long made it a popular site for astronomers. A 7-hectare expanse on the summit, managed by the University of Hawaii, is home to one nighttime observatory and two privately funded solar observatories run by the university; a U.S. Air Force surveillance observatory; and a robotic telescope run by the Las Cumbres Observatory Global Telescope Network.

    Taking the heat

    Many native islanders, however, resent the presence of so many telescopes on the mountain and don't want to see another one built. Officials of the Haleakala National Park, which borders the site, have raised concerns that the project could harm the park's environment and spoil the view for park visitors. In a letter sent last year to the National Science Board (NSB), NSF's oversight body, the National Park Service complained that NSF was ignoring issues such as the threat to native plant and animal species on the mountaintop—including the Hawaiian dark-rumped petrel, an endangered bird that nests there. NSF officials say these concerns are being addressed in an ongoing impact assessment: For example, there is a plan to monitor the nests with video cameras to determine if construction might be disrupting the birds' nesting cycle.

    Cultural impacts might prove to be a bigger problem. As a designated historical site, the Haleakala summit is protected under the National Historic Preservation Act (NHPA). In 2005, after NSF officials announced that Haleakala had been chosen for ATST, agency officials began holding public meetings with islanders to discuss ways of mitigating the environmental and cultural impact of the project—a process required by NHPA. The leaders of ATST were keen to start these consultations early, especially in light of vehement opposition to a proposed NASA telescope atop Mauna Kea on the Big Island.

    Kiope Raymond, a professor of Hawaiian studies at the University of Hawaii's Maui Community College, was hired as an interpreter for one of the early meetings. “I had no idea at the time what the project was about,” says Raymond. Over 3 nights, he listened as NSF officials made presentations about the project and took questions from local citizens. “I was incognito to the NSF people—they thought I was on their side,” he says. “And I heard them making remarks to the effect that the project was a done deal and that the public meetings were simply a formality. They were simply going through the motions.”


    Angered, Raymond joined a growing public campaign against the project. Last year, he and a handful of other citizens founded Kilakila o Haleakala (Majestic is Haleakala), an organization dedicated to blocking further development on the mountaintop. He argues that besides taking away some of the summit's awe-inspiring natural beauty, this will inevitably damage the “spiritual connection” that native Hawaiians feel with the place.

    Not all opponents of the project are that uncompromising. Some community leaders have put forth proposals for mitigation such as NSF funding for a center for traditional Hawaiian navigation and astronomy. A proposal from the Maui Community College asks the federal government to provide funding for improving science and math education on the island.

    “We have also discussed measures like limiting the lifetime of the telescope to a certain number of years and steam-cleaning all vehicles that go up to the construction site to minimize harm to its sacredness,” says NSF's Craig Foltz, program officer for the project. He says efforts are under way to negotiate an agreement with different citizens groups before the end of the year.

    Even if no agreement is reached, the project could still go forward, says NSO Director Stephen Keil. “All that we are required to do under NHPA is show that we went through the process of considering environmental and cultural impact,” he says. Officials expect a final environmental impact statement to be ready by the end of the year.

    However, opponents say proving that the process was duly followed may itself be tricky, leaving the door open to legal challenges like the one that scuttled the NASA project on Mauna Kea. Indeed, the Advisory Council on Historic Preservation in Washington, D.C., sent a letter to NSF last week asking the agency to justify why it did not wish to consider alternative sites for the telescope.

    The fire next time?

    Meanwhile, even though NSB last year added ATST to NSF's queue of future initiatives, funding for the project is by no means assured. NSF has asked Congress for $2.5 million in fiscal year 2009 to complete the final design of the facility; it must now pass a final review by the NSF director and NSB before the agency asks Congress for construction money for the project. If all goes smoothly, Keil and others expect NSF to ask for construction dollars in its 2010 request.

    But the project will be competing for funds in a tight budget. ATST's architects have had to explain why its estimated cost, currently $253 million, has more than quadrupled since the telescope was first proposed 9 years ago. They pin the increase partly on spiraling steel and concrete costs.

    ATST also faces competition from a dark-sky astronomy project: the $389 million Large-Aperture Synoptic Survey Telescope, currently undergoing a preliminary design review after which it will be considered by NSB. “NSF obviously has a limited budget and may not be able to fund multiple astronomy initiatives in parallel,” says Foltz. “Solar astronomers could argue that the nighttime astronomy community is already getting the Atacama Large Millimeter Array [an international telescope project in Chile]; they have had Gemini [a twin-telescope observatory]—whereas this is the first ground-based solar telescope being funded by the federal government in 30 years.”

    That's exactly the argument Rosner makes in support of ATST. “In a world where there is an infinite amount of money, everybody gets to play, but when resources are constrained, disciplines need to take turns,” he says. “We think it's the turn of the solar community now. We think ATST's time has come.”


    Building a Scientific Legacy on a Controversial Foundation

    1. Jeffrey Mervis

    Most scientists deplore the practice. But the first wave of congressional earmarks for academic research created two centers that have stood the test of time.

    Most scientists deplore the practice. But the first wave of congressional earmarks for academic research created two centers that have stood the test of time

    Pouring it on.

    Molten waste is poured from a platinum container as part of a process developed at Catholic University's Vitreous State Laboratory, built with a congressional earmark. (Overleaf) Lab director Ian Pegg holds a chunk of material after vitrification.


    BOSTON—Age-related macular degeneration (AMD) is the leading cause of blindness among older adults in Western countries, and a major study has shown that antioxidants and zinc supplements may slow its progression. But last year, after poring through data from that study, the U.S. government-funded Age-Related Eye Disease Study (AREDS), Tufts University protein chemist Allen Taylor found preliminary evidence suggesting another way to stop this vision killer: Cut your intake of dietary carbohydrates. White bread and other foods with a high glycemic index, he argues, contribute to AMD by destroying proteins in the retina and lens and making them less able to remove damaged tissue.

    Taylor is a long way from winning over his colleagues. “He's identified an interesting association that needs to be replicated. But it could be only an epi [secondary] phenomenon,” says Frederick Ferris, clinical director of the National Eye Institute, which funded AREDS and is about to launch a follow-up to test the value of other nutrients in slowing the progression of the disease.

    Such skepticism is normal for human nutrition studies, which are notoriously hard to interpret. That's no problem for Taylor, head of the vision lab at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University. The center is the only U.S. research facility focused on the intersection of nutrition and older adults, and the financial support from the U.S. Department of Agriculture (USDA), combined with outside grants, helps Taylor and his colleagues pursue the type of long-term studies needed to unravel these complex relationships. It's also the product of the first major modern congressional earmark for basic science.

    Earmarks—directives by Congress to fund specific projects that have not been requested by an agency nor vetted by congressional committees—have traditionally been used by legislators to build roads and other civic projects in their districts. They are often disparagingly called pork-barrel projects. Thirty years ago, Jean Mayer, then president of Tufts, hired a fledgling Washington, D.C., lobbying firm to persuade the U.S. Congress to fund academic research this way. The resulting $32 million appropriation allowed Tufts to build a commodious home for the nutrition center—a 14-story glass-and-stone structure on the university's health sciences campus in downtown Boston that includes a hospital and medical and dental schools.

    Some 700 kilometers to the southwest, on the tree-lined campus of the Catholic University of America (CUA) in northeast Washington, D.C., Ian Pegg enjoys the fruits of another early example of a federal research earmark. In 1983 and 1984, his university—aided by the same firm, now Cassidy & Associates, that persuaded legislators to fund the Tufts center—received $14.2 million to erect a four-story science building. In addition to housing the physics department, previously scattered around campus, the building is home to the sprawling Vitreous State Laboratory (VSL) that Pegg directs.

    Most scientists, and their professional organizations, look down their noses at earmarks. They see them as a threat to the merit-review process that most federal agencies use to fund basic science (Science, 16 December 1983, p. 1211). Many politicians agree. Senator John McCain of Arizona, the presumptive Republican nominee for president, has made an election promise to eliminate them, calling them a waste of scarce government resources.

    But that criticism has done little to curb the flow of earmarked federal dollars to academic institutions. The CUA and Tufts earmarks, together with a similar one to fund a chemistry building at Columbia University, opened the floodgates. The amount for universities exceeded $2 billion in 2003, the last year that the Chronicle of Higher Education tallied them, and this year, AAAS (which publishes Science) calculated that the total for all types of research projects has reached $4.5 billion. “Once the genie was out of the bottle, nothing could put it back,” says Robert Rosenzweig, a former president of the Association of American Universities (AAU), who in 1983 led the first academic protest against this new phenomenon. “In some ways, it's remarkable that universities had abstained for so long.”

    Earmarks tend to recede from the news once the money has been allocated. So Science wondered what had become of the two projects often credited with launching the earmark era in science. Was the research sustainable once the earmark was spent? If so, has it influenced the course of research?

    There's no way to know if the Tufts and CUA earmarks were typical or whether the money would have been better spent if it had been awarded in the type of competitive process that most scientists prefer. But there's abundant evidence that both projects have evolved to occupy unique niches. The Tufts center has contributed to an understanding of nutrition and aging, and the CUA earmark has improved the U.S. capacity to immobilize the detritus of its nuclear weapons program.

    “I'm not in favor of earmarks, but this one [at Tufts] was certainly a good investment,” says Walter Willett, a Harvard University epidemiologist who has worked with Taylor. “A lot of what they are doing may not be sexy, but it's critically important.”

    “Ahead of its time”

    The Jean Mayer nutrition center sits on the edge of the crowded, commercial Chinatown section of Boston. It contains office and lab space for 68 scientists and a total of 340 employees, as well as living, recreational, and eating accommodations for volunteers participating in clinical nutrition trials. The in-house facilities allow scientists to closely manage the diets of patients enrolled in dozens of studies every year. “We're a Noah's ark for diseases that affect the elderly,” says Taylor, who joined the center when its building opened in 1982. “There's one scientist working on this and two working on that.”

    Mayer, a prominent nutrition scientist, hatched the idea for a federally funded center shortly after leaving Harvard to become president of Tufts in 1976. He had helped organize the 1969 White House Conference on Food, Nutrition, and Health and thought that nutrition could become a signature program for the university. USDA was already conducting nutrition research at its Beltsville, Maryland, facility, and Harvard and the Massachusetts Institute of Technology (MIT) in Cambridge had more prominent academic programs at the time. But Mayer believed that the government needed an academic-based center to study the relationship between aging and nutrition and that Tufts was the best place for it.

    To promote the idea, Mayer hired Kenneth Schlossberg and Gerald Cassidy, who had just opened up shop as lobbyists after staffing a Senate select committee on nutrition that grew out of the White House meeting. Together, they won over the powerful Massachusetts congressional delegation and House Speaker Thomas “Tip” O'Neill, whose district included Tufts. After O'Neill squashed a last-minute attempt by the other Boston-area schools to make it a multicampus center, Congress ordered the agriculture secretary to establish both a comprehensive human nutrition research program that would expand the department's existing efforts and a facility at Tufts that would focus on adult nutrition. One year later, in 1978, legislators committed construction money and put the project under a new science and education division at USDA that included its Agricultural Research Service (ARS).

    “[Tufts] would not have done it on their own,” says center director Robert Russell, who was recruited in 1980 by the founding director, Hamish Munro, a protein chemist at MIT. “Neither would a large, hard-to-move bureaucracy like USDA. But I think they are proud of what we have done.”

    “It's an outstanding center,” agrees Joseph Spence, former head of the human nutrition program and now area director at ARS, which provides $12.7 million a year for program activities. “We don't have clinical capabilities at Beltsville. By establishing a center at a medical school, we were able to combine agricultural production with human nutrition. And the emphasis on aging was ahead of its time.”

    The idea for a center was a no-brainer to Russell, a gastroenterologist then at the University of Maryland who was running a clinical nutrition program at a Veterans Administration (VA) hospital at the time. “[Munro] wanted to study the links between nutrition and age-related degeneration and the chronic diseases of aging,” recalls Russell, who is leaving this month after 27 years at the center, the last seven as its director. “I was working with a malnourished VA population. And when I looked at the pending demographic changes, I realized that we would be entering uncharted territory.”

    Part of that growth involved defining the center's boundaries and scope. “USDA wasn't anxious for our people to apply for NIH [National Institutes of Health] grants because they wanted it to be a USDA program,” says Russell. “So we had turf battles.” Irwin Rosenberg, a gastroenterologist who succeeded Munro as director in 1986, also struggled to carve out a medical niche within the agriculture community. “I fought with USDA when they said, ‘NIH does disease; you should do healthy people.’ They were reluctant for us to use words like ‘osteoporosis’ or ‘Alzheimer's.’ But we eventually won those battles”—and access to NIH funding—says Rosenberg.

    Outsiders concur that the first few years were rocky. “They got off to a slow start, but under Rosenberg's leadership things really picked up,” says nutrition scientist Cutberto “Bert” Garza, a senior official at Boston College who has managed food and nutrition programs around the world. And Garza has a quick answer when asked how they succeeded: “They did it like any university, by recruiting better people.”

    The approach has translated into a steady stream of outside funding, including hard-to-get NIH grants. As of last year, for example, 18 researchers at the center had a total of 25 active R01 grants, the bread-and-butter NIH award for individual investigators. And their success rate for the past 3 years has been 28%, an enviable achievement given the stiff competition for NIH's flat budget. Overall, the center now receives almost half of its $22 million annual budget from other sources.

    Aging well.

    Robert Russell and Irwin Rosenberg flank a bust of the late Jean Mayer, who obtained an earmark for Tufts to build the USDA Human Nutrition Research Center on Aging that bears his name. (Inset) An 84-year-old volunteer exercises during a study.


    Still, the center couldn't do its job without USDA's annual contribution. “It's a commitment that's rare in nutrition research outside of a hospital,” says Rosenberg, who stepped down as director in 2002 but maintains an active research program. “It gives us an institutional base for planning human nutrition research on a scale of a decade rather than just a few years.”

    Unfortunately for the center, that contribution has remained flat for the past several years even as the cost of research has risen. As a result, Tufts officials were forced to lay off six people last year, and Russell says the gloomy fiscal outlook is one reason—along with his age, 67—that he's stepping down as director: “The job is a lot more fun when the money's rolling in.” Russell is joining NIH's Office of Dietary Supplements to work on strategic planning.

    Nevertheless, the university hasn't lost faith in the center. Mary Teka, Tufts's vice president for university relations, says she spends “a fair amount of her time every year” shoring up support among the Massachusetts delegation for ARS's human nutrition program by disseminating the center's accomplishments. “This is a very high priority for the university, and we want to maintain its high quality,” she says.

    Clear solutions

    Hidden in plain sight in the middle of the CUA campus, the VSL fills the warehouse-sized basement of a four-story building. The lab's most notable feature is a 10-cubic-meter tank, holding 2000 kilograms of molten glass maintained at 1150°C, that is a one-third-scale prototype of the melter system being built for the $12 billion Waste Treatment and Immobilization Plant (WTP) in Hanford, Washington. Its job is to help dispose of 200 million liters of radioactive and chemical waste now sitting precariously in 177 metal tanks in Hanford. Through their work on characterizing the properties and composition of glass, VSL scientists have a long and successful record of contributing to government projects aimed at immobilizing nuclear waste.

    The university got into the nuclear cleanup business by accident. In 1967, the physics department won a competitive grant from the Department of Defense as a center of excellence in glass science to apply its work to potential military hardware such as night-vision sensors and high-powered lasers. The scientists—Theodore Litovitz and two of his students, Charles Montrose and Pedro Macedo—decided that the $600,000 award, a princely sum for those days, warranted a more formal name for their workplace.

    The grant helped the group, renamed the Vitreous State Lab with Litovitz as director, become a pioneer in fiber optics. Working on ways to improve the refractive index of the glass fiber to enhance the flow of light along the cable, the scientists replaced the sodium in the glass with potassium and, then, cesium. But the ability to extract cesium from solution also turned out to have important applications in cleaning up the vast amounts of water used by commercial nuclear power plants, which produce isotopes of cesium that are radioactive. Further refinements of that ion-exchange technique were licensed to a spinoff company, Duratek, which went public in 1984 and last year became part of Energy Solutions, a nuclear fuel cycle company based in Salt Lake City, Utah.

    Pegg says the university wouldn't have built a new home for the lab on its own. “We weren't at the top of its list of priorities, that's for sure,” he admits. But CUA President William Byron decided to use the school's unique status as “The” Catholic University to seek help from Speaker O'Neill in addressing the lab's pressing need for more space to handle a growing workload. He hired Cassidy and Schlossberg, who also took on Columbia University as a client. In 1983, each school received a $5 million down payment—CUA got the rest the next year, and Columbia ended up with $20 million for a chemistry building—with the money carved out of the Department of Energy's science budget.

    More than 20 years after he joined the lab, Pegg says colleagues still ask what attracted him to CUA. The answer, he says, is its unwavering focus on glass sciences. That's increasingly rare in a discipline now dominated by materials science departments, says the British-born Pegg, who was trained as a physical chemist at the University of Sheffield, U.K. And staying the course has paid off for him and the lab.

    In the 1990s, Duratek joined with VSL to carry out the only completed pilot project to date of the technology chosen by the federal government to vitrify—immobilize in glass—such hazardous wastes. The lab is currently providing technical support for the company's role as a subcontractor for a piece of the WTP project, the last stop for the waste before it is entombed in an underground repository in the Nevada desert.

    The lab's extensive facilities for the characterization and testing of materials, including five glass melters, are unusual for an academic setting. But they are well-suited for the WTP project, which, after several delays, is now scheduled to be completed in 2019. “They're known for their scientific acumen, and the work they do for us is geared to solving specific problems,” says Ivan Papp, a process engineering supervisor for Bechtel National Inc., the main contractor for WTP. In the past 7 years, for example, VSL scientists have tested some 500 glass formulations tailored to the different types of waste that must be processed.

    Since moving into its new digs in 1987, the lab has employed as many as 110 people, on a budget of $13 million. That peak came in 2003, at the height of its work for Duratek on the Hanford project. The current staff of 67 includes 30 Ph.D.s, of whom five are tenured or tenure-track faculty members in the physics department. Although VSL scientists publish regularly, the lab's emphasis on contract work limits the scope of their research. “The scientific impact of their work is not so evident,” says Rod Ewing, a mineralogist and materials science professor at the University of Michigan, Ann Arbor, and co-chair of a 1995 National Research Council workshop on the topic.

    Ewing says the science of vitrification is more advanced in France and elsewhere in Europe because of the contrasting requirements for vitrifying and entombing their nuclear waste. “In the United States, the emphasis is on making a consistent product and relying on the container to last a long time, so the glass is less important,” he says. “In contrast, the French are trying to understand the long-term behavior of the glass within a repository and the conditions that would affect its long-term durability.”

    Pegg doesn't dispute Ewing's assessment, but he thinks Ewing is comparing nuclear apples and oranges. “In France, they reprocess the waste, extracting the uranium and plutonium before converting it into glass,” says Pegg. “The glass itself is the barrier. In the United States, the waste is mostly fuel assemblies, coming straight out of the reactor. So the repository has to be the barrier.”

    An uphill fight

    Back at Tufts, Taylor and his colleagues are collecting evidence from animal and in vitro studies and combining it with data from population studies in other countries that have found a similar correlation between dietary carbohydrates and AMD. He suspects that excess carbohydrates or their derivatives modify retinal (and lens) proteins, rendering them less functional. They also modify the proteases (protein-degrading enzymes) that would otherwise recognize and eliminate the damaged proteins.

    A costly legacy.

    Congress approved $4.5 billion this year for research earmarks, continuing a 30-year upward trend that began with Tufts.


    Paul Mitchell, a professor of ophthalmology at the University of Sydney, Australia, who leads a longitudinal eye study in Australia that has found a high glycemic food index to be an independent predictor of the risk of AMD, believes that dietary carbohydrates will turn out to be as important as antioxidants for the general population. (Among smokers, cigarettes are by far the leading cause of the disease.) And he credits Taylor for making an important contribution to understanding the importance of the dietary glycemic index, a topic that he says “is a real buzz area of medicine.”

    Because none of the researchers and administrators now at Tufts and Catholic universities played any role in obtaining the initial money for their school, none feels the need to justify it. For them, the enabling earmark is a piece of historical trivia. Not so for former president of AAU Rosenzweig. Although he's long since retired from the science policy arena, the subject can still get his blood boiling.

    Rosenzweig came to AAU in 1983, when CUA and Columbia won their much-publicized earmarks. He mounted an immediate counterattack. “It sent a message,” he recalls. “If Columbia could do it, then it was all right for everybody else.” In October 1983, the AAU presidents passed a resolution in favor of the “processes based on the informed peer judgments of other scientists.” The vote was unanimous, as Byron and Columbia's president, Michael Sovern, abstained.

    Rosenzweig's prediction came to pass, and for better or worse, earmarks are now a firmly established feature on the federal science landscape. Whether individual projects have been successful isn't the issue, says Rosenzweig. “I never heard a university say that the money wasn't going to a worthy project,” he says. “And I never challenged the work itself. What I said was, ‘If you're spending government resources on something as important as research, then you should have a process that assures it is put to the best use.’ Looking back, I feel justified in leading the fight, … for all the good it did me.”


    Water Everywhere on Early Mars But Only for a Geologic Moment?

    1. Richard A. Kerr

    Planetary scientists pursuing water and life on Mars must reconcile mounting evidence of a young planet awash in life-sustaining water with a growing realization that the martian surface was likely almost always dry.

    Planetary scientists pursuing water and life on Mars must reconcile mounting evidence of a young planet awash in life-sustaining water with a growing realization that the martian surface was likely almost always dry

    The early Mars of human imagination has swung from invitingly moist to brutally dry and back again more than once in the past half-century. Hopes for some sign of life that might have struggled into existence in that first billion years of martian history have likewise been alternately buoyed and dashed. In recent years, much of the news has been decidedly wet: a shallow, salty sea, rivers languidly flowing into crater lakes, and an exploding palette of spectral colors denoting water-altered minerals.

    Most of these sorts of once-wet martian features are in the running to be the lone landing site for the next U.S. Mars rover, the $1.9 billion Mars Science Laboratory (MSL). Its mission: “follow the water” to understand whether the planet has ever been able to support microbial life.

    But while the media were touting these striking examples of “sustained” liquid water on early Mars, less heralded evidence has been pointing to far less hospitable conditions. “I'm absolutely convinced there were periods of time when there was a very moist climate,” says longtime Mars geologist Michael Carr of the U.S. Geological Survey in Menlo Park, California, but “I'm skeptical the wet conditions were persistent.” In fact, says Mars fluvial geologist Robert Craddock of the National Air and Space Museum (NASM) in Washington, D.C., “the thinking has shifted to maybe punctuated, short-lived” episodes of warm and wet conditions. The rest of the time—maybe 999 years out of 1000—the surface of Mars would have been cold and drier than any desert on Earth and less hospitable to life.

    Dry, with wet moments

    The vision of a wet early Mars got a big boost in 2004 when the Opportunity rover spied fossil sand ripples now exposed on the Meridiani Planum of Mars. Only water flowing on the surface—not groundwater—could have formed ripples with their particular shapes. So was born the “shallow, salty sea” of early Mars, which has been drying up ever since. Rover team members have been increasingly emphasizing that almost all of the salty sediments of the Opportunity site were laid down as windblown dunes that were later altered by briny, acidic groundwater (Science, 5 January 2007, p. 37). That groundwater may have oozed to the surface to puddle between dunes once in a great while, allowing those water-formed ripples to form, but even then it may have been too briny for even the most salt-tolerant life known on Earth (

    Wet, but only briefly.

    The “warm and wet” times when water cut this valley network could have lasted mere centuries.


    Another way to have sustained, continual water flow on the surface of Mars has also lost ground of late. Imaging by the Viking orbiters in the late 1970s revealed so-called valley networks—branching channels up to several hundred meters deep—that formed during the Noachian geologic era of Mars, roughly the planet's first billion years. Many planetary geologists thought the channels were carved by water seeping up from underground. Springs emerging at the head of each valley would have weakened the rock of the valley head wall, causing it to collapse into an amphitheater shape, then the spring water would have slowly eroded the debris away. Such seepage, or “sapping,” was supposed to have formed some similar amphitheater-headed canyons on Earth. But a recent study published in Science (23 May, p. 1067) presented strong evidence that one classic sapping valley, Box Canyon in Idaho, resulted from one or more catastrophic floods.

    Now most experts think the treelike, twig-to-branch-to-trunk valley patterns on early Mars came about the same way most such patterns do on Earth: as drainage systems of rain-fed streams and rivers. But how could even the scarce rain of, say, the Nevada desert—going on for the better part of a billion years—leave so much of early Mars still standing? “Maybe Mars wasn't even like Nevada,” says planetary geologist Ross Irwin of NASM. Maybe it was only something like Nevada once in a great while.

    Fluvial geomorphologists Sanjoy Som and David Montgomery, both of the University of Washington (UW), Seattle, presented some of the latest evidence for such ultrarare rain at the Astrobiology Science Conference in Santa Clara, California, this past April. Using orbital imaging and altimetry, they compared signs of how water had flowed through 10 of the largest martian valley networks with flow-related characteristics of terrestrial drainage systems. For example, prolonged flows on Earth tend to widen channels and flatten their slopes downstream. The researchers concluded that even in the Noachian, Mars was much as it is today—cold and dry—with only rare episodic gushes during brief warm and wet intervals.

    Early Mars was like the Atacama Desert of the high Andes, only more extreme, says planetary scientist Tomasz Stepinski of the Lunar and Planetary Institute in Houston, Texas. Stepinski says the UW analysis supports conclusions he and others had reached earlier by mathematical analyses of valley network patterns: “If there was precipitation, it was probably in the form of bursts. Mars didn't have the time to develop the intricate [drainage] patterns seen on Earth.” Instead, he says, martian erosion works the same way it does on the Atacama: by prolonged dryness punctuated by an extraordinary gully washer of a storm.

    On Mars, “it probably wouldn't have taken millions of years” of rainfall to carve the valley networks, says Craddock. “Our best estimate is that valley networks were only active hundreds or at most thousands of years. It may have been punctuated events scattered over a long time of martian history.”

    Paradoxical puddles

    While valley networks were pointing toward an almost-always-dry early Mars, planetary scientists were also finding signs that early Mars was wet—so wet that water drained into crater lakes. Press releases heralded this evidence for “pervasive and long-lasting” wetness that had “the potential to support life.” But some researchers say that those lakes—which include three or four out of seven sites in the final running for the MSL rover landing—could have filled and dried up again within a geological moment.

    The latest evidence for a persistent lake on early Mars comes from 45-kilometer Jezero crater, planetary scientists Samuel Schon, Caleb Fassett, and James Head of Brown University reported at the Lunar and Planetary Science Conference in Houston last March. Examining the latest high-resolution images from Mars Reconnaissance Orbiter (MRO), they point out features—such as distinctive cross-bedding of sediment layers—that form only when river channels meander across a delta building out into a lake. And delta channels can meander only if the standing water the delta is growing into remains more or less steady at one level. That implies a “long-lived” lake in Jezero crater, the group says, much as proposed for 65-kilometer Eberswalde crater, a potential MSL target.

    The problem is that no one can put a number on “long-lived.” “There's almost no question these [crater] deposits are fluvial,” says fluvial geomorphologist Douglas Jerolmack of the University of Pennsylvania, but “there's also a lot of evidence they could have been done very rapidly.” In 2004, Jerolmack and colleagues used a computer model to estimate that Eberswalde's fan of sediment could have formed in several decades to centuries. Fluvial geomorphologists Montgomery and Craddock both agree that geologists could well be looking at lake deposits built up by one or more brief gushes down valley networks like the one that fed Jezero.

    Watery colors

    The latest watery news of early Mars came last week, when Nature published the most comprehensive spectral survey yet of Mars, setting off a media storm. The MRO spectrometer discovered the spectral signatures of clays—the product of prolonged water weathering of rock—at a couple of thousand sites. Mars was a warm, soggy, water-logged planet for hundreds of millions of years in its early history, news stories proclaimed.

    How persistent?

    The sediment-laden flows that formed Eberswalde delta could have been short-lived.


    The Nature paper by planetary scientist John Mustard of Brown and 35 MRO colleagues was a good bit more restrained than its media coverage. Although it pointed to the existence of clays, it never placed them definitively on the surface of the planet. Primitive life might have arisen in the subsurface, Mustard notes, ever so slowly feeding on chemicals from the rock. But nothing in the spectral data contradicts the valley network picture of a surface almost always dry.

    If the “punctuated precipitation” model is correct, how did Mars generate such rare, geologically momentary episodes of rain? Some researchers credit cosmic collisions. In a 2002 Science paper, planetary scientist Teresa Segura of Northrop Grumman Space Technology in Redondo Beach, California, and colleagues proposed that large asteroids or comets striking the martian surface flung hot rock and rock vapor around the planet; the heat vaporized water and ice stored beneath the surface and in the polar caps, driving it into the atmosphere (Science, 6 December 2002, p. 1866).

    Not everyone was convinced. “I had problems with the Science article,” says Craddock, as did others. The atmospheric physics of Segura's model was incomplete, some noted, and the very large impacts they modeled would have come too early in Mars's history to explain the observed fluvial geology, among a number of criticisms.

    Segura and colleagues listened and are back with a new and improved paper that is in press in the Journal of Geophysical Research. They added more atmospheric processes to their model and considered smaller, later arriving impacters. The more detailed model supports the conclusions of the earlier one: Impact-induced greenhouse conditions could have lasted for centuries, driving up to 18 meters of rainfall. The group calculates that rainfall due to Noachian impacts would have eroded away at least 50 meters of the planet's surface—roughly the amount of erosion that planetary scientists estimate actually occurred. The once-doubtful Craddock thinks that “what they've done now is the best solution we have. Now we need to test it a little.”


    Voting: In Your Genes?

    1. Constance Holden

    At the Behavior Genetics Association meeting, a political scientist presented evidence that DNA has a hand in the intensity of people's partisan political attachments and even in whether they bother to vote.


    How strong do you lean?

    Twin studies suggest that the intensity of a person's partisan attachment, and even whether that person votes, may be influenced by genes.


    Behavior geneticists say almost every human behavior that can be reliably measured—from TV-watching to optimism—is significantly influenced by genes. Now they're extending their reach into the voting booth.

    Numerous studies over the past 2 decades, the first led by psychologist Nicholas Martin at the Queensland Institute for Medical Research in Australia, have indicated that genes have a significant influence over whether you're “liberal” or “conservative” on various political and social issues. Some heritability estimates have been as high as 50%. That's roughly the heritability found for many personality traits such as “extraversion” or “agreeableness,” and it implies that, in a given population, about half of the variation in a particular trait is attributable to genetic differences.

    Now James Fowler, a political scientist at the University of California, San Diego, and grad student Christopher Dawes say they've produced fresh evidence that DNA also has a hand in the intensity of someone's partisan attachment and even in whether someone bothers to vote.

    As they reported here, they did that by crunching data from twin registries and the government's long-running National Longitudinal Study of Adolescent Health (NLSAH). In one study, the researchers matched data on voting by 396 Los Angeles-area twins, including identical (who share 100% of their genes) and fraternal (who average 50% genetic overlap) twins, obtained from Los Angeles voter-turnout records. All twins were same-sex pairs to avoid confounding results with sex differences. The researchers corrected for environmental factors such as whether more of the identical than fraternal twins were living together, which might inflate their degree of similarity. The researchers concluded that the correlation for voting was much higher between pairs of identical (.71) than fraternal (.50) twins. From this they estimated the heritability of voting behavior—that is, whether people eligible to vote actually do so—at 53%, suggesting that at least half the individual variation can be traced to genetic influences. They found an even higher heritability—72%—when they replicated the study with data on 806 twins from NLSAH, they reported in the May issue of the American Political Science Review.

    The San Diego researchers also argued for a biological twist to how strongly someone identifies with a given party. The group, led by grad student Jaime Settle, gave questionnaires to 353 pairs of same-sex twins in Twinsburg, Ohio, where twins from all over the world hold a summer gathering every year. The twins were asked to rank their partisan attachment on a seven-point scale. From that, the researchers report in an as-yet-unpublished paper, they calculated a heritability of 46% for party loyalty, independent of affiliation. Whereas “partisan direction” seems mainly influenced by social and demographic factors, the researchers conclude, “partisan intensity” is not.

    Several groups are now trying to correlate personality data with DNA markers from studies such as NLSAH, which contains DNA as well as behavioral data from many subjects, in hope of identifying specific genes that feed into underlying traits, such as “desire for cooperation,” that Fowler, for one, believes have been selected for throughout human evolution. Studies so far have focused on the same genes that are of interest in psychiatric genetics—in particular those involved with neurotransmitters such as dopamine and serotonin that are known to be important in regulating higher brain activities.

    The heritability studies are “intriguing,” says David Goldman, chief of the neurogenetics lab at the National Institute on Alcohol Abuse and Alcoholism in Bethesda, Maryland. But he is skeptical about attempts to translate findings from twin and family studies into molecular hypotheses. “In any questionnaire you'll find heritability,” he says, “but you don't know what's being inherited.” So “it's premature at best to attack a complex phenotype like political leanings at the molecular level.”

    Martin, who pioneered twin studies on such behaviors, applauds social scientists for plunging into biological and evolutionary issues. At least some “are starting to acknowledge that humans are genetically unique individuals and not just cloned pawns” of their environment. And that suggests that prophets and pundits, however prescient, are probably never going to get much better at predictions than they are now.


    The Sociable Brain

    1. Constance Holden

    A recent test of the "social brain theory," which suggests that human brain size was selected in particular for capabilities that are useful in social groups, found no correlation between IQ and number of friendships, according to results presented at the Behavior Genetics Association meeting.


    What was the selective benefit of a big brain? Anthropologists have long puzzled over what drove the astounding growth of the hominid brain, which, unlike that of any other primate, tripled in size over 2 million years.

    Behaviors such as language and tool use have been postulated to drive the evolution of cognitive abilities hand-in-hand with brain size. One theory that's garnered great attention has been “the social brain” proposed by University of Oxford anthropologist Robin Dunbar, who suggests that human brain size was selected in particular for capabilities, such as the ability to sense what another person is feeling, that are useful in social groups. Dunbar has backed this theory with evidence that among primates, species that form larger social groups have larger neocortexes on average.

    Timothy Bates, an evolutionary psychologist at the University of Edinburgh, U.K., decided to give Dunbar's theory a field test on a “complete social system”: 200 young primates living in Baird House, a student college at the university. “If the social brain theory is correct, head size variation between humans should be reflected in individual differences in support and sympathy group size,” he reasoned, so that people with bigger brains should have larger circles of friends.

    Past studies have shown that head size is strongly correlated with brain size (about .60), and brain size has a low but significant correlation (about .30) with IQ. (The IQ-head size correlation is even lower at about .20.) Bates and his helpers gave the male and female students IQ tests and measured their heads to get rough estimates for brain size. He also gave them personality and “theory of mind” tests to probe how well they thought they could sense the feelings and motivations of others. Finally, the students were asked to assess their relationships to everyone else in the dorm, indicate how many friends each had, and rank closeness of friendships on a scale of one to three. Bates was able to crosscheck the data by asking students to indicate which of their peers were “well-liked.”

    Social intelligence?

    People with bigger brains don't seem to have more friends, as one theory would predict. Above, an RAF pilot being measured for a uniform in 1970.


    The result? Head size correlated modestly with IQ. But neither head size nor IQ correlated with the number of friendships, Bates reported at the meeting. “Most variance in social group size was explained not by cognition but by personality traits, especially extraversion,” he says. This suggests that the human ability to form large groups may depend on selection not for advanced cognitive abilities but for “agreeable” personality traits, says Bates. The evidence in this experiment suggests that “the sole correlate of the unique size of the human brain appears to be intelligence.”

    Evolutionary psychologist Geoffrey Miller of the University of New Mexico in Albuquerque calls Bates's experiment “a creative and revealing new way to shed light on the social intelligence hypothesis”—even though it's “not a clear disproof.” Miller himself thinks “our runaway brain evolution” must have been helped along by additional factors including sexual competition and technological innovation.


    Do Good Sperm Predict a Good Brain?

    1. Constance Holden

    In work presented at the Behavior Genetics Association meeting, researchers found a low but significant correlation between IQ and sperm quality.


    Weak link.

    Is the quality of a man's sperm, played here by Woody Allen in a 1972 movie, linked to his intelligence?


    Could high-quality brains and high-quality sperm travel together? Some scientists wonder if there is a “latent fitness factor” that would cause evolutionarily desirable traits, both physical and mental, to be correlated with one another.

    Rosalind Arden, a psychology grad student at University College London, with evolutionary psychologist Geoffrey Miller of the University of New Mexico in Albuquerque and sociologist Linda Gottfredson of the University of Delaware, Newark, decided to test the question by looking for a correlation between IQ and sperm quality, a direct measure of reproductive fitness. They obtained data on sperm quantity, motility, and density from a health study of 425 Vietnam war veterans aged 31 to 44 and compared them with results of the vets' intelligence tests. After correcting for factors such as drug use, they found a low but still significant (.13) correlation, roughly the same as that for height and IQ (.15).

    Psychologist Todd Shackelford of Florida Atlantic University, Davie, is skeptical about a general fitness factor. He says there is no evidence for a correlation between sperm quality and left-right symmetry, a measure of health and physical quality, and only small relationships have been found between such measures and intelligence. Nonetheless, he says, it's “certainly an interesting area of work worth pursuing.”

  13. The Great Funding Surge

    1. Jon Cohen

    HIV/AIDS now attracts billions of dollars each year, extending millions of lives. But many remain untreated and, without better prevention, the money will soon fall short.

    HIV/AIDS now attracts billions of dollars each year, extending millions of lives. But many remain untreated and, without better prevention, the money will soon fall short

    Deep conversation.

    An HIV/AIDS peer educator works the morning shift at the BCL mine in Selebi-Phikwe, Botswana.


    A decade ago, when the wealthy countries of the world reached into their pockets to help the less fortunate combat HIV/AIDS, they came up with a mere $485 million. Last year, the HIV war chest for these developing countries, including some money from their own budgets, totaled $10 billion, more than a 20-fold increase.

    A variety of factors contributed to this extraordinary surge in funding, but one stands out: success with anti-HIV drugs. Drugs made little headway against the virus in the decade following the proof in 1984 that HIV causes AIDS. But in 1994, a study showed that AZT could prevent transmission from an HIV-infected pregnant woman to her baby. Then in late 1995, researchers reported that potent anti-HIV drugs used in combination could stave off AIDS and improve the health of those already sick. By the late 1990s, studies in Thailand and Uganda had shown cheaper, simpler ways to prevent mother-to-child transmission (MTCT) with anti-HIV drugs, and Brazil and Haiti demonstrated that if the will existed, treatment could reach rich and poor alike. But for tens of millions of people, that wasn't happening.

    At the 2000 international AIDS conference in Durban, South Africa, the issue of “universal access” came to a full boil, and the next year, the United Nations General Assembly held a special session on HIV/AIDS, sparking a global effort to increase access to, and reduce the costs of, anti-HIV drugs. Billions of new dollars from new sources began flowing into poor countries. First came the World Bank's Multi-Country HIV/AIDS Program (MAP) in 2000 that spread grants and loans with generous terms to many hard-hit spots. In 2002, the Global Fund to Fight AIDS, Tuberculosis, and Malaria—a partnership of governments, philanthropies, civil society, industry, and affected communities—opened its doors to all comers and, in a novel twist, asked governments to detail their needs and linked payments to performance. U.S. President George W. Bush the next year launched the President's Emergency Plan for AIDS Relief (PEPFAR), which quickly ramped up treatment and prevention efforts in 15 “focus” countries. The Bill and Melinda Gates Foundation made HIV/AIDS a priority, investing nearly $2 billion in treatment, prevention, and research to help the poor. In 2006, the General Assembly upped the ante and declared that every HIV-infected person in need of treatment should receive it by 2010. The response “has transformed … how the developed world partners with the developing world in addressing a catastrophic health crisis,” says Anthony Fauci, an architect of PEPFAR and head of the U.S. National Institute of Allergy and Infectious Diseases (NIAID).

    HIV-infected people around the globe are now living longer, and several communities have even seen their epidemics start to wane. “Seven years ago, there wasn't a single African on treatment from a donor program in a global pandemic of unprecedented proportion,” says Jeffrey Sachs, a health economist at Columbia University who in 2000 called the underfunding of AIDS “perhaps the most shocking feature of our generation.” Today, Sachs has toned down his chiding of the wealthy world and even applauds some of its actions. “Now there's finally a process in place and a glimmering that the epidemic is peaking. Incidence is coming down in some places, treatment is steadily increasing, and health care systems are beginning to rise from nothing.”

    But serious problems remain. Many countries, short on health care workers and infrastructure, have had difficulty building prevention and treatment programs. Several “donor darlings” have received the lion's share of aid money, while some politically troubled countries have received scant help. The Global Fund has suspended or canceled grants because of corruption. Current funding levels won't come close to providing universal access by 2010, and high rates of new infections—an indication that prevention programs are having limited success—are placing an ever-increasing demand on treatment programs. The vaccine search, the best hope for slowing HIV's spread, has failed so miserably that leaders in the field recently persuaded Fauci to shift millions slated for clinical trials to more fundamental studies. Several microbicides (topical gels to prevent transmission) similarly have proven worthless—or even harmful—in large, expensive human studies. In addition, serious questions have emerged about whether all this new money for HIV/AIDS has come at the expense of meeting other pressing health needs.


    During the past 6 months, Science has examined how the dollars are being distributed and spent. Which countries, institutions, and researchers have received the largest slices of the pie (see p. 520)? Who has been left out? Which efforts have gotten the most bang for the buck (see p. 518)? What happens when corruption surfaces (see p. 522)? What lessons can governments, clinicians, and communities learn from the smart investments, missed opportunities, and outright mistakes made by other countries (see p. 526)? And how sustainable is the massive treatment rollout now under way?

    Hard answers remain elusive, but a few common themes have emerged. Money alone does not solve every problem, but it sure helps. Unfortunately, no master logic matches the distribution of aid to those most in need. Money can do good only if it's spent in the right ways, and many agree that prevention, in particular, has been shortchanged. For each person who starts treatment, nearly three people become infected, according to recent estimates. “This is not something where you can say, ‘Okay, I fixed it,’ and walk away,” cautions Fauci. “You have to make a long-term commitment with a lot of resources, and it will only be successful if you can bring down the infection rate to a dramatically lower level than it is now. It's a phenomenal challenge.”

    Fair share?

    The Global Fund, PEPFAR, the World Bank, and the Gates Foundation have contributed the bulk of the funds to help countries cope with HIV/AIDS. An analysis by Science combined all the money contributed since 1989 by these four sources to the 29 countries with the most HIV-infected people. (The analysis omits China, India, Russia, and Indonesia because they have large populations and relatively low HIV prevalences, which means that their prevention and treatment needs differ markedly from those of the other countries.) In committed funds, the 15 PEPFAR focus countries—which account for about half of the HIV-infected people in the world—have received more than 80%. Ethiopia, a PEPFAR country that reports a relatively low HIV prevalence of 2.1%, has more committed money than any other country. Looking at disbursed dollars per HIV-infected person puts the disparities in a harsher light still. Rwanda, a PEPFAR country, has received $2015 per infected person. Disbursed funds to the Democratic Republic of the Congo (DRC), the Central African Republic, Myanmar (formerly Burma), Sudan, and Zimbabwe amounted to less than $150 per infected person; these five countries together have 3.7 million infected people—more than 10% of the global total.

    The universal-access ethos contends that everyone, everywhere should benefit equally from anti-HIV drugs, and the funding surge has ended the era in which the rich had access and the poor did not. But the billions of new dollars have created a new division of haves and have-nots within the developing world. “This large imbalance exists,” says epidemiologist Robert “Robin” Ryder of the University of California, San Diego, who co-runs the Central African portion of the U.S. National Institutes of Health-funded International Epidemiologic Database to Evaluate AIDS. As Ryder points out, six of the top 10 recipients of disbursed Global Fund money are also PEPFAR focus countries. “The rich get richer and the poor get poorer,” he says.

    Donors have sound reasons for offering little aid to some countries that have large HIV/AIDS epidemics: Corrupt governments, civil wars, and the absence of infrastructure increase the likelihood that money will be wasted. And many of the most fragile states have shaky relations with the biggest donors, including the United States, Europe, Japan, and Australia. “Foreign aid is an extension of foreign policy,” says Peter Piot, head of the Joint United Nations Programme on HIV/AIDS (UNAIDS). “It's an illusion that it's based on objective criteria. That's why I'm a big supporter of the Global Fund. It's far less influenced than others.”

    But unstable countries also have a distinct disadvantage with the Global Fund, Piot concedes, as they are less likely to be able to submit strong proposals. “We're actually funding to the maximal level that the country is asking and the level in which it can bring evidence that it can make the money work,” says Michel Kazatchkine, head of the Global Fund. “And of course the weaker the country, the greater the gap will be between demand and need.” Kazatchkine adds that the best funded countries continue to struggle, too: “Even in the countries that are darlings of Global Fund and PEPFAR and Gates, … these amounts of money are below the actual need.”

    Clean shot.

    This heroin user in Chennai, India, had access to clean needles, but many don't.


    Stefano Bertozzi, a health economist at the National Institute of Public Health in Mexico City, says the distribution of money is more rational today than in the past, but he argues that the “funding orphans” deserve serious attention. “We need to make sure countries in greatest need have access to the funds,” he says. To this end, Aidspan, a Global Fund watchdog based in Nairobi, proposed in an April report that a mentoring program of independent consultants be set up to help countries conceptualize but not write their proposals. “The Global Fund has no mechanism for saying publicly or privately, ‘The gap is huge in country X and small in country Y: What can we do to get more money to country X?'” explains Bernard Rivers, who heads Aidspan (see sidebar, p. 524). “They're very hands-off. They can't say, ‘Help us to help you to write a great proposal so we can get you a lot of money.’”

    Measuring impact

    Donors and researchers have tried to assess the impact of the funding surge and disentangle the overlapping investments. A few clear success stories have emerged, such as prevention of MTCT and reduction of deaths in Botswana. But hard data about reduction in new infections from sexual transmission, and direct evidence that mortality and morbidity have dropped on a country level because of anti-HIV drugs, are the exception to the rule.

    PEPFAR and the Global Fund regularly report results of their investments, and the World Bank does periodic assessments. The Gates Foundation, a private philanthropy that does not have to answer to constituents, offers little information about the impact of its programs.

    As of June 2008, PEPFAR says it has prevented 7 million infections, trained some half-million care providers, and “supported” the anti-retroviral (ARV) treatment of 2 million HIV-infected people and the care of 10 million others. The word “support” underscores that PEPFAR often cannot separate its contributions from those made by the Global Fund and domestic spending.

    The same month, the Global Fund reported that it had provided anti-HIV drugs to 1.75 million people, helped 2.8 million orphans, provided counseling and testing to 46 million people, and trained 7.6 million people to provide care for HIV/AIDS, TB, and malaria in 136 countries. The World Bank has calculated that 40% of its MAP funds in Africa have gone to “strengthening systems,” which includes everything from training staff of nongovernmental organizations (NGOs) to building infrastructure to improving the supply chain of drugs and testing kits. About one-third of the bank's money went to prevention efforts, “contributing” to the enrollment of some 1.5 million HIV-infected pregnant women in programs to thwart transmission to their babies. Only 16% of bank funds supported care and treatment, accounting for a modest 27,000 people on anti-HIV drugs by the end of 2005.

    Last year's annual UNAIDS update illustrates the difficulty of determining on a country level the impact of funding. Kenya, which has received ample support from PEPFAR and the Global Fund, had sharp drops in prevalence that appeared in part related to changes in behavior. But so did Zimbabwe, which is not a PEPFAR focus country, has received relatively little from the Global Fund, and, all told, has taken in one-seventh as much aid per infected person as Kenya. Roeland Monasch, a UNICEF representative in Zimbabwe who helped that country prepare a successful Global Fund proposal, says one of the factors accounting for the drop may be the economic crisis. “There's much less mobility of people in the country, and men can't afford girlfriends and to travel up to the country in the weekend,” says Monasch.

    Recognizing reality.

    Peru acknowledges that men who have sex with men are at high risk—and recruits them for an AIDS vaccine study.


    Ryder contends that the skewed funding to the darlings also undermines attempts to assess the effectiveness of ARV treatment in lowering mortality rates. He notes that PEPFAR focus countries such as Rwanda have the resources to track people who are on anti-HIV treatment, whereas poorer countries such as the DRC don't. “It really affects assumptions about efficacy,” says Ryder. Say researchers in Rwanda discover that a woman on treatment died from AIDS, whereas if that same woman lived in the DRC, she might be “lost to follow-up” and excluded in the final analysis. “It's paradoxical,” says Ryder. “The more money you put into a country, the more likely you are to show a higher death rate because you have the wherewithal to know someone died.”

    Strengths and weaknesses

    The “big three” publicly funded HIV/AIDS efforts—the Global Fund, PEPFAR, and the World Bank's MAP—have all received intense scrutiny—but PEPFAR has attracted by far the most, in part, says Bertozzi, because of initial skepticism about an ambitious new program created by Bush, who many thought had shown little interest in the HIV/AIDS epidemic.

    PEPFAR has won over many doubters because of the speed with which it delivers treatment and prevention. Yet some of PEPFAR's policies have dismayed researchers and HIV/AIDS advocates, who contend that they promote Bush's religious and political agendas while disregarding scientific evidence on which interventions work best. In particular, critics have assailed PEPFAR for emphasizing abstinence-only education, which they say does little good, and requiring recipients to sign a pledge against prostitution that they say further stigmatizes sex workers and discourages prevention outreach efforts geared toward them.

    Hands-on training.

    A woman at a brothel in Guatemala City shows an outreach worker that she's condom savvy.


    Another concern is that PEPFAR funnels much of its aid through international NGOs—big winners are the U.S.-based Family Health International and Management Sciences for Health—instead of trying to strengthen in-country capacity. In an April 2008 report, epidemiologist Nandini Oomman and colleagues at the Center for Global Development, an independent think tank in Washington, D.C., noted that about 70% of PEPFAR funds have gone to international organizations, many of them faith-based. Says Oomman, “If you're thinking about a sustainable long-term response, you really do have to think about how you develop local capacity.”

    PEPFAR's head, Mark Dybul, concedes that some investments are skewed to international NGOs, but he says that's what an effective emergency response requires. “You don't respond to a tsunami by just sending money to a country and hoping that they take care of all the problems,” says Dybul. And he says that in countries like Uganda that have “more mature” epidemics, this skewing doesn't occur because they have had time to develop their local response. “It takes a while to build capacity,” Dybul says.

    As Science went to press, Congress was expected to reauthorize PEPFAR for the next 5 years, tripling its budget and doing away with some of the most restrictive requirements. The draft law also calls for training and retaining 140,000 new health care workers. Dybul says PEPFAR may decide to make substantial investments beyond the original 15 focus countries.

    In contrast to PEPFAR, the Global Fund is more hands-off, seeing itself as little more than a financing mechanism. “Our funding is based on a fundamental principle: country ownership,” says director Kazatchkine. Yet some contend that the fund would have more impact if it had people in countries who helped, as PEPFAR and the World Bank do.

    Country ownership sometimes trades autonomy for economy. Consider the purchase of drugs, which Global Fund recipients negotiate independently. Epidemiologist Brenda Waning of Boston University School of Public Health says there is a “ridiculous” variability in how much different Global Fund recipients pay for anti-HIV drugs. “Some countries are paying 15 times as much as other countries,” says Waning. “The Global Fund, from what I can tell, doesn't seem as though they bother looking at prices people are paying.”

    The World Bank's MAP program, too, has struggled to conduct proper evaluation and monitoring and has created overly cumbersome procedures to disburse money, according to two in-depth analyses published by the bank in 2005. These sharply self-critical reports described the impact of the bank-sponsored projects as “uneven” and also faulted MAP for “grossly” neglecting research to evaluate the cost-effectiveness of different interventions.

    The big three are all still fairly young, and the introspection and outside criticism continues to push each one to improve. But health economist Bertozzi says more attention should be paid to how they fit together. “It's a shame that there's no demand to look at the relative strengths and weaknesses and efficiencies of funding HIV programs through three different models,” says Bertozzi. “Probably the most efficient way to spend the money is some mix of those three.”


    Even if they differ on which funding mechanism works best, experts agree on one thing: The massive influx of dollars is not keeping up with the pace of the HIV/AIDS epidemic.

    In an article in the February 2008 issue of AIDS, researchers reported that Uganda, a PEPFAR country and one of the top aid recipients, expects to more than double the number of people receiving anti-HIV drugs between 2005 and 2010. Given the country's projected population growth, however, the number of people who need treatment but aren't receiving it will hardly decline. “It's hard to imagine, at least with the way we're currently doing things, that we can achieve universal access by 2010,” says co-author John Stover, a public health analyst who heads the Futures Institute in Glastonbury, Connecticut. “Not only is the number newly in need increasing each year, you need to continue the people on treatment who are surviving.” The study bluntly concludes: “Although current prevention and treatment programmes have a measurable effect on the burden of disease, they may not substantially alter the face of the epidemic in the near future.”

    Using global projections from Stover and others, UNAIDS projects that if prevention and treatment scale-up continues at the same pace as today, by 2010, it will cost $42.2 billion—more than four times the amount available today—to reach 80% (13.7 million people) of those who will then be in need. As of the end of 2007, UNAIDS said 3 million were receiving treatment in low- and middle-income countries, which is about 30% of those who need it.

    The only way out of this dilemma, assert Stover, UNAIDS's Piot, and many others, is to invest more in proven prevention interventions and tailor the response to each country's epidemic. “The critical question is not just how much money is available [for prevention], but how much is being spent in the right ways,” says epidemiologist Elizabeth Pisani, author of the Wisdom of Whores, published earlier this year.

    One problem, says Pisani, who previously worked for Family Health International in Indonesia, is the misconception that HIV/AIDS is one epidemic, when in fact it is two: One is in sub-Saharan Africa, where several countries have “generalized” prevalences above 2%; the other is the “concentrated” epidemic in the rest of the world that occurs mainly in high-risk groups such as men who have sex with men (MSM), injecting drug users, and sex workers. For generalized epidemics, everyone above the age of 13 is at risk, she says, and prevention efforts should have a broad agenda. But for concentrated epidemics, it makes more sense to focus on the high-risk groups.

    Far too often, says José Antonio Izazola-Licea, who heads the financing and economic division of UNAIDS, countries with concentrated epidemics don't focus their efforts on their high-risk groups. Similarly, says Stover, many countries disproportionately spend prevention money on MTCT even when they have low infection rates and low birth rates. Ten leading AIDS researchers recently argued that not enough effort has gone into promoting male circumcision and the importance of reducing multiple partners (Science, 9 May, p. 749).

    Prevention efforts directed at high-risk groups can have a major impact in generalized epidemics, too, says epidemiologist Prabhat Jha of the University of Toronto in Canada. In a meta-analysis of 68 epidemiologic studies from Africa in the October 2007 issue of PLoS One, Jha and colleagues found that “superspreaders” accounted for a disproportionate amount of transmission even in high-prevalence countries. “The role of superspreaders is still very central to the African epidemic,” says Jha.

    Epidemiologist Sharon Weir of the University of North Carolina, Chapel Hill, suggests that one way to find superspreaders is to identify where sexual transactions occur—such as truck stops, bars, and street corners—and provide prevention interventions there. People in high-risk groups, notes Weir, often don't identify themselves as MSM or sex workers.

    Techniques to identify the newly infected could also slow HIV's spread. In some studies, nearly half of the people who became infected had partners who had recently become infected themselves. These highly infectious people in the acute stage of the disease often have yet to develop antibodies against HIV, but tests exist that can pluck out viral genetic material from blood. In 2005, researchers described how they used a relatively inexpensive technique to identify acutely infected people who gave blood at HIV testing sites (Science, 12 August 2005, p. 1002). Basically, they cut costs by removing a small amount of blood from individual vials and pooling them. If a pool tests positive for HIV RNA, they could backtrack and find the acutely infected people, who were then contacted and counseled. Principal investigator Christopher Pilcher of the University of California, San Francisco, is now testing the approach in Brazil, and other groups are trying it in Malawi, Tanzania, and South Africa. Detecting acute infection will be a major prevention strategy, Pilcher says, but cautions that their test is still technically difficult in most developing countries: “The truth is very, very few people are working on this because it has not been identified as a priority.”


    Amid all the back and forth about how best to provide treatment and prevent HIV transmission, some analysts are arguing that maybe the disease receives proportionally more money than it merits.

    In a paper in the 21 December issue of Health Policy and Planning, Jeremy Shiffman, a political scientist at Syracuse University in New York, compared donor funding for HIV/AIDS from 1992 to 2005 with money spent on infectious disease, health sector development, and population control. Shiffman found declines in the latter two, leading him to ask whether HIV/AIDS had “displaced” these important public health issues. Shiffman emphasizes that he believes HIV/AIDS doesn't receive enough funding. But he thinks global health equity matters, too. “Do we really want a situation where if you have AIDS you get treated and if you're a baby with pneumonia you die? Wouldn't we rather have a health system for both folks?”

    Stover of the Futures Institute questions the displacement idea, arguing that money for HIV/AIDS may well be strengthening health systems across the board. He also doesn't rule out the possibility that the wealthy world may devote even more to HIV/AIDS. As Stover sees it, “I'd hate to say, ‘No way.’ If you asked me 5 years ago whether we'd get to 3 million on treatment, I would have scoffed. One of the things Jeff Sachs has taught us all is because we haven't been able to get that amount of money in the past, it doesn't mean we won't be able to get it in the future.”

  14. Bang for the Buck

    1. Jon Cohen

    Three modest investments by the U.S. National Institutes of Health are yielding big dividends to many in the field of HIV/AIDS research.

    Three modest NIH investments yield big dividends

    Much of the nearly $3 billion the U.S. National Institutes of Health (NIH) spends on HIV/AIDS research each year supports basic studies that may not yield insights for decades. But three relatively modest investments continue to advance the field in ways large and small, year after year. Together, they consume about $20 million a year—not even 1% of the entire budget—and help thousands of researchers around the world at no cost. “I think of these three as the gifts that keep on giving,” says Anthony Fauci, head of NIH's National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, which funds these projects.

    NIH AIDS Research and Reference Reagent Program

    Annual budget: $3.75 million

    Location: Germantown, Maryland

    Say you're running an experiment that calls for some HIV in the flavor known as subtype C. Or maybe it's a dash of the protease inhibitor indinavir, a dollop of a monoclonal version of the b12 antibody, or a sprinkle of the human version of the APOBEC3B protein. Each of these reagents is yours, free, aside from a nominal shipping fee.

    Since 1988, the NIH AIDS Research and Reference Reagent Program has asked investigators to share interesting samples of HIVs, antibodies, peptides, antivirals, cell lines, proteins, and expression vectors. A nondescript office building in an aging business park now warehouses 8500 unique reagents. Last year, the program sent out 15,800 small samples of reagents to nearly 4000 scientists in 65 countries, often within a week.

    Opendra Sharma of NIAID, who runs the program, says researchers typically are “very happy” to supply samples as long as recipients agree not to use them for commercial purposes. And when Sharma and his team run across someone who does not want to share, they have their methods of persuasion, he says: “We twist their arms, but we don't break them.”

    A recent survey of nearly 800 users showed 98% or higher satisfaction. But 10% complained that they did not receive enough reagents in high enough quantities. As a rule of thumb, investigators are allowed two samples per grant per year, though Sharma says they make exceptions.

    Multicenter AIDS Cohort Study

    Annual budget: $14.4 million

    Location: Chicago, Los Angeles, Baltimore, Pittsburgh

    How long does it take to progress from HIV infection to symptomatic disease? What percentage of people live with HIV for more than a dozen years and suffer no harm? Why do some people remain invulnerable to HIV, despite repeated exposure? These are a few of the questions that researchers have probed, thanks to blood samples collected during nearly 25 years by the Multicenter AIDS Cohort Study (MACS). This unusual study has followed thousands of people at high risk of becoming infected with HIV or developing AIDS.

    When MACS began in 1984, researchers had yet to prove that HIV causes AIDS. The study at first recruited 5622 gay and bisexual men in four U.S. cities, and each agreed to provide a blood sample and personal history every 6 months. When an HIV antibody test became available the next year, the researchers realized that half the men were infected at the study's start. “The real strength of the MACS is we had these men who had the same lifestyle but were uninfected,” says John Phair of Northwestern University in Chicago, Illinois, who chairs the MACS executive committee. Basically, the researchers had a built-in control group that enabled them to tease out just how HIV causes AIDS.

    Today, 150 MACS investigators follow about 3000 men: Roughly 1600 are infected, and nearly 90% of those are taking anti-HIV drugs. Over the course of the study, investigators have stored more than 1 million samples of plasma, serum, and cells. Culled data, made publicly available, include more than 100,000 entries of CD4 counts—the white blood cells that HIV progressively destroys—and tens of thousands of measurements of the amount of virus in individuals at different times. “The participants give a lot of blood,” says Phair. “They're very generous.”

    The HIV Databases

    Annual budget: $1.95 million

    Location: Los Alamos National Laboratory, New Mexico

    Working on GenBank, the genetic sequence database at Los Alamos, Gerald Myers in 1986 became fascinated by the genetic differences between HIV variants. He soon emerged as a world expert on HIV genetic diversity, building a public database that has helped researchers trace the origin of the epidemic, design vaccines, understand viral evolution, track drug-resistance mutations, and even investigate possible skullduggery between competing AIDS researchers.

    World of difference.

    Los Alamos tracks locales of different HIV subtypes.


    Myers handed off the project more than a decade ago to immunologist Bette Korber, who added an immunology database that offers some of the most detailed, comprehensive information available about how the virus interacts with immune cells. The immunology database can also interact with what are now almost 250,000 HIV sequences in the older database. Yet another database lets researchers peruse results of all known AIDS vaccine studies done in nonhuman primates. “It's not the quantity of the data but the quality that make the databases stand out,” says Korber.

    And that quality keeps the quantity of Web site hits high: Last year, the total came to 1.5 million unique visits.

  15. Where Have All the Dollars Gone?

    1. Jon Cohen

    Science gives the lowdown on who has received the most money for HIV/AIDS research from the National Institutes of Health and which authors and institutions have published the highest impact HIV/AIDS papers.

    [Expand chart]

    During the past decade, the U.S. National Institutes of Health (NIH) nearly doubled its annual HIV/AIDS research budget to $2.9 billion (see graph). More than half of that money—$1.6 billion—supports research grants. Of the remaining $1.3 billion, the big-ticket items include contractors ($443 million), intramural NIH research ($288 million), and research centers at academic institutions ($252 million).

    [Expand table]

    To gain a better understanding of the money flow in fiscal year 2007, Science asked the NIH Office of AIDS Research which institutions, networks, and individuals received the meatiest portions. These tables frequently overlap: The best funded principal investigators all have links to large collaborations (see “Top Dogs”). Several funding streams also exist, and to simplify this analysis, one table looks at Top Dogs defined by a different metric: researchers who received the most “investigator-initiated” support through the R01 mechanism.

    [Expand table]

    The R01 Top Dogs had 28 grants among them and received $1.95 million to $2.6 million each—four to five times as much as the average AIDS researcher. But many of these R01 Top Dogs ran expensive clinical or epidemiological studies outside of established networks funded by NIH. These networks account for $300 million annually (see “Pack Mentality”). And the 10 best funded universities (see “Fat Cats”) run many of them, which helps explain why they rake in about one-fourth of NIH's entire HIV/AIDS research budget.

    [Expand table]

    An analysis of publications, done with the help of Thomson Reuters's Institute for Scientific Information, assesses the impact of the 123,752 HIV/AIDS-related papers published between 1998 and 2007 (see “Territorial Markers”). The average paper was cited nearly 12 times. The single most cited paper shows that potent anti-HIV cocktails led to a steep decline in disease and death in the United States (see “Blue Ribbon”). Researchers who had the most citations per paper, with a minimum of 100 publications, are defined as having had the most impact. And with institutions, money does correlate with impact—seven Fat Cats rank in the top 20 in number of cites per 500 papers—but only to a point: Northwestern University has the second-highest citation impact and does not even rank in the top 20 for NIH funding. Money speaks volumes, but it often doesn't have the final word.

    [Expand table]

  16. Uganda Confronts Corruption, Slowly

    1. Jon Cohen

    When allegations surfaced that Global Fund grants had been pilfered, a high-level commission promptly investigated and wrote a scathing report--that sat on shelves.

    When allegations surfaced that Global Fund grants had been pilfered, a high-level commission promptly investigated and wrote a scathing report—that sat on shelves

    The sum total of the enormous catalogue of flaws, shortcomings, errors, mistakes, and hiccups enumerated and detailed in all the above … adds up to a humongous picture of grand managerial inefficiency and incompetence. … The great losers in this sordid story were the people of Uganda; the international donor community; and, particularly so, the new experiment in Global Fund Public-Private Sector partnership. Above all, the most poignant and pathetic losers were the millions of persons infected and affected by the three scourges of HIV/AIDS, TB and Malaria. These millions watched in pain and agony as their dire hopes were dashed to dust through the incompetence of the [money's] stewards, and the naked greed of the middlemen (the sub-recipients) of the Global funds.

    —Final report, the Judicial Commission of Inquiry into Alleged Mismanagement of Global Fund to Fight AIDS, Tuberculosis, and Malaria in Uganda.

    KAMPALA, UGANDA—This blistering report landed on the desk of Ugandan President Yoweri Museveni in May 2006. The Judicial Commission of Inquiry concluded that officials, from government ministers to workers at community organizations that nominally exist to help HIV-infected people, had stolen money from the $45.3 million disbursed to Uganda from the Global Fund to Fight AIDS, Tuberculosis, and Malaria. As a result, Uganda, which had been widely praised for its exemplary response to its HIV/AIDS epidemic, has endured unprecedented public humiliation. “What is sad is this money is given to Uganda by other governments, and they're trying to help us with a huge problem,” says AIDS researcher David Serwadda, who heads the School of Public Health here at Makerere University. “There's a lot of hope and trust put into us. To find that this resource has not been used to its intended purpose makes you wonder … whether we are not our own worst enemies.”

    Museveni appointed the judicial commission to show that Uganda would use all its muscle to root out corruption in the use of money from the Global Fund and punish wrongdoers. Headed by James Ogoola, an esteemed judge on the country's High Court who for more than 20 years worked as a legal counsel for the International Monetary Fund, the commission interviewed more than 150 witnesses over 6 months and introduced some 500 exhibits into evidence. The Ogoola commission's final 485-page report to Museveni cataloged how between 2003 and 2005 an astonishingly large cast of characters plundered five Global Fund grants in an equally astonishing array of alleged swindles.

    On 30 November 2006, 6 months after Museveni received the commission's report, the Ugandan government issued a “white paper” that agreed with almost all of the findings and urged aggressive prosecution of several government officials; it also agreed that individuals and organizations should pay back at least $1.6 million.

    And then nothing happened.

    Not until April of this year did any follow-up to the Ogoola commission's recommendations occur, and even now, the wheels of justice appear to be spinning slowly. The government pleads guilty for the delay but says it lacked the money to carry out the prosecution. Others are far harsher. “What was the point of spending so much money on this commission of inquiry, on top of what already was embezzled, and then the government does not proceed to prosecute these individuals?” asks Beatrice Were, an HIV/AIDS advocate based in Kampala and co-founder of the National Community of Women Living With HIV/AIDS. “It does look like corruption is normal and that anyone can do what they want and walk away scot-free in this country.”

    Stig Barlyng, the Danish ambassador to Uganda and one of the most outspoken crusaders against corruption in the country, says the “lack of concrete follow-up” is “an embarrassment” to both Uganda and the donors. The scandal is “a litmus test” not only for how serious Uganda is about corruption, he says, but also for how well the 6-year-old Global Fund monitors recipients and reacts to wrongdoing. And this is no “victimless” white-collar crime, he adds. People were directly harmed. “When we're dealing with AIDS, it's a deadly issue. It's as simple as that.”

    The $1.6 million or more that was stolen from the Global Fund grants—the full amount remains unclear—might not seem like a lot, says Were, but “every coin counts” in Uganda. “If you translate it to what it means to people in a small village outside of Kampala, it's a lot.” People who are affected most by this epidemic actually don't need much to transform their lives, she says. And that little was taken away.

    Strong words

    The Global Fund, which prides itself on rigorous monitoring and evaluation of grant recipients, did not discover the corruption in Uganda. The problem surfaced on 13 June 2005 when a whistleblower sent an e-mail to Bernard Rivers, head of Aidspan, an independent watchdog of the fund (see sidebar, p. 524). Rivers did not know the whistleblower, who worked at a Ugandan nongovernmental organization (NGO), and the first e-mail he received was all of four sentences. “It was so cryptic that I hardly knew what he was claiming, let alone whether I believed it,” said Rivers. With the whistleblower's permission, Rivers passed the tip to the fund. “I was amazed when I got a reply within 2 hours, making it quite clear that Global Fund was taking it quite seriously,” he says.

    A few weeks after receiving the tip, the Global Fund's chief legal counsel met with the whistleblower in Kampala. Convinced that the allegations had substance, the fund asked the auditing firm PricewaterhouseCoopers to evaluate $26 million the Global Fund had disbursed through the first of five grants it had awarded to Uganda. (The fund planned by 2010 to disburse $371 million to Uganda for all five grants, which would help the country battle HIV/AIDS, tuberculosis, and malaria.) The confidential evaluation, a copy of which Science obtained, identified several of the problems that the Ogoola commission later would report.

    On 24 August, shortly after reading the evaluation, Brad Herbert, then the chief operating officer of the Global Fund, suspended all five grants to Uganda, allowing funding to continue only for “lifesaving treatments” and critical prevention needs such as condoms. “The Pricewaterhouse report very clearly indicated to my satisfaction that Global Fund money was not being utilized for what it was intended for,” says Herbert.

    Just 1 week earlier, the fund had canceled grants to Myanmar because of new restrictions imposed by the ruling junta. Uganda's grants were not terminated but merely put on hold, Herbert stresses, adding that he explained to a senior Ugandan official that if the government responded properly, he'd lift the suspension. “I said, ‘Either you can embrace me or fight me. If you embrace me—I know that every country has corruption, my own country has corruption—what is it you will do to get the suspension lifted?’”

    Herbert went to Uganda at the end of August and met with President Museveni and other officials to determine how to proceed. “There was a very serious commitment from Museveni to get to the bottom of this,” says Herbert. “I think he stepped up to the plate.” On 6 September, Museveni announced the formation of the Ogoola commission.

    Two months later, on 10 November 2005, the Global Fund lifted the suspension, noting that Uganda had taken “significant steps” to strengthen grant management and oversight.

    The Ogoola commission handed Museveni its report on 31 May 2006. Among the many alleged offenses spelled out in the report:

    • »Recipients billed for “ghost trips” that never occurred, inflated hotel charges, and engaged in activities to push forward a national referendum unrelated to HIV/AIDS.

    • »The Ministry of Health spent nearly $25,000 on medical care for a former government minister and Museveni ally.

    • »Another $19,832 was “borrowed” to send the minister of health on a multicountry trip to lobby for a Ugandan to win the slot as the next director-general of the World Health Organization.

    • »Forgeries of receipts were “rampant,” and there were outright frauds, cover-ups, and kickbacks.

    • »The Uganda Centre for Accountability—an NGO that received more than $70,000 to monitor and evaluate other subrecipients of Global Fund money—“had absolutely no accounting capacity.” (It also had the audacity to bill for fuel for a tractor, which it claimed was a vehicle used by supervisors to visit sites.)

    • »Nepotism led to jobs and travel grants.

    • »Another NGO, the National Forum of People Living with HIV/AIDS, was supposed to funnel some $160,000 to 21 other groups but ended up keeping about half of that money and billing for expenses that the commission deemed “extremely suspicious.”

    After receiving the commission report, Richard Feachem, then the executive director of the Global Fund, in a press release commended the Uganda government. “The openness and thoroughness with which President Yoweri Museveni addressed the Global Fund's concerns about the management of the grants it finances in Uganda has set an example for how allegations of corruption should be dealt with,” wrote Feachem. Community representatives similarly were impressed.

    Little action

    President Museveni went even further. He passed the commission report on to his Cabinet, which issued a November 2006 white paper calling for pursuing potential refunds and criminal prosecutions “within 6 months.” But by that deadline, May 2007, the Global Fund corruption case had disappeared from the headlines and the prosecutor's docket. “The cause of the delay was sorrily lack of funding,” says Uganda's director of public prosecutions, Richard Buteera, a lead investigator in the case. An investigation this complex required help from several branches of government, Buteera says, and ordinary budgets could not cover the costs. The Cabinet did approve extra funding, but, he says, “unfortunately, it was not released in the last budget.” Buteera and his colleagues had to put the case on hold.

    The notion that Uganda could not immediately afford to pursue the Ogoola commission's recommendations strikes advocate Were as a flimsy excuse. She notes that the government poured tens of millions of dollars into hosting the Commonwealth Heads of Government Meeting—which the Queen of England opened—last year. “It's the commitment and the will to address corruption that [are] lacking,” says Were. The country also quickly found the money to prosecute three of the same health ministers implicated in the Global Fund case who in June 2006 were charged with misusing funds from what was then known as the Global Alliance for Vaccines and Immunization. Each was arrested and is out on bail pending a trial that has been delayed because of procedural issues. (Museveni, without explanation, replaced all three of them in May 2006.)

    Adolf Mwesige, the minister for general duties who chaired the Cabinet's evaluation of the Ogoola commission report, says he is not frustrated by the pace with which Uganda has followed up on its recommendations. “I'm realistic,” says Mwesige. “I know the conditions in which we are operating are a little more difficult than in the West.” He notes that Uganda is confronting many similar corruption cases and says that “we can't overwhelm all our institutions of prosecution.” He says the government moved more quickly in the vaccine fund case because the evidence was more clear-cut. “It didn't even require a commission of inquiry.”

    Nor did Global Fund head Michel Kazatchkine push, telling Science in March 2008 that he did not see pursuing prosecution of wrongdoers as a Global Fund responsibility. “That's a Uganda process,” said Kazatchkine. “This is for Uganda to fix.” He claimed, too, that the fund has already recovered $700,000 of the pilfered money.

    Push to prosecute

    But when John Parsons joined the fund as its inspector general early this year, he put the Uganda case at the top of his priority list. In April, several members of the Global Fund's board also urged Parsons to take aggressive action. As one board member wrote Parsons, “Unless the investigations commence in the coming months, it is unlikely that the suspects can be successfully prosecuted given the lapse of time, the evidence going cold and key witnesses no longer being available, willing or reliable.”

    That same month, Uganda's Ministry of Finance allocated 200 million Ugandan shillings (more than $125,000) to Buteera and his colleagues, about 10% of what they need but enough to get started. The U.K.'s Serious Fraud Office also offered to help. “I'm strong that we should solve this problem, take the appropriate action, get the culprits, and bring them to book,” said Buteera in early May. “I wish we had the funds to do it earlier than now.”

    Poverty? Pshaw.

    Beatrice Were doubts that Uganda couldn't afford to prosecute.


    In mid-May, Parsons went to Uganda to meet with people connected with the case, and they committed to investing another 760 million shillings as of July. “My mission had an impact in unlocking political will and funds to investigate,” Parsons told Science. “I'm very keen to encourage them to do what they should be doing and should have done some time ago.” In all, he says the Ugandans agreed to investigate 373 cases and to reassess how much money is due to the fund. (Even the fund is confused about this last point: To date, Parsons says only 698 million shillings, less than $450,000, have been returned—about 65% of the amount that fund director Kazatchkine told Science had been recovered.) Parsons plans to update the finance and audit committee of the Global Fund in late September.

    Herbert, the fund's former chief operating officer, says he expects that similar corruption has probably gone undetected with several other Global Fund grants and that there's only so much that can be done to prevent and catch thievery without causing harm. “For every 100 apples in the barrel, you probably have 10 that are bad,” says Herbert. “If you put so many procedures in place that those 10 bad apples don't do anything, you might hurt the other 90. The only way I could guarantee that a dollar would not fall into corruption is to never, ever spend that dollar.”

  17. The High Cost of Stolen Funds

    1. Jon Cohen

    Mayanja Lubwama, a 44-year-old HIV-infected man who lives with his wife and four of their six children in a cramped house on the outskirts of Kampala, is one of many Ugandans who were hurt by the Global Fund to Fight AIDS, Tuberculosis, and Malaria corruption case (see main text).

    Dashed hopes.

    Mayanja Lubwama says the Global Fund theft hit home.


    NSANGI, UGANDA—Mayanja Lubwama, a 44-year-old HIV-infected man who lives with his wife and four of their six children in a cramped house on the outskirts of Kampala, is one of many Ugandans who were hurt by the Global Fund to Fight AIDS, Tuberculosis, and Malaria corruption case (see p. 522). “Some of us benefiting from those funds felt very sad,” says Lubwama.

    In many ways, Lubwama, whose wife and eldest son are also infected, is lucky: He started receiving anti-HIV drugs 8 years ago and has responded to the same regimen ever since. But during the time that the Global Fund suspended Uganda's grants, between August and November 2005, Lubwama says the clinic where he gets his anti-HIV drugs had “stock outs.” He also had a job working for an HIV/AIDS nongovernmental organization that received Global Fund support; they had to let him go, and the project he worked for never restarted. “All of these projects were stopped because of the Global Fund saga,” says Lubwama. And short on cash, Lubwama sometimes had to choose between paying for food for his family or transportation to a clinic to pick up his drugs.

    There's no way to tally the number of people who were hurt by the corruption, but according to the latest data, at the end of 2006, 60% of the people who needed antiretroviral drugs in Uganda had yet to receive any. The Global Fund also declined to renew Uganda's grants for malaria and TB in October 2006 because of the management problems that surfaced during the corruption probe. More recently, a progress report for the main HIV/AIDS grant showed “unacceptable” performance for money disbursed between October 2006 and March 2007. “Implementation of this grant has been delayed due to the loss of momentum that occurred when all of Uganda's [Global Fund] grants were suspended,” the report states.

    The corruption case also forced Uganda to reorganize how it moves money from the Global Fund to various recipients. This restructuring, in turn, has slowed the country's ability to build a more sophisticated program that, for example, can routinely provide second-line treatment to people whose first-line treatment has failed. That problem now confronts Lubwama, who has started to have serious side effects from his anti-HIV drugs, including neuropathy in his feet and stomach pains, but his doctors say they don't have other drugs to offer him. “I don't have any options,” he says.

    Jennifer Bakyawa, a Kampala-based journalist who now does HIV/AIDS community outreach at Makerere University, points out that the corruption harmed many people beyond those in need of treatment. Bakyawa, who has lost two half-sisters and a half-brother to HIV, says when people don't receive free anti-HIV drugs, they often turn to family and friends for financial help. If a person dies from AIDS, it's the family and friends who step in to care for his or her children. And with an adult HIV prevalence rate in the country that has ranged from 6% to 15% during the past decade, Bakyawa says, “if someone in Uganda tells you they haven't been affected by HIV/AIDS, they're lying.”

  18. The Global Fund's Best Friend?

    1. Jon Cohen

    By Bernard Rivers's own description, he's a "loving watchdog" of the Global Fund to Fight AIDS, Tuberculosis, and Malaria, "a dog that spends much more of its time wagging its tail than barking," he adds.

    NAIROBI, KENYA—By Bernard Rivers's own description, he's a “loving watchdog” of the Global Fund to Fight AIDS, Tuberculosis, and Malaria, “a dog that spends much more of its time wagging its tail than barking,” he adds.


    Bernard Rivers.


    Rivers and his two-person team here run Aidspan, which began publishing an electronic newsletter, the Global Fund Observer, shortly after the fund opened for business in 2002. The Observer, published every month or so and now a must-read for nearly 8000 subscribers in 170 countries, offers original analyses of Global Fund data. These include a grants-evaluation system that tracks whether disbursements are on time, news reports on Global Fund board meetings, and critical editorials about how the fund can improve. He has endorsements on his Web site from the current director of the fund, the chair of its board, and the head of UNAIDS. Rivers is “very open-minded and stubborn at the same time,” says Peter van Rooijen, a former board member of the Global Fund, who now heads the International Civil Society Support in Amsterdam. “He performs his watchdog role quite eloquently.” But when Rivers triggered an investigation of the Global Fund itself, its spokesperson, Jon Lidén, publicly complained. The investigation unfairly stained the credibility of the leadership, Lidén now says, noting that the probe found no serious wrongdoing.

    Rivers became intrigued by the Global Fund's design soon after it formed. “Over the past 50 years, Western governments have all too often told developing countries, ‘We will provide you with aid if you will support us in the Cold War, or buy our products, or follow our moral agenda, or let our nationals run your project,’” says Rivers, an economist by training. “This is an outdated and inappropriate approach, which the Global Fund model seeks to circumvent.” Rivers sold his company, which provided grants-management software to foundations, and invested his own money in starting Aidspan.

    With a total of four staff members (others work from England and Thailand) and an annual budget of $750,000, Aidspan finances its work with help from foundations, industry, and individuals. Rivers maintains a strict independence from the fund and takes no money from it. Although he is a critic, he says he shares the group's vision of “country-led” and “results-based” funding; he also calls it “remarkable” that in 6 years the fund has gone from $0 to giving out $3 billion annually. “Of course, not everything has worked perfectly from day one,” he says, pointing to the recent corruption scandal, among other problems (see main text).

    This past winter, Rivers interviewed more than 50 Global Fund recipients in seven African countries to examine the barriers that have prevented countries from aggressively scaling up anti-HIV drug treatment and prevention efforts. In a report published in April, he concluded that the proposal process is too “long and complex.” Countries that have several grants for different diseases must contend with an “administrative burden” that makes them feel as though they have been “punished for success.” The report also advocates that the fund dramatically increase assistance for strengthening health systems more broadly.

    Ultimately, Rivers believes that developing countries should run Aidspan, which is one reason he moved its headquarters from New York City to Nairobi in 2007 and began hiring Kenyan staff members. “The sooner Aidspan can get to that point, the better,” he says, estimating that the process will take two more years. “Founders of organizations should always get out in less than 10 years,” says Rivers. “Otherwise, the organization will find it very hard to grow beyond simply being an extension of that person.” But for now, as the saying goes about a happy dog, it's like he has two tails.

  19. Botswana's Success Comes at Steep Cost

    1. Jon Cohen

    HIV/AIDS has walloped this tiny country, but it has hit back hard with a pioneering treatment program. Prevention efforts have lagged, however, and could unravel the gains.

    HIV/AIDS has walloped this tiny country, but it has hit back hard with a pioneering treatment program. Prevention efforts have lagged, however, and could unravel the gains

    FRANCISTOWN, GABORONE, AND SELEBI-PHIKWE, BOTSWANA—A few minutes before dawn on this cool June morning, 67 men at the BCL mine slip into overalls and gum boots, belt on heavy batteries that power their head lamps, and then cram into elevators large enough to hold pickup trucks. After descending 750 meters, the men trudge for 30 minutes through muggy, mud-floored tunnels that lead 135 meters deeper underground, pinning themselves against the rock walls each time a front loader hurtles by. Their lamps illuminate flecks of nickel and copper in the walls and ceiling, and later today they will harvest these valuable metals. But before the drilling and blasting starts, the men gather in a cave carved into a wall and take seats on wooden benches. As sweat pours from their faces, they join in prayer, closing with a robust “Amen.”

    This morning, as occurs twice a month, the prayer is followed by a “toolbox talk” about HIV/AIDS. Mines are dangerous places, but collapses and suffocation are not the only threats. Here in Selebi-Phikwe, a small town in Botswana's northeast, mining is closely linked to the spread of HIV.

    Safety first.

    Novel prevention efforts aim to dig Botswana out.


    About 300,000 of the 1.8 million people in Botswana have been infected with HIV, which, according to government estimates, translates to an adult prevalence in 2007 of 26.9%, among the highest in the world. Selebi-Phikwe, where BCL employs 4200 people, is one of the country's hardest hit districts. A 2003 study of BCL miners found an overall HIV prevalence of 41.3%, which jumped to 57% among 30- to 39-year-olds. “It was really staggering for us to realize this,” says Montwedi Mphathi, the mine's general manager. The mine decided that it was good business to launch a comprehensive workplace program to help the infected and promote prevention.

    Deep underground, the peer educator promotes the value of positive living and the merits of condoms. He holds up a flip chart that shows gruesome images of lesions from other sexually transmitted infections, urging the men to get tested if they suspect they have caught syphilis or gonorrhea. But when the educator opens the floor to questions, it's clear that the miners are more concerned about their HIV infections. “If both parties are positive and want to have a baby, what should they do?” asks one man, who wears the gold watch earned after 25 years at BCL.

    “Don't decide on your own,” the peer educator advises. “See a medical doctor.”

    Like BCL, Botswana has aggressively responded to its HIV/AIDS epidemic, and this miner's sophisticated question—and the sound answer—reflect that infected people have options not available in much of sub-Saharan Africa. The government of this relatively wealthy country provides anti-HIV drugs to almost everyone in need; free medical care is widely available; and campaigns for prevention of mother-to-child transmission (PMTCT) have made great strides. Festus Mogae, who ended a 10-year term as president in April, has won international praise for his bold battle against Botswana's HIV/AIDS epidemic. Under his leadership, this tiny country formed novel partnerships with leading universities, pharmaceutical companies, foundations, and developed country governments, which have provided generous funding, state-of-the-art equipment, training, and expertise. On most fronts, says Peter Piot, head of the Joint United Nations Programme on HIV/AIDS (UNAIDS), Botswana is “doing a great job.”

    But progress has not come easily, and there is one glaring deficiency, says Piot: prevention. Botswana has made precious little headway slowing HIV's spread, which is transmitted here mainly through heterosexual sex. “Prevention of new infections should be priority number one, number two, and number three,” says former President Mogae, who continues to chair the National AIDS Council. “We cannot treat the epidemic away.”

    Threatened extinction

    When struggling Botswana made its transition from British rule to independence in 1966, it mainly exported cattle. But the economy exploded with the discovery of diamonds in the 1970s, and today the country is solidly middle income, akin to Russia or neighboring South Africa. An excellent highway system connects the entire country, crime is low, and the political environment is relatively stable and corruption-free.

    When Mogae took office in 1998, he realized that HIV had begun to undermine many of the country's gains. “Like a war, it was taking the cream of society in terms of youth and health,” says Mogae, an economist by training. Improvements in infant mortality rates, adult life expectancy, and other development indices disappeared.

    Taking it to the streets.

    The Ghetto Artists in Francistown play miners and their pregnant wives deciding whether to take HIV tests.


    On the eve of the international AIDS conference held in nearby Durban, South Africa, in July 2000, UNAIDS pegged Botswana's adult prevalence at 35.8%, the highest in the world. “We are threatened with extinction,” Mogae said at the meeting.

    The Durban meeting marked the beginning of a unique public-private partnership that would catalyze Botswana's drive to become the first country in sub-Saharan Africa to provide widespread access to antiretroviral drugs (ARVs): what's now called the African Comprehensive HIV/AIDS Partnerships (ACHAP). The pharmaceutical giant Merck & Co. and the Bill and Melinda Gates Foundation announced that they would each chip in $50 million of assistance over 5 years to help “reduce the spread of HIV and to significantly increase the awareness, prevention, diagnosis, and treatment of HIV/AIDS.”

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    But the initiative had a bumpy start. Its first director, a Merck executive, clashed with government employees, who complained that he didn't understand the “culture of consultation” in Botswana. And putting together a nationwide treatment program required a massive recruitment of new professionals: A team of pro bono consultants from McKinsey & Co. estimated that the country needed staggering increases in doctors (29%), lab technicians (115%), and pharmacists (179%).

    Realizing that the program was having teething pains, ACHAP's director asked one of the McKinsey consultants, Ernest Darkoh, to move to Botswana in late 2001 and help. Shortly after he arrived, Darkoh, a young American physician who also had a master's in business administration, deemed the situation “an impending disaster.” Morale was poor. Leadership roles in the new program went to clinicians who had little experience as managers. Government ministries had difficulty working together; no one seemed capable of making budgetary decisions; and Darkoh had no real authority himself. “They couldn't get themselves out of the starting blocks,” says Darkoh, who now lives in South Africa and heads BroadReach Healthcare.

    When the government decided to start rolling out treatment in January 2002, Darkoh was convinced that they weren't ready. But he also felt that they had to succeed. “I knew what this represented to the continent; everyone said if you can't do it in Botswana, the easiest place, you can't do it anywhere,” he recalls.

    Darkoh's frustration mounted over the next month—Botswana, he concluded, did not deserve its reputation as an easy place to work. When he threatened to resign, the government responded by offering him a slot in the Ministry of Health (MOH) as operations manager of the program. Darkoh, then 31, took the job. “I went back to my hotel room and literally sat on my bed, saying, ‘Good god, what am I going to do now?’”

    The program slowly began to make progress, but it also faced intense criticism, some of which Darkoh says was unfair. The initial McKinsey feasibility study projected that with staff and other resources in place, Botswana could have 19,000 people on treatment within a year. At the end of 2002, only 3200 people had begun treatment. “Despite the herculean success in getting the program on its feet, we had a big sign around our neck that this was somehow a failure,” says Darkoh. “I got nasty e-mails from around the world from experts who claimed they would have done better.” (McKinsey, he notes, did fail to consider that the first patients to seek treatment would have late-stage AIDS and need extra resources.)

    Firsthand knowledge.

    An HIV-infected counselor at a Francistown clinic helps a patient decide whether to start ARVs.


    By the time Darkoh left ACHAP in 2005, it was a trusted partner, helping Botswana provide free anti-HIV treatment and state-of-the-art monitoring to 50,000 people. “The government ARV team was functioning like an efficient machine,” says Darkoh. But the success in 2005 was qualified: More than twice that number still needed treatment. The problem wasn't money—ACHAP had spent only about $55 million of the $100 million offered by the Gates Foundation and Merck—but “absorptive capacity,” concluded the Gates Foundation in a 2006 report. As the report explained, “we underestimated just how hard it is to build up the systems necessary to confront HIV/AIDS across an entire country.”

    Not only did Botswana have a dearth of trained professionals and middle managers, the “culture of consultation” meant it had an abundance of bureaucracy. “The irony in Botswana is that part of the problem is the inheritance of the British civil servant's approach,” says Michael Reich, a political scientist at Harvard University who co-authored an analysis of the early ACHAP efforts in the July 2006 issue of Social Science & Medicine. “Some people say they're more British than the British.”

    Stopping spread

    As of March 2008, 97,265 people at 32 dedicated ARV sites around Botswana were receiving anti-HIV drugs—nearly 90% of those most in need. And the drugs are working. Researchers from Botswana's MOH and Harvard jointly run an AIDS institute in Gaborone, and in 2007, they reported that potent cocktails of anti-HIV drugs had powerfully suppressed HIV for more than 2 years in the patients they studied, and only 2% developed drug-resistant mutations. “The era of ARVs has saved the nation,” says epidemiologist Khumo Seipone, head of HIV/AIDS prevention and care at MOH.

    The Botswana government has financed the bulk of its HIV/AIDS response—it spent about $130 million last year alone—and it has also received more than $250 million from the U.S. President's Emergency Plan for AIDS Relief since 2004. But many say ACHAP's investment had far-reaching impact. “ACHAP did not just support Botswana; it galvanized the global commitment to treatment,” says Joy Phumaphi, the minister of health from 1999 to 2003 and now a vice president at the World Bank in Washington, D.C.

    Alarming point.

    Former President Mogae warned that HIV could wipe Botswana from the map.


    Merck and the Gates Foundation extended ACHAP through 2009, and when it ends, the program will have spent $106 million. They are considering launching a second phase to help Botswana address the elephant in the room: prevention. “Clearly there's a need for a catalyst in the area of prevention,” says Themba Moeti, ACHAP's managing director.

    Botswana has encouraged people to have fewer partners, delay the age of first sex, increase their condom use, and adopt other behavioral changes, but none has made dramatic progress. The PMTCT program, which offers anti-HIV drugs to infected pregnant women and newborns to protect the babies, has had trouble too since its start in 1999, even with substantial support from ACHAP and the U.S. Centers for Disease Control and Prevention (CDC). In 2003, only 47% of women who visited a hospital in Francistown, the country's second-largest city, knew their HIV status, and of those who tested positive, 71% did not take ARVs to prevent transmission, reported CDC pediatrician Tracy Creek and colleagues in the 1 May 2007 issue of the Journal of Acquired Immune Deficiency Syndromes. Many pregnant women were simply not volunteering to take HIV tests, and those who did often did not act on the results.

    But PMTCT also shows that a struggling prevention effort can, like the treatment program, find its footing. In a New Year message at the end of 2003, Mogae announced a more aggressive policy that would alter PMTCT's fate: Bucking the international standard of “voluntary counseling and testing,” clinics would routinely test people for HIV unless they specifically opted out. According to government figures, in March 2007, 83% of pregnant women took an HIV test, and 89.9% of those who tested positive chose to take ARVs. Transmission to babies has dropped from 40% in 2001 to 4% last year. “Routine testing has been a smashing success,” says Creek.

    Yet outside of PMTCT, Botswana has little to show for its prevention interventions. When prevention efforts work, new infection rates should drop. The scant evidence here suggests that at best, says MOH's Seipone, incidence has stabilized and may have dropped in pregnant women between 2005 and 2007. But prevalence remains astonishingly high among pregnant women: Reports from antenatal clinics show a prevalence of 33.7% in 2007. One of the key reasons for the failure of prevention efforts, says former health minister Phumaphi, “is we are not addressing the drivers of the epidemics,” by which she primarily means heterosexual behaviors. She worries, too, that the success with ARVs has increased complacency about becoming infected.

    Botswana set the goal of “zero new infections by 2016” and last December issued an intensified prevention plan. At the top of the list is reducing concurrent sexual partnerships. In Botswana tradition, men have a large house for their main wives and small houses for their mistresses. Women often also have more than one partner, who some jokingly refer to as their ministers of cell phone, rent, food, or jewelry. Many Botswanans have highly mobile lifestyles: Cars are abundant, and on weekends, urban workers—say, miners in Selebi-Phikwe or professionals in Gaborone—often return to their rural villages, without their city partners.

    The prevention plan also urges Botswana to better communicate the dangers of young women having sex with older men (who have a high prevalence), heavy alcohol use, stigma, and inconsistent condom use. And it faults the country for having “often ignored” the role of sex workers, who do a busy trade in mining towns and on major transport routes. Fewer than 20% of men in Botswana are circumcised, and many expect that the government will soon endorse this proven prevention option.

    Precisely how Botswana will scale up these efforts remains an unknown. Phumaphi urges her country to rely on evidence-based strategies. “We have to be much more methodical,” she says.

    Civil discourse.

    A community group hands out female and male condoms at a shebeen, a homebrew pub.


    Daniel Motsatsing, head of the Botswana Network of AIDS Service Organizations (BONASO), thinks prevention efforts should rely more heavily on community-based organizations. Botswana's generally strong government, he contends, gives people things “on a silver platter,” unintentionally squelching grass-roots efforts. He also faults the government for losing more than half of an $18.6 million grant from the Global Fund to Fight AIDS, Tuberculosis, and Malaria that would have supported prevention work done by some of BONASO's 160 members. The fund ended the grant because the government's National AIDS Coordinating Agency (NACA) failed to file a required report.

    Unless prevention efforts make more headway, Mogae says a crisis “is bound to come” as ever more people seek treatment and stretch resources to the limit. “We are fast approaching a situation where we cannot afford what we are doing even now,” says Mogae. NACA official Monica Tselayakgosi says the country plans to apply for Global Fund money again, is attempting to purchase ARVs more cheaply, and is even considering charging some people for treatment. “The response to the epidemic is not sustainable,” she says. “We need to sit back and really take a hard look at what it is that we really can afford.”

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