# News this Week

Science  26 Oct 2007:
Vol. 318, Issue 5850, pp. 546
1. GENETICS

# Ancient DNA Reveals Neandertals With Red Hair, Fair Complexions

1. Elizabeth Culotta

What would it have been like to meet a Neandertal? Researchers have hypothesized answers for decades, seeking to put flesh on ancient bones. But fossils are silent on many traits, from hair and skin color to speech and personality.

Personality will have to wait, but in a paper published online in Science this week (www.sciencemag.org/cgi/content/abstract/1147417), an international team announces that it has extracted a pigmentation gene, mc1r, from the bones of two Neandertals. The researchers conclude that at least some Neandertals had pale skin and red hair, similar to some of the Homo sapiens who today inhabit their European homeland. The paper comes on the heels of one that used similar techniques to show that Neandertals shared the modern human form of the only gene so far known to influence human speech, FOXP2. Although researchers are working to sequence the entire Neandertal genome (Science, 17 November 2006, p. 1068), these are the first specific nuclear genes to be retrieved. “These are the two genes you'd most like to see from a Neandertal,” explains Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, who led the FOXP2 study.

The mc1r paper is “logical, elegant, and convincing,” says anthropologist Nina Jablonski of Pennsylvania State University in University Park. “It's a great paper,” agrees molecular geneticist and pigmentation expert Rick Sturm of the University of Queensland in St. Lucia, Australia.

Many of the Neandertals cavorting in museum dioramas around the world already have pale skin or red hair, because anthropologists have long predicted this coloration on the basis of evolutionary theory. The dark skin beneficial in Africa offers no advantage at high latitudes, and in cloudy Europe, pale skin facilitates vitamin D production, Jablonski says. But there was no proof of Neandertals' looks until a team led by Carles Lalueza-Fox of the University of Barcelona in Spain and Holger Rämpler of the University of Leipzig in Germany set out to retrieve the mc1r gene from a 43,000-year-old Neandertal from El Sidrón, Spain, and a 50,000-year-old specimen from Monti Lessini, Italy.

MC1R is a cell membrane receptor that helps regulate the balance between red-and-yellow-colored pheomelanin and black-and-brown-colored eumelanin. Living people with variations that make the receptor work poorly tend to have red hair and pale skin, although other pigmentation genes also have strong effects (Science, 2 March, p. 1215).

Using the polymerase chain reaction (PCR) to target and amplify the gene, the researchers found a point mutation not seen in living humans. They checked about 3700 people, including everyone involved in the project, to be sure that the variant was unique to Neandertals. Next, they explored the variant's function by expressing it in human cells and found that it impaired the receptor's activity. “If you have a variant with this low action in modern humans, you get classically Irish-looking red hair and pale skin” in homozygotes, people with two copies of the variant, says team member Michael Hofreiter of the Max Planck Institute in Leipzig. The researchers calculate that at least 1 in 100 Neandertals would have been homozygotes. Thus Neandertals and Homo sapiens in Europe followed independent evolutionary paths to a similar phenotype, Lalueza-Fox says.

“I'm convinced that what they're saying is real,” says Sturm, who has used similar functional assays to check mc1r variants in living people. Lalueza-Fox adds that Neandertals may have carried a variety of changes in mc1r, as we do, and so may have had a spectrum of skin and hair colors.

Pääbo and colleagues also used targeted PCR to isolate the FOXP2 gene. They chose FOXP2 because people with mutations in the gene have impaired speech. Pääbo's team had previously traced the gene in living people and suggested that the unique human variant was selected relatively recently, less than 200,000 years ago—long after Neandertals and modern humans had diverged (Science, 16 August 2002, p. 1105). The implication was that Neandertals lacked the modern human form, Pääbo says.

But to their surprise, that's not what they found when they sequenced the gene from two bones from El Sidrón, where Lalueza-Fox runs a “clean” excavation for DNA analysis. Both bones carried the modern human version of FOXP2. That doesn't necessarily mean Neandertals spoke as we do, because many genes presumably influence speech. But “from the point of view of the one gene we know, there's nothing to say that Neandertals were different from us” in their language abilities, Pääbo says.

Because the Neandertal FOXP2 gene matched that found in living people, Pääbo's team used extra controls to try to rule out contamination with modern human DNA. For example, they sequenced the Neandertal Y chromosome and found that it differed from that of living men at five key sites. No contamination of the Y chromosome strengthens the case that the FOXP2 result is real, Pääbo says.

The Y chromosome finding also argues against interbreeding between Neandertals and the modern humans then entering Europe. “I find it paradoxical in some ways,” says Lalueza-Fox, who is an author of both studies. “The papers make Neandertals more like modern Europeans, with light skin and hair color and language abilities, and yet there are no signs of interbreeding with modern humans.”

But others aren't yet ready to concede that either contamination or mixing has been completely ruled out. “The additional controls give one more confidence that contamination is not a problem, but we can't be 100% sure,” says evolutionary geneticist Jeff Wall of the University of California, San Francisco, who in August reported what he saw as contamination in Pääbo's group's bulk Neandertal sequencing (ScienceNOW, 29 August, sciencenow.sciencemag.org/cgi/content/full/2007/829/4).

Wall adds that if the FOXP2result is real, it's possible that Neandertals acquired the human FOXP2variant by mixing. “If there was admixture, it wasn't very much. But we can't tell if there was a small amount.” Pääbo says he can't rule out that scenario but considers it “unlikely,” given the genetic data so far.

2. ENERGY POLICY

# National Academies Make Case for Sustainable Growth

1. Eli Kintisch*
1. With reporting by Richard Stone in Beijing.

Use energy more efficiently. Put a price on carbon emissions. Develop green energy sources.

Those recommendations on sustainable development, from a report released this week by dozens of the world's national science academies, may be familiar. But the scientists behind the 174-page effort believe that the urgency of the problem will make up for its lack of originality in grabbing the attention of policymakers around the globe, and they intend to launch a major effort to get the message out. “The goal is to work fairly deeply into governments,” says Hal Harvey of the Menlo Park, California-based William and Flora Hewlett Foundation, which helped fund the report, dubbed Lighting the Way.

The peer-reviewed report's recommendations reflect the diverse perspective of the 15 experts, nominated from more than 90 national academies, working under the auspices of the 7-year-old InterAcademy Council (IAC) in Amsterdam, the Netherlands. “Meeting the basic energy needs of the poorest people on this planet is a moral and social imperative” that technology transfer and international efforts could address, the report begins. On energy efficiency, it recognizes that most building construction will occur in cities of the developing world, and it calls on local governments and scientists to develop sustainable practices. California and Brazil are held up as models for energy efficiency and the use of biofuels. Report co-chair and director of Lawrence Berkeley National Laboratory Steven Chu calls the “international flavor” of the 2-year effort unique, noting that its proposed doubling of applied energy research says that the money must be “internationally coordinated.”

Co-chair José Goldemberg, secretary for the environment in São Paulo, Brazil, believes that governments are eager to hear those messages, and he notes that many national academies in the developing world already “have close ties to governments.” The report, requested by the science academies of Brazil and China, was rolled out this week with a workshop in Beijing and with plans for a follow-up symposium in Brazil. The Chinese Academy of Sciences brokered a meeting between Chu and Chinese Premier Wen Jiabao, and CAS President Lu Yongxiang announced plans, including the creation of a renewable energy R&D center, to help wean China from its heavy dependence on coal. A major element, Lu says, will be a rapid expansion of China's nuclear industry, which currently generates just 1.6% of the nation's power supply.

The report's emphasis on the developing world should be popular in Washington, D.C., predicts Paul Bledsoe of the nonprof it National Commission on Energy Policy. Although Bledsoe believes that “speedy U.S. action is a necessary precursor” to sustainable policies in the developing world, he notes that the willingness of developing nations to tackle the problem has been “the sticking point [in Washington] all along.” Roughly one-fourth of the $550,000 the Hewlett Foundation spent on the report is devoted to an international media push that would bolster outreach by individual academies. Chu hopes the new report will make a bigger splash than other academic efforts; previous IAC reports on women in science and African agriculture, for example, have caused barely a ripple. His model is the 2005 U.S. National Academies' report on U.S. science priorities, Rising Above the Gathering Storm, that served as the basis for the America COMPETES Act, which became law this summer. “We didn't make claims for originality,” says Chu, a member of that panel, too. “[But] that report was incredibly successful.” 3. NUCLEAR PHYSICS # Neutron-Laden Nucleus Pushes Limit 1. Adrian Cho Nuclear physicists are striving to find out how many neutrons can be packed into a nucleus. But a newly discovered nucleus suggests that the limit may be higher than theorists had thought—perhaps too high for experimenters to reach. The new nucleus, aluminum-42, contains 13 protons and 29 neutrons, so many neutrons that calculations had suggested that it could not form. Yet Thomas Baumann and colleagues at the National Superconducting Cyclotron Laboratory at Michigan State University (MSU) in East Lansing produced 23 copies of the highly unstable nucleus, as they report this week in Nature. “It's beautiful,” says Olivier Sorlin, an experimenter at the French laboratory GANIL in Caen. “I'm quite surprised that they found it. We tried and did not succeed.” Aluminum-42 could cast a long shadow in the study of rare isotopes. Physicists plot the known nuclei on a gridlike chart with the number of protons running up the chart and the number of neutrons running across it. The nuclei lie in a broad swath that is bounded above by the so-called proton drip line, which shows which combinations of protons and neutrons are too rich in protons to form a nucleus, and below by the neutron drip line, which shows which combinations are too loaded with neutrons to stick together (see figure). According to two theoretical models, aluminum-42 lies on the wrong side of the neutron drip line and should not exist, even fleetingly. If aluminum-42 exists, then aluminum-43, −44, and −45 may also exist, says MSU's Michael Thoennessen. That's because aluminum-42 has one lone neutron in a “shell” that can hold as many as four. In fact, the team spotted one possible example of aluminum-43, as well as the nucleus magnesium-40. But the possibility that 32 neutrons could be packed into the aluminum nucleus means that the neutron drip line may lie too far away to be reached even with new facilities such as Japan's Radioactive Isotope Beam Factory at the RIKEN laboratory in Wako or Germany's Facility for Antiproton and Ion Research under construction at GSI in Darmstadt, Thoennessen says. To make aluminum-42, the MSU team blasted calcium-48 nuclei, which have 20 protons and 28 neutrons, through a tungsten target. Very rarely, the violent collision stripped off seven of a calcium-48 nucleus's protons and gave it an extra neutron to make aluminum-42. To make aluminum-45, the incoming nucleus would have to snatch up four neutrons, an event so improbable that seeing it is “really at the edge of what's possible in any foreseeable future,” Thoennessen says. Not everyone is convinced that the drip line has retreated beyond reach. “It's an open question whether this [observation] pushes the drip line out generally or if there is a little bulge in that region” around aluminum, says Richard Casten of Yale University. Witold Nazarewicz, a theorist at the University of Tennessee, Knoxville, and Oak Ridge National Laboratory, says that the position of the drip line was not known precisely to begin with. “I think that most theorists would say that the models they looked at are simply not reliable for subtle details along the drip line,” he says. Even so, the existence of aluminum-42 undermines a key concept in nuclear physics, Sorlin says. Researchers know that nuclei with 28 neutrons are generally especially stable. So the fact that aluminum-42, with 29, holds together even for an instant suggests that the “magic number” 28 disappears at the drip line, Sorlin says. No matter where the drip line lies, aluminum-42 has given physicists plenty to think about. 4. NUTRITION # Dietary Guidelines Spark Flap Over Fish Consumption 1. Jennifer Couzin Recommendations from a nonprofit group urging pregnant women to boost their fish consumption—contrary to U.S. guidelines—sparked widespread criticism earlier this month, in part because the review was funded by the fisheries industry. The advisory from the National Healthy Mothers, Healthy Babies (HMHB) Coalition has been dismissed by health advocates and government officials alike. Yet some researchers not involved in the furor say that industry sponsorship should not obscure the fact that fish consumption has plummeted because of federal guidelines—and that standards should be reconsidered. In a statement issued on 4 October, HMHB and 14 researchers who reviewed the literature advised pregnant women to eat at least 12 ounces of fish each week to provide the developing fetus with brain-building omega-3 fatty acids. That contrasts with the position of the U.S. Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA), which in 2004 recommended that pregnant women consume no more than 12 ounces a week to limit their intake of mercury. Government agencies reacted swiftly to HMHB's pronouncement. Three of HMHB's members—the National Institute of Child Health and Human Development, the Centers for Disease Control and Prevention, and the Health Resources and Services Administration—rejected the advice in a letter in The Washington Post. FDA and EPA announced that their guidelines wouldn't be changing. Critics fault HMHB for accepting$60,000 from the National Fisheries Institute, an industry group, to disseminate the recommendations, along with honoraria of $1000 to$1500 per researcher. HMHB Executive Director Judy Meehan says the group gave no thought to how the industry funding would be perceived.

“People seem to have strong opinions” about fish consumption, but the science is “open to lots of interpretation,” says Gary Myers, a pediatric neurologist at the University of Rochester in New York who has helped lead a major study of fish consumption in pregnancy, in the Seychelles northeast of Madagascar. He and others say it's difficult to identify the tipping point at which the risks of mercury in fish outweigh the benefits of omega-3 fatty acids.

The topic also pits scientific disciplines against each other. “Environmental health people see the effects of mercury on the brain and get scared; nutrition people says there's this great nutrient and people aren't getting enough,” says Emily Oken, a nutrition researcher at Harvard Medical School in Boston who focuses on women's health. In her own study of 135 babies and their mothers, Oken found that higher fish consumption boosts cognition at 6 months of age, whereas mercury levels, measured in a mother's hair, decrease it. But on balance, she wrote in a 2005 paper in Environmental Health Perspectives, more fish in the diet was still associated with better cognition.

In general, scientists note that both the benefits and drawbacks of fish are small for individuals, although they can be significant across a population. Exposure is usually measured as mercury in maternal hair. Some studies show that an increase in this index is linked to very subtle cognitive changes, including reduced word recall and a 1-point loss in IQ. HMHB's guidance gave little weight to the risks of mercury and did not recommend that pregnant women avoid high-mercury fish.

Even some who worry that pregnant women consume too little fish say that HMHB's guidelines focus too much on the benefits of fish, just as the federal recommendations are faulted for overemphasizing the risks. In response, Patricia Nolan, a public health physician at Brown University who helped craft the HMHB recommendations, said in an e-mail that “we emphasized the positive because women are decreasing or eliminating already low fish consumption.”

But what's really needed, says David Bellinger, a neuropsychologist at Harvard Medical School, is a more nuanced review that would give pregnant women a fuller picture of how specific types and quantities of fish in the diet could affect their baby-to-be.

5. PUBLIC POLICY

# Watson Condemned for Comments on Intelligence

1. Yudhijit Bhattacharjee

James Watson visited the United Kingdom this month to promote his new book, Avoid Boring People: Lessons from a Life in Science. But the tour came to a premature and ignominious end last week after the 79-year-old Nobelist told a British newspaper that, in effect, blacks are less intelligent than whites. As Science went to press, Watson was back in the United States hoping to save his job as chancellor of Cold Spring Harbor Laboratory (CSHL) in Long Island, New York.

Watson has been the lab's most public face for nearly 40 years, serving as director and then president before becoming chancellor in 2004. His current responsibilities include fundraising for the 117-year-old nonprofit and helping transform it into a university. But the lab's board of trustees, of which he is a member, moved swiftly to distance the institution from him after he was quoted in the 14 October Sunday Times as saying that he was “inherently gloomy about the prospect of Africa” because “all our social policies are based on the fact that their intelligence is the same as ours—whereas all the testing says not really.”

Watson's comments in “no way reflect the mission, goals, or principles of Cold Spring Harbor Laboratory's Board, administration, or faculty,” explained CSHL President Bruce Stillman on 17 October. “Cold Spring Harbor Laboratory does not engage in any research that could even form the basis of the statements attributed to Dr. Watson.” In a second statement the next day, the board said it was suspending Watson “pending further deliberation.” As Science went to press, Jim Bono, a spokesperson for CSHL, said a decision was expected in the next few days.

Watson has a history of making sweeping remarks, including his suggestion in 2000 that libido is linked to exposure to sunlight. But this time he seems to have gone too far. “You get to the end of the rope at some point,” says one trustee who spoke to Science on the condition of anonymity. “The feeling was that something very inappropriate had occurred and some action needed to be taken.”

Watson has apologized for the remarks, which also prompted London's Science Museum to cancel a scheduled talk. “I cannot understand how I could have said what I am quoted as having said,” he told The Associated Press. “To all those who have drawn the inference from my words that Africa, as a continent, is somehow genetically inferior, I can only apologize unreservedly.” But in a 19 October commentary published in The Independent, Watson seemed also to put up a defense. “The overwhelming desire of society today is to assume that equal powers of reason are a universal heritage of humanity,” he wrote. “It may well be. But simply wanting this to be the case is not enough. This is not science.”

Neither were his own comments, says Harvard University psychologist Howard Gardner. “He has taken an extremely complex set of issues—what is intelligence, what is race, how valid are IQ tests—and reduced them to a provocative sound bite,” says Gardner. As someone “of almost unique prestige in the scientific community,” Gardner notes, Watson “has a special responsibility to watch his tongue.”

6. GLOBAL CHANGE

# Tinkering With the Climate to Get Hearing at Harvard Meeting

1. Eli Kintisch

Should scientists and engineers seriously consider large-scale alterations of the climate to stave off the worst effects of global warming? Several dozen top U.S. climate scientists will explore that controversial question next month in a 2-day invitation-only workshop at Harvard University designed to explore whether direct interventions might be needed to supplement efforts to reduce greenhouse gas emissions.

Curbing greenhouse warming manually, so to speak, could offer a more immediate and possibly simpler solution to climate change than the massive overhaul of energy systems that would be needed to cut global greenhouse gas emissions. Ideas include removing CO2 from the atmosphere by forcing air through absorbers or stimulating plankton growth, and shading the planet with aerosols. But many prominent climate scientists have been leery of even discussing such possibilities for fear that they could provide policymakers with an excuse not to cut carbon emissions, or that the technology comes with serious side effects. As a result, says Harvard geochemist Daniel Schrag, who is organizing the meeting, discussions have occurred mostly among advocates. “I wanted to get the mainstream climate community … to look closely at this thing,” he says.

The 8 to 9 November meeting will include climate heavyweights such as James Hansen of NASA, Kerry Emanuel of the Massachusetts Institute of Technology in Cambridge, and Mark Cane of Columbia University. Its focus will be on ways to lower the atmosphere's temperature, including releasing massive amounts of sulfates into the atmosphere to mimic the natural cooling effects of volcanic eruptions. Such an approach was publicized last year by Nobelist Paul Crutzen, an atmospheric chemist at the Max Planck Institute for Chemistry in Mainz, Germany (Science, 20 October 2006, p. 401).

Scientists pondering geoengineering ideas argue that such cooling schemes could be hard to control and wouldn't address the acidification of the oceans caused by CO2. Others worry that any discussion of the topic will undermine political momentum to cut greenhouse gas emissions. These include atmospheric scientist Elisabeth Moyer, who before leaving Harvard for the University of Chicago told Schrag that the conference should be held off campus or without publicity. “I had concerns about lending the conference the prestige of the Harvard name. … The conference can be viewed as an endorsement [of geoengineering],” she says. Even so, Moyer thinks that “it is critical to discuss the idea.”

Hansen says better forest practices, advanced agriculture techniques, and geologic carbon sequestration could supplement the real emission cuts required to stave off dangerous climate change and avoid the need for geoengineering efforts. He hopes to spread that message at the meeting. “The potential for stabilizing climate is more than realized,” he says. But he agrees with Schrag that geoengineering should still be explored, as future policymakers might seek to do it whether or not scientists understand it. “I don't think scientists should shy away” from the topic, he says.

The fact that the meeting is taking place at all marks a new phase of urgency among climate scientists, says modeler Ken Caldeira of the Carnegie Institution of Washington in Stanford, California. In a 1998 paper, Caldeira called the aerosol approach “a promising strategy,” although he argued that emissions cuts remain “the most prudent” course of action. “A decade later, a bunch of people are coming to the same point,” says Caldeira.

7. NEUROSCIENCE

# Two Therapies Release Different Brakes on Impulsive Behavior

1. Greg Miller

To unlock rigid limbs and restore their mobility, people with Parkinson's disease often require strong therapy, such as drugs that boost levels of the neurotransmitter dopamine—and if that fails, stimulating electrodes implanted deep in the brain. Yet these treatments can trigger impulsivity: Pathological gambling and hypersexuality have been associated with dopamine drugs, for example. Impulsive behavior can also accompany deep brain stimulation (DBS), but the electrical treatment promotes it in different ways than the drugs do, according to a study published online this week by Science (www.sciencemag.org/cgi/content/abstract/1146157).

Michael Frank and colleagues at the University of Arizona, Tucson, report that DBS interferes with patients' normal tendency to hesitate when faced with a difficult decision, whereas dopamine drugs interfere with the ability to learn from bad experiences. Although the study doesn't immediately point to ways to counteract such impulsive tendencies, other researchers say that the work does shed light on the neural mechanisms that control our thoughts and actions. “It's an advance towards understanding the architecture of cognitive control in the human brain,” says Adam Aron, a cognitive neuroscientist at the University of California, San Diego.

Frank and his team used a computer game to investigate decision-making in 15 people with Parkinson's disease taking dopamine drugs and 17 patients receiving DBS targeted to the subthalamic nucleus, part of the network of brain regions disrupted by the disease. In the initial learning phase, the participants saw pairs of unfamiliar squiggles (actually Japanese hiragana characters) and were told, without further instruction, to pick the one that was “correct.” Unbeknownst to the subjects, each character had a fixed success rate: In one pair, for instance, one character caused the word “Correct!” to flash on the screen 80% of the time, whereas the other was correct the remaining 20% of the time. With practice, the people generally picked the character with the highest success rate.

Next, the researchers presented new pairings of the same characters. Healthy subjects and medicated patients hesitated for a split second when faced with a pair of characters with similar success rates. DBS patients, on the other hand, made faster choices when the alternatives were similarly attractive. This tendency to rush close calls vanished when researchers tested the same DBS patients with the stimulating electrodes turned off. The findings, says Frank, bolster his group's suggestion that when a difficult decision presents itself, the normal role of the subthalamic nucleus is to send a “hold your horses” signal to other parts of the brain to allow more time to weigh the options. DBS interferes with this signal, leading to hasty choices, Frank hypothesizes.

Dopamine-boosting drugs had no effect on the speed of decisions, but they did reduce patients' tendency to avoid bad choices that had burned them in the past (such as picking the character with a 20% success rate). That fits with previous work, and it may help explain why some medicated patients with Parkinson's disease keep gambling despite repeated losses, says cognitive neuroscientist Roshan Cools of Radboud University Nijmegen in the Netherlands.

“What's really novel is the argument here that there are multiple pathways by which these impulsive behaviors can occur,” says Cameron Carter, a cognitive neuroscientist at the University of California, Davis.

8. ARCHAEOLOGY

# University Suppresses Report on Provenance of Iraqi Antiquities

1. Michael Balter

University College London (UCL), one of Britain's premier universities, has become embroiled in a dispute over its handling of a large collection of religious artifacts that may have been part of the illicit trade in archaeological relics from Iraq in recent years. Last year, a committee of experts UCL established to investigate the matter concluded that “on the balance of probabilities,” the artifacts were illegally removed from Iraq, and in the past months Iraqi officials have taken steps to recover the relics. Their actions come after UCL agreed this summer to return the collection to its owner, a wealthy retired Norwegian businessman who had sued UCL for their recovery. As part of a settlement of that suit, UCL agreed not to publish the committee's report.

“It is shameful that a university should set up an independent inquiry and then connive with the collector whose antiquities are under scrutiny to suppress the report through the vehicle of an out-of-court settlement,” says Colin Renfrew, an archaeologist at the University of Cambridge, U.K., and a longtime critic of trade in antiquities of questionable provenance. Renfrew was one of three experts appointed by UCL in early 2005 to look into allegations about the provenance of the Aramaic incantation bowls and to propose new antiquities guidelines. Neil Brodie, an archaeologist at Stanford University in Palo Alto, California, and former research director of Cambridge's Illicit Antiquities Research Centre—created by Renfrew in 1996—calls suppression of the report “an attack on academic freedom, because the illegal trade in antiquities is a legitimate research subject.”

Salah al-Shaikhly, Iraq's ambassador to the United Kingdom, told Science last week that Iraqi authorities have asked British authorities to block the export of the bowls and that the Iraqi government hopes to go to court to recover the bowls “in a matter of weeks.” The removal of the artifacts, al-Shaikhly says, is “a great loss to the Iraqi national heritage.”

The affair has also caused considerable discomfort within the university's Institute of Archaeology, which has played a leading role in developing strict antiquities rules. “I deeply regret the fact that the panel's report will not be published,” says UCL archaeologist Kathryn Tubb, who co-wrote the institute's guidelines. “The results of the deliberations were to have informed future policy for the whole of UCL.”

UCL officials have refused to comment on the matter, and Martin Schøyen, the owner of the bowls, declined to be interviewed for this story. But a series of press statements on the Schøyen Collection's Web site (www.schoyencollection.com/news.htm) explains that “any assertion that the bowls in the Schøyen Collection might be looted is incorrect.” The Web site notes that the artifacts came from a Jordanian collection “built over many years.”

The UCL committee of inquiry's report—a copy of which Science has reviewed—concludes that the bowls most likely left Iraq illegally sometime after August 1990, when Iraq invaded Kuwait. Schøyen subsequently bought them from dealers based in Jordan and London. The 94-page report says that the committee found “no direct evidence that positively contradicts or impugns Mr. Schøyen's honesty” in his account of how he obtained the bowls and credits him with “openness” in the way he purchased them. But it sharply criticizes UCL for agreeing to store the bowls without looking into their origins or “the manner in which Mr. Schøyen came to possess them.”

## “A potentially damaging position”

During the 5th to 8th centuries C.E., many people living in Mesopotamia (present-day Iraq) buried pottery bowls under the thresholds of their houses to ward off evil demons. The bowls were inscribed with biblical passages and other incantations in Aramaic, an ancient Semitic language. Today, about 2000 of these Aramaic incantation bowls are known to exist in public and private collections around the world. Schøyen owns one of the two largest collections, numbering 656, and beginning in 1995, loaned 654 of them to UCL's Department of Hebrew and Jewish Studies to be cataloged and studied. The research was led by linguist Shaul Shaked of the Hebrew University of Jerusalem, in collaboration with UCL's Mark Geller, an expert in ancient languages.

In September 2003, a documentary aired on Norwegian public television that questioned the provenance of a number of antiquities in Schøyen's collection—which is based in Oslo and London—including the incantation bowls. According to the committee's report, questions from the program's producers led UCL Vice-Provost Michael Worton to write Geller on 2 December 2003, directing him to make arrangements to return the artifacts to Schøyen—an order that the report says was never carried out. (Both Worton and Geller declined to comment on this and other matters related to the bowls.) UCL also consulted its attorney, who, according to the committee report, told UCL on 10 September 2004 that it was in “an anomalous and potentially damaging position” because it might be violating international and British antiquities laws by keeping the bowls—or returning them to Schøyen—if the bowls had been removed illegally from Iraq.

In early 2005, UCL set up the committee of inquiry that, Worton explained in a 16 May 2005 press release, would allow UCL “to be absolutely clear about the provenance of these bowls, and to satisfy ourselves that they were not removed illegally from their country of origin.” He said the committee's report would also “provide a model for best practice in dealing with the complex cultural issues that can arise from such situations.”

The committee—comprised of David Freeman of the London law firm Kendall Freeman; Sally MacDonald, now director of UCL Museums and Collections; and Renfrew—took testimony from three dozen witnesses, including Schøyen and two London-based antiquities dealers who, the committee determined, sold him many of the incantation bowls. Schøyen and the dealers told the committee that nearly all of the bowls had come from the family collection of Ghassan Rihani, a Jordanian antiquities dealer who reportedly died in 2001. But the committee found “unconvincing” two Jordanian documents that Schøyen offered in support of his claim that the incantation bowls had been legally transferred from Jordan to London.

In an interview with Science, one of the two London dealers, Chris Martin, says that Rihani had some incantation bowls in his collection at least “3 or 4 years” before the 1991 Gulf War. The committee calculated that Martin sold Schøyen 444 of the incantation bowls, of which at least 300 came from Rihani. After a time, Martin says, Schøyen began to buy directly from Rihani and, according to the report, acquired another 174 bowls this way.

The committee's report cites the testimony of four experts in ancient Mesopotamia that nearly all known incantation bowls come from Iraq, which since 1936 has forbidden the export of antiquities except for exhibitions and research. “The bowls were present in Iraq when the 1936 Law came into force … [and therefore] were the property of the State of Iraq” at the time that Schøyen purchased them, the report concludes, even if Schøyen may not have realized this. Nevertheless, the committee found that, under U.K. law, Schøyen could still claim title to the bowls if he had already possessed them for 6 years and could demonstrate that he had bought them in good faith.

## Claiming the bowls

The committee's report, dated 27 July 2006, contains a number of recommendations, including that it “be published in full.” Indeed, Renfrew told Science, the panel prepared the report “in the expectation that it would be published.” Nevertheless, the panel proposed delaying publication for 6 months while copies were sent to Schøyen, the antiquities departments of Iraq and Jordan, London's Metropolitan Police, and two other British government agencies. Although UCL officials have declined to comment on any aspect of the affair, Renfrew says UCL attorneys told the committee early in 2007 that the university would “omit the legal arguments and conclusions and recommendations” in summaries being sent to Iraq, Jordan, and the police.

The report has not been published, however. On 9 March 2007, the Schøyen Collection announced that it was suing UCL to recover the incantation bowls. A press release explained that it “has become frustrated with the waste of time and money caused by a lengthy and inconclusive inquiry into its provenance” and added that it had “los[t] confidence in UCL's conduct of its inquiries.”

Meanwhile, on 26 June, Schøyen and UCL issued a joint press statement signaling an end to the litigation. “Following a searching investigation by an eminent panel of experts, and further inquiries of its own,” the statement declared, “UCL is pleased to announce that no claims adverse to the Schøyen Collection's right and title have been made or intimated” and that “UCL has no basis for concluding that title is vested other than in the Schøyen Collection.” The bowls have been returned, the statement said, “and UCL has agreed to pay a sum in respect of its possession of them.”

Jenina Bas, media spokesperson for the Schøyen Collection, declined to say where the bowls are now located, citing “security reasons.” However, Shaked told Science that they are still in the United Kingdom. Al-Shaikhly says that Iraq did not immediately make a claim on the bowls because “lawyers in England are very expensive.” He adds that culture ministry officials in Baghdad discussed the matter for several months before agreeing to proceed.

In the meantime, Shaked says that he plans to continue his research. “It is my responsibility as a scholar to work on any ancient artifact that has information to tell us,” he told Science, staking out one side of a bitter debate among archaeologists about whether researchers should work with unprovenanced antiquities (Science, 28 April 2006, p. 513). The other side believes that researchers and collectors are morally obligated to carry out what archaeologists call “due diligence” into the provenance of the antiquities they work with. “Due diligence is at the heart of the discussion about the antiquities market,” says archaeologist David Gill of Swansea University in Wales. “If respected international institutions are unable or unwilling to release the findings of this process, archaeologists begin to smell a rat.”

Renfrew agrees with Gill's assessment of the situation. He calls suppression of the report a “huge mistake” and believes it was motivated by the university's desire to avoid a costly legal battle. “If so,” Renfrew says, “they have sold their souls for a mess of pottage.”

9. COMBATING MALARIA

# Battling Over Bed Nets

1. Leslie Roberts

A collision of big thinking and logistical realities has sparked an intense debate over how best to deliver bed nets to combat malaria in Africa.

Jeffrey Sachs is an impatient man. In a widely promoted editorial in The Lancet on 21 June, the economist, public health advocate, and head of Columbia University's Earth Institute lit a fire under the organizations and individuals involved in battling malaria. He called on international donors, in essence, to blanket sub-Saharan Africa in insecticide-treated bed nets (ITNs)—for free, and right now.

The delay in delivering bed nets “is one of the shocking crimes of our time,” says Sachs. He blasts donors for trying to save money instead of lives by targeting nets only to the most vulnerable groups, pregnant women and young children—and often charging the recipients a modest fee. That strategy penalizes the poor, who can't afford to pay, and fails to take full advantage of the “herd effect” nets can provide by reducing the numbers of mosquitoes that transmit the disease, Sachs argues. By contrast, providing one bed net for every sleeping space—which he estimates would cost about 60 cents a year per person—could slash malaria transmission in Africa by 90%, he says. In the absence of a vaccine, he maintains, free universal bed-net distribution, accompanied by rapid access to state-of-the-art anti-malaria drugs, is the best solution to Africa's malaria crisis, which kills an estimated 1 million people a year.

It sounds simple, and it's hard to argue with the goal, especially against someone of Sachs's stature. But some malaria experts disagree vehemently on whether such a grand plan is feasible, much less desirable. “There is no universal one-size-fits-all solution to malaria,” says malaria researcher Christian Lengeler of the Swiss Tropical Institute in Basel, who says he has developed a different perspective from 15 years of working on the ground in Africa.

Without question, bed nets are the best intervention available to prevent malaria. And everyone agrees that coverage, although rising, remains far too low. But they differ on whether giving a net to almost everyone, adults and children alike, is the best use of scarce resources. Critics complain that a big new program would disrupt existing strategies for malaria control that have worked reasonably well, if not perfectly. And they question whether donors would continue to foot the bill once malaria cases plummet and other diseases become relatively bigger killers of Africa's children.

“These are real substantive issues,” says Mark Grabowsky, the malaria program manager at the Global Fund to Fight AIDS, Tuberculosis, and Malaria, which was created in 2000 to help the world's poorest countries fight those diseases. “There are true believers on both sides,” agrees Richard Steketee, the science director of the nonprofit Malaria Control and Evaluation Partnership in Africa, headquartered in Seattle, Washington, which is helping Zambia scale up its ambitious malaria-control program.

Sachs did win a key endorsement from Arata Kochi, head of the Global Malaria Programme at the World Health Organization (WHO). In late August, Kochi announced that WHO would now recommend universal access to bed nets, free or at sharply reduced costs. Data just in from Kenya, showing a 44% drop in mortality following a huge upswing in bed-net coverage, “ended the debate” on how best to distribute them, Kochi said.

That may have been wishful thinking on Kochi's part. When Sachs started promoting his idea—which he estimates would cost $3 billion a year, including drugs—he touched a raw nerve in the malaria community, exposing existing fissures and reopening old wounds, and the debate has taken a nasty personal turn. As special adviser to directors general of the United Nations, past and present, and chief architect of the Millennium Development Goals, Sachs commands the global bully pulpit like few others. And he has used it to denounce those who resist his plan as obstructionists and even immoral. They, in turn, accuse Sachs of heavy-handed interference in country policies and of almost monomaniacally pushing his view to the exclusion of all others. “There is one way to do things, and that is Sachs's way,” says Nick Brown, who coordinates bed-net efforts for the National Malaria Control Programme in Tanzania, where these issues have recently come to a head. ## Net work Nobody disputes that ITNs work. A series of big clinical trials in Africa in the 1990s consistently showed a 20% drop in childhood mortality from regular ITN use. Even untreated nets protect against mosquitoes, at least until they rip. And the treated versions work even when they are torn, because they not only block contact but also repel or kill the mosquitoes that transmit the malaria parasite. Until recently, however, they have had to be retreated at least yearly, a significant hurdle. New long-lasting nets that are effective for 5 years are helping solve that problem. Lack of money for malaria control has been the big barrier to widespread net distribution. Over the years, donors and countries alike have scrambled to stretch dollars to get nets to where they would do the most good. That limitation gave rise to the consensus strategy—adopted in the late 1990s by WHO, the Roll Back Malaria Partnership, and donors such as the World Bank, the U.S. Agency for International Development, and the U.K. Department for International Development—of targeting those most likely to die from malaria: pregnant women and children under age 5. And because dollars were short, donors, health workers, and researchers also threw their support behind a strategy known as social marketing, which involves priming, or in some cases creating, a commercial net industry that, in principle, could help make nets available at prices most people could afford. This was the approach adopted in Tanzania, long held up as a model for Africa. The program there focused on “creating a net culture”: convincing people of the benefits of sleeping under nets and shoring up a retail industry to provide them. Because much of the country is too poor to pay full price, a voucher system was created to provide subsidized nets to the most vulnerable groups. Distributed at antenatal clinics, the printed vouchers entitled a pregnant woman to get an ITN for about$1 or $1.50, instead of$3 or $4. “It was the paradigm,” says Lengeler, who helped develop the Tanzania program. At a Roll Back Malaria summit in Abuja, Nigeria, in 2000, the leaders of malaria-affected countries set a target of getting bed nets to at least 60% of the vulnerable groups by 2005, a target that has since been boosted to 80% by 2010. But progress has been painfully slow. By 2002, less than 5% of African children, on average, were routinely sleeping under a bed net. And a disturbing inequity has persisted: Coverage across Africa has been far lower among the rural poor, who are at greatest risk of malaria, than among urban and wealthier people. ## Sea change All that began to change about 2003, with the congruence of a big jump in funding for malaria, new evidence that nets work even in the most challenging settings, and new models for net distribution. Thanks in no small part to the advocacy of Sachs and others and the entry of big donors such as the Global Fund, the Bill and Melinda Gates Foundation, the World Bank, and the U.S. President's Malaria Initiative, global funding has increased more than 10-fold over the past decade. Between 2003 and 2006, the Global Fund alone pumped$1.7 billion into malaria, and the number of bed nets it distributed in Africa surged from 1.35 million to 18 million. Available funds continue to climb, says Grabowsky: “The rate-limiting step is no longer money but the ability of countries to absorb it.”

Also in 2003, the last of the five big clinical trials of ITNs in Africa provided the firmest evidence yet of the so-called community effect, akin to the herd effect provided by vaccines. People in nearby control villages who weren't sleeping under nets experienced a substantial drop in malaria mortality as well. That's because ITNs, which in the trial were targeted to the entire household and not just vulnerable groups, were reducing the vector population and thus the chances a person would encounter an infected mosquito.

The new results from Kenya changed perceptions. They meant that bed nets, like vaccines, should be seen “as a public good, worthy of public support,” wrote William A. Hawley of the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and other leading malaria researchers in an accompanying article in The American Journal of Tropical Medicine and Hygiene. To make a real dent in malaria, everyone should have a bed net, Hawley and colleagues proposed. And increasingly, experts such as Sachs and colleagues Christopher Curtis of the London School of Hygiene and Tropical Medicine and Awash Teklehaimanot of the Earth Institute were saying bed nets should be free.

Exactly how many nets are needed for maximum impact is hard to quantify. A 2007 study by Gerry Killeen of the Ifakara Health Research and Development Centre in Tanzania and others, including Lengeler, suggests that 60% coverage of all adults and children is enough. Sachs thinks it is closer to 80% and argues that the cost is so low, it is absurd to settle for less than full coverage. Whatever the number, “there is likely some incremental value to every bed net in the community,” says Grabowsky.

People widely credit Grabowsky for coming up with the model that would transform net delivery. Then in charge of measles vaccination for Africa for the American Red Cross, Grabowsky decided to piggyback ITN delivery onto the measles infrastructure. Pilot projects in Ghana and Zambia in 2002 and 2003 began giving out free bed nets to every family with a child younger than 5 years old during measles vaccination campaigns.

The first nationwide campaign was launched in Togo in 2004: Over the course of 7 days, about 900,000 nets were distributed free of charge, and the number of households owning a bed net skyrocketed from 5% to 91%, says Grabowsky, who adds that education is essential to ensure that ownership translates into use.

Sachs raves about the results. These joint campaigns “have the capacity to reach the very isolated rural areas in the poorest countries,” Sachs told Science. “It is astounding how much coverage it is possible to get in these campaigns. In 2, Niger, a 1- or 2-week campaign gets 70% to 80% coverage.”

Other countries and donors, such as the Global Fund and the U.S. President's Malaria Initiative, took the cue. Since then, there have been a dozen more mass campaigns, in Ethiopia, Kenya, Niger, São Tomé and Príncipe, Angola, and Rwanda, to name a few, usually integrated with measles immunization or other childhood interventions. One of the biggest is now under way in Zambia, which is on target to provide bed nets to 80% of the population by 2008 (see sidebar).

## Free for all

That's the model Sachs wants to capitalize on. But rather than giving nets to children only, he wants countries and donors to give out enough nets for every sleeping space, roughly three per household. This would protect children and adults alike and remove the reservoir of infection, taking full advantage of the net's community effect. He thinks it should be done within 4 years, if not sooner.

Who could be opposed? asks Lengeler: “In theory, we would all love to do it.” But in reality, he and others say, it might not be the best strategy to try to reach almost every person in Africa, especially single men, who have no regular point of contact with the health system. Early in the Zambian effort, for instance, the military was engaged after nets sat around unused for months, says Steketee, who concedes that campaigns are taxing, time-consuming, and hard to organize, but worth it. Skeptics say discussions of Sachs's plan tend to gloss over those difficulties. And even Sachs's staunchest supporters agree, confidentially, that although he is a brilliant advocate for malaria, his genius does not lie in such operational details.

Lengeler also questions whether Sachs's scheme is worth the cost, because covering even half the population still provides considerable community protection. He suggests donors could get a bigger bang for the buck by doubling the salary of health-care workers in Africa and ensuring regular drug supply instead.

The program in Tanzania, where 95% of the population lives in highly malarial regions and the disease claims 100,000 lives a year, has become a battleground in this debate. In many ways, the national malaria-control program, which received one of the first grants from the Global Fund in 2003, has been a success, says Brown, who coordinates the program's ITN efforts. The country now boasts four domestic net manufacturers and some 5700 retailers, mostly small stores that also sell soap, sugar, and batteries. But bed-net coverage hasn't climbed as fast as anyone would like, and it has remained stubbornly low among the rural poor. By 2006, “we covered 35% of the children and 25% of adults,” says Lengeler. “That is clearly too low. … We accept the criticism.”

The various partners working in Tanzania set out to fix those problems last spring, holding a series of meetings to chart a way forward. The debates were intense, with some arguing to jettison the voucher scheme, and Lengeler, Brown, and many of the donors saying don't throw the baby out with the bath water.

One of their chief concerns was that Sachs's plan would destroy the commercial market that has been built up so carefully over the years in Tanzania. “It's all your eggs in one basket,” says Lengeler. “If the government plans a mass campaign and it doesn't happen, there is no backup.” And if campaigns aren't repeated, he warns, within 3 to 5 years, the country “will go backwards. Nets are destroyed or lost, new babies are born, and it happens fast.”

With Tanzania's application for continued support due to the Global Fund in July, the partners settled on a middle ground: They would continue giving out the vouchers but increase their value so that the maximum a woman would pay would be 40 cents per net. They would also switch to the more expensive long-lasting nets, which cost about $5 each. And in 2008, they would launch a massive catch-up campaign to give a free net to each child younger than 5. Sachs, however, wasn't impressed. When he jetted into Dar es Salaam for 2 days in July, he tried to convince the president and the minister of health to change course and rewrite the proposal. In a series of e-mails and phone calls before and after his visit, Sachs blasted the Tanzanian plan in general and Lengeler in particular. Tanzania is being encouraged to be bold, and Lengeler is standing in the way, Sachs wrote to one of Lengeler's colleagues. He called Lengeler's defense of the current system “shocking” and “reactionary.” In an e-mail to Lengeler, Sachs dismissed his approach as “disreputable” and “economically ignorant.” “Jeff Sachs is entitled to his opinion,” responds Alex Mwita, the National Malaria Control Program manager in Tanzania's Ministry of Health. But he denies that Lengeler blocked anything. “No partner was interfering. It is the government that makes policy.” And the priority is clear, he says: Get nets out fast, whichever way works best. Mwita adds that he is all for universal coverage: “Everyone deserves to be protected … if we have the resources,” he says. “We would need$200 million for universal access in Tanzania. That is almost three-fourths of the Ministry of Health budget. The government doesn't have that much money. Bill Gates can give it. Or Warren Buffet can. … But you can't depend on Bill Gates and Warren Buffet always.” Until such funding is assured, Mwita says Tanzania will continue to focus its efforts on getting bed nets to children who are most at risk of dying.

And so the debate continues, with more commentaries in various journals and more phone calls between Sachs and Tanzania's president. The Tanzanian Ministry of Health submitted its proposal as written, although at Sachs's urging, it is now drafting a new proposal for a free mass campaign in 26 of Tanzania's hard-hit districts. Sachs, who is pushing for a nationwide campaign and says he has the president's support, has vowed to find money for it. Meanwhile, Sachs has continued to rebuke the skeptics on the global stage.

## Resolution?

Grabowsky is optimistic that the feuding factions will coalesce eventually, if not this year, around a game plan for getting bed nets out fast to most, if not all, of the population. And there is still a long way to go. A recent study estimated that as many as 264 million nets are needed just to reach the Abuja goal—80% coverage of vulnerable groups—much less fulfill Sachs's vision of universal coverage.

There will need to be catch-up and keep-up strategies, says Grabowsky, and to date, few countries have managed to implement both. There is probably room for multiple approaches, even vouchers and the commercial sector, he suggests. He says the Global Fund is “agnostic” on which approach countries should take; its strategy is to fund those programs that seem to have the best chance of working on the ground. And right now, there are lots of experiments but few definitive answers, he says.

As for the intensity of the debate Sachs has ignited, Grabowsky says, “at its best, public health is a public process. We are all better off having a vigorous debate. There was a time when few people cared about Tanzania's malaria problem. Now we all do.”

10. COMBATING MALARIA

# A Proof of Principle

1. Leslie Roberts

What if money were no object and you could employ all the weapons that exist today to fight malaria in one country? How much could you reduce mortality? That experiment, known as the Malaria Control and Evaluation Partnership in Africa (MACEPA), is going great guns in Zambia.

A collaboration of the Zambian government, the various Roll Back Malaria partners, and the nonprofit PATH (Program for Appropriate Technology in Health) in Seattle, Washington, the Zambia project is employing long-lasting insecticide-treated bed nets, indoor spraying with insecticides, and rapid access to the most effective antimalarial drugs, artemisinin-based combination therapies. Started in 2005 and funded by the Bill and Melinda Gates Foundation, the World Bank, and the Global Fund to Fight AIDS, Tuberculosis, and Malaria, the goal of the project is to slash malaria mortality 75% by 2008, an achievement that has been estimated to cost between $30 million and$50 million a year. It is well on its way to achieving that goal, says the scientific director of MACEPA, Richard Steketee of PATH.

With MACEPA's support, the Zambian government aims to deliver bed nets to 80% of the population, adults and children alike, by the end of 2008. The first year was not a rousing success. The partners finally called on the military to help distribute the 526,500 nets that were sitting unused in Lusaka—the running joke is that they probably spent more on gas than on nets. For the second shipment of 200,000 nets, they settled on a decentralized plan. Nets are now delivered directly to districts where health-management teams work with local leaders to arrange big community events where people come to pick up their nets. Health teams are trained to explain why and how nets should be used, a key component in any net-distribution strategy, says Steketee. It is working, he says. Last year, 1 million nets were distributed, and this year, the target is 3.4 million. “By the end of the year, we will be close to covering the entire nation with three nets per household.”

Mass campaigns are supplemented by net distribution during vaccination campaigns and at antenatal clinics, where women pay about 50 cents for a net, although next year, nets may be provided for free, says Steketee.

Of course there are problems and nets that go undistributed, he says. “But we have seen a huge drop in malaria. Houses with nets have way less malaria and less severe anemia in young kids. It is entirely consistent with the data from controlled trials.” And although final data on mortality reduction won't be available for a year or two, evidence so far “consistently shows a good number of lives are being saved.”

11. COMBATING MALARIA

# Malaria Treatment: ACT Two

1. Martin Enserink

An influx of money and a new generation of drugs called artemisinin-based combination therapies (ACTs) are raising optimism that malaria's toll can be reduced

KUNKURA KEBELE, ETHIOPIA—Fanta Dargie and his family live in a modest mud hut, furnished with little more than a table, a few chairs, two hammocks, and some shelves holding the basic necessities for life in Ethiopia's poor countryside. And yet, he's on the forefront of a medical revolution.

Hidden in a corner on the dusty floor of Dargie's hut, in a hamlet 450 kilometers north of Addis Abeba, is a white box the size of a photocopier. After opening a minuscule padlock, Dargie shows the contents: blister packages containing the latest generation of malaria drugs. Rummaging through the box, he also pulls out dozens of simple diagnostic tests, each smaller than a cigarette lighter, as well as rubber gloves, some pens, and meticulously filled-out patient forms.

Every morning before Dargie goes to work, people from his and surrounding villages can come see him if they, or their children, have a fever. He will draw a drop of blood and test it for the presence of Plasmodium falciparum, the deadliest malaria parasite, a procedure that takes just minutes. If the test is positive, he can immediately give the patients free pills to take home, along with simple instructions on how to use them.

Dargie, a farmer who volunteers as a “community health worker,” knows all about the importance of the drugs distributed in this study. He lost two children to malaria. “I don't want that to happen to other people,” he says.

Many people ask why it has taken so long. The new generation of drugs, called artemisinin-based combination therapies (ACTs), has been around for a decade. They're effective and easy to use, and they cost less than $2 for a potentially lifesaving 3-day treatment course. And yet, a shortage of money, a lack of political will, and logistical problems have long prevented the drugs from reaching those who need them—especially in Africa, where malaria kills an estimated million people a year. Not any more. Money to buy the drugs has started pouring in through agencies such as the Global Fund to Fight AIDS, Tuberculosis, and Malaria. Affected countries have become serious about introducing ACTs, and they are coming up with new ways—such as the pilot project Dargie is participating in—to bring them almost to the patient's doorstep. These fine-grained distribution systems are a logistical puzzle—but they're crucial, because a child can die from malaria within 24 hours of the onset of the first symptoms. Meanwhile, an unprecedented new plan to serve private markets through a “global subsidy” may see the light of day next month. This new push to introduce ACTs—along with the massive distribution of insecticide-treated bed nets (see p. 557)—is giving many malaria fighters hope that, after years of failures and broken pledges, they may finally be on the cusp of making a significant dent in the disease's toll. The experience in places such as Zanzibar, where new data suggest malaria transmission has collapsed, has given them hope that results may come fast as well. “We do get real, perceptible, stunning results,” says Kamini Mendis of the World Health Organization (WHO) in Geneva, Switzerland. “I really think we are in a good position now,” adds Nicholas White, a malaria researcher at Mahidol University in Bangkok, Thailand, who has long battled to get ACTs introduced. ## An old new weapon Artemisinin is a compound derived from Artemisia annua, or sweet wormwood, a plant that has long been known to help fight fever in China. After groundbreaking Chinese studies in the 1970s, the compound made its way to Western labs in the 1980s. Along with a small slew of chemical relatives, it was found to be highly effective against Plasmodium, and despite widespread use, especially in Asia, there have been few signs of resistance in the malaria parasite. To keep it that way as long as possible, experts agree that the drugs should always be taken with another, existing malaria drug. Hence the combination therapies. But as the evidence of their efficacy grew—and older drugs such as chloroquine and sulfadoxine-pyrimethamine became increasingly useless—patients still weren't benefiting. “I think we were naive to think that evidence would naturally translate into new policies,” White says. “It does in rich countries. But in Africa, mothers who lose their child don't come banging on the doors of Parliament.” Money was long a key problem, but so was institutional inertia. Compared with older drugs, which cost a dime or less per treatment course, the cost of ACTs was prohibitive for many African governments. Although WHO officially started advocating ACTs in 2001, it didn't push hard enough for the switch, says White. A vast partnership called Roll Back Malaria (RBM), launched to much fanfare in 1998, also proved a disappointment. Comprised of almost every organization or agency involved in malaria, RBM went through one leadership change after another and ended up in turf battles with WHO; meanwhile, a set of ambitious targets set in the Nigerian capital Abuja in 2000—including the plan to halve the malaria burden by 2010—were going nowhere. “There was far too much talk, and endless meetings, but no action,” White says. Donor countries and the Global Fund, too, have come under fire for not acting swiftly enough. Leading the criticism has been Amir Attaran, a Canadian law professor and immunologist, who, with others, accused the fund and WHO of “medical malpractice” in an article published in the 17 January 2004 issue of The Lancet—a charge that the organizations say was unfair and based on inaccuracies, but which they also recognize as having helped speed change. Meanwhile, there were problems with the supply of artemisinin as well. The compound is extracted from A. annua plants, grown mostly on farms in China and Vietnam that had trouble keeping up with the booming demand. Researchers are working to synthesize the compound or make Escherichia coli churn it out (Science, 7 January 2005, p. 33), but this is expected to take at least another 5 years. The landscape looks very different today. Donors are pushing ACTs, and a United Nations Children's Fund (UNICEF) report issued last week showed that all but a few African countries have switched their policies—at least on paper—to make ACTs the standard treatment. Although long-term worries about the artemisinin supply remain, the price has come down sharply. Pharmaceutical companies have started mass-producing four WHO-recommended ACTs, and the Medicines for Malaria Venture (MMV) in Geneva, Switzerland, has three more combinations in phase III clinical trials. Many say RBM is working better since the latest reform, 2 years ago. But the biggest change has been the increasing political attention and the new money. Few would have predicted 10 years ago that a U.S. president would celebrate Africa Malaria Day—and do a goofy dance with a West African dance company—at the White House, as President George W. Bush did last May. (“I think I made his day by saying the European Union should do the same,” says MMV President Chris Hentschel, who attended the event.) The Global Fund is flush with cash, and other funds—such as Bush's 5-year,$1.2 billion President's Malaria Initiative and UNITAID, paid for by a tax on airline tickets in eight countries—have also begun disbursing money.

As a result, more than 100 million ACT treatment courses found their way to patients in 2006, up from just 3 million in 2003. Some 63 million of those were a combination of artemether and lumefantrine, produced by Novartis under the brand name Coartem; the company is making more of it than any company has ever produced of any drug, a Novartis spokesperson says.

That doesn't mean there aren't still major problems. One hundred million is less than one-fourth of the number of malaria treatments taken worldwide every year. And the UNICEF report shows that in 14 sub-Saharan countries for which good data were available between 2004 and 2006, Zambia provided just 13% of febrile children with ACTs; all the others scored less than 6%. (The numbers are expected to be much higher in the next survey.)

Procedures to apply for the drugs through the Global Fund are complicated and lengthy, says Mendis; many countries saw their proposals rejected in the fifth and sixth round of funding. Because countries often apply with integrated control plans, ACT delivery can suffer if, for instance, a country's bed-net strategy is judged insufficient. RBM and other organizations are helping countries put together better proposals for the current, seventh round.

But even when the drugs arrive, the logistics of distributing them are often difficult. Several ways to change that are on display in Ethiopia, where 50 million people live in malaria-ridden areas. The government is in the process of employing 30,000 health-extension workers, who, after a full year of training, visit villages and dispense medicines as well as advice for prevention and family planning. They play an indispensable part in delivering ACTs, says Ethiopia's federal health minister Tedros Ghebreyesus, who also chairs RBM's board. Ethiopia has also earned praise for delivering almost 20 million insecticide-treated bed nets within the past 2 years.

The program in the northern province of Tigray in which Fanta Dargie participates goes a step further. Instead of distributing ACTs through clinics or salaried health-extension workers, it uses community volunteers who have received just a few days of training. In this trial, supported by WHO and Novartis, researchers are trying to find out whether distributing ACTs this way is safe, what the effects on morbidity and mortality are, and how many are used, says Asefaw Getachew of the Carter Center in Addis Abeba, who coordinated the trial while at the Tigray Regional Health Bureau.

But many are already convinced that distribution through volunteers will prove the way to go—especially for the rural poor who live too far away from a clinic or health post to take their sick child, says Awash Teklehaimanot, a malaria expert at Columbia University's Earth Institute in New York City who also runs the Center for National Health Development in Addis Abeba. There are concerns about overuse, but the lack of resistance seen so far suggests “that we shouldn't be too conservative,” he says. “It's no use hoarding these drugs in health centers when people are dying in the village.”

But although many applaud Ethiopia for expanding its health-care system, the private market is a different story, and for now, it's the bigger one. At the moment, some 75% of malaria patients worldwide buy their drugs at a local pharmacy or drugstore, where ACTs, if available at all, are often much more expensive than a bewildering array of older drugs, artemisinin monotherapies, traditional medicines, or counterfeit drugs.

The plan for a global subsidy—although it might also benefit public procurements of ACTs—is hoped to have the biggest impact in this private business. The idea is that consumers will choose ACTs if they cost 10 cents or less; to get there, while still allowing wholesalers and retailers their usual profit margin, a new fund—recently christened Affordable Medicines Facility for malaria (AMFm)—would make a substantial copayment to the producer whenever a wholesale company or government agency decides to buy a shipment of WHO-approved antimalarial drugs. The goal is for the buyer to pay just 5 cents per treatment course—including shipment to the country. The current plan calls for an annual budget climbing to $300 million by 2010; UNITAID has expressed an interest in footing the bill. First proposed in a 2004 Institute of Medicine report from a group led by economist and Nobel laureate Kenneth Arrow, the idea languished for a while; some worried that a subsidy would line industry's pockets, whereas existing funding agencies felt it threatened their turf, says Harry van Schooten of the Dutch Ministry of Foreign Affairs, which has been pushing the plan. But it gained traction after a January meeting in Amsterdam, and now agencies such as the Global Fund, UNICEF, and WHO are vying to host the AMFm's secretariat, he says. RBM's board is expected to approve the plan at a November meeting. Still, the devil is in the details, says WHO's Mendis. Dealers may be tempted to charge high prices for ACTs anyway, for instance. “How do we prevent the subsidy from going to the pockets of the middlemen?” she says. Several measures can help prevent that, answers Van Schooten; ACT packages could have a printed price on them, patients will need to be educated, and countries will have to regulate their domestic ACT market and monitor drug quality. Whether African governments are up to that job remains to be seen. Other concerns remain as well. A stagnating demand for the raw product in 2007 has caused artemisinin prices to drop from a high of$1100 to $1400 a kilogram to about$200 now. At that rate, farmers can make more by planting rice, says WHO's Andrea Bosman, who worries about new price hikes and shortages in 2008. And although the lack of resistance to ACTs is encouraging, that is probably just a matter of time, and new drugs need to be developed rapidly, says Ghebreyesus. “What's plan B? We don't have alternatives at the moment,” he says.

But these concerns can't dampen the sense of optimism in the air for the first time in many years. Whether that means Abuja's goals can still be met is under dispute. Attaran—who does concede major progress—believes far too much time has been wasted for that. Former Senegal health minister and RBM executive director Awa Marie Coll-Seck asserts they're still achievable—or at least in some countries. So does Teklehaimanot, who coordinated a Millennium Project working group that proposed setting an even more ambitious goal: a 75% reduction from the 2005 level in 2015.

The truth is that we may never know for sure, says Mendis. Malaria mortality can only be estimated because many patients die at home without being counted, and although much is being done to strengthen data collection, there are few baseline data for 2000 on which claims of success could be based.

But things such as bed-net and ACT coverage can be measured more easily, and where they have shot up, malaria rates appear to be dropping encouragingly fast, she says. In Zanzibar, for instance, where ACTs and bed nets were widely introduced from 2004 on, cases had dropped by almost 90% in the first half of 2006. São Tomé and Príncipe, a small island nation off Africa's West Coast, has also seen its rates plummeting, says Teklehaimanot. In Ethiopia, malaria now accounts for 10% of deaths, compared with 25% a few years ago, says Ghebreyesus.

Those developments—as well as encouraging reports from vaccine trials—have even brought back a word last heard in the 1960s in the context of malaria: eradication. “To aspire to anything less is just far too timid a goal for the age we're in,” Melinda Gates, who, with her husband, Bill, has invested billions in the malaria battle, said last week at a meeting in Seattle, Washington.

But others say it's much too early to talk about that. For White, all the newfound optimism is cause for a new worry: What if the fight is so successful that politicians and donors lose interest? “We better get prepared for the next phase,” he says, “because there will be a lot of good news in the next few years.”