News this Week

Science  02 Nov 2007:
Vol. 318, Issue 5851, pp. 726

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    CDC Director's Message on Risk Runs Afoul of White House Edits

    1. Eli Kintisch
    A matter of words.

    Senator Barbara Boxer (D-CA) and CDC Director Julie Gerberding (right) confer before a hearing on health impacts of climate change.


    Late on Monday evening, 22 October, the director of the U.S. Centers for Disease Control and Prevention (CDC) settled into a Washington hotel room for a ritual familiar to bureaucrats who regularly brief lawmakers: a late-night cram session with a three-ringed briefing binder. Julie Gerberding, was testifying the next morning before the Senate Environment and Public Works committee, which was holding the first-ever Senate session on the health impacts of climate change. Next to her was a 12-page summary of the scientific issues, prepared by agency researchers, to be distributed at the hearing.

    But shortly before the hearing began, Gerberding learned that the White House Office of Management and Budget (OMB) had slashed the handout in half. Gone were details on how climate change could worsen allergic diseases, exacerbate deadly heat waves, and broaden the geographic range of infectious diseases. Gerberding didn't flinch. As she presented her 3-minute opening statement, a slide listed asthma, allergies, and harmful algal blooms as “potential negative health impacts.” She expanded on those issues in response to questions from the committee chair, Senator Barbara Boxer (D-CA), and other members. The cuts didn't come up.

    But the matter didn't end there. Within hours, reporters had their hands on the original version. It asserted, among other things, that the United States “is expected to see an increase in the severity, duration, and frequency of extreme heat waves” and that studies showed higher urban temperatures could increase ground-level ozone, worsening asthma and “chronic lung diseases.”

    Why was her written testimony altered so severely? A White House spokesperson said the edits were done because details “didn't align with” the conclusions of the Intergovernmental Panel on Climate Change (IPCC), the group of thousands of scientists whose reports earned it this year's Nobel Peace Prize (Science, 19 October, p. 372). The president's science adviser, John Marburger, went into more detail 2 days later in a rare explanation of his role. Marburger said staff found “appropriate connections between climate change and human health” in the draft but criticized “several nuanced but important differences between the IPCC report's findings and the draft testimony.”

    Cutting-edge science.

    Science adviser John Marburger suggested removing parts of Gerberding's scheduled Senate testimony.


    Boxer called the editing the latest example of the White House “interfering [with] the scientific facts.” And in private, CDC scientists were outraged. “They gutted it,” said one. “For them to say that other agencies had a problem with it is just a weak cover … for suppressing the science.” Gerberding says she got across her message, namely, that “from a public health perspective that climate change is an important … issue.” But she told Science that she regrets that the incident has “raised questions about the credibility of the CDC science.”

    Central to the controversy is whether Gerberding had accurately represented what's known about the effects of climate change on global health. On heat waves, IPCC this year assigned “medium confidence” to the assertion that climate change has already led to “increased heat-wave related deaths.” OMB removed words in the CDC handout describing the “likelihood of higher mortality” among the elderly from a heat wave. (In her oral remarks, Gerberding mentioned the more than 25,000 fatalities linked to the 2003 heat wave in Europe but focused on how U.S. officials were dealing with the problem.)

    In terms of infectious diseases, the IPCC's 2007 report mentioned a recent study showing a Vibrio bacteria outbreak in oysters “linked to atypically high temperatures in Alaskan coastal waters.” It noted that extreme spring rains in North America and Europe “may explain” patterns in cryptosporidiosis bacterial disease. Both examples were cut from the handout and went unmentioned at the hearing.

    Gerberding, an infectious-disease scientist, says her role didn't require her “to go into detail on every single complication of climate change. … Rarely, if ever, does the written testimony get read [by the public].” But Rick Piltz, formerly of the White House Climate Change Science Program, disagrees. “The official statement on a problem from the top-ranking public health official to Congress? It matters.”

    Those familiar with the process say the testimony, submitted to the White House 5 days before the hearing, was vetted by agencies including NASA, the Environmental Protection Agency, and Marburger's Office of Science and Technology Policy (OSTP). But Gerberding said none of the comments she saw were “showstoppers.” OSTP, for example, took issue with specific wording on hurricanes, food scarcity, and mental health. An OSTP official says that the office “had no problem” with sections on infectious diseases and heat waves but that “I don't know what happened to our edits,” which were submitted on Monday. Marburger's statement said that OSTP “did not seek to redact sections.”

    Gerberding says she's skeptical of the OSTP assertion that OMB's heavy editing was necessary because of insufficient time to reconcile the various comments, calling that “just a hypothesis.” She's asked her staff to review the 12-page draft and the vetting process “to make sure this doesn't happen again.”

    If the goal was to suppress the issue, extensive media coverage suggests that the attempt failed. Gerberding says she'd be pleased if the flap about her testimony leads to more talk about CDC's role in studying climate change, calling it “a silver lining.” She says she has tried to “get this issue on the map for public health, and I will continue to do so.”


    Drone Spy Plane Helps Fight California Fires

    1. Jon Cohen

    SAN DIEGO, CALIFORNIA—One unsung hero in the weeklong battle against the massive wildfires that devastated southern California last week was an unmanned Predator B airplane, originally designed to gather intelligence for the military. By providing firefighters with up-to-the-minute data on the many conflagrations, it helped in the coordination of firefighting efforts that spared many lives and structures—including the venerable Palomar Observatory.

    The plane now flies for NASA and the U.S. Forest Service, which have outfitted it with state-of-the-art, thermal-infrared sensors to help firefighters decide where to do battle. The 5-year demonstration project, dubbed Ikhana after the Native American Choctaw word for “aware” or “intelligent,” transmitted hot-spot data to a satellite. Within 15 minutes, fire command centers all over San Diego received color-coded Google Map images that indicated the temperature on the ground at different locales. “The fire commanders love the data,” says aerospace engineer Brent Cobleigh, who leads the project from NASA's Dryden Flight Research Center inside Edwards Air Force Base.

    The Forest Service for 40 years has relied on images from piloted planes, notes Everett Hinkley, a lead investigator on the project who is based at the Forest Service's Remote Sensing Applications Center in Salt Lake City, Utah. Ikhana represents a technological step up, he says, with a novel sensor that can penetrate smoke and delineate hot spots by detecting temperature differences as small as 0.5° up to 1000°C. “We can get very finite and fine temperature discrimination from surface events,” says Vincent Ambrosia, Ikhana's principal investigator at NASA's Ames Research Center at Moffett Field, which developed the sensor.

    Ikhana's near-real-time information is also a huge improvement. Piloted airplanes don't have this equipment and can only transmit their data by airdrops or after they land, so several hours often pass before firefighters receive it. “In an environment like southern California, with very high winds and fires moving rapidly, thermal imagery can be out-of-date quickly,” says Hinkley. NASA hopes eventually to transfer that capability to piloted planes.

    Ikhana's pilots sit in a trailer at NASA's Dryden Center, so the plane can fly into dense smoke plumes or high winds without putting a crew's life in danger. Ikhana can circle a hot spot for hours on end, for example, and fly for as many as 30 hours straight, assignments that would severely stress an onboard crew. Ikhana made its first flights over fires in August, but the dozen fires that burned in San Diego County last week put it to a tougher test. “Everything's happening a lot faster,” said Ambrosia on Friday, 26 October, the third day of Ikhana's San Diego mission.

    That day, the plane flew over the Poomacha fire, which came within several kilometers of the Palomar Observatory. Owned and operated by the California Institute of Technology, the observatory's five telescopes include the 508-cm “Big Eye.” Astronomer W. Scott Kardel, a spokesperson for the observatory who had to evacuate his own home nearby, said, “I don't know of a fire that's ever been this big of a threat here.”

    Getting the picture.

    Thermal-infrared images from the unmanned Ikhana (inset) helped firefighters battle the Poomacha fire near San Diego's Palomar Observatory.


    Fortunately for the observatory, the Poomacha fire was one of the last to break out. “Many other fires had reached their conclusion, and support from across the state had arrived,” says Kardel. “If we had been first to break out, we'd be talking about what a great place this used to be.”

    With the demonstration project coming to an end, researchers are awaiting word on a funding request to sustain the effort. Money isn't the only hurdle, however. Strict rules about flying unmanned aircraft in prime national airspace (Ikhana flies at an altitude of 7 km) make it difficult to secure permission for each flight. And NASA's mission to develop these technologies doesn't cover responding to natural disasters. That puts Ikhana's future as a firefighter up in the air.


    Tumor Suppressor May Also Affect Gestational Diabetes

    1. Jennifer Couzin

    Stanford University's Seung Kim was treating cancer patients when he first encountered a clue about the biology of diabetes. The patients suffered from a rare inherited syndrome called MEN1, or multiple endocrine neoplasia type 1, which triggers tumors in endocrine glands. In some cases, beta cells in the pancreas multiply and overproduce insulin.

    This reminded Kim of a very different state: pregnancy. There, placental signals and the burden of a fetus lead to insulin resistance and a demand for more hormone. An unlucky 4% of women cannot produce enough and are diagnosed with gestational diabetes.

    Supply problem.

    Insulin-making beta cells in normal pregnant mice expand to meet demand (top), but not in mice with higher levels of menin protein (bottom).


    On page 806, Kim, a developmental biologist, and his Stanford colleagues describe a connection in mice between menin, the protein encoded by the MEN1 gene, and gestational diabetes. Menin had long been known as a tumor suppressor; MEN1 occurs when the protein is lacking. Now, Kim and his colleagues report that in healthy animals, menin inhibits the replication of beta cells. Dialing it down allows beta cells to proliferate, increasing insulin supply. It's a clever insight, says Robert Sorenson of the University of Minnesota, Minneapolis, who studies how these cells adapt to pregnancy: “I knew about multiple endocrine neoplasia, for years and years, … but I never thought about linking it to pregnancy.” If its role holds up in humans, menin may offer clues about gestational diabetes and the ways beta cells regenerate.

    Kim's group first examined what happens to menin during pregnancy. In normal mice, menin levels drop and climb back up after the animal gives birth. To test whether this was driving beta cell expansion, Kim and his colleagues created transgenic mice whose menin production didn't decline during pregnancy. When these mice became pregnant, their glucose rose to levels comparable to those in gestational diabetes. Autopsies confirmed that when menin didn't fade in pregnancy, beta cell proliferation was impaired, and the animals didn't produce the insulin they needed.

    In mouse and human cells, Kim's team found that prolactin, a hormone that rises during pregnancy and that Sorenson had found triggers beta cell proliferation in rodents, was what caused menin levels to fall. This, says Sorenson, suggests a distinct chain of events: A boost in prolactin causes a drop in menin, which increases beta cell mass. The discovery is “quite different than the tumor story,” because here the normal functions of menin take center stage, says Stephen Marx of the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, who helped lead the team that cloned the MEN1 gene. Still, because the work is in mice, “it's hard to extrapolate too much,” Kim cautions.

    The work suggests that menin might become a tool for developing beta cells in diabetes patients who lack them. “Up until about 2004, everybody said that you can't get new beta cells from replication; if you lose your beta cells, too bad,” says Andrew Stewart, an endocrinologist at the University of Pittsburgh in Pennsylvania. The find that suppressing menin induces beta cell expansion is “one small step in a long quest” to understand beta cell replication, says Yuval Dor, a developmental biologist at the Hebrew University-Hadassah Medical School in Jerusalem, Israel. Admittedly, devising a menin-based therapy could be complex, because it might interfere with menin's role as a tumor suppressor.

    Menin's relevance to gestational diabetes remains unclear. Some studies suggest that women who are diagnosed with gestational diabetes may have had insulin deficits before pregnancy. “You happen to intercept them” once they're pregnant, says Thomas Buchanan, an endocrinologist at the University of Southern California in Los Angeles, who doubts that menin is “an important contributor” in human gestational diabetes. Still, that's something scientists won't know until they assess menin in people.


    Pentagon Research Chief Seeks 11% Boost in 2009

    1. Yudhijit Bhattacharjee

    U.S. academic lobbyists have long urged the Department of Defense (DOD) to boost its investment in science and technology (S&T) to enhance the nation's strategic and economic competitiveness. But although the agency's overall S&T portfolio has grown modestly since 2002, funding for basic research has stagnated. Now, in an unprecedented step, the Pentagon's research boss is seeking an 11% increase in DOD's S&T budget for the next fiscal year. Observers say the request, which Pentagon officials appear eager to publicize, improves the long-term prospects for more defense-related research despite the continued cost of the wars in Iraq and Afghanistan.

    The proposal comes from John Young, director of Defense Research and Engineering (DRE). In a 24 August memo to Defense Secretary Robert Gates, which recently became public, Young warns that the agency's S&T investment “may be inadequate to meet the imposing security threats that challenge the nation.” Citing the modernization of China's military, the decline in basic research by corporations, and the increasing sophistication of terrorist organizations, Young proposes establishing new S&T initiatives worth $1.2 billion in the 2009 fiscal year (FY). Congress has yet to complete action on this year's request for $10.8 billion for the program.

    Smaller sliver.

    Spending on science and technology hasn't grown as fast as the rest of the military's research, development, testing, and evaluation budget.


    At the top of Young's list is a $300 million investment in foundational sciences, covering areas such as biosensors, photonic crystals, and the computing sciences. That represents a 20% hike in the agency's $1.5 billion basic research budget. “We are pleased to see this discussion occurring within the higher levels of the Pentagon,” says M. Matthew Owens of the Association of American Universities, adding that the DRE director hasn't asked for such a hike in recent history. “We are optimistic that it will have some impact on the FY '09 budget.”

    Supporters point to the fact that the memo was requested by Gates, a member of a National Academies panel that in 2005 called for a 10% increase in basic defense research spending (Science, 21 October 2005, p. 423). Adds Alan Shaffer, one of Young's senior executives: “We're not getting the same type of pushback we used to get. Yes, there are a lot of claimants for dollars. But there's a groundswell of support for the idea.”

    Nonetheless, everybody admits that the proposed increase faces a big hurdle. “The commitments the department has made extend far beyond available resources,” says Loren Thompson of the Lexington Institute, a Washington, D.C.-based nonprofit. For example, he says, the Air Force urgently needs 321 F-21 fighter aircraft, but “there's not enough money in the 2009 proposed budget to purchase even half” that number. “What the services want right now is hardware, not science,” he says.

    A congressional staffer agrees that a big research boost next year is unlikely. “Just because Mr. Gates asked for the proposal and Mr. Young produced it does not make it a slam dunk,” he says. But he believes that the plan prepares the ground for bigger increases down the road. Lobbyists also note that Young is awaiting congressional approval to become the agency's under secretary for acquisition, technology, and logistics, which would give him oversight of a $157 billion budget that includes DRE.


    California Stirs a $600 Million Pot of Solutions

    1. Robert F. Service

    California researchers could soon be able to tap a 10-year, $600 million climate initiative. The project would create the California Institute for Climate Solutions to foster research so the state can meet strict greenhouse gas emissions limits enacted over the past 2 years. The president of the state's public utilities commission (PUC), Michael Peevey, recently announced that PUC is looking at the proposed institute as a way to help meet the new targets. The commission is weighing a plan to finance it through a $1-a-month hike in electricity rates.

    “This is really exciting to see,” says Daniel Kammen, an energy policy expert at the University of California (UC), Berkeley, who views the institute as a way to translate climate goals to action. “It will really put financial muscle behind the climate-change laws.” Omar Yaghi, a chemist at UC Los Angeles, who works on materials capable of separating carbon dioxide from power-plant emissions, likes the idea that utility commissioners are paying attention to more than just the industry's bottom line. “I'm really happy to hear the PUC is taking the initiative on this,” Yaghi says.

    The institute's design is still in flux. But Kammen and others say it's likely to focus on a range of projects that offer near-term energy savings. A preliminary list, Kammen says, includes research centers for energy efficiency, solid-state lighting, carbon sequestration, and green buildings, and a policy center to mesh California's climate regulations with those of other states and countries.

    California needs technological advances to meet its new greenhouse gas emission standards. The first standard, enacted last year, requires a 25% reduction in greenhouse gas emissions, to 1990 levels, by 2020. Two years ago, Governor Arnold Schwarzenegger signed an executive order targeting 80% reductions by 2050.

    The new institute is not expected to fund new buildings, Kammen says, but rather will support and extend existing campus research efforts across the state. “Coordination is key here,” says Ellen Auriti, executive director for research policy at UC's Office of the President. A public comment period closes next week, followed by hearings early next year. If all goes smoothly, the institute could have money to spend by next summer.


    Reconstructing the Origins of the AIDS Epidemic From Archived HIV Isolates

    1. Jon Cohen

    Five HIV isolates that had been forgotten in freezers for 2 decades are revealing new details about how and when the virus spread from Africa to Haiti and then exploded on the world scene. Evolutionary biologist Michael Worobey of the University of Arizona in Tucson led the new study, which analyzed HIV saved from five Haitian AIDS patients treated in Miami in 1982 and 1983. “It was the next best thing to being able to travel back in time,” says Worobey, who obtained the samples through the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia.

    In a paper published online this week in the Proceedings of the National Academy of Sciences, Worobey and co-workers focused on what's known as HIV-1 subtype B. “This was the variant that led to the discovery of AIDS and so much of the story that reared its head after 1981,” says Worobey.

    Much controversy has swirled around the origins of the AIDS epidemic. Because some of the first AIDS cases surfaced in Haitian immigrants to the United States, CDC—to the consternation of many—once included Haitians as a special risk group. Some prominent Haitian researchers have rejected the idea that the virus spread from Haiti to the United States, contending that it likely moved in the other direction.

    Molecular analyses of the archival isolates confirmed earlier reports that subtype B traveled from central Africa to Haiti about 1966, entering the United States 3 years later. The researchers' estimated probability that the virus instead traveled from the United States to Haiti—0.00003—is infinitesimal. “The methods are beautiful, and the analysis is elegant,” says Bette Korber, an immunologist at Los Alamos National Laboratory in New Mexico, who published similar results in Science in 2000 (9 June, p. 1789).

    Some are not persuaded. Jean “Bill” Pape, who heads the largest AIDS research program in Haiti, says Worobey and co-workers simply “restate prejudices advanced 2 decades ago.” Pape notes that the authors offer no details about the sexual histories of the five Haitian immigrants, who he contends could have been infected by Americans. He also questions whether HIV arrived in 1966, pointing to retrospective studies in Haiti that did not find an AIDS case until 1978.

    Other AIDS researchers counter that the Worobey paper offers the clearest picture yet of how the young epidemic matured. “It's a very nice piece of evolutionary sleuthing,” says Beatrice Hahn, a virologist at the University of Alabama, Birmingham, and a coauthor of the Korber study. One provocative finding, says Hahn, suggests that although several different isolates of subtype B came from Haiti to the United States, only one got a foothold. It had not evolved ways to transmit more readily, says Worobey, and appears to have been “lucky” to have spread among high-risk populations—primarily, gay males in the United States. It then spread to Canada, South America, Europe, Asia, and even back to Africa (see figure).

    Descent of HIV.

    A new analysis of stored blood samples from early AIDS patients shows Haiti (green) as a steppingstone between central Africa and the rest of the world.


    Anne-Mieke Vandamme, a molecular epidemiologist at the Rega Institute for Medical Research in Leuven, Belgium, and co-author of a 2003 study that arrived at similar conclusions, says the new work underscores a fundamental feature of HIV epidemiology. Most of the early isolates found in Haitians quickly “died out,” she notes. “You need an event that boosts the transmission, and the epidemic takes off.” In this case, Vandamme says the promiscuity of gay men appears to have boosted the prevalence above a threshold that allowed the virus to thrive.


    Scientists Fete China's Supreme Polymath

    1. Richard Stone

    SHANGHAI—In the early 17th century, this humanist and experimentalist helped avert starvation in China by disseminating hardier crops and devised dams and canals for irrigation and flood control. He launched a decade-long effort to improve the accuracy of the Chinese calendar by incorporating a more precise knowledge of celestial geometry. His monumental contribution was to team up with a Jesuit scholar to translate part of Euclid's Elements, introducing late Ming Dynasty intellectuals to new mathematical concepts—and Western thought. For his achievements, he has been compared to Leonardo da Vinci and Francis Bacon.

    Who was China's Renaissance man? Go to the head of the class if you guessed Xu Guangqi.

    Last month, scientists from a variety of disciplines met here at the Partner Institute for Computational Biology (PICB) to commemorate the 400th anniversary of the publication of the first six volumes of Elements in Chinese and to explore Xu's remarkable legacy. “He started China's enlightenment,” says cell biologist Pei Gang, president of Tongji University in Shanghai. “Xu promoted the idea of learning from the West.” Over the past century, Chinese leaders have taken Xu's advice to heart, including a reference by President Hu Jintao at last month's Communist Party's 17th National Congress to the importance of taking a “scientific view of development.”

    Xu (pronounced like “sue”) was born in Shanghai in 1562 and was groomed to be a civil servant. A watershed moment came in 1600, when Xu met Matteo Ricci, an Italian Jesuit and one of the first Westerners allowed to live in China. No intellectual slouch himself, Ricci had been a student of Europe's leading mathematician of the time, Christopher Clavius. “Xu was wholeheartedly attracted to him,” says Hung-lam Chu, a historian at the Chinese University of Hong Kong. The kindred spirits came to realize that planar geometry and other higher mathematical concepts then unknown in China were essential to progress. “Elements is basically a book about Western logic,” says Yu Sanle of Beijing Administration Institute.

    In translating Elements, Xu and Ricci also coined a host of terms, including jihe as the character for “geometry.” Ricci deserves equal billing, Yu argues: “His was the greatest contribution of any foreigner to Chinese culture and civilization.” Knowledge flowed both ways: Ricci also translated several Confucian classics into Latin.

    Leading light.

    Among many contributions to China, Xu Guangqi helped disseminate Western knowledge of geometry; title page of Euclid's complete Elements.


    After earning a jinshi degree, the equivalent of a Ph.D., in the palace examination of 1604, Xu was admitted to Beijing's prestigious Hanlin Academy. He ascended smoothly through the government ranks until late in his career he came to be known, simply, as “The Minister.” Throughout his life, one constant was his dedication to improving agriculture. His experiments in Shanghai with yams, then a new import from South America, led to the widespread adoption of the high-energy crop. “This was decades before the West began taking a scientific approach to agriculture,” says PICB director Andreas Dress. Xu also trained imperial soldiers to use a newfangled device from Europe, the cannon. “He was a fascinating polymath who spread his interests far and wide for a specific purpose: statecraft,” says Dagmar Schäfer of the Max Planck Institute for the History of Science in Berlin, Germany.

    Xu was also a key figure in China's calendar reform. China's calendar was based on observed motions of the sun and moon, whereas the West's was based on average motions. “The Jesuits had better data than Late Ming astronomers and a clear geometry of the heavens,” says Peter Richter, a theoretical physicist at the University of Bremen in Germany. With such knowledge, Ricci predicted that an eclipse would occur on 15 December 1610—right on the money. “That impressed Xu Guangqi,” Richter says.

    After Xu and Ricci's successors correctly predicted an eclipse in 1629, the emperor appointed Xu as leader of the calendar reform, which he embarked on with the assistance of Jesuits. The reform was completed after Xu's death in 1633. The reams of data used to justify the revision amounted to the first scientific collaboration between scientists in Europe and the Far East.

    Xu's tomb is a 20-minute drive from PICB, jointly run by the Chinese Academy of Sciences (CAS) and the Max Planck Society. “That's how we learned about this guy,” says Dress, a computational biologist with an abiding interest in science history. “Suddenly it dawned on me” that 2007 is the anniversary of Chinese Elements. Accordingly, Dress broadened the workshop into an International Xu Guangqi Conference, organized by CAS, the Shanghai Institutes for Biological Sciences, and Shanghai Xuhui District Government.

    One aspect of Xu's remarkable life that the Chinese government rarely talks about is his conversion to Roman Catholicism and baptism in 1603 as Paul Xu Guangqi. Although some scholars argue that Xu converted out of gratitude or in recompense for Ricci's help, Chu and others are convinced that he was both a devout Christian and a faithful Confucian, noting that Xu's writings consistently adhere to Confucian philosophy. Nor were the Jesuits as zealous in their missionary work as groups that came later: After all, notes Richter, Ricci helped translate Elements—not the Bible—into Chinese.

    Xu's legacy was imperiled by the collapse of the Ming Dynasty in 1644. But his seminal contributions are cherished by modern China. “He forged a dialogue between the West and China,” says Li Tiangang of the Shanghai Academy of Social Sciences, a dialogue that grows richer, and more relevant, by the day.


    Who Owns Glycobiology?

    1. Jocelyn Kaiser

    A group of biologists who claim to be cleaning up their field are battling a Texas company that makes glyconutrients; the company, threatening legal action, says these scientists are spreading falsehoods

    Sweet treatment.

    Mannatech's flagship product, Ambrotose Complex, is a blend of plant extracts containing polysaccharides.


    Most basic biologists probably don't give much thought to ginseng, herbal teas, and the other dietary supplements that fill the shelves of health-food stores. But one group has been caught up in an escalating controversy over supplements in recent weeks, pitting them against a nutraceuticals company that has been charged with illegal sales practices in Texas. Several prominent U.S. glycobiologists allege that the company, Mannatech, threatens to “taint” their field by linking glycobiology discoveries with claims for sugar pills of unproven medical benefit. The company and its consultants have fired back, urging the withdrawal of a critical commentary and warning of legal action.

    The dispute began when a leader in the field and the editor of the journal Glycobiology co-authored a scathing critique of Mannatech, which was posted as an online preprint in September. Other scientists joined in, urging speakers to reconsider their participation in a scientific meeting last week in Dublin that was partly sponsored by Mannatech. In another twist, after Mannatech and others complained about the Glycobiology editorial, the publisher, Oxford University Press, removed it 3 weeks ago, promising to repost it later with responses.

    Mannatech Inc., a publicly traded company in Coppell, Texas, with more than $400 million in sales last year, was under fire from legal authorities before this controversy broke. In July, the attorney general of Texas charged the company with violating Texas laws and has sued to stop its sales associates from making claims that its products cure diseases. The company has denied the charges but has said that it is revising its literature.

    Independently, several U.S. glycobiologists say they want to set the record straight and prevent damage to their field. “It's none of our business as glycobiologists if nutraceutical companies want to sell bark extract. When they begin to tie it to our discipline, that is the problem,” says Ronald Schnaar of Johns Hopkins University in Baltimore, Maryland, editor-in-chief of Glycobiology and lead author of the withdrawn editorial. Adds Ajit Varki, a glycobiologist at the University of California, San Diego, this “striking example” illustrates “the responsibility of scientists to speak out.”

    But others, including several European glycobiologists, suggest that these criticisms are overreaching. The chief organizer of the Dublin conference, John Axford—a British rheumatologist and until recently a Mannatech board member—says he and other organizers were “flabbergasted” by the letter suggesting speakers not attend the conference. He says Mannatech's support is no different from the drug company money that funds countless scientific meetings. His camp argues that the Mannatech critics are unfairly dismissing the entire complementary medicine industry, which should be encouraged to take part in scientific meetings, not banned from them.

    Sugar therapy

    The science at the heart of this dispute concerns not dietary sugars but sugar molecules linked to most proteins and many fats in the body. These glycoproteins and glycolipids dot the surface of cells and serve as identification markers recognized by other cells. The field took off in the past 2 decades, and carbohydrates are now widely studied for their roles in normal biology and disease (Science, 23 March 2001, p. 2337).

    Mannatech, started by entrepreneur Samuel Caster, who had previously run businesses selling pest-control devices and home insulation, launched its first product in 1994. That year, Congress passed a law allowing companies to sell dietary supplements without Food and Drug Administration approval, as long as they don't claim any therapeutic benefit. The company's Web site states that its glyconutrient products “apply concepts from the rapidly emerging field of glycobiology.” A press release goes on to say that eight sugars “are needed at the cellular level for optimum immune function” but that “six of these dietary glyconutrients … are often lacking in our modern diets.” The company's main product, Ambrotose Complex—a mixture of larch bark arabinogalactan, aloe vera gel, gum ghatti, and gum tragacanth—is “a blend of specific plant saccharides that support the immune system” and “support optimal cell-to-cell communication,” a product data sheet says.

    Mannatech relies on more than 500,000 independent salespeople, or associates, to sell Ambrotose. According to a lawsuit filed in July 2007 by the Texas Attorney General, the company's sales associates promote its products with testimonials from people who claim glyconutrients have cured diseases such as Down syndrome and cancer. The company also “claims scientific validation from the field of glycoscience” for its products, the Attorney General concluded. Mannatech said in response that it “intended[ed] to cooperate to reach a resolution” with the state; meanwhile, the Attorney General's office says that it is pursuing the charges in court.

    In their commentary, Schnaar and co-author Hudson Freeze of the Burnham Institute for Medical Research in San Diego, California, examine Mannatech's educational Web site,, shuttered since August for revisions related to the Attorney General suit, Mannatech says. The archives include a self-described “peer-reviewed scientific journal” called Glycoscience & Nutrition, edited by Mannatech scientists and consultants. Its articles describe glycobiology findings “mixed with speculation about the potential of glyconutrients to positively impact” various disorders, write Schnaar and Freeze. Case reports on diseases such as breast cancer and cerebral palsy treated with glyconutrients also appeared in the Proceedings of the Fisher Institute for Medical Research, which is published by an independent organization described by the Texas Attorney General as “little more than a sham charity with the sole purpose of providing ‘scientific’ support to the illegal health claims made about Mannatech's products.”

    As for peer-reviewed research on the health benefits of Ambrotose in PubMed-listed journals, there's not much, according to Schnaar and Freeze. Their review of the literature in the past 25 years found that larch bark arabinogalactan isn't digested, and its main effect is flatulence. About 30 in vitro and animal studies on ingesting aloe gel glucomannan, largely funded by Mannatech or its supplier company, suggest some immune system effects, but the only clinical trial in a PubMed-listed journal found no benefit. The notion that any saccharide mixture will improve health is flawed, says Varki, because most people's cells can make all the sugars they need from glucose in the diet.

    Despite the scant support for glyconutrients in mainstream scientific publications, many glycobiologists have found their names on Web sites promoting Mannatech products. References to Freeze's papers appear on Mannatech sites because 12 years ago, he showed that ill children with a rare sugar-processing disease recovered if they were fed mannose. Ever since, Freeze says he has received calls and e-mails from families of patients with diseases such as cancer and autism. They want to know if spending $34, $100, or more per month on Ambrotose will help. James Paulson of the Scripps Research Institute in San Diego, California, began getting calls after he became head of a glycobiology consortium funded by the National Institutes of Health (NIH) in 2001. “It just tore me up knowing my name was being used in that way,” he says. Three Nobel Prize winners at Rockefeller University—including Günter Blobel—filed a complaint against Mannatech last year to make the company and associates stop using their names on Web sites. The company “has accepted some responsibility” to patrol such Web sites, says Rockefeller general counsel Harriet Rabb.

    Nutraceuticals heavyweight.

    Mannatech Inc., headquartered in Coppell, Texas, had sales last year of more than $400 million.


    Particularly disturbing, say Schnaar and Freeze, are references to the benefits of glyconutrients in a medical textbook called Harper's Illustrated Biochemistry from McGraw-Hill, whose lead editor is a retired University of Toronto biochemistry professor, Robert Murray. Murray, who is also a Mannatech consultant, added a paragraph to the 2006 edition noting that although the body can make other monosaccharides from glucose, “there is evidence that the other sugars may be beneficial in some circumstances when added to the diet. This has led to the development of glyconutrient supplements,” which are “under study,” the text notes. Schnaar and Freeze say this statement, which Mannatech cites in a fact sheet, could mislead young scientists and doctors.

    Murray responds that “there is some scientific basis to the way [Ambrotose] affects wellness,” noting that “thousands of people claim to have benefited” from it. He says he has done nothing wrong and has demanded through a lawyer that his name be removed from the editorial by Schnaar and Freeze.

    The Jenner meeting

    The most recent example of Mannatech's tactics, critics say, is its sponsorship of the Jenner Glycobiology and Medicine Symposium, a biennial meeting organized by the Royal Society of Medicine (RSM), a U.K. educational organization. Axford, a member of the RSM board and head of a research center at the St. George's University of London, has organized the meeting since it began in 1991. Axford served on Mannatech's board from 2002 until he stepped down in September; he has received at least $420,000 in compensation, $370,000 in stock, and $200,000 in research contracts from Mannatech since 2000, according to reports filed with the U.S. Securities and Exchange Commission.

    After the 2004 Jenner meeting, Mannatech posted on its site a summary by Axford with an added phrase stating that the meeting's “major sponsor was Mannatech, Inc.” Last year when Axford proposed holding the meeting in San Diego, some glycobiologists objected. According to Scripps's Paulson, he and other local organizers asked RSM to return $30,000 in support from Mannatech, and, after that, the meeting was canceled for lack of funding. Axford says the meeting fell apart because of low registration and a failure to find local sponsors.

    This year, the controversy blew up again when Schnaar and Freeze decided to send the speakers invited to the Dublin meeting a copy of their critical editorial along with a letter signed by themselves, Paulson, Varki, and Johns Hopkins's Gerald Hart. The letter alleges that Mannatech sites have “prominently displayed” the Jenner meeting and that “your participation may be misused to impress, mislead, or confuse desperate and vulnerable people.” It urges speakers to make sure the meeting is not sponsored by Mannatech and take “whatever actions you feel are appropriate.”

    The letter apparently had little impact. Several speakers told Science that RSM assured them that Mannatech was providing an unrestricted educational grant and that it would have no influence on the content of the meeting. RSM “set up the meeting in a responsible and sensible manner,” says Anthony Corfield of Bristol University in the U.K. RSM education director Jo Parkinson wrote Science that Mannatech is just one of five company sponsors, and that RSM policy “in no way allows the sponsoring company to claim any association with the RSM.” Axford told Science that he agreed that Mannatech could post his summary of the 2004 Jenner meeting on its Web site for educational purposes. He says he had overlooked until now that Mannatech had added a phrase stating that it was the “major sponsor,” which was incorrect, he says. Parkinson says there was no violation of RSM policy.

    Gray literature.

    Many clinical case reports and reviews of the health effects of glyconutrients have appeared in two journals that aren't listed in PubMed.


    The editorial vanishes

    Meanwhile, Oxford University Press has removed the Schnaar-Freeze commentary and plans to post it later with responses. Biosciences senior editor Claire Bird says Oxford Press had received complaints from Mannatech, Axford, and Murray that the article was not properly peer-reviewed. The authors and the press have agreed the posting should be revised. Schnaar says he hopes for “a real forum with space for all interested parties.” Bird says guest editors will oversee the submissions.

    In its letter to Oxford Press, Mannatech calls the editorial “a deliberate attack … based on false statements.” The company, which provided Science with a copy of the letter and a response to Glycobiology, cites more than two dozen studies, including human studies, it has published or presented at meetings and says it has spent more than $20 million on research.

    Axford defends his involvement with the company, saying he's “helped them turn around their R&D department.” The Texas Attorney General's allegations are “appalling” if true, he adds, but they remain “unproven.” Axford stepped down from Mannatech's board this fall to ensure the independence of his research for the company, he says.

    The other four European glycobiologists who co-organized the Jenner meeting agree with Axford's view that dietary supplements are widely used and should be studied. “This industry needs to be included in scientific meetings,” they wrote in a letter to Schnaar. Raymond Dwek of Oxford University, who coined the term “glycobiology” in 1988, concurs, noting that with U.S. health-food shops “full of remedies and Chinese medicine,” complementary medicine can't be ignored. NIH has reached the same conclusion, Dwek and others say, citing a recent NIH-sponsored study of glucosamine for arthritis.

    Dwek disagrees that Mannatech's practices are damaging the field he helped found. Although he once wrote the company to ask it to stop using the name of his institute, “I think glycobiology is bigger,” says Dwek. “I don't think it's harmed the field with scientists.”

    Even Mannatech's critics agree that research on the potential health benefits of consuming specific sugars has merit. Varki, for example, says he is interested in sialic acids as treatments but feels “inhibited” because of the stigma attached. If the field of glycobiology is to expand, many leaders agree, health claims must be based on solid science.


    A Lab to Get the Measure of Matter

    1. Daniel Clery

    Germany's GSI laboratory aims to become Europe's premier nuclear physics center with a set of accelerators and detectors that will be the envy of the world

    Old and new.

    FAIR's synchrotrons, storage rings, and detectors dwarf the existing facilities at GSI (left).


    DARMSTADT, GERMANY—Although it cannot yet claim instant name recognition, a German national lab in this small town near Frankfurt has earned its 15 minutes of fame several times over. GSI, as it's called, has forged new chemical elements never before seen on Earth. It celebrates its own successes by presenting visitors to the lab with a packet of six candies in different colors. The first is labeled “Bohrium” and bears the date 24 February 1981, the day on which GSI's nuclear alchemists created this element with atomic number 107. The last represents element 112, discovered in 1996 but still unnamed as it awaits verification.

    Although a rival lab has added five other superheavy elements to the periodic table since then, GSI hopes to soon grab the headlines again, in many areas of research. Over the next decade, the lab will more than double in size with the construction of two high-energy superconducting synchrotrons capable of accelerating any atom up to uranium, three storage rings to condition particle beams, and numerous new detectors serving five different fields of physics. Construction of the new additions, dubbed the Facility for Antiproton and Ion Research (FAIR), will be officially launched next week. FAIR will be an international affair, with more than a dozen other countries contributing to the €1.2 billion price tag. “It's a big, new venture, a multidisciplinary facility with a very broad range of experiments,” says Sydney Gales, director of France's heavy-ion laboratory GANIL in Caen. Those involved in designing the project are ecstatic. “Starting up such a facility is a once-in-a-lifetime chance,” says FAIR physicist Thomas Beier.

    With the wide array of high-energy particle beams available at FAIR, researchers will be able to study the particle soup that existed at the very beginning of the universe, the workings of atomic nuclei, the dense plasma in the cores of brown dwarfs and gas-giant stars, how stellar explosions create heavy elements, and whether antihydrogen differs from its normal form. Physicists here and elsewhere are already addressing these questions, but FAIR will provide particle beams with as much as 10,000 times the intensity and 30 times the energy of those now available at the lab, with the added bonus of antimatter beams that make new types of experiments possible. “This type of machine and energy is not available anywhere in the world today,” says Gales. “I'm eager to see what they find.”

    Exotic studies

    GSI was founded in 1969 as a shared resource for several universities in the German state of Hessen. The lab started out with a single linear accelerator that could accelerate any element from hydrogen to uranium up to 20% of the speed of light. A synchrotron added later boosted speeds to 90% of light's.

    In the late 1990s, GSI's researchers began discussions with the 1200 outside users on what the lab should do next. By 2001, the lab had drawn up a conceptual design report for a new facility that would expand on GSI's work with particle beams and add an ability to use antiprotons. Germany's federal government agreed to fund the plan if at least 25% of the costs were borne by foreign partners. So far, 13 partners apart from Germany have signed up, including European nations and Russia, India, and China. (The United States is working out its own plans for rare isotope research and is not involved.)

    Construction of FAIR will begin in a year, and the facility should be complete by 2016. GSI will remain a German lab, and a new company set up under German law will run FAIR but be owned by the 14 international partners. This arrangement didn't go down well with some countries, particularly France, which preferred an international body like other pan-European research centers. Although this issue didn't prove a showstopper, some countries have yet to confirm their financial contribution.

    GSI and FAIR intend to work closely together, but all that GSI will physically provide to the new facility is a beam of particles already sped up by its linear accelerator and synchrotron. The beam will then be passed to FAIR's new synchrotrons to be boosted to higher speeds. After that, the resulting particle beam will periodically smash into a target in a detector that will analyze the debris to provide insight into the state of matter at the moment of collision. At other times, the beam will hit a target, and the debris will be collected into a new beam containing all sorts of nuclei. These will be sifted on the fly to pick out particular unstable nuclei for study.

    These nuclei can be passed to a storage ring, which allows researchers to control the speed of nuclei and create a precise, high-quality beam for subsequent experiments. “FAIR will have two unique abilities,” says nuclear physicist Donald Geesaman of Argonne National Laboratory near Chicago, Illinois, “high energy and storage rings, which allow you to do certain types of experiments.”

    Planning for FAIR has involved about 2500 scientists and engineers worldwide. “We've never worked in such large numbers before,” says FAIR physicist Ingo Augustin. Although it serves several fields, GSI's biggest program is in exotic nuclei. FAIR will have a similar emphasis: Some 700 scientists from more than 30 countries devised FAIR's exotic-nuclei research program. Exotic nuclei are highly unstable isotopes that are key to finding out the origin of many of the chemical elements on Earth.

    Although a few elements were made by the extreme temperatures and pressures that existed soon after the big bang, many more—up to iron and nickel on the periodic table—are forged in the cores of stars. The heaviest elements have an even more violent birth in stellar cataclysms such as supernovae, gamma ray bursts, or x-ray bursts. In such explosions, lighter elements are bombarded with neutrons or with protons, swelling up to a large size but becoming increasingly unstable. Understanding how these unstable nuclei decay into something more long-lasting should tell physicists about the origins and abundance of the elements around us now. “If we know the nuclear physics, it constrains the astrophysics. Both are not well known now. This will change dramatically with FAIR,” says GSI research director Karlheinz Langanke.

    Other labs are chasing some of the same quarry, including CERN in Geneva, Switzerland, France's GANIL, Japan's new Radioactive-Isotope Beam Factory at the RIKEN lab in Wako, and the Facility for Rare Isotope Beams being developed in the United States. Although there will be overlaps with FAIR, the various facilities will ultimately deploy different techniques, creating complementary research programs. “In each main region of the world, there are major investments in this area of research because people are excited about the science,” says Geesaman. “None [of the facilities] can tackle all the problems coming from this large community.”

    FAIR is not all about nuclei. Atomic physicist Thomas Stöhlker is looking forward to more of the atomic dissection he does now at GSI but expects that FAIR will provide him with greater accuracy in nailing down atoms' properties. For example, FAIR should allow him to take a beam of uranium atoms, strip them of all their electrons, and then measure the mass of the naked nuclei with extreme precision, giving a better fix on electrons' binding energy.

    Back to basics.

    With a beam of antiprotons, FAIR's PANDA detector will probe the inner workings of protons, neutrons, and related particles.


    FAIR will also provide the world's most intense antiproton beams, allowing researchers to better study the spectroscopy of antihydrogen and compare it with normal hydrogen. Any differences might help solve the long-standing mystery of why there is so little antimatter in the universe. FAIR will offer a “qualitative jump” in what's possible because of its dedicated storage rings and decelerator, says Stöhlker.

    PlayStation, anyone?

    Researchers hope to step out into entirely new terrain with antiproton beams, which FAIR will be able to produce and handle as at no other lab. They plan to study the strong nuclear force and the structure of hadrons—particles such as neutrons and protons that are made of quarks. Current theory does not explain the particular masses or spins that hadrons have. The three quarks that make up a proton, for example, account for only 10% of its mass and 40% of its spin. According to GSI hadron physicist Klaus Peters, the main goal when FAIR is online will be to bombard hadrons with antiprotons to probe the binding of the quarks. The particles that mediate the strong force, known as gluons, “make most of the mass,” he says.

    Peters expects FAIR to become the most important lab in hadron physics: “There's no real competition.” About 400 hadron researchers from around the world—“almost half of the community,” Peters says—helped plan FAIR's program.

    FAIR also has its sights on another prize: a quark-gluon plasma (QGP). This state of matter exists under such extreme conditions that quarks and gluons move almost freely in a soup of particles rather than being confined in hadrons. It is thought that the early universe existed as this form of plasma 20 to 30 microseconds after the big bang. Physicists at the Relativistic Heavy Ion Collider (RHIC) at Brookhaven National Laboratory on Long Island, New York, believe that they have already created a QGP, but they have not yet detected the telltale phase transition from normal matter. Some researchers now think that at the high temperatures used at RHIC, there may not be a phase transition, just a gradual shift from normal matter to QGP.

    “What is still missing is proof of this new state of matter,” says GSI's Peter Senger. “RHIC has some indications but no smoking gun.” FAIR will approach the problem from a different direction. Instead of RHIC's high temperatures, FAIR will use high pressures, creating the sort of QGP found in neutron stars and one that has a detectable phase transition. But spotting the QGP will be no mean feat. In the fleeting instant of a particle collision, the putative plasma spews out thousands of particles, only a tiny fraction of which may carry the signature of a QGP. Senger and his colleagues have calculated that they must log 10 million reactions per second, beyond the abilities of today's computer processors. They've investigated prototype processors destined for PlayStation video game consoles not yet on the market. “These are the fastest processors, and if you have thousands working in parallel, it will be possible,” Senger says.

    Finding the phase transition to a QGP is “the major goal in heavy-ion physics,” says Senger. And who knows, confirming a new state of matter just might give physicists in Darmstadt a new reason to hand out candies.


    Testing the Line Between Too Much and Too Little

    1. Jennifer Couzin

    Keeping peanuts and other risky foods from toddlers in the hopes of preventing allergy has been common practice for years. But is avoidance actually safer?

    Eat or avoid?

    Peanut allergies are on the rise, but steering clear of them early in life may or may not help keep them at bay.


    In Israel, the joke goes, a child's first three words are Momma, Dadda, and Bamba. The last, a wildly popular kosher snack of peanut-flavored puffs, shows a cartoon baby with a tuft of red hair on its packaging. Many infants eat Bamba when they're as young as 6 months old.

    Bamba has become an unlikely poster child in the world of food allergy, where physicians are desperate to ease the soaring burden of hyperactive immune responses. In the past 10 years, peanut allergies—among the most common and lethal—have roughly doubled in both the United Kingdom and the United States, where they affect at least 1% of young children.

    A British study 4 years ago reported that peanut-allergic children have a lower quality of life than those with diabetes, suffering anxiety everywhere, from riding the bus to cruising the supermarket. “The kids don't go to camp like they should, they don't go to birthday parties,” says Brian Vickery, a fellow in allergy and clinical immunology at Yale University. They and their parents live with “fear and tremendous anxiety” that unexpected exposure will trigger shock and even death.

    For years, physicians in many countries have urged parents to avoid feeding high-risk children peanuts until they are 3 years old, on the rationale that one cannot become allergic to a food without being exposed to it and that the immune and digestive systems of older children will be better able to tolerate the peanut proteins that can elicit reactions. But in what seems a contradiction, the countries that endorse this view—including the United States, the United Kingdom, and Canada—have seen an explosion of peanut allergies. Meanwhile in Israel, with Bamba melting in the mouths of babies too young to walk, the rate of peanut allergy in toddlers is 0.04%.

    Is this association accidental, or can it tell us something about how food allergies develop? It's a question asked increasingly by allergists. Early this year, a British team launched the first trial aiming for a direct answer. Their study is recruiting 480 high-risk babies and offering peanuts to half of them while withholding them from the rest. Will one group be more allergic? There's no safe bet, as studies of food, pet, and other allergies span the spectrum, with conflicting results on whether exposure is preventive.

    Rethinking avoidance

    An intricate set of variables can shape the onset of allergies: genetics, eczema, not being breast-fed, and the route of exposure, whether by the skin or the mouth. Some allergists wonder if food preparation plays a role—in particular, if the boiled peanuts consumed in Southeast Asia and Africa are less allergenic than the dry-roasted form eaten in the West. The surge in food allergies also tracks an increase in asthma and autoimmune disease in Europe and North America, and all are thought to be related to the plunge in infectious disease in early childhood. The “hygiene hypothesis,” as it's known, postulates that exposure to pathogens trains the immune system to regulate itself.

    Given this complexity, there's little hope that avoidance will have universal effects. And indeed, the evidence so far is mixed. For some children, living with a cat may make cat allergies less likely, whereas living with more dust mites either helps or hurts as far as allergy prevention is concerned, depending on the study.

    When it comes to peanuts, many physicians are torn between how little they know and what they viscerally fear: Data favoring early avoidance are skimpy, but doctors are uncomfortable promoting peanut consumption. “Peanut allergy is so lethal; you don't get a second chance,” says Patrick Holt of the University of Western Australia in Perth, who examines mechanisms underlying allergy. Still, he says, “the story that we thought we were seeing 10 years ago,” with allergy risk tracking a dose curve, “doesn't hold up.”

    The thought that higher doses may not be worse has come gradually, as scientists dig deeper into how environmental cues prompt an immune response. That the immune system attacks something like Escherichia coli bacteria, a sickness-inducing pathogen, “makes sense,” says Stephanie Eisenbarth of Yale University School of Medicine, who performed allergy studies in renowned immunologist Kim Bottomly's lab for her Ph.D. thesis. “But why would you want to fight ragweed?” The common plant isn't a health threat. This is the question allergy experts have asked themselves for decades.

    In someone vulnerable—because of their genes or for other reasons—initial exposures to normally innocuous proteins stir white blood cells known as T helper 2 (TH2) cells into a tizzy. They alert B cells, which churn out antibodies to the protein. Those antibodies, part of a class called immunoglobulin E (IgE), bind to mast cells and set off a full-blown reaction the next time the offending protein, called an allergen, appears. The mast cells empty inflammatory chemicals such as histamines into the bloodstream, causing the classic symptoms of allergy.


    Scientists are testing whether exposure to peanuts, dust mites (above), and grass can help prevent allergies in high-risk toddlers.


    In the mid-1990s, Bottomly, now president of Wellesley College in Massachusetts, began reporting a more nuanced picture in cells and in mice: The immune response to a foreign substance shifted as the dose of that substance increased. At low doses, her lab saw a classic TH2 response. High doses set off the flip side of the immune system, activation of TH1, which served as a brake on TH2. In 2002, Eisenbarth and Bottomly revealed in mice that the same dose pattern held with an adjuvant, a substance in the environment that primes the immune system to respond to an allergen. “We still don't know” what's behind this, says Eisenbarth.

    Testing whether something similar occurs in people, some allergy-prevention studies uncovered a bell-shaped curve, particularly with exposure to pets: no reaction at the zero-dose end, a strong reaction with low or moderate doses, and little or no reaction again at the high-dose end.

    Some foods may fall under this rubric, too. In 2004, pediatric asthma and allergy specialist John Warner of Imperial College London described a cohort of babies at high risk for egg allergy and examined the effect of maternal diet during pregnancy. Infants whose cord blood had the lowest or highest levels of antibodies to egg proteins were least likely to experience allergic hypersensitivity, such as eczema, by the time they were 6 months old. Those with midrange antibody levels were the most hypersensitive. The evidence is suggestive, although it remains unclear whether a pregnant woman's diet can influence allergy in her unborn child.

    Still, studies such as this one have researchers questioning “whether we can really prevent exposure” completely, says Dennis Ownby, a pediatric allergist at the Medical College of Georgia in Augusta. At least half the toddlers he sees who have suddenly reacted to a food weren't known to have eaten it before. But because an allergy can't develop without exposure first, they must have encountered proteins somewhere. Foods not known to contain peanuts may be one place: In 2001, the U.S. Food and Drug Administration reported that 25% of foods surveyed that did not list peanuts on their labels tested positive for them.

    “The problem is the small amounts may be even more allergenic than the large amounts,” says allergist Hasan Arshad of the University of Southampton, U.K. No one knows whether this is true in humans. But in cells and animals, the allergy antibody, IgE, can be stimulated with small doses of certain allergens given intermittently, whereas a protective antibody, IgG, comes forward with large doses given regularly, says Allan Becker, a pediatric allergist at the University of Manitoba in Winnipeg, Canada. Arshad's own work, however, underscores the tension between avoidance and exposure.

    The Isle of Wight experiment

    Seventeen years ago, Arshad began following 120 infants on the Isle of Wight, a semirural island several kilometers off the coast of England. The children, all at high risk of allergy and asthma, were put in a limited-exposure group or one with normal exposures. In the low-exposure group, breastfeeding mothers avoided cow's milk, eggs, nuts, and wheat. Exposure to house dust mites was reduced with pesticides and mattress covers.

    In their first 8 years, these children were half as likely to suffer allergies as the control group. Limited exposure worked on the Isle of Wight, Arshad theorizes, because several allergies were targeted simultaneously and because the children steered clear of small exposures that may be deleterious, something other avoidance studies may not have accomplished.

    Some physicians are looking beyond the level of exposure and considering how food proteins get inside the body. In 2003, pediatric allergist Gideon Lack, now at King's College London, reported in The New England Journal of Medicine that by the time they were 6 months old, 21 of 23 preschoolers with peanut allergy had had creams containing peanut oil, which are typically used for diaper rash, applied to their skin. In a control group of 140 children, the number was 59%. Lack believes the route of exposure is key—specifically, that skin exposure in the absence of ingestion, rather than ingestion of small doses, is behind growing rates of peanut allergy. “It would be highly implausible to me that we've evolved as a species so that if we have tiny amounts of food through the gut,” an allergy develops.

    One effort to settle the question comes in a study Lack launched early this year. Funded by the U.S.-based Immune Tolerance Network (ITN), it is randomizing babies younger than 11 months old to receive peanuts in different forms, such as peanut butter mixed with banana, or no peanuts until they're 3 years old, and track who develops allergies. About 200 children have enrolled so far; the study will last 7 years.

    Holt, in Australia, is running a similar ITN study of grass, cat, and dust-mite allergy, recruiting 200 high-risk babies and giving half of them daily doses of allergen drops under the tongue. “For people on the outside, this sounds like very adventurous stuff,” says Holt. But “any early fears of ‘Oh my God, you're going to create havoc’” by exposing high-risk babies to allergens haven't yet come to be. Results are still a few years off.

    In both the United States and the United Kingdom, physicians and health officials are reconsidering guidelines that encourage parents to avoid giving high-risk children potentially allergenic foods; they may shift to a more neutral stance. But “I'm still nervous about peanut,” admits one leader in the field, Hugh Sampson of Mount Sinai School of Medicine in New York City. “I don't have proof, I just have this sort of sense that there's something different about it.” Asked by worried parents what he would do were the child his own, “I'll say, ‘I would probably avoid peanut.’” At the same time, Sampson admits to never quite knowing what to advise. “Whatever we're doing is not working,” he says, “because things have only gotten worse.”


    Do Wandering Albatrosses Care About Math?

    1. John Travis

    Repudiating a decade-old study of sea birds, a new report questions a popular model of how animals—as well as fishing boats and people—search for food


    As its name suggests, the wandering albatross (Diomedea exulans) is a fabulous flyer, flapping its way around the world with the help of its 3-meter plus wingspan, the longest of any living bird. A 1996 report seemed to offer clear proof of the bird's endurance: It found that the birds sometimes soared for as many as 4 days before touching down on water, presumably to catch fish or other food. One of the first studies in which recording devices tracked animal movements, the work also brought a little-known mathematical tool to bear on the study of animal foraging. It showed ecologists that a model of random motion called a Lévy flight described the way albatrosses searched for food.

    Inspired by the work of French mathematician Paul Lévy, Lévy flights are characterized by many short hops, with much longer jumps on rare occasions. Physicists have long used the mathematics behind Lévy flights to predict how particles move in liquids and how matter spreads in the universe, for example. And after analyzing the recorded albatross data, a team led by physicist H. Eugene Stanley of Boston University (BU) concluded in a 1996 Nature article that the tagged birds also followed Lévy flights.

    This strategy could work well when food supplies are concentrated in a few places—say, in schools of fish or fields of flowers—with long stretches of empty sea or bare ground in between. Indeed, in a 1999 Nature article, Stanley's group outlined the theoretical benefits of foraging with the strategy and asserted that deer and bumblebees followed a Lévy flight search pattern.

    Last week, however, a new study revealed flaws in both the 1996 and 1999 reports. In the initial albatross paper, Stanley's team misinterpreted key data on the birds, says Andrew Edwards of the Pacific Biological Station in Nanaimo, Canada. In the reanalysis by Edwards and colleagues, reported in the 25 October issue of Nature, the longest flight drops from 99 hours to 20 hours, for example. Moreover, using an arsenal of statistical tests on the 1996 and 1999 papers, the researchers show that the bird, bumblebee, and deer data support other search strategies equally well. Edwards goes so far as to say that none of the subsequent studies reporting animal Lévy flights that he has seen are “100% convincing.”

    Stanley's team apparently accepts this dramatic about-face. All the surviving authors from the 1996 and 1999 papers are co-authors on the new report. And Gandhimohan Viswanathan of the Federal University of Alagoas in Maceió, Brazil, who was the first author of the two earlier papers, agrees with Edwards that “the jury is out” on whether Lévy flights apply to any foraging animals. “One message that this new paper sends is clear: We must be more careful with data analysis,” he says.

    Wet and dry birds

    Physicists first discussed the notion that animals perform Lévy flight searches in the 1980s, but obtaining data on large-scale movements of animals in a natural environment wasn't easy at the time. When the 1996 albatross report came out, the idea of Lévy flights in animals really took off among ecologists. That publication has been cited more than 100 times. Researchers have since described Lévy flights in jackals, spider monkeys, seals, microscopic zooplankton, and even by fishing vessels and hunter-gatherer tribes.

    All this excitement piqued Edwards's curiosity in 2005. An ecological modeler, he had just landed a position with the British Antarctic Survey (BAS) in Cambridge, U.K., the source of the albatross data analyzed by Stanley, Viswanathan, and their colleagues. Edwards decided to take a closer look at the original study to understand the methods used.

    In 1992, BAS researchers had gone to Bird Island in South Georgia and attached a newly designed detector that registered contact with saltwater to a leg of each of five birds, retrieving the detectors about 2 weeks later at the birds' nesting sites. After a BAS group member met someone on the BU team interested in modeling animal movements, BAS agreed to provide the detectors' data.

    For their analysis, the BU team interpreted “wet” signals as moments when the birds stopped flying over open sea and grabbed a snack from the water. The time in between was considered to be flight time, with longer “dry” intervals signifying longer distances in the air. Viswanathan, then a BU graduate student, Stanley, and their co-authors found a “hop, hop … long jump, hop …” pattern among the albatross journeys. When they graphed these data a particular way, the probability for a jump of a specific distance seemed to follow a so-called power-law distribution, in which most jumps were very short, and the longer a jump was, the rarer its occurrence. This type of probability distribution fit the definition of a Lévy flight pattern.

    Yet Edwards noticed that the first and last flights for each bird were suspiciously long. When he removed those flights from the original analysis, any evidence for Lévy flights vanished. The clincher came when, during a coffee break with a BAS albatross specialist, Edwards learned about data that the BU team didn't know about. For some of the recorded trips, some of the birds also wore rudimentary location trackers for a separate study. When Edwards and his colleagues at the survey pulled those data from the archives, they discovered that for much of the initial long “flights,” the birds had never left their nests. Similarly, the last “flights” tended to be much longer because the birds had returned to their nests and were high and dry for hours. Flights recorded as 69, 67, 44, 26, and 23 hours in the original paper were actually all 4 hours or shorter, sometimes less than an hour.

    Edwards and his colleagues also joined with the original BU authors to repeat the sea-bird study, drawing upon BAS data taken in 2004 from 20 Bird Island albatrosses equipped with more sophisticated tracking equipment. The new study confirmed that Stanley's team had been misled. “The birds aren't performing Lévy flights when foraging,” Edwards says.

    Edwards then took another look at the 1999 work on bumblebees and deer. He found other data of questionable relevance to Lévy flights: The deer “foraging” times analyzed by the BU team, for example, turned out to be the amount of time spent eating at a location rather than the time spent traveling between feeding sites.

    Moreover, in both the 1996 and 1999 studies, the BU team had used a simple graphical approach to demonstrate the power-law distribution that signified Lévy flights, one that has since been applied by others in their analyses of animals'movements. But, says Edwards, the strategy can often produce a spurious conclusion of Lévy flights. Indeed, when Edwards statistically compared whether a power-law distribution fit the bumblebee and deer foraging data better than non-Lévy flight distributions, it didn't.

    This type of sophisticated statistical model comparison, note Edwards and Viswanathan, wasn't used in the 1990s. Still, the analysis removed from the two early papers the last bits of solid evidence for Lévy flights.

    Those papers are not being retracted, however. Viswanathan says that he and the other original authors seriously considered retractions but decided that the new analysis serves as the needed public correction. Rory Howlett, an editor at Nature who handled the new paper, adds that its peer reviewers didn't request retractions, either. “This is an unusual case in that new analytical methods and also new data became available that led to a re-evaluation of the original claims,” he says.

    From jackals to bees

    Edwards's reappraisal of the two Nature papers isn't the only recent attack on biological Lévy flights. Behavioral ecologist Simon Benhamou of France's national research agency, CNRS, in Montpellier has also called into question the benefits of this foraging pattern. In the August issue of Ecology, he described computer simulations indicating that Lévy flight-styled movement is no more efficient at searching an area than is a variant of classical Brownian random motion. Moreover, it takes a very close analysis of the data to distinguish the two types of movements. “Both my paper and Edwards's paper show that [the Lévy flight] concept is not likely to be useful to analyze foraging movements in most situations,” says Benhamou.

    Flight paths.

    Scientists have suggested that foraging jackals and bees and even fishing boats follow a Lévy flight pattern (computer simulation, above), which is random motion marked by short spurts and occasional longer jumps.


    To statistician Stephen Buckland of the Centre for Research into Ecological and Environmental Modelling at the University of St. Andrews in Fife, U.K., the application of the Lévy flight concept to ecology was always “a bit far-fetched.” “It's mathematicians taking a simplistic tool and pretending it is relevant to the real world,” he says. The idea that foraging animals conduct Lévy flight searches, or any similar random search strategy, ignores that animals use their intelligence and experience to guide them, Buckland adds.

    But not all ecologists share that dismissive view. They maintain that some Lévy flight studies may be valid. “My view is that the albatross work may well be flawed, but it has played a big role in stimulating some really good subsequent work on the whole issue of search strategies and animal behaviors,” says Christopher Rhodes of Imperial College London, who has reported that foraging jackals perform Lévy flight searches.

    Andy Reynolds o f Rothamsted Research in Harpenden, U.K., is equally adamant that Lévy flights are a useful tool for ecologists. “Theory shows that Lévy flights are a good way to search. My feeling is that animals evolved to do the best possible searches,” he says. Reynolds has found Lévy flight activity in starved flies searching for food in a container and in honeybees—tracked by radar—looking for food or hives in fields. He's also applied several statistical techniques to analyze his data. “I have used many methods to show Lévy flights rather than one method,” says Reynolds.

    Reynolds has been corresponding with both Benhamou and Edwards about his evidence for Lévy flights, but both remain unconvinced. Benhamou doesn't insist that ecologists abandon Lévy flights just yet. But he, like Edwards, argues that researchers must realize that there could be other, equally plausible explanations for how animals search: “Showing that data are well accounted for by a Lévy process is not enough.”