News this Week

Science  10 Dec 2010:
Vol. 330, Issue 6010, pp. 1460

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  1. Infectious Diseases

    Australia to Test 'Mosquito Vaccine' Against Human Disease

    1. Martin Enserink
    Mosquito man.

    After tests in a cage (left), a team led by Scott O'Neill is about to release Wolbachia-infected mosquitoes in two Queensland towns, Yorkeys Knob and Gordonvale (map below).


    In famous efforts setting one species against another, Australian scientists imported caterpillars to block the prickly pear—a wildly invasive cactus—in the 1920s and unleashed myxomatosis on rabbits in 1950. Now they want to take biological control to the next level. In January, entomologists will start deploying a strange bacterium called Wolbachia pipientis in an attempt to halt disease transmission by mosquitoes.

    Their target is Aedes aegypti, the mosquito that transmits dengue, a human viral disease that causes crippling joint and muscle pains. Recent studies have shown that infection with Wolbachia makes mosquitoes resistant to the dengue virus. Now, a team led by Scott O'Neill of the University of Queensland in Brisbane wants to test whether they can spread Wolbachia in the wild by setting free small numbers of mosquitoes infected with the microbe. It should work, they say—and it did in cage trials—because Wolbachia plays weird tricks on insects' sex lives, helping it spread like wildfire.

    Two towns in Queensland have been selected as the testing ground. Dengue occurs sporadically in this tropical region, but the team hopes to get approval next year for a study in Vietnam, where the disease is a much bigger problem. Thailand could come next. “We wanted to start in our own backyard,” says O'Neill, if only to show that the plan could make it through Australia's more rigorous regulatory system.

    Some studies hint that the approach could work for several other diseases, including malaria, a major killer. And the field trial follows the news a few weeks ago that a rival scheme to control dengue—using genetically sterile mosquitoes—has undergone a field test on the Caribbean island of Grand Cayman (Science, 19 November, p. 1030). Together, they represent an exciting acceleration for the field of mosquito-control research, says Jason Rasgon, an entomologist at Johns Hopkins University in Baltimore, Maryland. “If you had asked me 5 years ago when we would start releasing Wolbachia-infected mosquitoes, I might have said, ‘20 years from now,’ ” he says.

    Wolbachia lives inside the cells of more than half of all insect species, including many mosquitoes, but not the most important disease vectors. Female insects pass the bacteria on to their offspring via their eggs—but with a twist. All offspring from infected females carry the microbe, but when an uninfected female mates with an infected male, there are no viable offspring. This means that, once Wolbachia is in, it can spread through an insect species very fast. In the past 2 decades, for instance, scientists have watched it race through Drosophila simulans, a fruit fly species, around the world.

    Initially, scientists had different plans to use this uncanny trait. Their idea was to splice one or more genes into Wolbachia that would help make mosquitoes unable to transmit human disease. By setting these transgenic microbes loose in the mosquito population, they hoped to make the genes spread rapidly. Wolbachia would, in other words, be a vehicle.

    But in an explosion of papers published in the past 2 years, O'Neill and others have shown that infection by Wolbachia alone makes Ae. aegypti resistant to dengue. No extra genes are needed; once a vehicle, Wolbachia has now become the weapon itself. The big advantage, O'Neill says, is that because no genetic engineering is involved, the microbes face lower regulatory hurdles and fewer angry environmentalists. “You can think of it as a vaccine for mosquitoes,” he adds.

    To many researchers' surprise, that same “vaccine” also appears to protect mosquitoes from chikungunya, another human virus, and from filarial worms, which cause lymphatic filariasis (LF), a mosquito-borne tropical disease better known as elephantiasis that causes grotesquely swollen limbs. Wolbachia even appears to inhibit several species of Plasmodium, the parasites that cause malaria. Just how Wolbachia keeps so many agents at bay isn't clear. Some studies suggest it primes mosquitoes' innate immune system to better resist invaders; others say the pathogens lose in the competition with Wolbachia for certain key cellular components, such as fatty acids.

    Whatever the mechanism, scientists plan to exploit it to the hilt. Steven Sinkins of the University of Oxford in the United Kingdom hopes to enlist Wolbachia to help rid Polynesia of LF. He and Rasgon are also both hoping to develop a Wolbachia strain that will stably infect Anopheles gambiae, the most important malaria vector in the world. (So far, they have infected individual mosquitoes, but these didn't pass the microbe on to the next generation.)

    For the impending dengue trial in Queensland, O'Neill's team plans to release about 10 mosquitoes a week per household for 12 weeks. The goal is to find out how well the microbe spreads. Based on mathematical models, O'Neill thinks the infection could travel about 10 kilometers a year. Not every Ae. aegypti mosquito in the world will eventually become infected, he says. Geographical barriers keep separate populations apart.

    Its tendency to spread on its own makes Wolbachia an “elegant” and potentially cheap solution, says Willem Takken of Wageningen University in the Netherlands. But a release will also irreversibly change a mosquito population, he says, which is not something to be undertaken lightly. In theory, Wolbachia could make the mosquitoes more prone to carry certain diseases or alter their biting behavior. But an independent analysis by Australia's Commonwealth Scientific and Industrial Research Organisation has concluded that there is a “negligible risk” that infected mosquitoes would cause harm. The study has received a green light from the Australian Pesticides and Veterinary Medicines Authority.

    There is, of course, the possibility that mosquitoes or the pathogens will adapt to elude Wolbachia's effects. With some luck, that will take at least a couple of decades, says O'Neill, during which time humans may have developed vaccines or another way to thwart their enemies.

  2. Educational Assessment

    Shanghai Students Lead Global Results on PISA

    1. Jeffrey Mervis

    A group of teenagers from Shanghai, China, have posted the top scores on the latest version of an international test of practical knowledge in reading, mathematics, and science. It's the first time that students from mainland China have participated in the Program for International Student Assessment (PISA), which compares the performance of 15-year-olds from 60 nations and half a dozen so-called regional economies.

    The scores from Shanghai, one of China's 22 provinces, far surpass those of students from the top nations on previous PISA assessments, administered every 3 years since 2000. Their tallies of 600 in mathematics, 575 in science, and 556 in reading gave them a 38-point margin over Singapore in math, a 21-point margin over Finland in science, and a 17-point margin over Korea in reading (see tables). Singapore, which also participated in PISA for the first time, ranked in the top five in all three subjects. The test is administered by the Organisation for Economic Co-Operation and Development, which lists 500 as the average score for the 34 OECD member countries. Twelve mainland Chinese provinces participated this year, but Shanghai's are the only results that have been released.

    The 2009 PISA results show that the United States continues to trail much of the industrialized world and rising economies in Asia. The 5233 U.S. students from 165 schools, chosen to be a representative sample, did worst in mathematics. Their score of 487 puts them in a tie for 31st place, well below the OECD average of 496. In science, U.S. students occupied 23rd place, with a score of 502 that matches the OECD average of 501. Reading was their best subject, tying for 15th with a score of 500 that is statistically identical to the OECD average of 493.

    How they did.

    PISA ranks countries based on whether their scores are statistically significant above, on a par with, or below the OECD average.

    SOURCE: PISA 2009

    The Shanghai students not only outperformed the rest of the world but also had the largest percentage of test takers performing at the highest level. In mathematics, for example, 27% of them reached Level 6, defined as capable of advanced mathematical thinking and reasoning, versus 3% of the students from OECD countries and 2% of U.S. students.

    Stuart Kerachsky, head of the U.S. National Center for Education Statistics in Washington, D.C., calls Shanghai “an educational mecca” that is also much wealthier than the rest of the country. Andreas Schleicher, head of analysis for OECD's education directorate, acknowledges that “Shanghai is not representative of China” but notes that the sample does include a large immigrant population.

    One silver lining for the United States was a jump in its science scores, thanks to a better performance by its lowest-ranking students. Math scores returned to 2003 levels after a dip in 2006. The 2009 reading scores for U.S. students were not significantly different from previous tests.

  3. Italian Universities

    Italian Parliament Passes Controversial University Reforms

    1. Edwin Cartlidge*

    The latest attempt to reform Italy's archaic university system passed an important milestone last week when the Italian Parliament's lower house approved a proposed law aimed at eliminating nepotism in academic appointments as well as improving the quality of teaching and research. The reforms must still be given a final approval by the Italian Senate, however, and it is possible, although unlikely, that the bill will be abandoned following a no-confidence vote on the center-right government of Silvio Berlusconi on 14 December.

    The reforms have been contested by much of Italy's university community. Over the past few weeks, students and researchers have mounted protests up and down the country, ones that have seen university departments occupied, famous landmarks scaled by protesters, traffic blocked, and clashes with police on the streets of Rome and elsewhere. The protesters say the reforms will cut universities' already very limited funding, deprive researchers of promotion, and reduce academics' autonomy. But even among the detractors there are many who welcome a part of the reform that would set up a new system to distribute research funding according to international standards of peer review.

    Many acknowledge that Italy's university system is badly in need of an overhaul. Promotions and funding are often awarded on the basis of connections rather than merit, providing mediocre and unproductive professors with jobs for life while pushing many of the country's brightest minds abroad. The reforms, some 2 years in the making, were drawn up by Education and Research Minister Mariastella Gelmini and would set up nationwide standards for academic recruitment, transfer some governance powers from academics to administrators, and trim the huge number of courses that universities teach. Enrico Decleva, rector of the University of Milan and president of the Italian rectors' conference, says that it “presents solutions that should improve universities.”

    One of the popular reforms proposes that the roughly €800 million in research grants allocated each year by the ministries of education and health should instead be handed out by panels of independent experts, 30% of whom would be non-Italians. Ignazio Marino, an opposition senator who added this to Gelmini's plans as an amendment, says that this brings Italy into line with most developed countries, adding that it is a vital step if research funding is to be allocated on the basis of merit and not as a favor to a friend. Yet most funding for Italy's researchers will still come in the form of block grants from the government, and these allocations rarely go through a peer-review process.

    Critics of the overall university reforms are unhappy about a lack of new money in the plans; with universities facing a budget shortfall of about €300 million in 2011. There has also been opposition to the plan for a new tenure-track process in which, after a maximum of 8 years, a postdoctoral researcher must either gain promotion to associate professor or leave the university where they have been doing research. The government says the change should limit a university's ability to simply appoint whomever they like, because it will impose minimum quality requirements on promotion candidates. But existing permanent researchers say the new system is unfair because it will place little weight on experience.

    Political science.

    Opponents to Italian university reform, like these students in Rome, fear a reduction in funds and autonomy.


    Physicist Giovanni Amelino-Camelia of the University of Rome “La Sapienza” also believes that the new tenure track could stifle original research because postdocs will be tempted to follow the research interests of the professors who would promote them rather than what is most scientifically interesting. “In the U.S. or the U.K., the possibility of promotion enhances the quality of research, but here it will have the opposite effect,” he predicts.

    Assuming the reform plan is approved by the Senate in the coming weeks as expected, it would still face further hurdles. According to Renzo Rubele, an Italian physicist at the Free University of Brussels in Belgium, lawmakers would still need to work out a vast number of sublaws and bylaws, a process that could last up to 2 years. He says that a previous attempt at university reform in 2005, by then-research minister Letizia Moratti, came unstuck when this work was not completed.

    • * Edwin Cartlidge is a freelance writer based in Rome.

  4. National Institutes of Health

    A Government Niche for Translational Medicine and Drug Development

    1. Jocelyn Kaiser

    National Institutes of Health (NIH) Director Francis Collins has touched a nerve in the biomedical community with a plan to create a new center focused on translational science—his biggest initiative yet. Collins said this week that the center could be up and running a year from now, despite concerns about its cost, mission, and the fact that it could mean dismantling another NIH center.

    Debate over the proposal flared at an NIH advisory board meeting on 7 December. Nearly 20 groups and investigators supported by the National Center for Research Resources (NCRR), which would be partly absorbed by the new center, expressed concern that existing NCRR programs might be lost. “It's a very large organization being done on a very fast time scale, and the community that will be affected needs more time to provide input,” said biochemist Mark Lively of Wake Forest University School of Medicine in Winston-Salem, North Carolina, a member of NCRR's advisory council, before the meeting. Despite such concerns, the board voted 12-1 to create the new center.

    Only Jeremy Berg, director of the National Institute of General Medical Sciences, voted no; he is “concerned that the implications for the rest of NIH hadn't been adequately discussed,” he said afterward.

    The proposal for the new center came from the Scientific Management Review Board (SMRB), a panel of outside scientists and NIH institute directors whose task is to find ways to streamline NIH's structure. An SMRB working group on translational medicine and therapeutics headed by Arthur Rubenstein, dean of the University of Pennsylvania School of Medicine, began discussions in May and concluded in a draft summary in November that NIH needs to do more work in this area, particularly as drug companies are cutting back on research and development.

    The center would house several existing programs at NIH, including the Molecular Libraries screening program, an effort to develop drugs for rare and neglected diseases, and NCRR's Clinical and Translational Science Awards, big grants averaging about $9 million a year that support clinical research at academic medical centers. The center would also fold in the Cures Acceleration Network, a drug-development program created by the health care reform bill but not yet funded. It would have strong ties, not yet defined, to NIH's intramural Clinical Center, which could be opened to outside scientists.


    Collins may have a new institute by 2012.


    The plan has raised concerns that money to launch the new center might have to come from the budgets of other institutes. Some industry and academic scientists have also questioned whether NIH can do better than companies at developing drugs. However, Steven Paul, until recently head of drug development at Eli Lilly, says his impression is that NIH will do things “that are catalytic and complementary to industry,” which he calls “potentially pretty valuable.”

    The most controversial issue seems to be the fate of NCRR programs. The CTSA grants cost $490 million a year, about 40% of NCRR's $1.2 billion budget. It's not clear what would happen to the rest of NCRR's portfolio, which includes support for construction and instrumentation, primate centers, and grants for states that don't have much NIH funding. Only some would fit easily into the new center. NCRR Director Barbara Alving made a plea to expand NCRR into the new translational center and spend more time figuring out “what does industry want from NIH?”

    But Rubenstein said his group felt a new organization was needed. A working group headed by Lawrence Tabak, NIH's deputy director, and Alan Guttmacher, director of the National Institute of Child Health and Human Development, will report back in 3 months on NCRR programs. “We want to protect the programs and the people,” Collins said.

    NIH staffers worried that Collins had to dissolve an institute if he wanted to move quickly to establish a new one. A 2006 law that created SMRB also capped the total number of NIH institutes and centers at the current 27. Collins decided last month to combine the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism in a new addictions institute, which would free up a slot (Science, 26 November, p. 1166). But that complex merger is on a longer timeline. Collins says Congress might allow NIH to preserve NCRR and exceed the cap as “sort of an overlap” for 1 year.

    These proposed changes require congressional notification. Collins must send recommendations to Health and Human Services Secretary Kathleen Sebelius, who forwards them to legislators. Congress will have 180 days to object; otherwise, the new institutes will move forward.

  5. ScienceInsider

    From the Science Policy Blog

    NIH is defending its cancer scientists whose travel has been questioned. Senator Charles Grassley (R–IA) had complained that 16 NCI intramural scientists took 10 or more trips a year in 2008 or 2009 that sometimes cost over $10,000, sponsored by scientific societies or companies. “It is vital that NIH scientists participate in scientific meetings,” NIH brass said in a letter.

    The British charity Sense About Science has released initial polling data on how frequently medical and scientific journal editors are threatened with libel. A third of a small sample of medical and scientific editors reports that their journal has been threatened with libel action. The government is drafting a bill to reform U.K. libel laws.

    An Irish court has ruled that the punishment for a biologist at University College Cork who read aloud a scientific paper about fruit bat fellatio was “grossly disproportionate.” Dylan Evans was ordered by the school to attend 2 years of sexual harassment counseling. But the judge said an admonishment or verbal warning would have been more suitable for Evans, who says, “I won my battle.”

    The president of the Kentucky Paleontological Society has criticized the state's involvement with plans by a company to build Ark Encounter, a $150 million biblical amusement park related to Noah's Ark that will include models of dinosaurs. Daniel Phelps says the project, which may be eligible for up to $37.5 million in tax breaks if built, amounts to “government entanglement with religion” and could make the state unattractive to scientists and technically minded individuals.

    The new Google Earth Engine, funded by the company's philanthropic arm, provides easy-to-monitor and configure satellite data that could help poorer nations start to monitor and protect their own forests.

    For more science policy news, visit

  6. Marine Ecology

    Chinese Initiative Aims to Comprehend and Combat a Slimy Foe

    1. Richard Stone
    Slippery as she goes.

    Chinese researchers haul jellyfish from the Yellow Sea last year; the Nomura's jellyfish (left) can tip the scales at 200 kilograms.


    QINGDAO, CHINA—Physical oceanographer Wei Hao first encountered her nemesis in the summer of 2001, during a research cruise through a Yellow Sea brimming with slimy, gelatinous masses. “Jellyfish were everywhere,” recalls Wei, dean of marine science and engineering at Tianjin University of Science and Technology. Since then, three more massive blooms have beset the region. The outbreaks have Wei and other scientists worried that the Yellow Sea is on the brink of regime change, in which jellyfish supplant fish as the dominant open-ocean species. “For so long we were focused on tracking fish,” says marine ecologist Sun Song, director of the Institute of Oceanology of the Chinese Academy of Sciences here. “But now we realize jellyfish may be more important … as a major indicator of environmental change.”

    Antitakeover bid.

    Sun Song leads the China Jellyfish Project.


    Last month, researchers met in this port city to plot strategy on a 5-year, $4 million mission to understand the disturbing ascendancy of jellyfish in Asian waters, one that parallels the apparent rise of the animals in the Mediterranean and Caspian seas and other bodies of water (Science, 16 September 2005, p. 1805). “It's an amazing amount of money directed at a neglected problem,” says Anthony Richardson, a marine ecologist at CSIRO Marine and Atmospheric Research in Cleveland, Australia. One objective of Sun's team of 70 researchers from six institutions is to probe the creature's life cycle and interactions with other organisms. Another aim is to pin down the cause of blooms; in Asia, chief suspects are overfishing, climate change, and eutrophication, or excess nutrients in coastal waters. Such knowledge may prove critical to thwarting an ecological hijacking. “Once the ecosystem shifts to jellyfish, it may be impossible to go back,” warns Yu Zhigang, a marine chemist here at Ocean University of China.

    Jellyfish already take a heavy toll on society. Stings kill dozens of people a year—far more than shark attacks. “It's the most dangerous marine creature in the world,” says Sun. The box jellyfish is especially lethal: A victim can die within 3 minutes of being stung. The jellyfish's long rap sheet also includes fouling fishing nets, killing farmed fish, closing down popular beaches, and clogging cooling intakes at coastal power plants.

    Although data are sparse, anecdotal reports indicate that jellyfish blooms are becoming more frequent worldwide. East Asia has been particularly hard hit. In the Sea of Japan, outbreaks of Nomura's jellyfish (Nemopilema nomurai), which can reach up to 2 meters in diameter and weigh 200 kilograms, once were a rare phenomenon. But massive blooms have occurred almost every summer since 2002, inflicting billions of dollars' worth of damage to fisheries, says Shin-ichi Uye, a marine ecologist at Hiroshima University. He estimates that in 2005, up to 20 billion of the refrigerator-sized jellyfish choked the Sea of Japan. That breathtaking abundance may sound like a bonanza for researchers, but studying jellyfish isn't easy. Even titans like Nomura's are fragile and break easily, and fishers are loath to handle them. Satellite imaging is useless: During their medusa stage, jellyfish mostly hover meters below the surface. “We're dealing with something that's very hard to measure,” says Richardson.

    Much about jellyfish consequently remains an enigma. One aim of the new initiative, called the China Jellyfish Project, is to shed light on the animal's “mysterious and complicated life history,” Sun says. The vast majority of jellyfish belong to the phylum Cnidaria, which includes the Portuguese man-of-war and the three species—Nomura's, Aurelia aurita, and Cyanea nozakii—plaguing Chinese waters. Cnidaria species can spend years on the sea bottom as polyps. These reproduce asexually, popping off medusae that drift up the water column toward the surface. In the Chinese project, scientists will search for the elusive polyps in the Yellow Sea and East China Sea. The team also plans to integrate sonar fish finders with cameras to hunt for medusae. That approach will be “much better” than using plankton nets or trawl nets, says Uye.

    The most pressing task may be to unravel the cause of blooms. Overfishing of certain species “opens up ecological space for jelly fish,” says Richardson. Decimated sardine stocks may be to blame for the rise of Chrysaora jellyfish off Namibia. Fish prey on jellyfish, so overfishing removes a check on jellyfish population growth. And jellyfish prey on fish eggs and larvae, making it harder for battered fish stocks to mount a comeback.

    Another concern is eutrophication. A surfeit of nutrients from agricultural runoff and sewage spurs phytoplankton blooms in coastal waters that can trigger jellyfish outbreaks. Such conditions also create low-oxygen dead zones. Compared with fish, jellyfish—both polyps and medusae—are much more tolerant of hypoxic conditions. Because the number of marine dead zones worldwide has doubled each decade since the 1960s, there's more habitat better suited to jellyfish, says Richardson.

    Recent climate change also appears to have given jellyfish a helping hand. Warmer ocean temperatures are correlated with jelly fish outbreaks, “but we don't know the mechanism,” says Sun. He and others fear that warming, overfishing, and eutrophication may work in concert to create jellyfish-dominated ecosystems reminiscent of those during the Precambrian world, more than 550 million years ago.

    The waters off China may be nearing the tipping point beyond which fish predators are unable to hold jellyfish in check. In the past 5 years, says Sun, anchovy catches in the Yellow Sea have decreased 20-fold. During a Yellow Sea research cruise in the summer of 2009, jellyfish constituted 95% of hauls. In coordination with colleagues in Japan, Korea, and Russia, Sun says, field surveys and modeling may allow researchers to calculate “how many jellyfish it will take to change the ecosystem.” That, in turn, could lay the groundwork for interventions that forestall doomsday for fish.

  7. Climate Change

    El Niño Lends More Confidence to Strong Global Warming

    1. Richard A. Kerr

    One of the biggest technical uncertainties in gauging how hot it will get by century's end lies with clouds. How will they react to global warming? Two scientists have independently argued from observations that warming will alter clouds in ways that will largely counter warming by greenhouse gases. But computer climate models show clouds changing in ways that amplify warming, not dampen it. The overwhelming majority of climate scientists sides with the models. Whom to believe?

    To help sort it out, climate researcher Andrew Dessler of Texas A&M University in College Station looked at the example of El Niño and La Niña, naturally occurring weather patterns that cause warming (El Niño) and cooling (La Niña) in the tropical Pacific and around the globe. In a report on page 1523, he analyzes how they have actually influenced clouds. His result is “convincing evidence” that—at least on the scale of decades—clouds do not counter warming, says climate researcher Brian Soden of the University of Miami in Florida. Many of Soden's climate colleagues would agree, but even Dessler notes that “my analysis doesn't settle the question” of just how much the world can warm.

    As others have done before, Dessler used the global warmings and coolings induced by El Niño and La Niña every few years as a substitute for the long-term warming to come. In a warmer greenhouse world, the high, wispy clouds that tend to trap heat that would otherwise escape to space might thicken or expand to cover larger areas. Such a positive feedback would warm the planet further. Or greenhouse warming might thicken or expand low-lying clouds that tend to reflect solar energy to space, cooling the world. That would be a negative feedback.

    Whither clouds?

    As the greenhouse strengthens, changing clouds may either amplify or minimize the warming. A new analysis shows no sign that the warming will be countered.


    In principle, scientists could tell whether negative or positive feedbacks prevail under a warming by comparing observed surface temperature with the amount of energy actually radiating to space, but satellite records of such radiative losses are too short to reveal what has happened in the past century. So researchers have had to rely on records of only a decade or two. Dessler did the same but with some differences. He considered the whole globe, not just the tropics or single regions as previous researchers had done. He used only the past 10 years of satellite data, the best observations available. And he removed feedbacks due to other factors, such as changing water vapor.

    Dessler found a small positive feedback overall. He writes that, given the scatter in the data, he “cannot exclude the possibility of a small negative feedback,” but he sees “no evidence to support … a large negative cloud feedback” capable of counteracting global warming. When Dessler analyzed the cloud feedbacks in eight leading global climate models in the same way, he found that on average the models produce a similarly small positive feedback during a century. That provides “some indication that models successfully simulate the response of clouds to climate variations,” he writes.

    “This is a very important check of the models,” says climate researcher Qiang Fu of the University of Washington, Seattle. “It shows no evidence of a large negative cloud feedback.” But climate researcher Roy Spencer of the University of Alabama, Huntsville, disagrees. He published one of the two papers finding evidence of a strongly negative cloud feedback. He finds in his own analyses signs that Dessler is seeing not only cloud changes caused by temperature changes but also temperature changes caused by natural cloud fluctuations. Such effects garble the true negative feedback beyond recognition, he says.

    Spencer's “interpretation is wrong,” says Soden, but even if Spencer were right that there's a cause-and-effect problem, Dessler's method of comparing observations and models “eliminates some possibilities, such as the models being egregiously wrong. It's about as good as we can do with current data sets.”

  8. Vaccine Introduction

    The Beginning of the End for Africa's Devastating Meningitis Outbreaks?

    1. Leslie Roberts

    Nine years ago, a small group of infectious-disease experts gambled on an unorthodox strategy to make a much-needed—and affordable—vaccine for Africa. Last Monday in Burkina Faso, it paid off in spades with the kickoff of a massive campaign to immunize 20 million people in three African countries against deadly meningococcal meningitis by the end of December. The eventual goal, if the money comes through, is to immunize some 250 million people in 25 countries over the next several years, putting an end to the ferocious epidemics that regularly sweep across Africa's so-called meningitis belt (Science, 27 June 2008, p. 1710).

    MenAfriVac, as it is called, is the first new vaccine made to the highest international standards and designed specifically for Africa—and for a particularly African scourge, meningitis A. (Meningitis A is virtually nonexistent in Western countries.) What's most remarkable, experts say, is its price, a mere 44 cents a dose, and the speed with which it was developed and delivered—less than 10 years from when the idea was hatched.

    All-star cast.

    Burkina Faso's first lady, Chantal Compaoré, was one of the dignitaries at the launch of a new meningitis vaccine, which promises to put an end to the deadly epidemics in Africa's meningitis belt (above).


    “That quick an introduction hasn't happened before,” says Chris Elias, president of the nonprofit PATH in Seattle, Washington, which has played a key role in developing this and other vaccines for poor countries. “I think it is one of our most important milestones of the decade. And I'm not the only one who thinks so,” Elias said in an interview from Abuja, Nigeria, en route to Burkina Faso to witness the symbolic first shot.

    Also there to celebrate were Blaise Compaoré, the president of Burkina Faso; Margaret Chan, director-general of the World Health Organization (WHO); Tachi Yamada, head of the Global Health Program at the Bill and Melinda Gates Foundation, who calls MenAfriVac an “amazing success”; and Helen Evans, interim CEO of the GAVI Alliance. And, of course, Marc LaForce, who shepherded the vaccine through its rocky birth and adolescence as head of the Meningitis Vaccine Project, a collaboration of PATH and WHO that was launched with a large grant from the Gates Foundation. “I'm pretty excited,” says the 71-year-old LaForce, who says witnessing the launch was “humbling.”

    Until now, there has been no way to prevent the deadly meningitis epidemics that erupt across a swath of sub-Saharan Africa (see map) each year with the onset of the dry season in January or February and stop abruptly with the rains in May or June. (Burkina Faso, Mali, and Niger, the three countries where the vaccine is first being launched, are particularly hard hit.) An infection of the thin membrane that lines the brain, meningococcal meningitis can kill within 24 hours and often leaves its survivors deaf or intellectually impaired. Several strains of Neisseria meningitides can cause meningitis, but group A accounts for about 85% of epidemic disease.

    An older polysaccharide vaccine was developed in the 1960s. But its effectiveness is so limited—immunity lasts for just 2 or 3 years, and it has minimal benefit in children under 2—that it is used only as a “Band-Aid” in reactive campaigns to limit the spread of epidemics that have already begun. The vaccine often arrives too late to do much good.

    The new conjugate vaccine uses the same polysaccharide from the bacterium's coat but links, or conjugates, it to a protein that makes it far more immunogenic. LaForce thinks that MenAfriVac will protect for at least 10 years. And unlike the older vaccine, the conjugate prevents those infected from transmitting the bacteria, thus conferring “herd immunity,” or protecting those who don't receive the vaccine. It is modeled on a far more expensive conjugate vaccine that has all but wiped out the related meningitis C in several European countries.

    When LaForce took on the job, he quickly realized that the accepted strategy—working with big pharma to adapt a vaccine, then negotiating to get the price down—would not deliver a vaccine that met his definition of “affordable.” A conjugate pneumococcal vaccine now poised for introduction in developing countries, for instance, costs roughly $3.50 a dose. Instead, LaForce insisted on a guaranteed selling price of less than 50 cents and set out to find partners who could make it happen. When big pharma did not step up, LaForce hatched a scheme to work with an Indian manufacturer, Serum Institute of India Limited, among others. Some of his partners in the project were skeptical, says LaForce.

    “We asked some tough questions,” recalls Elias. “Marc was convinced it was going to work. But he had to convince the global health community.” It was risky, he says, to “work with a company that did not have a major research focus like big pharma and that hadn't worked with a conjugate vaccine before, in a country that had never regulated a conjugate vaccine before.”

    Now Elias calls MenAfriVac a model for delivering all sorts of public health interventions, not just vaccines, to poor countries. So does Yamada, who says the Gates Foundation is investing in a new pneumococcal vaccine that is being developed at Serum in India as well. “We have high hopes it will come in well under $3.50,” says Yamada.

    But despite all the fanfare surrounding last week's launch, LaForce notes that MenAfriVac's widespread introduction is by no means assured. In 2008, GAVI approved the $370 million plan for the full vaccine rollout, but, in an unexpected move, the financially strapped organization provided limited funding—$29.5 million—for introduction in just the first three countries, as well as $55 million to stockpile the old vaccine for emergencies until the new one is widely available. “It's an ongoing challenge, what will GAVI do for the next countries,” says LaForce, who says he won't breathe easily until the money is in the bank.

    Helen Evans of GAVI says the organization, facing a roughly $4 billion funding gap over the next 5 years, is committed “in principle” to providing the full $370 million by 2015—if GAVI's donors step up. Otherwise, “choices will have to be made about which vaccines to prioritize,” adds a spokesperson.

    The vaccine must still prove its mettle in the follow-on studies that are already beginning. A key issue is serotype shifting. The worst case, which LaForce considers unlikely, is that the vaccine will prove effective against type A, but then another strain would move in to fill that niche. That's why work is already beginning on a multivalent vaccine, says Elias, but it will be harder to make and will undoubtedly cost more.

    In the best case, Elias says, if the meningitis A vaccine works as expected, those districts that were immunized in December will be spared this season's epidemic. “We should know by June,” Elias says.


    From Science's Online Daily News Site

    Why Diets Fail Bad news for dieters: New research shows that dieting makes the brain more sensitive to stress and the rewards of high-fat, high-calorie treats. And that can cause you to regain lost weight.

    Stress triggers the release of cortisol, a “fight or flight” hormone that, if chronically elevated, can cause increased appetite and weight gain. Tracy Bale, a neuroscientist at the University of Pennsylvania, and colleagues hypothesized that dieting leaves people more susceptible to the stresses of everyday life, leading them to pack on lost pounds.

    To test the idea, the team put lab mice on a 3-week diet until the rodents had lost about 10% to 15% of their original body weight. After exposure to mild forms of stress, the mice's blood cortisol levels shot up higher and stayed elevated longer compared with levels in control mice. But even after a week of normal eating, the ex-dieters remained more sensitive to stress and were more likely to eat large amounts of high-fat mouse chow when under pressure, the team reports in The Journal of Neuroscience.

    The team also found that the diet, although short, resulted in long-term changes in gene expression that would undermine any dieter's efforts. The mice that dieted had significantly higher levels of the protein that stimulates cortisol release, indicating higher sensitivity to stress, as well as higher levels of appetite-stimulating hormones after exposure to the high-fat binge food. This may help explain why so many diets fail: Dieting increases stress sensitivity, and stress makes us seek relief in high-fat, high-calorie “comfort” foods.

    How Swine Flu Killed the Healthy One of the most baffling questions of the 2009 H1N1 “swine flu” pandemic was why the virus killed healthy individuals while sparing the very young and the very old. The answer may be an immune system gone haywire, according to new research.

    Fernando Polack of Vanderbilt University in Nashville and his colleagues found that lung samples from 75 young and middle-aged adult victims of the 2009 pandemic contained a surprising amount of a protein called C4d. C4d usually binds to antibodies to form virus-fighting immune complexes. But in this case, he says, C4d probably did more harm than good. That's because the adult antibodies—trained to fight seasonal flu—were a poor match for H1N1. They recognized the virus and latched on to it but weren't able to stop it from replicating, says Polack.

    The lungs of this adult H1N1 victim contain C4d (orange).


    Unable to fight back, the system spiraled out of control, Polack speculates. Instead of punching holes in the viruses, the C4d-antibody complexes punctured the victims' veins, flooding their lungs with water and plasma, the team reports in Nature Medicine.

    It makes sense that the old and the young didn't have this strange reaction, Polack says. Young children and infants have few or no antibodies against seasonal flu strains, whereas elderly people had antibodies to an earlier H1N1 strain, known to be a much better match for the 2009 version.


    Pollutant Changes Sexual Preference A new study shows that mercury in the environment can change an animal's mating habits. Peter Frederick of the University of Florida, Gainesville, and Nilmini Jayasena of the University of Peradeniya in Sri Lanka raised 120 wild white ibis chicks for 3 years, lacing some of the birds' diets with mercury. The team reports in The Proceedings of the Royal Society B that 55% of male birds in the group exposed to the highest level of mercury, 0.3 parts per million, formed mating pairs with other males. Male-male pairs can occur in the wild when females are unavailable, but these birds had an ample supply of mates. Although the mechanism is unknown, the study suggests that mercury, a common pollutant from coal-burning power plants, may threaten the survival of ibises and other species, as no laws exist to protect them from exposure.

    Read the full postings, comments, and more at

  10. To Fight Illegal Fishing, Forensic DNA Gets Local

    1. Erik Stokstad

    A new generation of genetic tests could give authorities a much better idea of exactly where fish have been caught.

    Illegal catch.

    Fisheries inspectors such as these can't nail all violators, but genetic tests may prove another deterrent.


    In 2003, geneticist Einar Nielsen of the Technical University of Denmark got an unexpected phone call from Danish fisheries inspectors. They suspected that a fishing vessel had violated its quota by catching too many cod from the North Sea. But the captain claimed that he had caught the fish legally in the Baltic Sea. The difficulty for the authorities was that the fish from both places were the same species, the Atlantic cod (Gadus morhua), and they look alike. Nielsen had been studying the genetics of the Atlantic cod, however, and he used DNA markers called microsatellites to show that the fish in question were very likely from the North Sea. A judge agreed, fining the captain $8800 and confiscating his $44,000 catch.

    It was a rare victory against the massive problem of illegal fishing. For technical reasons, however, microsatellite tests for identifying the local origins of caught fish haven't been widely adopted. A €3.9 million European research project, called FishPopTrace, aims to now lay the groundwork for a different kind of test that could be broadly useful not only for enforcing fisheries regulations but also for catching fraudulent labeling of fish in supermarkets.

    The consortium, which began in 2008, is exploring a range of possible techniques, such as protein patterns in fish tissue and the composition and shape of ear bones called otoliths. But the group is betting heavily on genetic variants called single-nucleotide polymorphisms (SNPs). That's because SNPs should lead to tests that are faster, cheaper, and easier to scale up than those based on microsatellites. The ultimate payoff is the advent of reliable and widely used tests to determine not just which species of fish has been caught but which particular local population it came from. “Being able to take [enforcement] to the population level is a big step forward,” says Michael Hirshfield, chief scientist of the advocacy group Oceana, based in Washington, D.C., who is not a member of the consortium.

    At a meeting last month in Madeira, Portugal, the FishPopTrace consortium discussed its results, and although most of its work is unpublished, other fisheries experts there say the use of SNPs is promising. “This is going to explode,” predicts Kevin Glover of the Institute of Marine Research in Bergen, Norway. “They've shown it's feasible.” In February, the consortium will present final results to policymakers, environmental groups, and others at a meeting in Brussels.

    Fishing fraud

    Although it's difficult to get reliable information on the extent of illegal fishing, researchers estimate that this shadowy business is worth as much as $23 billion worldwide each year. Sometimes the violations consist of boats catching more fish than allowed. More egregious is the taking of fish from areas that have been closed to recover from overfishing. Another problem is consumer fraud: the intentional mislabeling of fish as a more valuable species or as coming from a more desirable location.

    Government agencies fight illegal fishing using a variety of tools. Some place observers on larger vessels to keep an eye on what's hauled in, checking that only fish of the right size are caught, for example. In the European Union, larger boats must have GPS units to make sure they're not fishing in off-limits areas. But observers can't follow all fishing vessels, and monitoring systems can be bypassed. So when it comes to catching scofflaws, forensic genetic approaches that distinguish between species have been critical. For more than 20 years, DNA tests have been used to identify species that have been illegally caught or mislabeled.

    It is much harder to track a fish to its native population. DNA tests look for unique markers, and there are fewer genetic differences between populations of the same species than between species. This is particularly true in the oceans, where populations tend to be large and overlap, which can wash out genetic differences between locales. The microsatellite approach, used by Nielson for cod, can find markers unique to populations, but it isn't particularly efficient or always feasible. And the technique hasn't been scaled up as an enforcement tool, in part because of calibration issues between laboratories.

    In December 2006, the European Commission put out a call for proposals to develop tools to better characterize populations of marine fish and improve the traceability of fish products. FishPopTrace, coordinated by Gary Carvalho of Bangor University in the United Kingdom, won the competition.

    FishPopTrace is focusing mainly on SNPs, specific nucleotides in a DNA sequence that can vary and thus can help tell apart individuals or species. SNPs are much more common in the genome than are microsatellites, which improves the odds of finding patterns specific to different populations. This approach has been successfully used by managers to distinguish among Pacific salmon, whose populations spawn in particular streams and rivers and tend to be more genetically distinct than fish that spend their whole lives in the ocean.

    To see whether they could expand the technique to exclusively marine fish, Carvalho's team picked four economically valuable species as test cases: Atlantic cod, European hake, common sole, and Atlantic herring. These species represent different life habits and geographic ranges, and all suffer from illegal fishing. The researchers obtained samples from about 50 fish from each of 20 populations around European waters, then team members at Aarhus University in Denmark sequenced the samples and identified possible SNPs. By June 2009, they had created one “SNP chip” for each of three species: sole, hake, and herring. (Canadian researchers had already created a SNP chip for cod to assist in aquaculture research.) These DNA-covered microchiplike devices can test the identity of 1536 possible SNPs. For each population, they tallied up the frequencies of all the SNPs, creating what they hoped would be a diagnostic pattern.

    Population control.

    Genetic analysis of fish populations from across European waters is revealing patterns that can be used to identify the source of fish.


    The next step was to find out if the SNP chips could accurately and reliably distinguish among samples from different populations: a North Sea cod from a Baltic one, as Nielsen had done with microsatellites, for example. An important part of this process was figuring out how few SNPs were needed; minimizing the number will lead to cheaper, simpler tests.

    Fish and chips

    The researchers investigated questions relevant to fisheries and to European consumers. A common concern for the latter is the source of Atlantic cod. Fish from the Baltic are worth less because they tend to have lower quality flesh and higher levels of contaminants. The cod team used its SNP chip to examine, without knowing the source, samples from both locations. By looking at 20 SNPs, the researchers correctly identified every sample's origin. With just 10 SNPs, 96% of the samples were still correctly identified. “The results look very promising,” Nielsen says.

    The SNP chip for sole (Solea solea) also performed well. This flatfish fetches the highest price of the four species and is severely overfished in Europe. A key question is whether sole from the North Sea can be distinguished from populations in the Mediterranean, which are considered to be higher quality. Just one SNP could reveal which sole was which with 96% accuracy. “Technically, it's a piece of cake,” says Filip Volckaert of the Catholic University of Leuven in Belgium.

    European hake (Merluccius merluccius) has been a contentious species because of differing regulations. Atlantic hake must be 27 centimeters long to be legally landed. But in the Mediterranean, vessels can catch hake that are only 20 cm. So fishing vessels in the Bay of Biscay sometimes catch smaller fish and then misreport their origin as the Mediterranean. The FishPopTrace team showed that just 10 SNPs could reveal the origin of hake with near-perfect accuracy.

    The most demanding test case was herring. An abundant, migratory species with a wide distribution, European herring have long resisted attempts to tease apart genetically distinct populations. By looking at SNPs, however, it was possible to accurately distinguish herring, such as those in the northeast Atlantic and those in the North Sea—a goal important to a joint E.U.-Norwegian management plan. But more SNPs were required to identify fish from various sources around the United Kingdom, where there is substantial misreporting of catches. Further refinements could reduce the number of SNPs, says Sarah Helyar, a postdoctoral researcher at Bangor University.

    FishPopTrace is also checking the rate at which local fish populations evolve, a determinant of how long their SNP tests may be useful. For each species, the teams are using computer models and looking at decades of tissue samples to see if specific fish populations will maintain the same patterns of SNP frequencies over time.

    Rob Ogden of TRACE Wildlife Forensics Network, a nonprofit in Edinburgh, U.K., is validating the consortium's new genetic tests. This involves confirming that they work under a range of conditions and creating standard operating procedures for other labs to use. “It's absolutely essential if you want to move from an academic environment to testing,” Ogden says. And there is growing interest among regulators; a major E.U. fishing law passed last year mentions genetic tests explicitly as possible enforcement tools. “I'm pretty convinced that they will be much more extensively used,” says Jann Martinsohn, who studies marine policy at the European Commission's Joint Research Centre in Ispra, Italy.

    How SNP-based tests are ultimately used—by port inspectors, for example, or commercial labs testing frozen fillets—will depend on their accuracy, cost, and ease of use. SNPs that end up on the witness stand may remain the exception, Ogden predicts. He says that just the act of random testing will encourage compliance, at a fraction of the cost of litigation.

    That view matches Nielsen's courtroom experience, which was the first introduction of genetic testing of populations to the Danish fishing fleet. “The case did certainly have a deterrent effect,” he says. “They know that we can test, so they are probably less likely to put themselves in situations where testing could reveal fraud.” The task now is to create genetic tests that will broaden the scope of this deterrence.

  11. Materials Science

    What Shall We Do With the X-ray Laser?

    1. Adrian Cho

    A newfangled x-ray source exceeds expectations in creating new conditions of matter, probing materials, and deciphering the structures of proteins.

    MENLO PARK, CALIFORNIA—A year and a half ago, the SLAC National Accelerator Laboratory fired up the world's first hard x-ray laser. Shining 10 billion times as bright as any previous x-ray source, the Linac Coherent Light Source (LCLS) would probe matter in new ways: simulating conditions within a planet's core, resolving the ultrafast changes in a material's atomic-scale architecture, and determining the structure of a protein from individual molecules. Or so claimed the machine's designers. Some potential users questioned whether the $420 million LCLS would live up to its billing.

    Now scientists have results from the first experiments with the machine, which they discussed at a recent meeting here.* Although it's too soon to say that the LCLS will succeed at every task—three of six experimental “end stations” are not yet finished—the x-ray laser has already produced novel conditions of matter and demonstrated unprecedented capabilities. If anything, it appears to be more reliable, versatile, and fruitful than expected. “I think it's already been transformational,” says biophysicist Jasper van Thor of Imperial College London. Linda Young, an atomic physicist at Argonne National Laboratory in Illinois, likens using the LCLS to rocketing to the moon the first time: “Everything you do is new.”

    X-rays are scientists' best tool for probing matter on the atomic scale, and the LCLS is an x-ray source unlike any before. Most large sources are circular particle accelerators called synchrotrons. Electrons whizzing around them radiate x-rays, a bit in the way a twirled dish rag flicks off drops of water. In contrast, the LCLS is an x-ray free-electron laser (X-FEL) that uses a linear accelerator, or linac, to fire bunches of electrons through a chain of magnets called undulators. The undulators make the electrons wiggle and generate x-rays.

    In a flash.

    Blasting nanocrystals, biologists confirmed the diffraction pattern, ground out at a synchrotron, of the membrane protein PSI (inset).


    Traveling along with the electrons, the x-rays push them into subbunches that radiate far more effectively than the individual particles. Akin to feedback in a public-address system, that effect produces a hugely intense burst of x-rays. The photons in the pulse also wiggle in synchrony, like those in ordinary laser light. Moreover, the LCLS's pulses are extremely short, lasting as little as a few million-billionths of a second, or femtoseconds. So they can take snapshots of lightning-fast atomic-scale changes.

    When the LCLS turned on in April 2009, experimenters first shined the x-rays on a gas. Even that rudimentary study created something new: made-to-order “hollow” atoms. The electrons in an atom stack into “shells” with definite energies, and the innermost shell contains the two most tightly bound electrons. An x-ray with enough energy can knock out one of these electrons, although within femtoseconds, an electron from an outer shell falls into the vacancy. Rarely, the fleeing first inner-shell electron takes the second one with it, leaving a hollow atom with an empty inner shell.

    The LCLS shines so brightly that physicists can hollow out atoms at will. Argonne's Young and colleagues shined x-rays with an energy of 2 kilo-electron volts (keV) onto xenon. Had those pulses come from a synchrotron, each atom would have been hit by at most one photon. But a 230-femtosecond LCLS pulse bombards each atom with multiple photons, enough to strip some xenon atoms of all 10 of their electrons, the team reported in the 1 July issue of Nature. Moreover, by making the x-ray pulse shorter and more intense, the physicists could blast out both inner-shell electrons and leave the atom hollow.

    Paradoxically, such a double inner-shell vacancy persists longer than a single vacancy. It also renders an atom momentarily transparent to the x-rays, which are tuned to knock out only inner-shell electrons. So hollowing out atoms leads to a general slowdown of the electron-stripping process, which is how the scientists could tell they were making the atoms hollow in the first place.

    In fact, they deduced from the yields of xenon atoms with different numbers of electrons that the shortest pulses lasted as little as 20 femtoseconds, far shorter than the aimed-for 80 femtoseconds. Accelerator physicists said the pulse couldn't be that short, Young says, “but I said, ‘I'm sorry, but that's what the measurements show.’” LCLS operators can now make pulses a couple of femtoseconds long, too short to measure. That should make the LCLS even better at probing ultrafast atomic-scale processes.

    Condensed matter physicists have also been pleasantly surprised by what the LCLS can do. Wei-Sheng Lee of Stanford University in neighboring Palo Alto, California, and colleagues used it to track ultrafast changes in electronic and magnetic patterns within a material and found an unexpected relationship between them. They studied lanthanum strontium nickel oxide, which is a relative of lanthanum strontium copper oxide, a high-temperature superconductor that can carry electricity without resistance at temperatures as high as 40° above absolute zero.

    Physicists still do not agree on how high-temperature superconductors work. The copper oxide superconductor has planes of copper and oxygen ions in a square pattern with lanthanum and strontium layers between them. In lanthanum strontium nickel oxide, nickel replaces copper. Within the superconductor, free-moving electrons sit at most one to a copper ion. At temperatures above the superconducting transition, those on alternate rows spin in opposite directions to create stripes of magnetism. At the same time, some rows lack such electrons, leaving separated stripes of charge. The stripes may compete with or promote superconductivity.

    Similar stripes appear in the nickel compound, so the physicists used it to study the two types of stripes without having to account for superconductivity. They shook up their sample with a 50-femtosecond pulse from an infrared laser and, after a variable delay, applied a 70-femtosecond x-ray pulse to probe the fading and recovery of the stripes. They increased the intensity of the infrared pulse and found that the charge stripes faded completely at a lower intensity than did the spin stripes. It was “a big, big surprise” that the charge stripes vanished first, says Thomas Devereaux, a SLAC theorist not involved in the work, as it's easier to imagine electrons arranging their spins if they're already in rows.

    As important as the result was the fact that the experiment worked at all. Physicists had worried that the LCLS's ultraintense pulses might wipe out the stripes and obliterate the sample. However, the team attenuated the x-rays enough to preserve the stripes and still detect a signal. “We all did one of these wipe-your-forehead-in-relief things when that happened,” Devereaux says. That success suggests that the LCLS may be handier than hoped for condensed matter physics.

    The most tantalizing results at the meeting may have been those probing the atomic structure of proteins. Using less-intense x-ray synchrotrons, biologists have mapped the structures of tens of thousands of proteins. They make a crystal from many copies of a protein and then scatter x-rays off the planes of atoms in it, a process called diffraction. The directions in which the x-rays emerge reveal the structure of the crystal and, hence, the protein.

    That requires crystals at least a few micrometers wide, and some proteins, especially those embedded in a cell's membrane, will not readily form crystals so large. However, the LCLS shines so brightly that it might reveal the structure of a membrane protein if researchers drop into the beam either “nanocrystals” hundreds of nanometers wide or even individual molecules. The x-rays would scatter off the tiny samples, even as they blow them apart.

    Holography horse.

    X-rays passing through a pinhole and those scattered by a tiny object (horse) interfere to make a pattern (right) encoding the object's shape (below).


    Early results suggest that the technique works, at least for nanocrystals. A team of 84 researchers used the LCLS to study a membrane protein called photosystem one (PSI) that plays a role in photosynthesis. The researchers sprayed a jet of nanocrystals into a beam of 2-keV x-rays. They weren't quite able to resolve the atomic structure of the protein. However, data from 3 million individual shots yielded a diffraction pattern consistent with the one produced at a synchrotron in 2001, after a decade and a half of trying to grow large enough crystals of PSI.

    The result shows the LCLS's immense potential to study hard-to-crystallize proteins, says van Thor of Imperial College, who was not involved in the work. “If you can make nanocrystals, then you can skip these 15 years and just go to the LCLS,” he says. Researchers will reach atomic resolution simply by using more energetic x-rays, and studying membrane proteins will consume much of the LCLS's beam time, van Thor predicts.

    Others are not so sure that structural biologists will flock to the LCLS. Michael Blum, an x-ray crystallographer with Rayonix, a company in Evanston, Illinois, that makes x-ray detectors, says researchers at synchrotrons are improving their work with tiny crystals and predicts biologists will take more interest in the LCLS's ability to resolve rapid changes in proteins. It remains to be seen whether scientists can determine structures from individual molecules, he says: “Going from big crystals to small crystals is a step, but there's a leap in going from small crystals to no crystal.”

    Scientists are performing myriad other experiments, too. Some have used the LCLS to pump energy into solid carbon, simulating conditions in the cores of planets. Exploiting the x-rays' laser qualities, others are honing holographic techniques that might serve, for example, to trace rapid changes in magnetic materials. In the next few years, LCLS officials want to see which experiments pay off most handsomely, says Joachim Stöhr, SLAC's associate director for the LCLS. That's a key consideration because, unlike a synchrotron, the LCLS can service only one experiment at a time, making beam time scarce and precious. “The biggest challenge for us is to give you more beam time,” Stöhr told LCLS users. “How do we do that?”

    The answer is expansion. The LCLS uses 1 kilometer of the lab's 3-kilometer-long linac, which provided beams for particle physics experiments for 42 years, to fire electrons through one chain of undulators. By 2017, researchers plan to use a second length of linac to power two more undulator chains, with an eye to even bigger upgrades by 2025. They also hope to split the x-ray beam to run some experiments simultaneously.

    That extra capacity will come in handy, as the LCLS will soon have competition. Researchers in Germany, South Korea, and Switzerland are building X-FELs that will turn on in a few years. And scientists at the SPring-8 laboratory in Harima Science Park City, Japan, will begin operating their X-FEL in March. With new linacs, those machines will produce x-ray pulses at higher rates than the LCLS. So the pressure is on researchers at SLAC to make the most of their head start.

    • * 2010 LCLS/SSRL Users' Meeting & Workshops, 17–21 October 2010.

  12. American Schools Of Oriental Research Annual Meeting

    A Change of Biblical Proportions Strikes Mideast Archaeology

    1. Andrew Lawler

    At the meeting, a series of biblical archaeologists came to the podium for 2 hours of data-rich presentations—and put their colleagues on notice that their field is in the midst of a scientific revolution.

    New dig.

    Modern tools, seen at Megiddo, uncover the past, including residues in chalices (inset).


    It was the scholarly version of a military “shock and awe” campaign, quipped one archaeologist. At a packed evening session on 18 November, a series of researchers came to the podium for 2 hours of data-rich presentations—and put their colleagues on notice that their field is in the midst of a scientific revolution.

    Biblical archaeology has often been heavy on textual analysis and slow to adopt scientific methods such as radiocarbon dating. Attempts to prove the accuracy of biblical accounts or to legitimize Jewish claims to the region have dogged the field. Now archaeologist Israel Finkelstein of Tel Aviv University and structural biologist Steve Weiner of the Weizmann Institute of Science in Rehovot are revolutionizing the region's archaeology by applying a host of new technologies. Their 5-year, $4 million effort, funded by the European Research Council, includes more than 40 collaborators from many disciplines working at an array of sites, primarily in Israel. Finkelstein says the goal is to overcome the “strong ideological agenda” pervading the field. The team has adopted state-of-the-art methods, including analyzing human and animal DNA and ancient pollen, to resolve controversial questions about the pace and timing of migrations and construction, such as the size and power of 10th century B.C.E. Jerusalem in the time of David and Solomon (Science, 2 February 2007, p. 591).

    Work has been under way for a year and a half, and the first results are coming in. For example, at the large Canaanite site of Tell es-Safi—possibly the home of the biblical Goliath—archaeologists long assumed that a heavy layer of ash in one area demonstrated destruction by fire in the turbulent 9th century B.C.E. That seemed to match the biblical accounts of destruction at the hands of the neighboring King of Aram. But infrared spectrometry showed that floor clays had not been heated to high temperatures, and nearby ceramics showed evidence of lipids, which would have been burned away by a fire. Although exactly what did happen is not fully clear, the ash apparently was not part of a single catastrophe but was dumped there, perhaps after a series of partial burns. “It is a real surprise for all field archaeologists, who would reasonably have assumed that a fire occurred at the location,” Weiner said. Such “destruction events are generally regarded as ‘Pompeian’” and instantaneous, he said, but the new data challenges that view.

    Other researchers have evidence from sediment cores that this arid region of the Levant became wetter in the 10th century B.C.E., providing expanded grazing during the period when Israelite tribes wandered north into the area. And residue analysis is opening a new window on possible religious practices of 3 millennia ago. Chalices found at Philistine sites such as Tell es-Safi include remains of a hallucinogenic substance that could be local artemisia or even nutmeg obtained from India. The residue is found in chalices across the region, despite the fact that they were locally made and often have differing decorations, a sign of a widespread, common ritual that until now was unknown.

    Even critics of Weiner and Finkelstein were impressed by the battery of talks. The project is “a game changer” that is “stimulating a lot of us,” says archaeologist Thomas Levy of the University of California, San Diego, who thinks it will fundamentally alter biblical archaeology. Finkelstein says the team has 10 articles in the works, with more to come as DNA results arrive in the next year. Analysis of pig DNA is at the top of the list, he says, to show whether swine were an ancient local variety or were brought by sea peoples from the Mediterranean.

  13. American Schools Of Oriental Research Annual Meeting

    Tracking the Med's Stone Age Sailors

    1. Andrew Lawler

    By carefully sorting genetic data from living people, a researcher reported at the meeting that around 6000 B.C.E., Neolithic seafarers spread their seed—both agricultural and genetic—from their homeland in the Near East as far west across the Mediterranean as Marseilles, but no farther.

    Remains of Neolithic settlements dot the Mediterranean's islands and coastlines. Where did these seafaring migrants come from, or did indigenous peoples pick up technology from their neighbors as new ways of life, including farming, spread around the region?

    Genetic studies are helping to fill in key pieces of the puzzle. By carefully sorting genetic data from living people, Roy King of Stanford University in Palo Alto, California, said in a talk that around 6000 B.C.E., early seafarers indeed spread their seed—both agricultural and genetic—from their homeland in the Near East as far west as Marseilles, but no farther.

    To come to that conclusion, King disentangled seafarers' complex migrations across the Mediterranean from 10,000 to 2000 years ago. He focused on the most common genetic marker found in the Y chromosome of men living today in Anatolia and the Near East, called haplogroup J. The subgroup J2a is associated with people who traditionally lived in areas of higher rainfall and adopted agriculture rather than a semipastoral life.

    Go west.

    Neolithic seafarers spread from the Near East as far as Marseilles.


    Although the marker J2a appears across the Mediterranean, it is not necessarily a sign of a mass Neolithic migration. Much later peoples, such as the Greeks and Phoenicians around 700 to 600 B.C.E, also spread from the Near East to the west—and their genes also include J2a. That makes it tricky to determine when the marker first appeared in the central and western Mediterranean. King, however, pinpointed markers specific to the ancient Greeks that were not shared with Neolithic people. Then he examined the population in the French city of Marseilles.

    He found that 17% of the Marseilles population had Y chromosome input from the Greeks, and 18% carried Neolithic markers. This suggests a first wave of Neolithic settlers, followed millennia later by Greeks. But although the Greek genes spread far to the west, the Neolithic markers appear to stop in the Marseilles area, a sign that they ventured no farther. And because the markers are scarce inland, King says his results are yet more evidence that Neolithic farmers from the Near East spread to the region by sea.

    Archaeologist Helen Farr of the University of Southampton in the United Kingdom says King's study “adds compelling new DNA data to the evidence we have of the distribution and development of the Neolithic.” She adds that Neolithic seafaring is now well accepted and says what's needed now is to carefully examine the material record at specific sites.

  14. American Schools Of Oriental Research Annual Meeting

    Keeping Watch as the Old Kingdom Crumbled

    1. Andrew Lawler

    The round stone fort at Ras Budran on the southern Sinai Peninsula hints at the precariousness of Egypt's Old Kingdom, suggesting an increasingly desperate trading and military strategy in the waning days of the 22nd century B.C.E., an excavator reported at the meeting.


    This Egyptian fort, with reconstruction (below), was a key outpost.


    With walls 7 meters thick and 4 meters high, the round stone fort was a potent symbol of ancient Egypt's power, more than 250 kilometers from its Nile Valley heartland. And, so far, the building is unique. “We have no other example like it,” said excavator Gregory Mumford of the University of Alabama, Birmingham, after his presentation. But the structure at Ras Budran on the southern Sinai Peninsula also hints at the precariousness of Egypt's Old Kingdom, suggesting an increasingly desperate trading and military strategy in the waning days of the 22nd century B.C.E.

    Egypt's Old Kingdom is one of the best known ancient cultures, thanks to hieroglyphic texts and the material culture buried in famous pyramids such as those at Saqqara and Giza. But the Old Kingdom was long thought to have been a relatively isolated society before its collapse in the 22nd century B.C.E, and little is known about Egyptian outposts from this time. “Not many fortified structures survived from the Old Kingdom, and Ras Budran offers a wonderful opportunity to learn more about the several types of fortifications” of the period, said Carola Vogel, an expert in Egyptian defenses at the Johannes Gutenberg University of Mainz in Germany.

    Today, the Ras Budran fort is more than two football fields from the Red Sea. But back then sea levels were higher, and the fort likely stood at the water's edge and included a lengthy wharf for access by seagoing ships.

    Dated by pottery and radiocarbon to the end of the Old Kingdom, the structure paints a new picture of the society's outer rim. Mumford's team during the past three dig seasons has found copper ore, processed turquoise, and copper chisels in the fort's interior. The inhabitants made Egyptian-style pots from local clay and preferred a diet of bread and gruel while largely avoiding the local fish and mollusks. All this suggests that native Egyptians involved with valuable trade goods staffed the garrison. Ancient turquoise and copper mines are known in the area, and Mumford speculates that the fort may have protected precious wares from roving nomads before the material was shipped to the Nile. “Sinai was of utmost importance” at this time, says Vogel, for its resources and because it provided access to the Levant for trade.

    Pictorial evidence from this period shows nomad attacks on Egyptian expeditions. Miniature clay models depict other forts from the era, but they are tall and narrow towers rather than the broad, open, and circular structure at Ras Budran. Stone also typically was reserved for monumental buildings like pyramids. And oddly, the limestone structure eventually was not just abandoned but partially and carefully disassembled by about 2200 B.C.E.

    Shortly thereafter, a storm surge or seismic event destroyed much of what remained. A change of climate—increasing aridity combined with rising seas—plus increasing depredations by nomads likely prompted the withdrawal, said Mumford. Today, local Bedouin report a similar mound to the south, possibly the reconstructed fort on higher ground, he added. He intends to search for that site during next summer's expedition.

  15. Fisheries

    Chesapeake Crabs: Engineering a Rebound

    1. Christopher Pala*

    A new strategy to selectively spare pregnant females has brought the Chesapeake Bay crab population back from a precipitous collapse in just 3 years.

    The first hint of dawn has barely leached over the Chesapeake Bay's horizon when Buddy Evans gaffs his first crab pot floater. Using a fast-spinning hydraulic winch, he hauls up the pot into his boat. His mate Jonathan Tyler shakes out some 30 startled blue crabs, mostly females with bright red claws. Tyler tosses the old bait to a posse of hysterical herring gulls, rebaits the pot—actually a rectangular yellow wire cage—and tosses it back into the water.

    Below us, tens of millions of pregnant female blue crabs are walking up to 240 kilometers on invisible highways down to the mouth of the bay. Each will spend the winter there deep in the mud and then, between May and August, release between 750,000 and 5 million larvae. Then the females will move north into the bay to mate and return.

    Eleven hours and 675 pots later, we roar home to Smith Island, the heart of the bay's 3-century-old community of watermen. The 36-foot boat's ample afterdeck is piled high with 88 bushel baskets filled with 13,000 crabs. It's 10 November, the last day of the fall female harvest season, and as night falls, we arrive in Crisfield, the hub of the crab business on the Eastern Shore peninsula, where the round wooden boxes are loaded onto a truck headed for New York.

    “This is the best I've done in one day in years,” says Evans. “I just wish we could do it for another 3 weeks, like we used to.”

    Across the bay at the University of Maryland Center for Environmental Science on Solomons Island, marine biologist Thomas Miller says that it's precisely by stopping harvesting early, when the fall female migration is at its peak, that one of the world's largest crab fisheries was brought from the brink of collapse to a healthy population in just 3 years.

    For the second half of the 20th century, the Chesapeake's adult crab population oscillated around 400 million, with an average annual harvest of 250 million crabs. But in 1997, it declined to about 130 million, and up to 80% of these were caught each year. “You can't harvest 80% of anything and expect it to last,” says Miller. “Getting people to fish less anywhere is very hard. Usually you keep on rearranging the deck chairs on the Titanic and when it starts to sink, you impose a fishing moratorium, which is very disruptive to the communities.”

    Big haul.

    Since the crab population in the Chesapeake Bay has rebounded, business is again booming for Buddy Evans (left) and Jonathan Tyler.


    So how did Virginia and Maryland save the crab population from crashing? No thanks to Charles I. In 1632, he divided the bay, giving the northern half to Maryland and the rest to Virginia. “That's made it very hard to manage the Chesapeake as a single ecosystem,” says Miller. “If Charles I only knew,” says the British-born Miller's screensaver, over a portrait of the British monarch.

    The solution emerged when Richard Robins, the owner of a seafood packing business with an MBA, was appointed to the Virginia Marine Resources Commission in 2004. He realized that the piecemeal efforts in both states to curtail the catch weren't working and called for a commission to determine why.

    Miller was the senior scientist on the panel. He knew that 6 years of restrictions had only reduced the yearly catch from 80% to 63% of the adult population, not enough for it to rebound. The consensus on the panel was that they needed to focus the reductions on the female portions of the stock. “It was the kindergarten solution,” Miller explains, so easy a 5-year-old could have figured it out: If there aren't enough babies, stop killing the mommies. “We needed to save at least half the number of pregnant females that were being harvested, about 30 million crabs,” says Miller. “Overall, we wanted the harvest to be no more than 46% of the stock.”

    Miller had published an article in 2003 in the Bulletin of Marine Science demonstrating the benefits of sparing females. But because nearly 70% of them are caught in Virginia, near the mouth of the bay, it had never been tried in the Chesapeake because it was perceived as putting an unfair burden on Virginia watermen. “Without Robins taking the lead in Virginia, this approach would never have been acceptable,” Miller says.

    A broad array of measures was put in place in 2008; the shortening of the fall harvest of migrating females in both states has been the most effective. A winter dredge of buried hibernating pregnant females in Virginia—which killed two females for every one caught—was also closed. Those fishers were hired with federal funds to recover lost traps, which continue to kill scores of crabs. Finally, a spawning-season sanctuary was extended, says Robins. “There are a lot of things that you can do to reduce mortality in a fishery,” says Robins. “But this was the first time we used them all at once.”

    The watermen were not happy, but the spring 2009 survey of 1500 spots up and down the bay found that the female population had climbed by 70%, while the male population barely changed. This spring, the survey showed that the number of females was up 200% over the 2008 figure. Overall, the number of crabs has soared from 131 million in 2008 to 315 million this year.

    “Given this year's catch, I expect we'll be very close to 400 million in the next spring survey,” says Miller. “With two or three more years of increased reproduction, we shouldn't need to end the fall season so early, so the fishermen will catch more crabs in every pot and they can do it for longer.”

    “This brings the management of Chesapeake fishery closer to other crab fisheries, like the Alaska king crab and the west coast Dungeness crab, which ban the fishing of females,” says David Armstrong of the University of Washington, Seattle. Unlike in the Chesapeake, females in those fisheries are significantly smaller than males, so a simple size restriction does the trick. “Still, a recovered, healthy fishery in the Chesapeake can certainly include some female harvest,” Armstrong adds.

    • * Christopher Pala is a writer in Washington, D.C.

  16. Scientific Community

    Will Homebody Researchers Turn Japan Into a Scientific Backwater?

    1. Dennis Normile

    Few young Japanese scientists these days opt for long-term overseas experience; research leaders hope to find ways to broaden their horizons.

    CHIBA, JAPAN—When Rei Sakuma was completing his Ph.D. at the University of Tokyo in the mid-2000s, the theoretical physicist considered applying for overseas fellowships. His adviser talked him out of it. In Japan's shrinking academic job market, most positions are filled by word of mouth. Senior professors “do not want to hire strangers. If you're working in a foreign country, people in Japan forget about you,” Sakuma says. Heeding his adviser, Sakuma took a postdoc in Japan and in 2008 landed a faculty position at Chiba University.

    Staying home might have been a smart career move for Sakuma. But he became part of a trend: Fewer young Japanese scientists are going abroad for advanced training. “A lack of mobility leads to isolation at a time when our challenges [are] more and more global,” says biochemist Ernst-Ludwig Winnacker, secretary general of the Human Frontier Science Program in Strasbourg, France. “We are very worried that without young researchers gaining overseas experience, Japanese science will fall behind,” adds Kojiro Kakimoto of the Japan Society for the Promotion of Science (JSPS) in Tokyo. JSPS hopes to turn the tide with new programs that dispatch researchers abroad. But what's most needed, observers say, is a change in hiring procedures at home.

    Recent surveys reveal a deepening reluctance of Japanese scientists to venture overseas. Last October, the education ministry reported that the number of researchers of all ages and in all fields who go abroad for longer than a month dropped from a peak of 7674 in 2000 to 3739 in 2009. More tellingly, in 2009 just 373 Japanese researchers were abroad for a year or more; of those, 47% were under 45 years old.

    Other surveys affirm a stay-at-home tendency. According to the Institute of International Education in New York City, 24,842 Japanese students went to the United States for graduate and undergraduate education in the school year that ended in 2010, down from a peak of 47,073 in 1998. More Japanese might be going to other countries. But in 2009, the National Institute of Science and Technology Policy in Tokyo reported that of 60,535 Japanese who earned doctorates in Japan from 2002 to 2006, a mere 2% are known to have gone abroad for postdocs or other opportunities.

    Such immobility marks a sharp reversal from what was once the norm. Not long ago, “it was common understanding that if you didn't get a Ph.D. from an American university you couldn't get a job at University of Tokyo,” says Takashi Shiraishi, a political scientist who studied and taught at Cornell University before returning to Japan. Budding researchers once had to go abroad to find suitable graduate programs, mentors, and state-of-the-art equipment—all of which now abound in Japan. And institutions once commonly sent newly hired science graduates abroad for further training; that rarely happens these days.

    Staying put.

    Like hordes of colleagues, Rei Sakuma opted for a postdoc fellowship in Japan rather than one overseas.


    Other factors dampen academic wanderlust. Tight budgets and heavier teaching and administrative loads make it harder for faculty and staff members to go abroad for extended periods, says Sotaro Shibayama, a science policy researcher at the Georgia Institute of Technology in Atlanta. Meanwhile, a rapid expansion of graduate programs and postdoc fellowships since the mid-1990s is generating bumper crops of Japanese Ph.D. scientists who compete for a diminishing number of permanent positions.

    The biggest restraint on going abroad may be cultural: Those who stay close to decision-makers seem to advance. Ken-ichi Arai, a molecular biologist and University of Tokyo professor emeritus who worked and taught in the United States for 12 years, says that under the “hierarchical” Japanese system, senior professors steer positions to researchers they trained as Ph.D.s and postdocs. Scientists who have gone overseas “have a great deal of difficulty” fitting back into the system “unless they have a mentor in Japan,” Arai says.

    At the same time, scientists of all generations agree on the benefits of overseas experience. “Since Japan is isolated from other regions of the world culturally, geographically, and linguistically, I think it important for young Japanese people to spend some time abroad,” says Hiroo Imura, an endocrinologist who spent 2 years as a postdoc at the University of California, San Francisco, in the early 1960s and went on to become president of Kyoto University, his alma mater, in the 1990s. Thanks to JSPS grants, Sakuma has attended conferences and made lab visits abroad, including 2 months last summer at the Jülich Research Center in Germany. Longer visits would foster tighter collaborations and allow for stays at other institutions, Sakuma says, but “would be very difficult” because of his teaching duties.

    Hoping to make headway against the prevailing winds, JSPS in October selected 96 doctoral students and young researchers for 1- to 3-year stints in overseas labs under a new grant scheme. And with JSPS and other organizations, the Human Frontier Science Program is planning a career day in April 2011 for junior Japanese scientists “to make them aware of the advantages of working and living overseas,” Winnacker says. A lasting solution would be more-flexible career paths: “not just so young people can go abroad,” says Arai, “but so they can come back.”

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