News this Week

Science  12 Oct 2007:
Vol. 318, Issue 5848, pp. 178

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    A Knockout Award in Medicine

    1. Gretchen Vogel

    The one-two research punch that allowed the creation of designer mice has earned the 2007 Nobel Prize in Physiology or Medicine. Mario Capecchi, a Howard Hughes Medical Institute investigator at the University of Utah in Salt Lake City, Oliver Smithies of the University of North Carolina, Chapel Hill, and Martin Evans of Cardiff University, U.K., will share the prize for developing the techniques to make knockout mice, animals that lack a specific gene or genes. Such mice have allowed scientists to learn the roles of thousands of mammalian genes and provided laboratory models of human afflictions in which to test potential therapies.

    Against the odds.

    Pursuing ideas that others said would never work, the three researchers who share this year's Nobel Prize in physiology or medicine set the stage for the creation of designer mouse strains in which specific genes are altered or disabled.


    The techniques “truly provided a revolution in mammalian biology,” says Raju Kucherlapati, a geneticist at Harvard University. “It is not an exaggeration to say that there is no mammalian biologist today who does not use these tools in one way or another.”

    Biologists have long studied mutant mice for insights into the mammalian body. But for decades, they were limited to rodents whose DNA had been disrupted in random places by natural mutations or the application of mutagenic chemicals. In fact, most of the time, biologists studying a mutant mouse strain didn't even know which gene was broken. The ability to mutate a specific gene at will seemed a distant dream.

    Working independently in the 1980s, however, Capecchi and Smithies each crafted ways to slip foreign DNA into a specific place in the chromosomes of mammalian cells. A similar strategy, exploiting a natural DNA-swapping process called homologous recombination, had been used to alter genes in yeast and other organisms, but most people assumed it wouldn't work in mammals. Indeed, in the early 1980s, Capecchi's grant application was rejected by the National Institutes of Health in Bethesda, Maryland, with the advice that he should forget the idea.

    He persevered, using money cobbled together from other projects. And a few years later, both he and Smithies, then working at the University of Wisconsin, Madison, showed that targeting specific genes in mammalian cells via homologous recombination was indeed possible. But the work was in cells in culture dishes, and the technique seemed far too inefficient to be used to make whole animals with genetic alterations.

    Enter Martin Evans, then at the University of Cambridge, U.K. He led a group that in 1981 reported growing embryonic stem (ES) cells from mouse embryos. Evans, too, had faced skepticism. Experts had doubted whether such cells, which can become any cell in the body, could be grown in the lab. Even Evans was confused when he first saw the cells in culture, says Elizabeth Robertson of the University of Oxford, U.K., who was a postdoc in the lab. “He came to us and said, ‘Someone contaminated my media!’” because there were strange-looking cells growing in it. Lab members had to convince him that the cells were ES cells, she says.

    A few years later, Evans and his colleagues showed that they could produce live mice by injecting cultured ES cells into a developing embryo. The result is a chimera, an animal whose tissues are a mix of the ES cells and those from the host embryo. In many of those chimeras, the added ES cells by chance produce the animal's sperm or eggs, and when these chimeras mate, some of their offspring carry the stem cells' genes in all their tissues.

    Capecchi and Smithies both quickly saw that ES cells offered an opportunity to generate live animals with a desired mutation in every cell. Researchers could target genes in ES cells and then sort out the cells that carried the desired modification, using them to create chimeras. Some of the chimeras' offspring would have the altered gene in all their tissues, and by breeding these animals together, biologists could create mice that completely lack the two working copies of a given gene. Although they never formally collaborated, Evans “brought the ES cells to my lab in his own pocket,” Smithies says, while Capecchi spent time in Evans's lab learning the technology.

    Every biologist soon wanted a favorite gene punched out, and a handful of companies quickly began competing with places such as the Jackson Laboratory in Bar Harbor, Maine, to provide knockout strains to drug companies and academic labs. To date, researchers have knocked out at least 11,000 genes in mice, observing what goes wrong in development or adulthood and thereby gaining a sense of what the gene does. By deactivating specific genes this way, for example, Capecchi and his colleagues went on to identify ones that shape limbs, organs, and the overall mammalian body plan. Both Smithies and Evans developed mice lacking the cystic fibrosis gene, one of many knockout mouse strains created to mimic a human illness. Indeed, there is now a worldwide effort to knock out every mouse gene (Science, 30 June 2006, p. 1862).

    Skeptical grant reviewers were not the only hurdle Capecchi overcame on his way to scientific stardom. As a child in war-torn Italy, he survived alone—often begging and stealing on the streets—between the ages of 4 and 9 while his mother, a poet, was imprisoned in the Dachau concentration camp for her anti-Fascist writings. After the war, she tracked down a very malnourished Mario in a hospital, and a few days later they were on a boat to the United States to live with her brother in Pennsylvania. The young Mario expected the streets to be literally paved with gold, he told a press conference in Salt Lake City on the day he won the prize. What he found instead, Capecchi says, “was opportunity.”


    Effect that Revolutionized Hard Drives Nets a Nobel

    1. Adrian Cho*
    1. With reporting by Daniel Clery.

    If you work at a computer, play video games, or listen to music on an iPod, you've benefited directly from the efforts of the winners of the 2007 Nobel Prize in Physics. Albert Fert of France's national research agency, CNRS, in Orsay, France, and Peter Grünberg of the Jülich Research Center in Germany independently discovered an effect known as giant magnetoresistance (GMR) that fueled a dramatic increase in the capacity of computer hard drives. The discovery also laid the cornerstone of a new field known as spintronics, in which researchers try to exploit the fact that electrons spin like little tops to make novel devices.

    Thanks for the memories.

    Physicists Albert Fert (left) and Peter Grünberg independently discovered an effect that vastly increased the capacity of computer drives.


    “It's a physics discovery that has had real consequences,” says Robert Buhrman, an applied physicist at Cornell University. “Without GMR, we would not be able to carry our whole life around on a 3-inch hard drive.”

    Long before the discovery of GMR, researchers knew that applying a magnetic field to a material such as iron or nickel could change its conductivity. Electric current would flow less readily parallel to the direction in which the material was magnetized and more readily across it. Technologists harnessed that effect to make the “read heads” that sensed the setting of the magnetized bits in a computer hard drive. But the effect, known as anisotropic magnetoresistance, was small; the resistance varied by a few percent.

    In 1988, Grünberg and Fert found that they could greatly increase the change in resistance if they made layer-cake films with layers of iron separated by layers of nonmagnetic chromium only a few atoms thick. If two adjacent iron layers are magnetized in the same direction, then electrons spinning in one direction will pass along the film readily, whereas electrons spinning in the other direction will not. If, however, the iron layers are magnetized in opposite directions, then all electrons run into greater resistance, regardless of how they are spinning. That makes a GMR film an extremely sensitive magnetic field detector. As a result, all the bits and hardware in a disk drive can be made much smaller.

    The basic quantum mechanical concepts behind GMR were understood in the 1970s, but at the time technology was not available to exploit them, Fert says. “I put this idea in the fridge,” he says. “Then in the 1980s, it became possible to fabricate these materials.” Grünberg could not be reached for comment when Science went to press.

    Although Fert and Grünberg discovered the effect, Stuart Parkin of IBM's Almaden Research Center in San Jose, California, did much of the work to make GMR technologically useful. Stuart Wolf, a physicist at the University of Virginia, Charlottesville, says he was surprised that Parkin was not honored as well. But Tony Bland of the University of Cambridge, U.K., says that the Nobel committee apparently distinguished between the discovery and its cultivation. “This is properly a physics prize for a truly extraordinary and novel effect.”

    The advent of GMR helped launch the emerging field of spintronics, Wolf says. “This particular discovery seemed to crystallize a lot of people's interest in working in this area,” he says. Their efforts may someday lead to myriad other devices, such as computer memory that can hold information even when it loses power and microchips that exploit spin to perform computations.


    Into the Deep: First Glimpse of Bering Sea Canyons Heats Up Fisheries Battle

    1. Virginia Morell*
    1. Virginia Morell is a science writer in Ashland, Oregon.

    Marine biologists this summer peered for the first time into the depths of two massive canyons below Alaska's Bering Sea—canyons that may be key to sustaining the world's largest food fishery. Their firsthand glimpse of life in Zhemchug and Pribilof canyons may set conservationists and the Alaskan fisheries industry on a collision course, with conservationists arguing that the canyons need protection from fishing, and fisheries managers countering that the canyons' ecosystems are not necessarily unique and are not heavily fished.

    Underwater oasis.

    Submersible pilots spotted crinoids and other life in deep canyons on the Bering Sea floor.


    Last week in Anchorage, expedition members unveiled their preliminary findings in a packed but unofficial session of the North Pacific Fishery Management Council (NPFMC), the advisory board that works with the National Marine Fisheries Service (NMFS) to oversee the resources of the Bering Sea.

    The canyons sit in the middle of one of the most heavily fished areas on Earth, the Bering Sea Shelf break, where nearly 2 million metric tons of fish, particularly pollock, are caught each year. But little was known about other life in the canyons, with data from only a handful of dives by remotely operated vehicles (ROVs) and from by-catch hauled up by trawlers. “The canyons are one of the places in the world where nobody has looked before,” says Robert Stone, a benthic habitat ecologist at NMFS in Juneau, who helped design the survey. Last December, NPFMC ruled that it lacked sufficient data about the canyons to justify a closure. So John Hocevar, a marine biologist and Greenpeace representative who organized and led the more than $400,000 expedition, outfitted Greenpeace's vessel, Esperanza, with two human-piloted submersibles and one ROV. The team systematically surveyed parts of the canyons, one of which plunges 2730 meters down.

    They found rocks and stony outcrops protruding through the muddy canyon floors. And on every such hard substrate, submersible pilots spotted the bright colors of life: fan-shaped corals as orange as a tropical sunset, magenta-hued rockfish, crystalline barrel sponges, and young golden king crabs. “It was absolutely amazing to see the colors below the gray sea, and to have such a close view of fine features of the ecosystem,” says marine ecologist Michelle Ridgway, a consultant with Oceanus Alaska in Juneau, who piloted one of the submersibles.

    Ridgway is also a member of NPFMC's advisory panel and says she has “taken plenty of shrapnel” from colleagues for her part in the expedition because of Greenpeace's advocacy role. She, Stone, and other NMFS and university scientists say that they joined the cruise because of the rare opportunity to explore the region.

    The team has just started to analyze the collected specimens and videotape recorded during 25 dives. So far, Ridgway counts nine genera of coral, including red tree (Primnoa sp.) and black coral (Lillipathes sp.), dozens of sponge genera, and several unidentified sponges that Stone expects will prove to be new species. Similar coral habitat, which serves as a refuge for fish and crab, was recently protected near the Aleutians. The team also discovered swaths of sea whip coral (Halipteris sp.) as wide as “a freeway” that had been damaged by fishing lines dragged along the bottom, says submersible pilot David Guggenheim of the nonprofit 1planet1ocean in Washington, D.C.

    Hocevar notes that federal law requires the National Oceanic and Atmospheric Administration, of which NMFS is a part, to report new data about deep-sea corals to Congress and to outline steps that may be taken to protect these vulnerable, slow-growing organisms. “I think the council will have to consider a fishing closure in the canyons based on our findings,” says Hocevar.

    But council members aren't so sure. NPFMC “already took action on a Bering Sea conservation package,” says Patricia Livingston, NMFS fisheries biologist and NPFMC's scientific committee chair; she was referring to protections extended to other sea floor areas on the Bering Sea Shelf. To close them, “the canyons would have to be designated as habitats of particular concern,” which hasn't yet been proposed, she says. For now, the council is not taking any specific action in response to this unofficial presentation.


    Lawmakers Worry that Lab Expansion Poses Risks

    1. Jocelyn Kaiser

    A congressional committee last week took a hard look at the explosion of U.S. biodefense research since the 2001 anthrax attacks and concluded that the number of labs is growing without adequate oversight. At a 5-hour hearing, federal officials acknowledged gaps in monitoring safety at biocontainment labs. But although scientists agree there's a problem, they worry that hasty reforms could do more harm than good.

    The hearing by the House Energy and Commerce Committee oversight and investigations subcommittee was held to examine the growth in biosafety level 4 (BSL-4) labs, which study deadly pathogens for which there is no treatment, as well as BSL-3 labs, which study less risky bugs (Science, 28 September, p. 1852). The National Institute of Allergy and Infectious Diseases (NIAID) alone has spent more than $1 billion in the past 5 years on new BSL-3 and BSL-4 labs.

    Meanwhile, a spate of accidents is stirring concerns about safety, including an unreported infection and other violations at Texas A&M University in College Station that led federal officials to suspend its biodefense work in June. The Texas incident came to light only after public records requests by the Sunshine Project, an activist group in Austin, Texas. At the hearing, subcommittee chair Bart Stupak (D-MI) asked, “Are so many labs doing this research that you actually increase the chances of a catastrophic release of a deadly disease?”

    According to an analysis presented at the hearing, the risks are rising. In a preliminary report, Keith Rhodes of the Government Accountability Office (GAO) found that by its count there are five existing BSL-4 labs and 10 more under construction or planned by various funders (including separate labs at the same institution). GAO was unable to tally BSL-3 labs, which could number in the thousands. These labs mean more new workers and more dangerous pathogens in labs, Rhodes noted. Without any central oversight, “I would say we are at greater risk” for accidents and misuse, he said, adding that the FBI and intelligence agencies told GAO investigators that they share those concerns.

    Other federal officials acknowledged gaps in oversight of labs handling select agents, pathogens that could be used as bioweapons. A 2003 regulation requires that these labs register with the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and undergo inspections. But inspectors apparently missed serious problems at Texas A&M in 2006. Richard Besser, director of CDC's terrorism preparedness office, conceded a need to improve what he calls a “young program.” He said CDC now plans to conduct more indepth inspections, including unannounced visits. Besser also endorsed creating an accident-reporting system, like those run by NASA and the aviation industry, that would enable labs to share experiences without being punished.

    Under scrutiny.

    Congress is concerned about safety at the rising number of biodefense labs, including those like this Army BSL-4.


    To date, 105 possible exposures and losses have been reported to CDC under the existing rules. The oversight subcommittee last week disclosed details of those incidents, which included animal bites, needle sticks, and possible lost samples. Three releases were detected when five workers became ill from working with a select agent. None of the incidents posed a public health threat, Besser said. Another case involving two shipments of leaky vials of anthrax resulted in a $450,000 fine last month for the shipper, the Lawrence Livermore Berkeley Laboratory in California.

    Another gap highlighted at the hearing is that, unless the work involves recombinant DNA, no agency oversees labs working on pathogens not on the select-agent list, such as SARS and dengue. NIAID Deputy Director Hugh Auchincloss Jr. said agencies plan to form an interagency task force to improve biosafety oversight.

    Rhodes suggested that a single agency should oversee all BSL-3 and BSL-4 labs. But one lawmaker cautioned against stifling research. Michael Burgess (R-TX) noted the research community's success at identifying the SARS coronavirus and stopping its spread in 2003. “I don't want to see us do anything that would rob us of that ability,” he said. That concern is shared by the American Society for Microbiology (ASM) in Washington, D.C. “We need to be careful that whatever legislation emerges doesn't create such a burden that it actually interferes with public health measures and research,” says ASM's public affairs director Janet Shoemaker.

    The panel expects to hold more hearings on similar labs in other countries, and on the implications of closing the Plum Island Animal Disease Center, located off Long Island, New York, the U.S. laboratory where the most dangerous animal pathogens are studied.


    Piercing the San Andreas's Heart, But Missing a Vital Target

    1. Richard A. Kerr

    For the first time, drillers have retrieved rock from deep within an active fault where earthquakes can get a start, researchers announced last week. With a ton of rock core to take to the lab, excited scientists will be dissecting their haul for clues to how and why faults rupture in quakes. But the uncooperative San Andreas fault has frustrated drillers targeting their ultimate goal: a small patch of the fault that regularly breaks in tiny quakes.

    One hit.

    Drillers cored a creeping part of the fault but couldn't get to a quake.


    Drilling for the San Andreas Fault Observatory at Depth (SAFOD) began in 2004 just west of the fault near the tiny central California town of Parkfield and culminated early this past September, when drillers retrieved the last of 44 meters of rock core. In two summers, the drillers had bored the hole straight down before angling it off to the east to grind through the fault at a depth of 3 kilometers. This past summer, they bored out 10-centimeter-thick side cores across two active strands of the fault.

    “It was a challenging summer,” says seismologist William Ellsworth of the U.S. Geological Survey in Menlo Park, California, one of three co-principal investigators in the $24.6 million project funded by the National Science Foundation. The “damage zone” of hundreds of meters of contorted, broken rock created by millions of years of faulting “is a very unstable piece of rock,” says Ellsworth. Again and again, the hole's walls collapsed, and drill pipes got stuck.

    Despite the obstacles, SAFOD drillers retrieved cores across two “creeping” fault segments: active strands of the San Andreas where rock on opposing faces of a fault strand slips smoothly by without generating quakes of any size. Seismologists have long thought that something about creeping segments—perhaps the presence of particularly soft and slippery rock—in effect lubricates the fault and short-circuits quakes (Science, 11 October 1991, p. 197). Indeed, researchers found the slippery mineral talc, of baby-bottom fame, in debris from the initial SAFOD drilling of the fault. And cores through the ground rock at the heart of the creeping fault contain bits of serpentine (inset, greenish), which can give rise to talc.

    But mounting costs have pulled the research up short. “Because of a lack of funds, we were unable this year to drill into the repeating earthquake,” Ellsworth tells Science. The ultimate target of SAFOD drilling had always been a 100-meter-wide patch embedded in the creeping fault. Rather than creeping, that patch breaks every couple of years in a magnitude-2 earthquake (Science, 23 December 2005, p. 1898). Researchers hoped to learn how that part of the fault can accumulate enough stress to produce quakes even though the surrounding fault can't.

    Team members still want to drill the quake target, but they can't afford to do it now. Drilling through the rotten rock of the fault zone added unplanned costs. And the frenzied search for $80-a-barrel oil boosted costs across the drilling industry. Before researchers could target the quake patch, SAFOD funding for drilling ran out. They will soon install several kinds of sensors in the borehole just 100 meters from the patch, which should fail again in a year or two, but drilling into it will require new funding beyond SAFOD. Researchers outside the project strongly support more drilling. “I think it would be a crime if in the next few years we don't go back in and drill into” the rupturing patch, says rock mechanicist Terry Tullis, a professor emeritus at Brown University. “It's really worth it.”


    A Culture Under Siege

    1. Richard Stone

    Myanmar's military rulers have eroded the country's education system and damaged its heritage. Scientific cooperation might offer a lifeline to beleaguered academics


    YANGON, MYANMAR—When saffron-robed monks took to the streets last month in a rare display of public protest in Myanmar's cities, one familiar element in uprisings around the world was largely missing: university students. There's a good reason, say Burmese academics. The junta that has ruled Myanmar, formerly Burma, for the past 19 years has stultified and splintered the universities. “The military has a deliberate policy to not educate the people,” alleges a Western diplomat in Yangon. “They are afraid people will learn to think critically.” Burmese dissident Aung Zaw, editor of The Irrawaddy magazine, agrees. “The military leaders think it is easier to control an uneducated population,” he asserts.

    The protests have prompted a bloody crackdown. United Nations special envoy Ibrahim Gambari was in Myanmar last week to try to open a dialogue between the junta and opposition leaders, including Aung San Suu Kyi, the Nobel Peace laureate who has spent 11 of the past 18 years under house arrest. But as Science went to press, soldiers had embarked on a door-to-door campaign to round up activists and put the country in lockdown. This is discouraging news for those who hoped Myanmar's academic life might be revitalized soon. “The country has suffered catastrophic losses of human capacity,” says a United Nations Educational, Scientific, and Cultural Organization (UNESCO) official who requested anonymity.

    Venting frustration.

    Buddhist monk leaders speak at Yangon's Shwedagon Pagoda during a protest on 23 September.


    The turmoil has rekindled a debate about how to assist Myanmar's fading academic community. Sanctions and approbation have failed to sway the junta, which gets vital economic support and political cover from its neighbors, especially China. In the diplomat's view, attempts to engage the government haven't paid dividends either. Others argue for bolder outreach: “The best way to support our colleagues in Myanmar is to maintain and strengthen our professional ties with them, and to continue to provide them with opportunities to do their work and interact with the world beyond their country,” says Miriam Stark, an expert on Southeast Asian archaeology at the University of Hawaii, Manoa.

    Shortly before the recent protests, Science met informally with two dozen researchers* in Bagan, Pyay, and Yangon. Academic freedom is virtually nonexistent, they say: Even scientists in North Korea were freer to speak with a journalist from Science. Forging lasting bonds with skittish colleagues in the shadow of one of the world's most repressive regimes will not be easy. “Burma is a moral minefield,” says Aung Zaw. “There is no black and white.”

    A benighted populace

    After crushing demonstrations fomented by university students in 1988, the omnipresent military, or Tatmadaw, closed the country's premier higher education institution, the University of Rangoon. The university partially reopened—but only for graduate study and research. Science was not permitted to enter the campus. According to news reports, university facilities are being used to jail dissidents.

    The abolition of undergraduate programs at the University of Rangoon may have eliminated the problem of enlightened young men and women congregating in large numbers, but the country still required competent workers. As a solution, the Tatmadaw government, which in an Orwellian touch 10 years ago renamed itself the State Peace and Development Council, claims to have established 156 universities and colleges throughout the country, up from 38 in 1988. In a recent speech, the junta's leader, Than Shwe, cited the “promotion of the education standard of the nation” as one of three requirements to “practice democracy effectively.”

    “Than Shwe is living in a fantasy world,” fumes the Western diplomat in Yangon. She and other critics say that education levels have declined precipitously. “The tragedy is that the country is further behind than it was in the 1950s.” The University of Rangoon's closure to undergrads was a crippling blow, she says: “It was considered one of the finest universities in Southeast Asia.” Now, most Burmese undergraduates attend classes a month at a time at one of the campuses outside Yangon and take correspondence courses. Children of the Tatmadaw elite are sent abroad for study, says the diplomat. Apart from them, she says, “young people with good education are growing scarcer and scarcer.”

    This, combined with a dire shortage of funding, has made it harder for older researchers, many of whom received training in China or the Soviet Union, to recruit fresh talent. “University laboratories are in terrible condition. They are like ghost towns,” says one chemist. “That's why the government doesn't want foreigners to see the university,” he says. “Chemistry students can only read about experiments; they can't do them,” adds the Western diplomat. And scientific literature is scarce.

    Only a handful of science and technology projects receive significant government resources. One is the revival of plans to build a nuclear research facility. Five years ago, the government inked a deal to buy a 10-megawatt research reactor from Russia. The agreement stalled until Myanmar announced its intention earlier this year to follow through with the purchase. Projects can fall out of fashion abruptly, however. In Bagan, an ancient city in central Myanmar (see sidebar, p. 185), the excavation site of a royal palace is now fenced off by barbed wire. The dig has been dormant since its patron, former Prime Minister Khin Nyunt, was ousted 3 years ago.

    Any collaboration with foreign scientists is vulnerable to the Tatmadaw's whims. According to Burmese scientists, each ministry has a “Foreign Affairs Committee,” including representatives of the defense and security bureaus, that evaluates proposals; the minister must sign off on approved projects. That process got more complicated when the government relocated up country to Myanmar's remote new capital, Naypyidaw, in February.

    Yet there are a few bright spots in the landscape. Over the past 2 years, for example, the International Rice Research Institute's Irrigated Rice Research Consortium has run workshops and training in Myanmar on topics such as integrated weed control, nutrient management, and laser land leveling. “There is a great need to support the livelihoods of the poor farmers and to strengthen scientific capacity,” says Grant Singleton, the consortium's coordinator. These efforts will continue in 2008, he says.

    Other success stories include bird-flu monitoring with help from the United Nations Food and Agriculture Organization, the creation of the Hukawng Valley Tiger Reserve with the Wildlife Conservation Society in New York City, and the establishment of two facilities: a conservation center in northern Myanmar (see sidebar, p. 186) and an archaeological field school in Pyay.

    Throwing a lifeline

    Founded 20 centuries ago, the circular walled city of Sri Ksetra on the banks of the Ayeyarwady River was a key outpost of the Pyu civilization. Today, Sri Ksetra, near the city of Pyay, 270 kilometers northwest of Yangon, is a rarity in Myanmar: an active excavation site involving foreign researchers. Even more surprising is a cluster of whitewashed buildings just inside Sri Ksetra's overgrown brick and earthen walls: It's the Field School of Archaeology, Pyay.

    Opened in 2005, the school now has three dozen students in a 1-year diploma course in applied archaeology that emphasizes preservation. Easy access to Sri Ksetra provides hands-on learning. “It is a great site” because the huge ancient town offers lots of space for practical work, says Elizabeth Moore, an archaeologist at the University of London who has worked in Myanmar. Several field school instructors have completed the well-respected Archaeological Survey of India graduate diploma program.

    Getting their hands dirty.

    Students learn artifact preservation at the Archaeological Field School in Pyay.


    Crucially, Myanmar authorities have allowed foreign researchers, including Robert Hudson, an archaeologist at the University of Sydney, Australia, to lecture at the school. “A common and very heartening comment from the students is that the work here is much harder than at university,” says Hudson. With colleagues in Pyay, Hudson conducted a ground and satellite survey of Sri Ksetra in 2005 and 2006 that revealed an extensive system of waterworks for irrigation and flood control. The survey, building on excavations carried out sporadically since 1907, also revealed new features, including the remains of a vast brick complex of Pyu burials and iron furnaces outside Sri Ksetra's walls.

    Promising as these interactions are, their impact is limited. The archaeologists in Pyay have virtually no budget beyond their meager salaries. Restoration of Sri Ksetra's 1500-year-old Baw Baw Gyi pagoda has been frozen for 2 years due to lack of funds. Working farther afield is largely out of the question—for archaeologists anywhere in Myanmar—especially after the hefty increases in fuel prices that sparked the recent demonstrations.

    Now is the time to redouble efforts to reach out to Myanmar scholars, says John Miksic, an archaeologist at the National University of Singapore—and archaeology is a good place to start. Hawaii's Stark agrees. Foreign archaeologists, she says, “are now the lifeline for scientists in Myanmar.” She and others hope that unspecified sanctions announced last month by U.S. President George W. Bush will not target scholarly exchange. “Banning foreign scientists from working in the country will primarily isolate and weaken our colleagues in-country who will train the next generation,” Stark says.

    Nurturing young minds won't be easy, as the deterioration of the education system has taken a heavy toll. “Even if there is an overnight change in the country's openness,” says the UNESCO official, “it will take a long time to recover.”

    • *All the people in Myanmar interviewed for this article are anonymous, to protect them from retribution for speaking to a foreign journalist without government authorization.


    Myanmar's Magic Kingdom

    1. Richard Stone
    Blitzkrieg archaeology.

    A temple rolls off the assembly line at Bagan.


    BAGAN, MYANMAR—Its skyline is studded with more than 3200 temples and bell-shaped stupas: Bagan, a sprawling ancient city on the bank of the Ayeyarwady River in central Myanmar, is the largest assemblage of Buddhist monuments in the world. But its breathtaking vista is riddled with impostors.

    In the past decade, some 1100 monuments have been rebuilt from the ground up. At the construction site of a nearly finished temple, the foreman retreats into the building's shadow to escape the midday sun. This is the 21st temple his team has built, but he's in no mood to brag. “I'm losing out on this job,” he says, mopping his brow with a rag as masons use a rope pulley to haul cheap red bricks to the roof. They are behind schedule, having worked on the building for more than half a year, and the foreman has spent more on materials and labor than he received up front from the local administration.

    Over the centuries, bandits, floods, and earthquakes, including a devastating temblor in 1975, have eroded many of Bagan's medieval wonders. Not content with safeguarding a fragile heritage, in 1998 the government of Myanmar, formerly known as Burma, ordered a sweeping restoration. The result is what one prominent Burmese scholar has dubbed “blitzkrieg archaeology”: the quick and cheap erection of cookie-cutter temples and stupas. The shoddy structures, along with a 50-meter-tall, corn-silo-shaped viewing tower and a garish new museum built in a style from another region and period, are meant to attract more tourists—and cash. Cultural integrity is an afterthought, and many archaeologists are appalled.

    “So many sites have been pillaged or destroyed by misguided attempts at restoration and tourism development,” says John Miksic, an archaeologist at the National University of Singapore who has studied Bagan's murals, “that our chances of reconstructing an accurate picture of the evolution of civilization along the Ayeyarwady have been seriously compromised.”

    Miksic and others acknowledge that Bagan is a living monument, and as such, the Burmese have a right to restore temples for worship. “In Asia, to let your heritage go into a state of disrepair is not acceptable,” says a UNESCO official. The problem, he says, is that “nobody there now is professionally trained.” After the 1975 earthquake, Myanmar invited UNESCO to take the lead in shoring up weakened structures, a program that ran until money dried up in 1995. Since then, poor restoration work has rendered ancient structures more vulnerable to future earthquakes, says Pierre Pichard of the French Research School of the Far East in Bangkok. “It's quite dangerous,” he says.

    Ironically, the rapid rebuilding of the Bagan temples may be repeating history. Recent evidence suggests that some 2500 temples rose in Bagan over a 70-year period in the 13th century: a staggering rate of one temple every 10 days. “Perhaps your modern, harried, budget-cut artisans, pressured by donors and contractors, are actually continuing an ancient tradition,” says Robert Hudson, an archaeologist at the University of Sydney, Australia, who has excavated at Bagan. To Pichard, Nouveau Bagan's simple designs and bright colors have “spoiled” the site. “Officials there,” he says, “call it beautification.” Hudson puts it differently: The restoration at times “verges on Disneyfication.”


    Exploring Alternatives in Myanmar's Wild North

    1. Richard Stone
    All the more special.

    A research station rises in Myanmar's Special Region Four.


    BEIJING—Ask Burmese how they feel about China, and you're likely to get an earful about the hunger of their northern neighbor for Myanmar's timber, gas, and other natural resources. But an unusual new venture in sustainable development in the Shan State of northeastern Myanmar, just across the border from China, could be a small step in improving China's image—and a leap in both local living standards and access for scientists to a biodiversity hot spot.

    In January 2008, the private Research and Education Center for Alternative Development (RECAD) will open for business in Special Region Four (SR-4), a district of Shan that shares a stretch of the Mekong River with China's Yunnan Province, in the Golden Triangle. These verdant highlands where China, Laos, Myanmar, and Thailand converge are notorious for opium poppies. In SR-4, the illicit crop was eradicated in 1998. But poppies thrive in other corners of Myanmar, which is second only to Afghanistan in opium production. “They grow poppies not from desire. It's because they are starving,” says Wang Yingming, a Chinese entrepreneur with a Ph.D. in environmental sciences who is spearheading RECAD's establishment.

    Rubber and research.

    Wang Yingming is hoping to help cure Myanmar of its opium habit.


    Experts are concerned that SR-4 is poised to regain its addiction to opium. In the 1990s, casinos sprang up in the region, catering to moneyed Chinese tourists. Two years ago, as part of an antigambling campaign, Chinese authorities forced dozens of casinos to close and cut off power to the region, which is on the Chinese grid. “Without alternative development, there is a likelihood of excessive deforestation for the resumption of opium cultivation,” says Guofan Shao, a forest ecologist at Purdue University in West Lafayette, Indiana, who visited SR-4 in 2004 and 2005. This, he says, “would directly threaten biodiversity conservation.”

    Hoping to avert that prospect—while creating a sustainable business venture—RECAD, bankrolled by Pudu Co., a private investment firm in Beijing, will test plants such as Jatropha that can be used to produce biofuels for the Chinese market. The $5 million center will manage a 6500-hectare rubber plantation that hopes to break even within a decade, says Wang, Pudu's president.

    RECAD could also act as a brake on unbridled development. The center is “a good starting point” for helping SR-4 authorities with sustainable land-use planning, says Shao. He hopes that with an understanding of biodiversity and the value of preserving forest alongside plantations, SR-4 can avoid the fate of Xishuangbanna Prefecture in Yunnan, where rubber plantations have run riot. “It will be a total disaster if the same rubber-tree landscape model is repeated in SR-4,” Shao says.

    In a departure from the usual Chinese business model, Wang has put scientific concerns at the forefront. “No organization in Myanmar has done research to guide development,” Wang says. RECAD has dormitories for visiting scientists, who will pursue everything from applied projects in biofuels and sustainable development to basic forest ecology. Wang has established links with the Chinese Academy of Sciences, which plans to dispatch four to six teams of researchers to the SR-4 facility early next year. Foreign scientists will be warmly welcomed, says Wang. “I intend to turn it into a real international research center.”

    Wang concedes that launching the center in SR-4, which enjoys significant autonomy from Myanmar's central government, is a gamble. “Only high-risk investors come here,” he says. But Wang has won the hearts of locals with the promise of employment for as many as 1500 people and a pledge to build a school and a hospital with help from the Chinese government. Scientists, too, are eager to participate in the experiment. “SR-4 is a unique site for promoting alternative development and protecting forest biodiversity in Southeast Asia,” says Shao. An initial project, he says, could be a biodiversity inventory of the region.


    Grasping for Clues to The Biology of Itch

    1. Greg Miller

    Chronic itch afflicts millions of people, but little is known about the underlying mechanisms


    SAN FRANCISCO, CALIFORNIA—For most people, itch is an occasional, short-lived annoyance, provoked by a run-in with bloodthirsty insects or poisonous plants. But for Mary Ellen Nilsen, itchiness became a life-altering experience. In 1998, at age 38, Nilsen had a shingles outbreak, a resurgence of the chickenpox virus. Antiviral drugs cleared up the painful shingles rash on her face and scalp, but a ferocious itch took its place. “It was relentless,” Nilsen says. Over a 13-month period, Nilsen scratched and scratched, despite her best efforts not to and despite her horror at the growing lesions she saw in the mirror. At the time, Nilsen says, she had no idea that the damage she was doing to herself was more than skin deep, but she ended up in a Boston emergency room with brain tissue protruding through a hole she'd scratched in her skull.

    “She gave herself frontal-lobe brain damage,” says Anne Louise Oaklander, a neuroscientist and neurologist at Harvard Medical School in Boston, who treated Nilsen and described her case at a recent meeting* here. Oaklander blames the infuriating itch on severe nerve damage caused by the virus—damage that also left Nilsen unable to feel pain from her scratching-induced wounds. Although Nilsen's experience is extreme, to say the least, chronic itch is far from rare. Millions of people worldwide suffer from incessant and largely unexplained itchiness brought on by kidney or liver disease, HIV, or various other ailments. Chronic itch disrupts sleep, reduces the quality of life, and undermines the health of those who suffer from it—yet there is little doctors can do to help.

    At the meeting, a diverse group of clinicians and researchers tried to scratch beneath the surface of recent findings for clues about the biology of itch. “Itch remains one of the greatest puzzles in sensory physiology,” says Hermann Handwerker, a pioneering itch researcher at the University of Erlangen-Nuremberg in Germany.

    Once thought to be a lesser form of pain, itch does share some neural wetware with that other unpleasant sensation. But recent research points to receptors and nerves that may selectively signal itch. Drugs that turn the volume down on such signaling pathways could vastly improve the lives of many people who desperately need help, clinicians say. “Itch is absolutely a neglected area of medicine,” says Oaklander. “It's extremely disabling.”

    And chronic itch is surprisingly widespread. At the meeting, Gil Yosipovitch, a dermatologist at Wake Forest University School of Medicine in Winston-Salem, North Carolina, reeled off a long list of scratch-inducing statistics. A 2006 study in The Lancet Infectious Diseases estimated that 300 million people worldwide suffer from scabies, an itchy skin disorder caused by biting mites. A report published online in Dermatitis in August estimated that 31.6 million Americans suffer from the itchy, inflamed skin of eczema, and a 2006 study in Nephrology Dialysis Transplantation found moderate to severe itch in 42% of nearly 19,000 kidney-dialysis patients surveyed in 12 countries. Other studies have associated intense itchiness with bile duct obstructions, infectious diseases, and drug reactions. For reasons that are poorly understood, some conditions cause itch over large swaths of the body, whereas others tend to affect only the face, back, or other region, Yosipovitch says.

    Wherever it strikes, chronic itch isn't good for your health, Yosipovitch adds. The study of kidney-dialysis patients, for example, found a 17% higher mortality rate in those with chronic itch, a finding the researchers attributed to loss of sleep. In a literature review published in the July issue of Acta Dermato-Venereologica, Yosipovitch concludes that itch is often worse at night. He suspects that circadian fluctuations in compounds that aggravate or dampen itch may be the reason. Levels of the itch-suppressing hormone corticosterone, for example, wane in the evening.

    Biological roots

    If itch is so problematic, why do we have it in the first place? Many researchers think it evolved as a defense mechanism against insects. Unlike pain, which elicits a withdrawal response, itch draws attention to a particular area of the skin and elicits scratching, so it may serve to remove insects and any stingers, eggs, or other deposits they leave behind, says Handwerker. “It may have been more important for early man to protect himself against insects than against tigers or other large animals,” he says.

    Although itch and pain are different sensations tied to different behaviors, their biology appears to be inextricably intertwined. In fact, itch was once considered pain's little brother. Both sensations are conveyed from the periphery to the spinal cord by nerves called C fibers, and the thinking was that a little bit of C-fiber stimulation caused itch, whereas more stimulation caused pain. In this view, pain and itch share a communication link to the brain, and only one of them can talk at a time. This would explain why pain tends to quell itch and why certain painkilling drugs facilitate it.

    But in 1997, a research team led by Martin Schmelz, now at the University of Mannheim in Germany, reported the discovery in healthy human subjects of C fibers that respond vigorously to an itch-inducing injection of histamine under the skin but not to painful heat or pinching. The findings suggested that itch and pain may talk independently to the brain after all.

    A more recent strike for itch independence comes from geneticists at Washington University in St. Louis, Missouri. Yan-Gang Sun and Zhou-Feng Chen used DNA microarrays to search for itch-related genes in the spinal cords of mice. Based on its high levels in spinal neurons thought to convey itch, one candidate stood out: the gene for gastrinreleasing peptide receptor (GRPR). When the researchers created mice lacking the GRPR gene, the rodents scratched much less than normal mice when both sets of animals were injected with several itchy substances. Yet the mutant mice responded normally to painful poking, heat, and noxious chemical injections, Chen reported at the conference and in the 9 August issue of Nature.

    The findings offer an important insight into the biology of itch, other researchers say, and they may point to possible treatments. Part of the reason chronic itch conditions have been so hard to treat is that, unlike acute itchy reactions caused by mosquito bites and poison ivy, most of them are not mediated by histamine, and so they do not respond to antihistamine drugs. There must be molecular players in itch transmission besides histamine, but their identity is a mystery. Even so, when Sun and Chen gave genetically normal mice a drug that blocks GRPR, the rodents scratched less in response to subsequent injections of three itch-provoking compounds—including two that don't work through histamine. That's a good sign, Chen says: “Our results suggest that GRPR [blockers] could be particularly promising for treating chronic itch.”

    Other researchers reported on a variety of possible treatments for chronic itch—including medications more commonly used to treat depression (selective serotonin reuptake inhibitors) and epilepsy (such as gabapentin)—that may quiet hyperactive itch-transmitting neurons. One of the most promising leads, say several researchers, are drugs that stimulate so-called κ opioid receptors. Opioid receptors are best known as the site of action for powerful painkillers like morphine, which activates μ opioid receptors, dulling pain but often producing itch as a side effect. Drugs that stimulate κ receptors seem to have nearly opposite effects, reducing itch without dulling pain in a handful of recently published studies with patients suffering chronic itch related to kidney disease. (Pain does serve a purpose, after all, as Nilsen's case illustrates.) And at the meeting, researchers from the pharmaceutical branch of a Japanese chemical company reported encouraging findings from a small pilot study in cirrhosis patients with chronic itch.

    Itchy nightmare.

    Bandages protect Mary Ellen Nilsen's head after a chronic itch drove her to scratch through her skull (CT scan, inset).


    Scratch, scratch

    Some researchers are also studying the oldest itch remedy of all: scratching. Neuroscientists Steve Davidson and Glenn Giesler and colleagues at the University of Minnesota, Minneapolis, recently investigated the effects of scratching on the activity of neurons in the spinal cords of anesthetized monkeys. These neurons rev up when researchers inject histamine or other itchy compounds under the skin, firing impulses at an elevated rate. But when Davidson used a saw blade to gently scratch the site of the injection, the neurons interrupted their barrage of impulses for a few seconds. This inhibition only happened when the spinal neurons were signaling an itch—scratching in the absence of itch made them more excited, Davidson reported in a poster presentation at the meeting. The findings suggest that scratching inhibits itch in the spinal cord, before it even reaches the brain, he says.

    That's not to say the message never makes it through. Several recent studies have used functional magnetic resonance imaging to investigate how the brain responds to itch. In a study with 16 people, half with chronic itch caused by atopic dermatitis, Yosipovitch's group found hearty responses to itch in the anterior cingulate cortex, a brain area that, among other things, may attach emotional significance to sensory experience. Neural activity in the anterior cingulate ramped up when the researchers injected histamine into the skin of the subjects'forearms, Yosipovitch reported. This increase was greater in the dermatitis subjects and varied in proportion to the severity of their itch. In another study, Yosipovitch and colleagues found that scratching, even in the absence of itch, decreases activity in the anterior cingulate.

    Such studies may eventually shed light on why scratching is so addictive. “There is definitely a rewarding effect to the scratch itself,” Yosipovitch says. Perhaps that helps explain why people often scratch when they see others in an itchy state. A few years ago, German researchers videotaped people watching a public lecture about itch and caught them scratching more than usual. The effects of reading articles about itch have yet to be rigorously tested.

    • *4th International Workshop for the Study of Itch, 9–11 September.


    Wanted: A Barcode for Plants

    1. Elizabeth Pennisi

    Quick-and-easy DNA identification of animals is under way, but plants are proving harder to pigeonhole

    Identities revealed.

    Some taxonomists thought these two types of ginger were the same species, but DNA barcoding proved otherwise.


    Four years ago, Paul Hebert wowed researchers at the Smithsonian Institution's National Museum of Natural History (NMNH) in Washington, D.C., with the results of a pilot study that he said demonstrated a way to distinguish any animal species from any other, using only a short piece of variable DNA. Hebert, an evolutionary biologist at the University of Guelph in Canada, called it an organism's “barcode.” He appealed for a similar effort to find a unique identifier in plants. “He was staring right at me,” recalls W. John Kress, a botanist at NMNH. “I took it as a challenge.” Kress and his colleagues began what has become a controversial quest for a botanical barcode.

    At a meeting in Taipei last month,* hundreds of researchers described their successes in barcoding birds, moths, fish, and other animals, demonstrating rapid progress for this high-tech approach to cataloging biodiversity. Representatives from regulatory agencies outlined plans to use barcodes to track water quality, as well as invasive and endangered species. But despite a strong effort by Kress and dozens of other botanists and systematists, barcoding for plants has yet to gel. “We did not reach consensus” about a few issues, says Ki-Joong Kim, a botanist at Korea University in Seoul, who has come up with his own barcoding scheme.

    Debates have been raging about how many and what pieces of DNA it takes to tell one plant from another. Some groups have forged ahead, gathering representative sequences from plants ranging from mosses to daisies, and several teams are developing DNA catalogs of medicinal plants or endangered trees. Yet, for the most part, these data are of little use until everyone can agree on a standard. “Botanists around the world are champing at the bit to get involved in barcoding,” says Kenneth Cameron, a plant systematist at the New York Botanical Garden in New York City. “People are very frustrated” by the lack of consensus. And the potential for confusion is rising, as groups pursue selected DNA sequences and different cataloging strategies.

    On the table.

    Over the past 6 months, researchers have proposed several combinations of DNA regions for barcoding plants.

    View this table:

    No simple solution

    Barcodes on groceries instantly reveal the identity and cost of an item in just a few black and white stripes. In animals, a mitochondrial gene called CO1 seems to work in a similar way, as a kind of species tag. Its sequence varies enough to distinguish most animal lineages but is conserved enough that a single DNA probe works for most organisms. This simplicity has sparked plans to make hand-held sequencers that can provide quick readouts in the field (Science, 18 February 2005, p. 1037).

    From the start, Kress and others knew that plants would need a different tag. Mitochondrial genes wouldn't work because they evolve more slowly in plants than in animals; too few differences exist between, say, a potato and a tomato to tell them apart. Nuclear genes weren't very appealing either because plant cells often have many copies of a mitochondrial gene but relatively little nuclear DNA. So plant experts turned to a genome not found in animals—that of the chloroplast, the organelle that converts sunlight to chemicals.

    As a first pass, Kress and his colleagues scanned the two chloroplast genomes that researchers had already sequenced, picking out nine stretches that varied the most. “The sequences have to be similar enough to be [probed] easily but different enough to distinguish plant species,” explains Chang Liu of the University of Hong Kong. Kress's group evaluated these regions. In 2005, at the first international barcode meeting, they nominated about 450 bases, part of a “spacer” sequence between two genes for the plants' barcode, trnH-psbA. Spacers tend to be more variable than genes themselves and therefore better identifiers. “So far, it seems to work the best” of all barcodes, Kress insists.

    At that meeting, however, “a lot of the botany community said, ‘Whoa, there's problems with this,’” recalls Cameron. He and others thought more comprehensive, systematic studies were needed. Representatives from the Alfred P. Sloan and Gordon and Betty Moore foundations—which had financed work in the area—responded with $900,000 to support further evaluation of barcode candidates. Mark Chase and Robyn Cowan of the Royal Botanic Gardens, Kew, in Richmond, U.K., and researchers from about 10 institutions screened 100 gene and spacer regions in the chloroplast to see which could be pulled out by a single probe. They also checked 96 pairs of species representing the plant kingdom to see which were variable. And they evaluated the most promising half-dozen in specific plant groups. Kress's Smithsonian group declined to participate; they continued refining the spacer strategy they had proposed.

    In the 6 June issue of PloS One, Kress and his colleagues reported their results: They adopted a more complex strategy to conduct a survey of 50 plant species. “We all wanted the ideal—a single region,” Kress recalls. But as his team looked beyond flowering plants to mosses, liverworts, and other distant kin, they ran into too much variation. Although researchers could line up and compare sequences in closely related plants, those in unrelated plants such as ginger and tomato were too different. The remedy they suggest is a “two-locus barcode,” says Kress: both the trnH-psbA spacer and part of a gene called rbcL. Adding the gene, which has changed much more slowly over evolutionary time, is useful for distinguishing distantly related plants.

    “It's a concept that I actually like,” says Cameron. But Chase and Cowan haven't been eager to buy into the strategy. Earlier, their team turned away from rbcL, which codes for a key enzyme involved in capturing carbon dioxide for photosynthesis, because they couldn't come up with a universal probe for pulling out short, easy-to-sequence pieces. As for the trnH-psbA spacer, Chase says their results suggest that its variability limits its utility as a universal barcode.

    In the May issue of Taxon, Chase's team instead proposed a barcode using three DNA regions. A triple probe is needed, Chase explains, because “no one of them works universally.” His group had not quite settled on which probes work the best; different ones help distinguish certain groups of plants (see table).

    Meanwhile, Kim had struck out on his own in search of the best plant barcode. His group sequenced the chloroplasts from nine plants, including seven ginseng species, discovering several regions that provided unique species signatures. Kim's group also decided on a three-region barcode—a gene and two spacers—and could discriminate flowering plants belonging to 10 other genera, including dandelions, lilacs, and Cardamine. The gene they chose is matK, one of Chase and Cowan's choices. Using this method, Kim has already barcoded 500 Korean species.

    In all, about a half-dozen proposals came up during the Taipei meeting; discussions were intense. The Korean strategy bubbled up as quite promising, says plant systematist Sean Graham of the University of British Columbia in Vancouver, Canada. But “a final set of markers was not quite decided on,” he notes. Most of the researchers agree that Kim and Chase's matK and Kress's spacer should be used. And most are calling for a third region, likely one of the two other spacers proposed by Kim. Graham and his colleagues are going to evaluate these four candidates and report back later this fall on how well they work.

    Kress, however, left frustrated. He points out that several papers presented at the meeting supported his choices for a barcode, whereas there's little published data supporting other scenarios. He's hesitant about any three-gene scenario because it would create “an order of magnitude more work.” Anyway, he says, “we're moving ahead” for now using his twobarcode regions.

    Intense debate.

    In Taipei, plant researchers wrangled over potential barcode regions, making headway but not reaching full agreement.


    Conflicting needs

    Part of the problem is that plant researchers have different needs. For example, a unique barcode may not be all that critical for cataloging the plants in a given habitat, where typically the species aren't closely related. “Less than three, and often one, gene will work quite well” in a local survey, Graham points out. Indeed, last year, Pierre Taberlet of Joseph Fourier University in Grenoble, France, and colleagues found they could use just one DNA snippet—a noncoding part of a gene—to distinguish half of 132 Arctic species studied and the onion, potato, and leek ingredients in a dried soup mix. The snippet also worked on plant matter extracted from a 20,000-year-old frozen human fecal sample, the group reported online 14 December 2006 in Nucleic Acids Research. They suggest that this limited barcode would suffice for tracking plants used in the food and cosmetic industries.

    In contrast, taxonomists need more depth within a genus—enough DNA to reveal the degree of relatedness. Introns and spacer regions don't always do that; multiple genes are needed. And some systematists argue that nuclear genes will eventually have to be part of the barcode mix. “It's a Catch-22 situation,” says Graham. “The criteria to pick these markers are somewhat contradictory.”

    But there's a growing need to come up with a solution. Right now, the Barcode of Life Data Systems (BOLD) provides one-stop shopping for anyone seeking animal barcodes. But neither BOLD nor public databases that archive DNA sequences will accept plant barcodes until there is a single agreed-upon standard. Furthermore, BOLD will need to develop new bioinformatics to accommodate barcodes that include multiple DNA regions. “I am worried that if we don't start thinking about this database [problem], suddenly we will have thousands of sequences and no place to put them,” Kress says.

    The potential chaos is reflected in barcoding for medicinal plants. The Smithsonian group has developed a barcode library for 750 medicinal plants. But until recently, Kress wasn't aware that Liu has been using yet another barcode combination to catalog Chinese medicinal plants.

    And some researchers aren't waiting for the standard to be decided upon. Kress and his collaborators are barcoding the 300 tree species in a long-term study site in Panama, and they plan to do the same at 16 other study sites around the world. Chase's group is developing a barcode database of endangered tropical trees for the United Kingdom to use in detecting illegal timber imports. The Sloan Foundation has asked Cameron to draft a plan to coordinate the barcoding of the world's tree species. And Genome Canada is 500 plants into a scheme to develop barcodes for the country's 5000 plant species.

    Yet despite all this activity, David Schindel, executive secretary for the Consortium for the Barcode of Life based in Washington, D.C., argues for patience. “This process has taken longer than anticipated and certainly longer than what we hoped,” he points out. “But, at the end of the day, the data will reveal which are the most effective high-performing regions.”

    • *The Second International Barcode of Life Conference was held 16 to 21 September 2007 in Taipei, Taiwan.


    Tooled-Up Amateurs Are Joining Forces With the Professionals

    1. John Bohannon

    Hobbyists who love the night sky are finding that their skills, and telescopes, are in demand with academic astronomers

    BARCELONA, SPAIN—By day, Antonio Garrigós-Sánchez seems like an ordinary guy. The proud 46-year-old father of two girls works as a technician at a printing firm. But by night, he transforms. After sundown, Garrigós-Sánchez retreats to his underground lair, a basement office that would not be out of place at NASA headquarters. The walls are lined with shelves of instruments, journals, astronomical reference books, and stacks of data backup disks. And with a few clicks at the computer on his desk, Garrigós-Sánchez is staring into deep space.

    Behind the Garrigós-Sánchez domicile stands an observatory he built from off-the-shelf components. Through the open dome of the cottage-sized building points a telescope as big as a torpedo. Night after night, guided by his computer, it collects light from a zoo of strange celestial objects and records its data on disk. Garrigós-Sánchez doesn't do this only for the joy of watching the night sky; his data are vital for several ongoing academic research projects, and his name appears as co-author on a string of peer-reviewed papers.

    Among scientific fields, astronomy may be the last one in which amateurs can stand shoulder to shoulder with professionals and expand the envelope of knowledge. In some cases, they are even outcompeting professionals for research grants. The past decade has seen a renaissance in amateur astronomy due to technological innovations and cheaper components. Basic research can only benefit by tapping into this resource, says Joseph Patterson, a professional astronomer at Columbia University. “The sum total of ingenuity and energy among the world's amateur astronomers vastly exceeds that of professionals.”

    Cheap tools, long nights

    Amateur astronomers are quick to point out that their research has a long pedigree. Many astronomical pioneers were rich men who liked to play with telescopes. William Herschel was an organist and composer in the English town of Bath when, in 1781, he discovered Uranus. In North America, amateurs began exchanging observations and theory with professionals as early as 1868 with the founding of the Royal Astronomical Society of Canada. But things really got cooking in 1911 when the American Association of Variable Star Observers (AAVSO) started pooling data in what has become the world's largest database of amateur astronomical observations. It was founded at Harvard University to ensure that the observations made by amateurs would not be lost. AAVSO now logs about 1 million observations per year from amateurs in 45 countries.

    Top quality.

    Data like these observations of a variable star from amateurs are bread and butter for professional astronomers.


    The scale of such amateur scientific efforts is unknown in other fields. (Imagine 2500 volunteer biologists studying fruit fly development with state-of-the-art equipment in their own homes.) The AAVSO amateurs coauthored 30 peer-reviewed papers last year alone, and the association usually holds several active research grants at any one time. Dozens of other networks have sprouted up in the past decade. Garrigós-Sánchez is part of a Barcelona-based group called AstroGea that links amateurs with professional astronomy projects throughout Europe. The quality of these backyard observatories is such that professional astronomers are regular users.

    There are several reasons for this blossoming, says Richard Fienberg, editor of Sky & Telescope magazine. “But the biggest breakthrough was the CCD camera,” he says. “It immediately allowed us to see objects 10 times fainter with the same telescopes.”

    The CCD, or charge-coupled device, camera has become the sine qua non of astronomical data collection since its invention 3 decades ago, as well as making possible cheap video cameras and digital photography. CCD cameras allow astronomers to convert photons into data much more efficiently. In traditional photography, photons trigger a chemical reaction in the film that, after several steps of development, produces metallic grains that add up to an image. But in a CCD camera, incident photons directly create an electrical pulse in a circuit that can be recorded on a computer as a pixel. The boost in efficiency—CCD cameras detect 70% of photons compared with film's 2%—suddenly turned humble backyard telescopes into “very powerful tools,” says Fienberg, who was finishing his astrophysics Ph.D. at Harvard in the 1980s when CCD cameras were first coming into mainstream use among professional astronomers. Cheap mass-production put CCD photography in the hands of amateur astronomers by the early 1990s.

    The new bounty of digital data has required heavy-duty computing, and amateurs have played a role here as well. An amateur-scripted program called MaxIm DL controls telescope positioning and the CCD camera and processes the data. “The quality of this software is superb,” says AAVSO director Arne Henden, “and it is heavily used by professionals.” The program is one among many, he says.

    The other key breakthrough was online communication, because it enables observers to react quickly to fast-changing events. “The Internet is key to the blurring of the amateur-professional dividing line,” says Henden. A recent example is the observation of an extremely rare pair of stars, known as V455 And (for “Andromedae”), in which a white dwarf is sucking matter from its partner, a brown dwarf. Professionals have been waiting for the white dwarf to gather enough nuclear fuel to become “cataclysmic,” releasing a sudden explosion of light that provides valuable data on stellar evolution. The outburst was not expected for decades, but it happened on 5 September. A Japanese amateur spotted it and sent out a notice online, and amateur telescopes around the world swiveled to capture the brief event. “Amateurs are leading the observational studies,” says Henden, and “there will be many important papers that will come from this event.”

    Redefining amateur

    But are amateur astronomers aware of how their observations translate into real science? They are, says Fienberg. “It's amazing how well some of them follow the field.”

    Take Brian D. Warner, for example. (The initial distinguishes him from a professional astronomer in South Africa.) “I got my first CCD in 1992,” says Warner, who was working as a computer programmer and television reporter in Colorado Springs, Colorado, at the time. He is part of a network of more than 1000 international amateurs scrutinizing our solar system's minor planets—the asteroids and their ilk, most of which orbit beyond Mars. Many are as big as mountains, but just finding them in the inky blackness was a feat. Mapping the distribution of these bodies is needed to constrain models of how the solar system evolved. Armed with CCD cameras, amateurs became latter-day Galileos, reporting hundreds of previously unidentified astronomical bodies.

    That bonanza came to an end when the professionals caught up in 1997 with the first full-sky digital surveys. “But that just changed the game,” says Warner. Instead of identifying new minor planets, amateurs focused their efforts on characterizing them, making repeated observations to reveal their size and rotational speed and whether they are orbited by their own tiny moons. And this is where Warner and others got deep into the science.

    A burning question is how minor planets acquire their own satellites. The prevailing theory in the 1990s held that if a minor planet swings close to an enormous body like Mars, the pull of its gravity can break a chunk free from the small body's surface. To test that theory, Warner searched for dancing pairs of bodies far beyond the reach of the major planets. Over the past 3 years, he has identified five pairs. The discovery helped rule out the tug-of-gravity theory, and a new explanation—that solar heating causes rotational acceleration that flings chunks off—made the cover of Science last year (24 November 2006).

    For the love of it.

    Antonio Garrigós-Sánchez (right) in a homemade observatory. Backyard facilities such as these are luring professional astronomers into research collaborations.


    Warner is sheepish about calling himself an amateur these days, because he has earned a master's degree in astronomy from James Cook University in Townsville, Australia, and is a full member of the American Astronomical Society (AAS), an organization generally open only to professional astronomers, granted on the basis of his published work. But he still considers himself the amateur half of a collaboration that began at a minor planet conference in 1999 when he met Alan Harris, a planetary astronomer at the Space Science Institute in Boulder, Colorado. Warner himself won grants from the U.S. National Science Foundation and NASA this year. One of his missions is to catalog the spin properties of all known near-Earth objects, based on his observations and those in the literature. Aside from the value to basic science, the project “does have that extra Hollywood aspect of helping to prevent a global catastrophe,” says Warner. Any one of thousands of nearby asteroids could devastate the planet on impact.

    Warner's achievements in the field make him stand out, but he's not unique. The number of amateur-professional research collaborations has exploded simply because “professional astronomers need them,” says Patricia Lampens, an astronomer at the Royal Observatory of Belgium in Brussels. Her own field of research, variable stars, is a case in point. This class of stars is mysterious because they grow brighter and fainter periodically. To tease apart the many causes of variability, data must be collected continuously throughout a star's cycle, which can range from minutes to years in duration, to obtain a “light curve.” Getting just a single night at one of the major professional telescopes is like winning the lottery, but amateurs have the “luxury” of observing whenever they want, she says. Amateurs such as Garrigós-Sánchez “deliver very high-quality data” on the same target over “many weeks or even months” for free. The stellar light curves cataloged by AAVSO are of similar quality.

    For professionals to take full advantage of this free resource, some sort of dating agency is required. “What's needed is an efficient system to connect professional astronomers one-to-one with well-equipped amateurs,” says Fienberg. He is now helping to set up a “pro-amateur registry” through AAS. Profiles of international amateurs will include their telescope specifications, observing experience, and e-mail addresses. And professional astronomers will post details about their research projects and what kinds of observations they seek.

    The registry is bound to blur the amateur-professional line further. When it comes to astronomy, says Donald Kurtz, an astronomer at the University of Central Lancashire in Preston, U.K., “the term ‘amateur’ should be taken in its original French meaning”: a “lover” of astronomy, not necessarily lacking in skill.

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