News this Week

Science  12 Aug 2011:
Vol. 333, Issue 6044, pp. 806
  1. Around the World

    1 - Italy
    All in the Academic Family
    2 - Geneva
    Particle Physics Lab Launches Arts Boar
    3 - London
    U.K. Needs to Stop ‘Muddling’ on Gene Patents, Says Report
    4 - Mexico City and Washington, D.C.
    FDA Approves First Scorpion Antivenom


    All in the Academic Family

    Nepotism is rampant in Italian academia—and medicine and industrial engineering are among the most inbred disciplines, according to a statistical study published 4 August in PLoS ONE.

    Study author Stefano Allesina, an Italian researcher in the Department of Ecology and Evolution at the University of Chicago in Illinois, used a public database of Italian researchers to ground-truth abundant anecdotes of nepotism in Italian academia.

    The database listed the first and last names of about 61,340 tenured professors along with their institutions, departments, and disciplines. Allesina compared the actual number of last names in the database with the number of last names likely to crop up in a particular discipline by chance.

    He found “a severe paucity of names,” primarily in engineering, law, medicine, geography, and pedagogy. Linguistics, demography, and psychology had the lowest probability of nepotism. Allesina notes that his analysis is also an underestimate, because it does not take into account cases in which female professors hire close male relatives, as Italian academic women typically keep their maiden names.


    Particle Physics Lab Launches Arts Board

    CERN's “Cosmic Song” is a work of art and a cosmic ray detector.


    The European particle physics laboratory, CERN, near Geneva, Switzerland, has formed a five-member Cultural Board for the Arts to evaluate proposals from artists interested in working with or at CERN.

    The lab already receives more artistic proposals than it can handle, says Michael Doser, a physicist at CERN and the lone scientist on the board. “Some of these are great and some of them are not so great, and it will be really helpful to have a board that can pick the best ones.” Each year one or two projects will receive a letter from the board expressing CERN's interest; the artists must scrape up their own funding.

    The board will also weigh in on architectural issues at the lab and will help select artists in residence for a program that CERN will soon start. Other board members include the directors of Switzerland's Kunsthalle Zurich museum and France's Lyon opera house.


    U.K. Needs to Stop ‘Muddling’ on Gene Patents, Says Report

    In a report on intellectual property and DNA diagnostics, the Human Genetics Commission, an independent group that advises the U.K. government, urged health and research institutions to “stop muddling” on gene patent laws and develop a coherent policy—and soon. The report found that doctors and researchers in U.K. public institutions have mostly ignored biotech companies' patents on numerous genetic tests, often developing their own “homebrew” tests to avoid paying royalties. It might be only a matter of time, said policy expert Michael Hopkins of the University of Sussex, before a company tries suing the U.K. National Health Service for years of back royalties. At the report's launch, however, others defended the evasion of gene patents: Gail Norbury, governance director of genetics laboratories at Guy's Hospital in London, called them “unacceptable, unenforceable, and detrimental.”

    Mexico City and Washington, D.C.

    FDA Approves First Scorpion Antivenom


    Campers in scorpion country can sleep a little easier. A new drug this week became the first scorpion venom treatment to be approved by the U.S. Food and Drug Administration (FDA). The drug, called Anascorp, was developed by researchers at the National Autonomous University of Mexico in Mexico City and has proven to be enormously effective in treating scorpion stings in clinical trials conducted in the United States since 2004. According to FDA, about 8000 people in Arizona are stung by scorpions each year; in Mexico, the number is nearer 250,000. Stings from the most deadly species, if left untreated, can cause convulsions and even death.

    The clinical study, published in The New England Journal of Medicine in 2009, found that Anascorp quickly reversed the effects of scorpion stings in young children, who are especially susceptible to breathing difficulties caused by the scorpion's paralysing neurotoxin.

  2. Random Samples


    >As part of the continuing financial fallout from the Fukushima disaster, on 3 August the U.K. Nuclear Decommissioning Authority announced the closure of the 15-year-old nuclear reprocessing plant in Sellafield. The plant, which recycled used plutonium and uranium into mixed oxide fuel, could no longer afford to operate without the demand for MOX fuel from Japan, its largest customer.

    They Said It

    “I am shocked by Mark and Olly's … gross misrepresentations of Matsigenka culture, and their disregard for consequences inflicted on native communities. … I wonder what Living with the Machigenga was modeled on. Borat comes to mind.”

    —Anthropologist Glenn Shepherd accusing a reality TV show that aired on BBC of falsifying scenes and mistranslations to make an Amazonian tribe appear to be “sex-obsessed, mean savages.”

    Mastodons in the Smithsonian (Sort of)


    The American artist and naturalist Charles Willson Peale famously helped unearth a mastodon in 1801. That skeleton isn't on display at the Smithsonian American Art Museum in Washington, D.C., but Peale's painting of the dig, The Exhumation of the Mastodon (left), is there, side-by-side with 160 other art pieces and scientific relics. Together they convey a 19th century sense of the wonder and vastness of America, when everything in the country seemed huge: giant redwood trees, giant falls at Niagara, giant herds of buffalo, giant trains, and giant fossils. The newly opened Great American Hall of Wonders exhibition, on display through 8 January 2012, tries to capture this American sense of optimism and excitement about its own ingenuity, as exemplified by Peale himself.

    By the Numbers

    20 — Number of years arXiv, the electronic bulletin board of unpublished physics papers, has been around.

    145 — Number of cubic kilometers of groundwater humans extracted each year from 2000 to 2008, according to calculations reported in Geophysical Research Letters. That loss to the oceans accounted for 13% of reported sea level rise.

    1 in 11 — Chance that a woman with a faulty copy of the gene RAD51D will develop ovarian cancer, according to a study in Nature Genetics.

    A Bad Day for Goodyears


    Bison and junkyard tires have something in common: Both go thunk when they plummet off a cliff. That observation comes via researchers at the University of Arizona in Tucson, who recently engineered a Goodyear massacre, rolling about 20 tires off a steep drop in western Montana.

    The rubber slaughter was an attempt to recreate the final few seconds of a traditional bison hunt by ancestors of the Blackfeet tribe of Montana. By 1000 C.E. (and continuing until at least 1600 C.E.) the hunters were using a powerfully effective strategy: They first spooked the bison herds and then directed them down a hill toward a 25-meter-high cliff.

    As part of a larger study of prehistoric bison hunting societies in the Northern Great Plains, archaeologist María Nieves Zedeño and her colleagues wanted to reconstruct the bison kill sites and examine the physics of these “bison jumps” first-hand. Pondering a substitute for the bison that wouldn't enrage PETA, one of her team members, a member of the Blackfeet tribe, suggested tires. “There are quite a lot of abandoned tires lying around the reservation,” says Zedeño.

    Tires are a pretty good substitute, Zedeño says: Like bison, tires are heavy and build up good speed on their downhill run (the tires rolled at up to 20 kilometers per hour, compared with an estimated 30 kilometers per hour for a bolting bison). Old animal bones near the foot of the cliff suggest that the falling bison used to land up to 10 meters away from the cliff face. And, as Isaac Newton would no doubt be happy to hear, the tires landed in roughly the same spot.

  3. Hydropower

    Mayhem on the Mekong

    1. Richard Stone

    Hydropower dams planned for the lower Mekong could damage ecosystems and erode food security across the river basin.


    VIENTIANE, LAOS—Flooding of biblical proportions is a way of life for villagers in the region around Cambodia's Tonlé Sap Lake. Each summer, the lake expands from an area smaller than Rhode Island to a Connecticut-sized basin—from 2500 km2 to as much as 15,000 km2. Average depth increases from 0.5 m to 8 m or more. The spectacular phenomenon occurs when the Mekong River, swollen from monsoon rains, forces a tributary, the Tonlé Sap River, to reverse course and feed the lake instead of drain it.

    One million people depend on the seasonal filling and emptying of Tonlé Sap, the “Heart of Cambodia.” “It's the biggest inland fishery on Earth,” says Kim Geheb, Mekong Basin leader for the Consultative Group on International Agricultural Research's Challenge Program on Water and Food. During the dry season, when Tonlé Sap drains, migratory fish head upstream to spawn in deep pools in the Mekong and its tributaries; when the lake is replenished in summer, young fish descend en masse to feed. The rising water washes organic matter from the floodplain into the lake, nourishing primary productivity. “The flood pulse is the engine of the ecosystem,” says Dirk Lamberts, an aquatic ecologist at Catholic University of Leuven in Belgium.

    That dynamo is now in jeopardy. Newly built dams on the upper Mekong and its tributaries are expected to modulate the river's flow. At first the effect will be subtle. But in the next couple of decades, Tonlé Sap will begin to stabilize, models predict. A large area of permanent inundation will swallow thousands of hectares of floodplain, disrupting the ecosystem and possibly devastating the fishery.

    That gloomy scenario doesn't take into account the latest threat to Tonlé Sap and the rest of the Mekong River Basin. Leaders here in the Laotian capital are preparing to build the first dam on the lower Mekong mainstream, the 2700-km segment that wends from the China-Laos border to the South China Sea. The $3.8 billion Xayaburi Hydroelectric Power Project, slated for completion as early as 2019, would generate 1285 megawatts of electricity—enough to power a medium-sized Southeast Asian city—mostly for export to Thailand. But the plan is raising tensions. The Mekong River Commission (MRC), which includes Laos, Cambodia, Thailand, and Vietnam, requires prior consultation on any major project that might affect sustainable development on the Lower Mekong Basin (LMB). Xayaburi dam is the first major proposal to trigger such a review. And the other three MRC members are not satisfied with the information they've received so far from Laos.

    Vietnam, expressing “deep and serious concerns,” called last April for a 10-year moratorium on hydropower development on the lower Mekong mainstream. Laos quickly deferred a final decision on Xayaburi, at least publicly. In May, Lao Prime Minister Thongsing Thammavong assured his counterpart from Vietnam that the dam would be postponed pending further studies involving international experts. That gesture won praise last month from U.S. Secretary of State Hillary Clinton at a regional meeting. “I want to urge all parties to pause on any considerations to build new dams until we are all able to do a better assessment of the likely consequences,” she said.

    But Laos may not wait long. In an 8 June letter to the general contractor that will lead the dam's construction, the director general of the Electricity Department of Laos's Ministry of Energy and Mining declared the MRC consultation process “complete.” The letter, subsequently leaked to the press, “changed everything,” Geheb says. The powerful energy ministry, he says, has argued that Xayaburi dam's benefits would outweigh its costs, and that environmental consequences can be mitigated.

    Feast or famine.

    Mekong dams would alter the flood pulse that transforms Tonlé Sap from dry-season puddle (below) into a lake (left) sustaining the world's biggest inland fishery.


    There's evidence Laos has already opted to forge ahead. At the dam site in Xayaburi Province 350 km north of Vientiane, preparatory work has been going on for several months. One environmental scientist who recently visited the site estimates that there are a few hundred people in the construction camp. “It's not a small-scale operation,” he says. Some observers expect Laos to announce a new timetable for the Xayaburi dam at a meeting of MRC's council of ministers in autumn.

    Untapped potential.

    The Mekong River dynamo could generate a whopping 53 megawatts of electricity.


    The stakes are enormous. Critics fear that Xayaburi dam and 11 other hydropower projects planned for the lower Mekong would unleash a cascade of ecological changes. Beyond threatening many migratory fish with extinction, including some of the world's largest species, the dams could collapse fisheries and destroy productive agricultural land throughout the LMB. The resulting ecosystem damage “will result in increasing food insecurity for millions of people,” declares an MRC-commissioned Strategic Environmental Assessment (SEA) of Hydropower on the Mekong Mainstream released last October. “The proposed development of the mainstream Mekong River is the most important strategic decision ever made by LMB countries on use of their shared resources.”

    The dams could alter geopolitics as well. “We are strongly concerned that there may be widespread conflicts or, in the worst scenario, wars over water resource management,” Chheang Vannarith, executive director of the Cambodian Institute for Cooperation and Peace, told Voice of America last month. As Geheb says, “Laos is under savage pressure to get this right.”

    Domino effect

    The Mekong River is one of the few great rivers not dammed for much of its length. That's not for lack of hydropower potential. From its headwaters in Tibet to the China-Laos border, the 2200-km-long upper Mekong, known as the Lancang River in China, drops 4000 m in elevation. The lower Mekong follows a gentler descent, losing several hundred meters in elevation.

    The main Mekong dynamo could generate an estimated 53,000 MW of power. In the four LMB nations, Mekong tributaries could add up to 35,000 MW. A sizable portion of hydropower potential of the tributaries has already been tapped or will be soon. By 2015, 36 dams on LMB tributaries are expected to be operating, with roughly 30 more to come online by 2030. Critics question whether adequate mitigation measures are being implemented for the biggest Mekong tributary dam thus far, the $1.5 billion Nam Theun 2 in central Laos, which started operations last year (Science, 23 April 2010, p. 414).

    Hydropower is the best way for Laos to utilize the river, says George Radosevich, an expert on international water law who as senior legal adviser to the four LMB nations helped draft the 1995 Mekong Agreement that created the MRC. Laos, he says, “contributes the most water to the Mekong system and has the least amount of irrigable land.”

    By the early 1990s, Laos and Cambodia had blueprints for 11 dams and one diversion on the lower Mekong (see map). The show-stopper until recently was iffy economics. Unlike impoundment dams that use reservoirs to manipulate river flow, the 11 proposed dams are “run-of-the-river” barrages designed to slightly perturb average flow rate. They would generate electricity aplenty during the 4-month rainy season, when 75% of the Mekong's annual flow occurs. The rest of the year, a languid Mekong would generate much less power, raising doubts about the market value of the electricity.

    China's hydropower program tipped the balance in favor of the lower Mekong dams by advancing another claimed benefit: reducing the flood pulse. In the late 1990s, China started work on a cascade of at least seven impoundment dams on the upper Mekong. Four have been completed, including 292-m-high Xiaowan, the world's highest arch dam (see map). Although China is not an MRC member state and thus is not bound by the 1995 agreement, under international law its use of upper Mekong water must not harm downstream nations. As an MRC observer, China's hydropower officials at commission meetings “have always emphasized the leveling out of the flood pulse as a significant benefit” of their dams, which are designed to fill their reservoirs during the rainy season and release extra water during the dry months, Geheb says.


    By one estimate, Xayaburi dam would obstruct about 125,000 km2 (red), or 36% of habitats in upstream watersheds not already obstructed by other dams. Experts urge Xayaburi designers to incorporate sluice gates (top) that allow sediment to flow downstream.


    Regular flow would allow turbines to feed the electricity grid more consistently during the dry season, and thus is a huge selling point for Laos. In 2007, Laos asked CH. Karnchang Public Co. Ltd. in Bangkok to study the feasibility of Xayaburi, the first installment of a planned six-dam cascade north of Vientiane. Xayaburi dam would be 820 m wide, 49 m high, and would create a 49-km2 reservoir extending 60 to 100 km upstream. Some 2100 villagers would be resettled. Last September, Laos informed MRC of its intention to proceed with Xayaburi, triggering the required consultation. Laos plans to award a 30-year concession to CH Karnchang, after which Laos would assume ownership of the dam. The company and Lao authorities are negotiating a power purchase agreement with the Electricity Generating Authority of Thailand, which has offered to buy about 95% of Xayaburi's electricity.

    Xayaburi dam, if built, could pave the way for the other 11 hydropower projects on the drawing board. “Whatever happens with Xayaburi will set a precedent on whether it is acceptable to go forward with other mainstream dams,” asserts Ame Trandem, Southeast Asia program director at International Rivers, a nonprofit that opposes large dams. “The scale of hydropower being proposed in the basin is truly staggering,” Geheb says.

    If all 12 projects go forward, Laos would receive the lion's share of an estimated $25 billion in foreign direct investment and 70% of electricity export revenues, or $2.6 billion a year. The landlocked country with a per capita income of under $1000 per year is counting on hydropower to alleviate poverty, raise living standards, and improve transportation for its 6 million people.

    None of the MRC nations has a veto over Laos's plans, but they have influence. Thailand and Vietnam account for 96% of the power demand of the LMB over the next 15 years and would purchase about 90% of the electricity generated by Laos's proposed hydropower projects. “If Thailand and Vietnam decided not to purchase mainstream power, the projects—all designed for export—would be very unlikely to go ahead,” states the SEA.

    The environmental costs of going forward would be steep, according to the SEA. If implemented, the 12 projects—including 11 dams that would span the river channel—would convert a staggering 55% of the lower Mekong mainstream, from northernmost to southernmost dam, into reservoirs with slow-moving water. The dams would block migratory fish, interfere with navigation, and impede nutrient-rich sediments from settling in the Mekong delta in Vietnam and in the Tonlé Sap floodplain. The SEA estimates that fisheries and agricultural losses would run $500 million a year, offset by only $30 million a year in added income from reservoir fisheries and new irrigation potential. If all envisioned LMB hydropower projects were to go forward and using worst-case assumptions, the evisceration of Mekong fisheries and loss of wetlands and other ecosystem services could result in the basin losing $274 billion in value, according to an analysis released last month by a team led by Robert Costanza, an ecological economist at Portland State University in Oregon.

    In harm's way.

    Xayaburi dam would threaten the migratory goonch catfish (Bagarius yarrelli).


    Fisheries and agricultural losses in the delta, in Lake Tonlé Sap, and elsewhere could have a domino effect on nutrition and food security. In Cambodia and Laos, “up to 30% of the national protein supply would be at risk if all mainstream dams were to go ahead,” the SEA warns.

    Migratory purgatory

    As the first dam on the lower Mekong mainstream, Xayaburi lays down a marker for how environmental consequences of all 12 hydropower projects will be assessed. The experience so far has proved unsettling.

    Last September, CH Karnchang submitted to the Lao government an environmental impact assessment on Xayaburi prepared by Bangkok-based TEAM Consulting Engineering and Management Co. The assessment acknowledges that the dam could alter the lower Mekong's hydrology. Rebutting an earlier feasibility assessment, however, it claims that upstream of the dam, “transformation of the habitat from a river with rapids” into a “standing ecosystem due to impoundment will not occur.”

    Many who study the Mekong are baffled by that assertion. In a 24 March review, the MRC Secretariat estimates that water flow rates in a Xayaburi reservoir could decline as much as 90%, from about 1 m per second to 0.1 m per second. Under proposed operating conditions, the review states, the reservoir would lose about 60% of its capacity due to sedimentation after 30 years, compromising power generation. And based on the Xayaburi dam's current design, the reservoir would trap two key nutrients: about 40% of phosphorus and 33% of nitrogen that enter it. The review warns that the cumulative effects of Xayaburi and other lower Mekong mainstream dams on sediment and nutrient trapping “would be significant.” Less sediment in floodwater would mean less soil fertility and a loss of rice production, as well as increased riverbank erosion, says Eric Baran, a fisheries biologist with the World-Fish Center in Phnom Penh.

    In this respect the Mississippi River offers a cautionary tale. “Hydropower development in the upper Mississippi River Basin over many decades has resulted in sediment deprivation to the Mississippi River delta,” says D. Phil Turnipseed, director of the U.S. Geological Survey's National Wetlands Research Center in Lafayette, Louisiana. “Mekong River development could have the same results as we have experienced.”

    Perhaps the harshest criticism is reserved for TEAM's prognostications on how the Xayaburi dam could affect fish stocks. An appendix to the environmental impact assessment states that hydropower development on the lower Mekong mainstream “will submerge spawning and rearing habitats of migrating fish species.” It recommends that the characteristics of these habitats be identified and described “for future habitat recovery before impoundment.” But the main body of the report simply states that the Xayaburi dam would result in “no significant change” in fish spawning. That conclusion “is not substantiated by any results presented in the assessment,” Baran says.

    The report presents an incomplete picture of fish species that the dam could adversely affect. TEAM drew up a list of 16 species, including five that are migratory, based on a 1994 MRC report. It supplemented that list with field surveys conducted in November 2007 and March 2008 in which it captured 54 fish species using gillnets. Based on that meager haul, the impact assessment concludes that “fish biodiversity in the project area [is] quite low.”

    Critics blast that contention. TEAM's field surveys were an “unrealistically low, restricted, and biased sampling effort,” says Baran, who with three colleagues analyzed the report for WWF Greater Mekong, an environmental advocacy group. Their 31 March review notes that the field surveys “resulted in a biodiversity assessment representing less than a third of the actual species richness in the impact area.” And the TEAM report didn't even cite the MRC's own Mekong Fish Database, a 2003 resource that lists 120 fish species in Xayaburi Province. According to the WWF review, field surveys in the literature raise that figure to 229 fish species that “exploit habitats upstream of the planned dam site for spawning and/or dry season refuges,” including 70 migratory species. Those migratory fish are what experts most worry about. According to Baran's group, by the time Xayaburi dam is completed it “would obstruct about 125,000 km2 or 36% of habitats in upstream watersheds” not already obstructed by other dams.

    Some charismatic species could suffer, including several of the world's biggest freshwater fish. The Xayaburi dam could be the coup de grâce for the critically endangered Mekong giant catfish (Pangasianodon gigas), a species that can grow up to 3 meters long and weigh 300 kilograms. Because the titan's only known spawning area is north of the Xayaburi dam site, the MRC review holds that there is a “strong possibility” the species would go extinct in the wild if the dam is built.

    The dam would threaten another critically endangered leviathan, the giant pangasius (Pangasius sanitwongsei). Also known as the dog-eating catfish, giant pangasius migrate upriver and spawn in springtime at unknown grounds, says Zeb Hogan, an ecologist at the University of Nevada, Reno, who has done extensive fieldwork on the Mekong. Sightings in Laos suggest that the Xayaburi dam site “is within the migratory corridor and may be in the vicinity of a spawning area,” Hogan says, adding that it is “very likely” that the dam site is critical habitat for the giant pangasius.

    Overall, the MRC says, “no large migratory species are predicted to persist” if Laos were to proceed with all six dams in the planned cascade. It adds that the dams would also obstruct smaller migratory fish that are important food sources, such as the Siamese mud carp (Henicorhynchus siamensis).

    Although Xayaburi would be equipped with a pair of structures known as fish ladders, which help fish bypass dams, it's unclear which Mekong species would be able to climb them. Fish ladder designs are geared to salmon, whose jumping abilities enable them to scale waterfalls—and ladders—more successfully than other fish, the MRC review states. According to Hogan, Xayaburi dam as currently envisioned would present an “impassable barrier” to large fish. TEAM's environmental impact assessment “puts unsubstantiated trust in the ability of existing technology to solve the fish migration obstruction problem,” Baran adds.

    Critics also blast the assessment's narrow focus. TEAM's field surveys extended only a few kilometers downstream, and they did not examine possible effects upstream of the reservoir. The assessment “ignores all transboundary aspects of possible impacts,” the WWF review states. The report “is flawed and does not meet international standards by far,” Baran says. Cambodia has called for a transboundary and cumulative impact assessment.

    The Laos government appears ready to accept TEAM's findings. In February, it declared in a statement that the Xayaburi dam would be “environmentally friendly” and “not have any significant impact on the Mekong mainstream,” the Associated Press reported. “I don't think Laos has fully understood the environmental consequences,” Trandem says.

    Under way.

    Roadwork at Xayaburi dam site.



    Any environmental assessment limited to Xayaburi, or even the six-dam cascade it would anchor, ignores the combined impact of all 12 hydropower projects on the lower Mekong Basin. “You can't look at Xayaburi in isolation,” says Matti Kummu, a hydrologist at Aalto University in Finland. The SEA, prepared by the International Centre for Environmental Management in Glen Iris, Australia, provides that broader context.

    Diminishing returns.

    Dams are predicted to harm fisheries.


    Fisheries losses and erosion of food security could overshadow gains in energy security. Although the region's fisheries data are notoriously poor and fragmented, the MRC review calculates that the few dozen tributary dams in operation in 2015 will reduce LMB's total annual catch of roughly 2.5 million tons of fish by 17% to 23%. It predicts that the six-dam cascade would decrease yields by another 6%. And if all 11 mainstream dams come online, the SEA estimates the total loss in fish resources would be as high as 880,000 tons, or 42% compared with the 2000 baseline (see graph).

    Tonlé Sap is an acute concern. The Mekong River provides 57% of the lake's water, and alterations to its flood pulse could erode water quality and trigger die-offs of fish eggs, larvae, and even adult fish, Lamberts says. Fisheries experts, he says, blame poor catches of Siamese mud carp in recent years on hiccups in Tonlé Sap's usually smooth filling. As dry season flows increase, models forecast a widening area of permanent inundation that would wipe out the gallery forest surrounding Tonlé Sap. “You lose that downstream vegetation, you lose a lot of the productivity,” Lamberts predicts.

    Of the dozen hydropower projects planned for the lower Mekong, the farthest downstream would be Sambor, one of two dams that Cambodia plans to build. The 18-kilometer-long barrage would span a confluence where three tributaries feed the Mekong, about 200 kilometers upstream of Tonlé Sap River. “It will be vast,” Geheb says, “and in my mind, most significant. … It's a mystery to me why the Cambodians don't make more noise about the likely collapse of their fisheries.” The answer, says one expert, is simple economics. Cambodia's feeble collection of taxes on fisheries means that Tonlé Sap “doesn't contribute much to the exchequer,” he says. It doesn't help, he says, that Cambodia's environment ministry is “small and powerless.”

    If dam building on the mainstream Mekong takes off, it will become even more important to implement technologies that mitigate ecological harm, experts say. For instance, dams can use advanced turbine designs that sharply reduce fish mortality and incorporate sluice gates that allow more sediments and nutrients to filter downstream.

    A growing chorus is urging Laos to suspend work on Xayaburi until more robust data are in. Vietnam, for one, holds considerable sway with its Socialist ally. “There is a lot of room for maneuvering,” Radosevich says. Laos must proceed with caution: Under the Mekong Agreement, it could be held responsible for damages to downstream nations.

    Inescapably, mainstream dams would change the river's character. It would be a tragedy, Lamberts says, if a region that has endured war, genocide, floods, and droughts were now to sacrifice the resilience of its ecosystems.

  4. Hydropower

    The Legacy of the Three Gorges Dam

    1. Richard Stone

    The travails of the Three Gorges Dam are a cautionary tale for Laos and its Southeast Asian neighbors as they wrestle with the pros and cons of damming the lower Mekong River.

    BEIJING—Scientists predicted that when the world's largest hydropower project came online in 2003, it would be an environmental bane. The Three Gorges Dam on the Yangtze River has unfortunately lived up to expectations. For that reason China is embarking on a 10-year mitigation effort that sources say will cost $26.45 billion.

    The travails of the Three Gorges Dam are a cautionary tale for Laos and its Southeast Asian neighbors as they wrestle with the pros and cons of damming the lower Mekong River (see main text). Two consequences have proved worse than anticipated: deteriorating water quality and erosion. And the potential for spreading a snail-borne disease apparently wasn't even on planners' radar.

    The decision to build the dam in 1992 came after decades of study and fierce internal debate. Benefits such as power generation and flood control are indisputable. But leaders also knew that the costs would be enormous. The newly created 1080-km2 reservoir submerged wholly or in part 13 cities and 466 towns, displacing roughly 1.3 million people, and triggered thousands of landslides. The reservoir wiped out fish spawning areas and raised an impassable barrier to one endangered mammal—the Yangtze finless porpoise—and two species that were in terminal decline: the Chinese river dolphin, or baiji, and the Chinese paddlefish (Science, 1 August 2008, p. 628).

    Before the Three Gorges Dam began holding back the river in 2003, local Yangtze water by national standards was suitable for drinking. Not anymore. In the past several years, toxic algal blooms have regularly blighted 22 tributaries. Slower tributary flow due to the reservoir and a surfeit of nutrients from land-use changes are to blame, a team led by Fu Bojie, an ecologist at the Research Centre for Eco-Environmental Sciences of the Chinese Academy of Sciences in Beijing, reported last year in Progress in Physical Geography. A second scourge, they say, is increased heavy metal pollution.

    Erosion, too, was underestimated. Because sediments accumulate in the reservoir, water released through the dam's turbines is relatively clear. Sediment-light water scours riverbanks to a degree that “is much higher than the designed and expected levels,” Fu's team states. Severe erosion has caused some riverbank sections to collapse.

    In control.

    A swollen Yangtze gushes through Three Gorges in July 2010.


    Another headache is schistosomiasis, known as snail fever in China. As many as 1 million Chinese are infected with the parasitic trematode, transmitted by Oncomelania snails. In endemic areas near lakes and wetlands in the Yangtze River Basin, prevalence hovers around 5%. The Three Gorges Dam increased the snail's habitat—and the infection risk. China's health ministry is improving sanitation and implementing other measures in a bid to reduce the infection rate to less than 1% by 2015.

    In May, the State Council announced a massive effort to rein in other potential harms—stabilizing river flow, reinforcing levees, improving water quality—and boost livelihoods of displaced people. “The fact that the government openly acknowledged negative impacts was a significant change toward more openness,” says Lars Skov Andersen of the E.U.-China River Basin Management Programme in Wuhan.

    Since then, however, few details have come to light. One researcher who studies the new reservoir's impact on plant populations told Science that he has been ordered to deliver his reports to the government and cannot speak publicly about his findings. The official authorized to speak to the media was unavailable before Science went to press.

    Secrecy aside, observers are confident that the initiative will have a robust scientific component. Some research lines may break new ground: for instance, probing habitat fragmentation after the reservoir turned dozens of hilltops into islands. But many findings are expected to be a sobering reminder that a big dam can bring unexpected consequences.

  5. Clinical Studies

    Trying to Reset the Clock on Type 1 Diabetes

    1. Jennifer Couzin-Frankel

    Researchers dream of permanently halting or reversing a major autoimmune disease; new drug studies show that, despite some promising signs, the goal is still far off.


    In H. G. Wells's classic novella, The Time Machine, a nameless English scientist reveals to dinner guests that he has invented an amazing capsule in which he journeys across thousands of years. The notion seems as fantastic now as it did more than a century ago. But like Wells's inventor, biologists today dream of resetting the clock—though on a more modest scale. Instead of sending a person swirling through the millennia, they want to turn back time on a dysfunctional immune system that threatens the pancreas.

    This may not sound particularly romantic, but it would be an incredible medical achievement, potentially reversing the course of type 1 diabetes, a disease in which the body destroys pancreatic beta cells that make insulin. By the time symptoms surface—extreme thirst, weight loss, fatigue—about 80% of those cells are gone. There's no going back.

    Or is there? Since the late 1990s, U.S. and European funders have poured hundreds of millions of dollars into preventing type 1 diabetes before its first symptoms appear, or bringing it to a screeching halt in newly diagnosed patients. Eight years ago, Science described these efforts during the shift to a new frontier: modulating the faulty immune system of recently diagnosed patients or those at high risk of disease (Science, 20 June 2003, p 1862). The stakes were high. Would the treatments work? Would they hurt the mostly young patients who develop type 1 diabetes in the first place?

    Earlier this summer, a slew of results was presented at the annual American Diabetes Association meeting in San Diego, California, with many published simultaneously online in The Lancet. They were mostly disappointing and in a sense, they show the price of taking the practical path to new treatments. Ethical, logistical, and financial constraints mandated clinical trials in patients less likely to be helped by the drugs. Companies, under pressure to perform and uncertain about where to set the goalposts, designed trials that many veterans of the field say were unlikely to succeed.

    Several of the drugs tested have helped protect the pancreas. But so far, researchers say, the benefit isn't enough to justify approving them, especially for a disease that's rarely fatal. “I don't think we're fundamentally wrong” about how to keep the pancreas safe from attack, says Jeffrey Bluestone, an immunologist at the University of California, San Francisco, who admits he's conflicted because he helped develop one of the key drugs. “I am discouraged by the environment,” Bluestone explains, where failures or semisuccesses are leaving behind malaise and uncertainty about what's next. “I'm not discouraged about the science.”

    Vital concern

    In type 2 diabetes, generally a disease of adults, the body stops responding properly to its own insulin. Type 1 diabetes usually appears earlier, with dramatic effect: Insulin production nearly vanishes. Over the past decade, reversing and preventing type 1 diabetes has become an ever more urgent priority. Like other autoimmune diseases and allergies, type 1 diabetes is on the rise in industrialized countries, and it is striking younger victims. In Finland, which has the world's highest incidence of type 1 diabetes, the steepest increase in cases is in children ages 4 and under. Between 1980 and 1984, 351 Finnish preschoolers were diagnosed with the disease; from 2000 to 2005, the number jumped to 910. In Europe, which has systematically tracked the disease for decades, researchers predict that between 2005 and 2020, the number of cases among children under age 5 will double. Environmental factors are likely the culprit, but no one knows what they are.

    The battle in type 1 diabetes has two sides: the immune system that attacks and the insulin-producing beta cells that must defend themselves or die. In the past 20 years, this picture has sharpened: The disease occurs when there's an imbalance between “effector” cells, the immune cell aggressors, and the “regulatory” cells, which push back against them. Furthermore, this imbalance develops long before symptoms do. Over time, as T cells attack the pancreas, the body releases autoantibodies, which can be detected in the blood. In Finland, studies have found that children who develop type 1 diabetes in the first 12 years of life begin to show these autoantibodies by their fourth birthday. The years-long gap between early immune attacks and full-blown disease gives a window to step in before much damage is done.

    But there are big hurdles to early intervention. For one, people with autoantibodies are still considered healthy, making it ethically tenuous to test even a low-risk treatment on them. And diabetes prevention trials are an enormous undertaking. There's no system in place to find participants, who aren't seeking out medical care. In one prevention study from the 1990s, researchers had to screen more than 84,000 people to find the 339 they needed. Prevention studies also take many years because researchers must wait and see who develops diabetes.

    “Prevention is really a challenge,” says immunologist Gerald Nepom, who directs the Immune Tolerance Network, a federally funded trials group. “It probably is where we want to be, but we can't do it”—or at least, not on a grand scale.

    As an alternative, researchers turned to a cohort that's far easier to study but also tougher to help: people diagnosed with diabetes in the past few months. Practically all of them still have some beta cells, meaning that stopping the immune attack could help. Studying these patients could also hint at which drugs might pack the biggest punch when used in young people at high risk for diabetes who haven't yet developed the disease.

    Several experimental drugs aim to reset the balance between effector and regulatory cells. One therapy, anti-CD3, blocks the T cells that target beta cells. In the 1990s, Lucienne Chatenoud of Hôpital-Necker Enfants Malades in Paris gave diabetic mice anti-CD3. “The surprise,” Chatenoud says, “was they stayed in remission forever.”


    Subsequent clinical trials—one led by Chatenoud, the other by Bluestone and endocrinologist Kevan Herold of Yale University—also had positive results, though they were relatively small. Still, patients needed less insulin for 2 years or even longer after getting the drug.

    Two biotech companies enthusiastically licensed rights to anti-CD3 and partnered with large pharmaceutical companies to finance definitive clinical trials. Results, reported last year and published and presented in June, were lackluster. The trial using Chatenoud's version of anti-CD3 failed completely. The second trial, with Herold and Bluestone's drug, didn't reach its goal of better diabetes control, either.

    For Chatenoud, the news was crushing but not a surprise. The companies that tested her anti-CD3 molecule—Tolerx and GlaxoSmithKline—used a dose that was about 1/15 of what she'd used in her earlier trial, out of concern for side effects that might torpedo the therapy. Anti-CD3 can cause fever and rash, and researchers have worried that it might reawaken dormant viruses in the body. But such a low dose was doomed to fail, Chatenoud says: “It's a drug. It's not homeopathy.”

    Chatenoud's and Herold's trials had focused on measuring a protein that's cleaved off the insulin hormone, called c-peptide; it's detectable in blood and more reliably measured than insulin. It's considered the most direct measure of how well beta cells are functioning, but it doesn't necessarily track how a person with diabetes is faring. For that reason—and because regulators and trial designers lack standard goals for type 1 diabetes trials—MacroGenics and Eli Lilly adopted different measures in their anti-CD3 trial. They tracked insulin use and the percentage of hemoglobin altered by high blood sugar. To find the 516 volunteers they needed, they recruited outside the United States, in particular in India, where diabetes is common.

    The results, reported last fall and also online in The Lancet in June, amounted to another failure. “Everybody was taken by surprise,” especially because the trial included a solid dose of anti-CD3, says Scott Koenig, the president and CEO of MacroGenics.

    A subsequent analysis suggested that, just as in earlier trials, beta cells appeared healthier, as revealed by c-peptide levels in the blood. At the same time, there were wild variations by geographic location, and by age. Patients in India, whose diabetes was in worse shape to begin with, didn't benefit much from anti-CD3; older patients were also less likely to be helped. The best off were the youngest children, the 8- to 11-year-olds, along with U.S. participants. Five percent of participants who got the drug were off insulin completely a year later, compared with no one in the control group.

    That wasn't enough for Eli Lilly: It dropped the drug shortly after the results were released. MacroGenics wants to keep testing anti-CD3 but can't afford to run another enormous clinical trial by itself and is hunting for a new partner.

    Tolerx and GlaxoSmithKline, meanwhile, halted recruitment in another anti-CD3 diabetes trial they were running. They have said they are contemplating what to do next.

    “It's difficult for a company that doesn't necessarily see the end in sight to stay on board when the process looks like it will be long and arduous,” says Jay Skyler, an endocrinologist at the University of Miami in Florida.

    At the same time, at least in the higher-dose MacroGenics trial, anti-CD3 did something to the overactive T cells that help drive diabetes, just not enough to eliminate disease long-term. And anti-CD3 is not the only therapy that's had this effect: In 2009, researchers described in The New England Journal of Medicine some success with using rituximab, which targets B cells; in June at the American Diabetes Association, another trial was presented that tested abatacept, which prevents T cells from becoming activated. Strikingly, the outcome of these two therapies and anti-CD3 were nearly identical: They all helped patients for similar short amounts of time and then their effects faded. Many patients then had to up the amount of insulin they injected. “The curves declined in parallel” after about 9 months, Skyler says.

    Rethinking basics

    Logistical roadblocks don't account for all of the mixed results; the science is in question, too. Are we not intervening early enough? That's one possibility: After all, these patients are already sick, and reversing their disease is bound to be an uphill battle. Drugs that could help prevent diabetes may flop in newly diagnosed patients. That's always been a concern.

    But another, equally discomforting idea is that diabetes is more multifaceted than we realize. “We've put all this money into this thing, hundreds of millions of dollars, and what have we gotten out of it?” Bluestone asks. “We've gotten prolongation [of health] but no cure. … There are people who are appropriately disappointed.”

    Some researchers suspect there's a fundamental problem in using mice with induced diabetes as stand-ins for the human disease. The mouse data suggest that giving a drug short-term can permanently reset the balance between effector and regulatory immune cells, turning a diabetic mouse into one without disease, Bluestone says. “Is it too much to expect that you can do that in humans?”

    One way to find out is to explore how closely disease in mice tracks what happens in people. A few years ago, Mark Atkinson, a pathologist at the University of Florida, Gainesville, took the helm of a new project called nPOD, the Network for Pancreatic Organ Donors with Diabetes, funded by the Juvenile Diabetes Research Foundation (JDRF). nPOD established a system that targets people who wish to be organ donors but whose pancreases aren't suitable for transplant. If the person has type 1 diabetes, or if the donated organ has autoantibodies, suggesting prediabetes, the pancreas, and sometimes other organs, too, are shipped on ice to Atkinson's lab. Atkinson has a team on call every hour of every day, to swoop in and process pancreases as soon as they arrive. The organs are “bread-loafed” into 30 slices and further subdivided into small blocks. Then they're shipped to scientists all over the world.

    The goal is to understand what's been thoroughly parsed already in mice: how type 1 diabetes starts. So far, nPOD has processed 170 pancreases from around the United States, and this summer the project is expanding to several European countries, including Finland, Italy, and Sweden.

    nPOD has been going for only 3 years, but already, Atkinson says, the human pancreases are “showing some quite dramatic differences from the mouse studies.” The human organs have surprisingly little “insulitis”: inflammation of the beta cells caused by infiltration of immune cells attacking them. Like his colleagues, Atkinson believes T cells are killing beta cells, but he also thinks there's more to the narrative. “The T cells are there, but they're rare. … There may be something else that we just don't understand yet.”

    Flawed model?

    Inflammation from T cell attacks is visible in a diabetic mouse's pancreas (top, blue), an effect less visible in a human sample (below).


    Another fundamental concern is that until now, the strategies for preventing diabetes or slowing it in newly diagnosed patients have gone after just one side of the battle: the immune system. The other side, the beta cells, has been largely ignored. “My own bias,” says Richard Insel, JDRF's chief scientific officer, “is to get ahead of this, we're going to need to address both.” Several trials are ongoing or gearing up using drugs that target interleukin-1β, which can cause beta cell dysfunction and death. JDRF is also funding work with an “artificial pancreas,” an external system that continuously monitors glucose levels and adjusts insulin accordingly, in hopes of reducing stress on the beta cells.

    Like the road already traveled, the road ahead is likely to be long. Researchers are heartened by a handful of youngsters who have responded unusually well to therapy like anti-CD3. Some have kept making some of their own insulin for 5 years. Bluestone treated a young San Diego man 10 years ago, then recently diagnosed, who's been producing insulin since, though he needs extra doses of the hormone, too. Stories like these, and nuggets of gold from the anti-CD3 trials, have captured the attention of TrialNet, a $30 million federally funded network that runs type 1 diabetes trials, which Skyler heads. It recently launched an anti-CD3 prevention trial in at-risk children and young adults. The network is also running a prevention trial of oral insulin; a similar one flopped 10 years ago, but this study focuses on a narrow group that was helped in the previous trial.

    Pushing these early therapies is a delicate balancing act, given that standard care for type 1 diabetes continues to improve and long-term complications, including kidney failure, amputation, and blindness, are dropping. Some trials failed recently, Bluestone believes, partly because the control group received excellent care and was tough to beat.

    Still, the notion that the standard of care is as good as it can be is roundly rejected by those chasing the time-travel dream. “I am always struck by those diabetologists who look at you and say, ‘But there is insulin,’” Chatenoud says. “Well, yes—but insulin is really not what you want.” It certainly can't send the immune system back in time for good. But then, we don't know yet if anything can.

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