News this Week

Science  18 Jan 2013:
Vol. 339, Issue 6117, pp. 256
  1. Around the World

    1 - Tasmania, Australia
    Bushfires Rage Across Tasmania
    2 - Washington, D.C.
    Appeal to Restore U.S. Gun Violence Research
    3 - Lake Vostok, Antarctica
    Russian Team Retrieves First Sample From Lake Vostok
    4 - Washington, D.C.
    Biologists Accuse Bureau Of Fishy Behavior
    5 - Washington, D.C.
    A New Look for House Science Panel
    6 - Washington, D.C.
    NOAA: 2012 Hottest Year on Record for U.S.

    Tasmania, Australia

    Bushfires Rage Across Tasmania

    Scorching.

    Fires blazed near Hobart, Tasmania, on 5 January.

    CREDIT: AP PHOTO/CHRIS KIDD, POOL

    Australia welcomed the New Year with raging fires and a record-breaking heat wave. On 7 January, the average highest daily temperature hit 40.33°C, beating the previous record of 40.17°C set in 1972. The first 2 weeks of January were "the hottest 13-day period in Australian history," says the Australian Bureau of Meteorology's David Jones.

    The extreme heat forced the bureau to top-up its color-coded weather map to accommodate temperatures up to 54°C. Trains were halted in the state of Queensland amid fears that tracks might buckle. As Science went to press, Tasmania continues to battle two major bushfires triggered on 4 January by what the state fire service classified as "catastrophic" weather conditions. Hundreds of grass- and bushfires are burning across the country, with the most severe in Victoria and New South Wales, where 33 homes were lost, as well as facilities at the Siding Spring Observatory.

    A report released on 12 January by Australia's Climate Commission says that the heat wave and bushfires were "exacerbated" by global warming. It concludes: "The length, extent and severity of the current heatwave are unprecedented in the measurement record."

    Washington, D.C.

    Appeal to Restore U.S. Gun Violence Research

    Targeting guns.

    A panel led by Joe Biden (right) considers new measures on gun violence.

    CREDIT: OFFICIAL WHITE HOUSE PHOTO BY DAVID LIENEMANN

    More than 100 academic leaders signed a letter asking the Obama administration to lift a virtual ban on U.S.-funded gun violence research. The 10 January letter, organized by the University of Chicago's social science group, the Crime Lab, was sent to Vice President Joseph Biden, head of the White House's new Gun Violence Commission. The letter says that "politically-motivated constraints" sought by pro-gun lobbies and adopted by Congress in the mid-1990s have cut short a promising area of study. After 1997, funding from the Centers for Disease Control and Prevention and the National Institutes of Health dried up. "Right now the research community is hampered in its ability to inform policymakers about the expected benefits and costs of different policy approaches because of politically-motivated limits on data access, and substantial federal under-funding of research on gun violence," writes Crime Lab Director Jens Ludwig, a co-author of the letter, in an e-mail to Science. The Biden panel is weighing new policies in response to the December mass shooting of schoolchildren in Newtown, Connecticut; its recommendations are due this week. http://scim.ag/gunviol

    Lake Vostok, Antarctica

    Russian Team Retrieves First Sample From Lake Vostok

    Collected.

    The team that drilled down to Lake Vostok last year now has an ice core.

    CREDIT: AP PHOTO/ARCTIC AND ANTARCTIC RESEARCH INSTITUTE PRESS SERVICE

    A long-running Antarctic drilling effort finally yielded an ice core, when a team of Russian scientists successfully retrieved its first sample this week from Antarctica's 20-million-year-old Lake Vostok, which is buried under nearly 4000 meters of ice. The team, from Russia's Arctic and Antarctic Research Institute, had completed drilling to the surface of the lake in February 2012. To prevent contamination during sampling, the scientists devised a plan to drill just to the lake's surface, but then allow the pressurized lake water to rise into the borehole and freeze there. They returned this Antarctic summer to retrieve the frozen core—and on 10 January, the team told RIA Novosti, the researchers collected their prize. "The first core of transparent lake ice, 2 meters long, was obtained on January 10 at a depth of 3,406 meters," declared the Arctic and Antarctic Research Institute in a statement. "Inside it was a vertical channel filled with white bubble-rich ice." Next up: Analysis of the core itself, which many hope will contain evidence of microbial life.

    Washington, D.C.

    Biologists Accuse Bureau Of Fishy Behavior

    Managers at the U.S. Bureau of Reclamation (BOR) committed scientific misconduct when they sought to shut down the agency's research division last year after it produced controversial studies about endangered fish populations, according to a complaint filed earlier this month on behalf of seven fisheries biologists working in southern Oregon.

    CREDIT: USFWS/TIMOTHY KNEPP

    The complaint alleges that BOR area office manager Jason Phillips called for scrapping the agency's Fisheries Resources Branch (FRB), in part because some FRB results conflicted with research results from the National Oceanic and Atmospheric Administration and the U.S. Fish and Wildlife Service (FWS). In one case, an FRB study found a stable population of endangered suckers in Lake Ewauna, where a previous FWS study had deemed the lake habitat of poor water quality. Phillips had stated in an 8 November memorandum that "[t]here's a concern that … in some cases we are simply carrying out studies to contradict the science of other agencies." The scrapping of FRB "will have a chilling effect of suppressing future scientific findings," the complaint states. BOR spokesperson Pete Lucero says the decision to close FRB was an attempt to make the agency more efficient.

    Washington, D.C.

    A New Look for House Science Panel

    Bucshon

    Lummis

    CREDITS: UNITED STATES CONGRESS/ERIC CONNOLLY; OFFICE OF CONGRESSMAN CYNTHIA LUMMIS

    The congressional committee that pays the most attention to U.S. science policy has three new subcommittee chairs.

    Last week, the House of Representatives' Committee on Science, Space, and Technology announced that second-term legislator Representative Larry Bucshon (R–IN), a cardiothoracic surgeon who is a deep skeptic of climate change science, would head its research subcommittee. Bucshon replaces Representative Mo Brooks (R–AL), who in his first term impressed the community with his understanding of the government's role in funding basic research.

    The new chair of the full committee, Representative Lamar Smith (R–TX), has split the environment and energy portfolio and given energy to a new member of the committee: Representative Cynthia Lummis (R–WY). A lawyer and career politician, she's a strong advocate of the fossil fuel industry and doesn't believe that humans are contributing to climate change.

    Finally, the new chair of the technology panel is freshman Representative Thomas Massie (R–KY). A Massachusetts Institute of Technology–trained mechanical engineer and entrepreneur who developed pioneering human-computer interface software, Massie is an acolyte of Tea Party favorite Senator Rand Paul (R–KY). http://scim.ag/scisub

    Washington, D.C.

    NOAA: 2012 Hottest Year on Record for U.S.

    Last year saw the warmest average temperatures on record—at least for the contiguous United States, according to a report released last week by the National Oceanic and Atmospheric Administration (NOAA). The average temperature was 13°C, compared with a 20th century average of 11.2°C. (The previous record-holder, 1998, saw average temperatures of 12.4°C). The year consisted of "a record warm spring, the second warmest summer, the fourth warmest winter, and a warmer than average autumn," said climate scientist Jake Crouch, of NOAA's National Climatic Data Center, in a press conference on 8 January. The data do not address global temperatures, however.

    Meanwhile, a draft of another climate-related report—the U.S. Global Change Research Program's National Climate Assessment on the impact of global warming in the United States, released every 4 years—was published on 11 January. It points to stronger evidence that the climate is changing rapidly, and primarily as a result of human activities, including the burning of fossil fuels—and notes that there will be increasing impacts on crops and fresh water supplies. The report, written by a group of 240 scientists, will now undergo a 3-month period of public comment and review.

  2. Random Sample

    ScienceLive

    Join us on Thursday, 24 January, at 3 p.m. EST for a live chat about the next big step in supercomputing—and which country might choose to take it. http://scim.ag/science-live

    Denizen of the Deep, Caught on Film

    CREDIT: NHK/NEP/DISCOVERY CHANNEL

    In 2004, the first still photographs of the giant squid roaming its deepwater habitat wowed the world. But this year, scientists have gone one better: They have video. The ghostly white creature was spied by a three-person team, led by Japanese zoologist Tsunemi Kubodera, in a submersible in waters 600 meters deep about 1000 kilometers south of Tokyo. The team included scientists and filmmakers from Japan's National Museum of Nature and Science, the Discovery Channel, and Japanese broadcaster NHK, which has made it a 10-year mission to capture images of the creature in its habitat. For hundreds of hours last summer, the team searched for signs of the sea creatures with the aid of chemical attractants, bioluminescent lures, and ultrasensitive cameras that used only infrared light. The lucky dive came in July 2012: The team spied a giant squid about 3 meters long—which is still small for the species; the largest ever caught was twice as long—and followed it to a depth of about 900 meters. NHK aired footage from the video in Japan on 13 January; the Discovery Channel will air it on 27 January.

    They Said It

    "The Administration does not support blowing up planets."

    —Paul Shawcross, chief of the Science and Space Branch at the White House Office of Management and Budget, rejecting an online petition to build the Death Star, the orbiting weapons system from Star Wars.

    Frankensteinish Flight of the Bumblebee

    Bumblebees seem to have subpar wings when it comes to wear and tear—at least, compared with their cousins the yellow jackets. But how does a more fragile wing benefit the bumblebee? Harvard University biomechanist Andrew Mountcastle took an unusual approach to the question: He glued yellow jacket wings to a bumblebee—and found that what's good for the wasp isn't necessarily best for the bee.

    Wing change.

    Gluing a yellow jacket wing to a bumble bee (right) tests the wing's performance.

    CREDIT: ANDREW MOUNTCASTLE; (INSET) WIKIMEDIA COMMONS/SFFUBS

    While examining insect wing adaptations, Mountcastle had noticed that, unlike the bee's wing, the wasp's wing has a joint that makes it flexible and possibly more resilient in crashes. Subjected to repeated collisions with a leaf, the bumblebee wing wore down 1.5 times faster than the yellow jacket wing, Mountcastle reported last week at the annual meeting of the Society for Integrative and Comparative Biology in San Francisco.

    But bumblebees beat their wings much more rapidly than do yellow jackets. And after attaching the yellow jacket wing, he says, he found that the quicktime beat caused the wasp wing to flex all the time, possibly lowering flight efficiency.

    Bumblebees have their own way of coping with collisions, too. The scaffolding veins on their wings are concentrated close to the body, leaving the tip less rigid and likely better able than the rest of the wing to withstand wear and tear. These findings could help the development of insect-sized aerial robots: "The more we know about biodesign, the better we will be able to emulate it with technology," says Robert Dudley, a physiologist at the University of California, Berkeley.

    Noted

    Gastrointestinal disease–causing Clostridium difficile is the scourge of hospitals; scientists have explored ways to introduce healthy gut bacteria to the afflicted via a controversial and somewhat unpalatable treatment called "fecal transplant" (http://scim.ag/GutBacteria). Enter RePOOPulate, a synthetic poop product made from purified intestinal bacterial cultures that can combat C. difficile—and, says its creator, microbiologist Emma Allen-Vercoe of the University of Guelph in Canada, it offers a "less icky" alternative to fecal bacteriotherapy.

  3. Who Will Step Up to Exascale?

    1. Robert F. Service

    The next big step in high-powered computers lies just ahead, but only if major players are willing to back their talk with coordinated programs and lots of money.

    New insights.

    Novel 3D supercomputer simulations revealed an unexpected new mechanism behind exploding type Ia supernovas, known as the gravitationally confined detonation model.

    CREDIT: FLASH CENTER FOR COMPUTATIONAL SCIENCE, UNIVERSITY OF CHICAGO

    Horst Simon doesn't often bet against progress. But several months ago, the supercomputer expert and deputy director of Lawrence Berkeley National Laboratory (LBNL) in California did just that. He bet Thomas Lippert—a German colleague—$2000 that supercomputer makers wouldn't create an exascale computer by the beginning of 2020. If built, this next major milestone in supercomputing will be capable of carrying out 1018 floating-point operations per second, or an exaflop. That's 57 times as fast as today's fastest supercomputer, Oak Ridge National Laboratory's Titan, which runs at 17.6 petaflops (1015 flops). Such intense computing power could vastly improve everything from climate models to the engineering of engines to work with advanced biofuels.

    A quick glance at supercomputing trends would suggest that Simon's bet is a bad one. The improvement of high-performance computers (HPC) has been on an unvarying upward trajectory. The industry marched from the first teraflop (1012 flops) machine to the first petaflop machine in just 12 years. Extrapolate this steady rate of progress, and supercomputers should reach exascale computing in 2018.

    But troubles are brewing. Supercomputer experts agree that scaling up existing technology won't get supercomputers to the exascale level. Intel, IBM, and other hardware makers say they won't pursue exascale computers without government backing. The United States, China, Japan, Russia, India, and the European Union are all flirting with exascale plans. But to date, governments have balked at committing the hundreds of millions to billions of research dollars likely to be needed to create the new technology.

    Just a year ago, supercomputer experts were confident that the industry would cross the exascale threshold between 2018 and 2020 (Science, 27 January 2012, p. 394). Now, that confidence is slipping. "There was a fair amount of traction with exascale," says Jack Dongarra, a supercomputing expert at the University of Tennessee, Knoxville, who closely tracks international supercomputing trends. "Some of that is gone now. That's a big disappointment," Dongarra says. John Hengeveld, the HPC segment marketing director for Intel in Hillsboro, Oregon, is more upbeat: "I don't think there has been any setback on the path to exascale." However, he adds, "there is a question about national will."

    For Dongarra, Hengeveld, and many others, the key question is which country will step up to create the first exascale computer. The answer will determine more than who gets bragging rights for leading high-performance computing technology into the future. Because the effort is expected to revolutionize the design of everything from computer logic and memory to the interconnections and software that make them all run, the race could determine which country's high-tech firms are likely to dominate computer technology in the decades ahead. And because scientists who take advantage of the world's top computers tend to be leaders in their own fields, the race to exascale could also affect which nation's researchers will drive developments in disciplines including materials science, alternative energy production, and climate research. "Exascale [computing] is going to have a tremendous impact on our future," says William Harrod, a division director at the U.S. Department of Energy (DOE)'s Office of Advanced Scientific Computing Research.

    Radical departures

    By all accounts, the transition from current petascale computers to exascale will be difficult. But this isn't the first time supercomputer makers have needed to radically shift technology to keep moving forward. In the 1980s, supercomputer designers switched designs from computers run by single central processing units to parallel computers containing multiple CPUs coupled together. More recently, they began making hybrid supercomputers that added in graphics processing units (GPUs) capable of carrying out some types of calculations faster. Titan, for example, contains 18,688 CPUs (each with 16 processors) and the same number of GPUs. Despite these fundamentally different architectures, the supercomputing performance has roughly doubled each year for 2 decades, a nearly exponential growth rate, according to Erich Strohmaier, a high-performance computing expert at LBNL, who helps run the TOP500 supercomputer Web site, which tracks trends in the industry.

    But unless things change quickly, this rate of progress may not continue. "There are great challenges ahead as we scale towards exascale," Dongarra says. Chief among them, Dongarra and others say, is power. Titan, today's top machine, already uses 8.2 megawatts of power, or a watt for every 2 gigaflops. That's a marked efficiency improvement over the previous generation of supercomputers. But if an exascale machine were to run at the same efficiency, it would require 466 MW, enough energy to power nearly half a million homes. To be viable, HPC leaders say an exascale machine must aim to use no more than 20 MW, which means researchers will need to improve the energy efficiency of their machines 23-fold.

    That's only the beginning. Researchers will also need to learn how to design massively parallel machines capable of executing a billion computational threads simultaneously. They'll need to redesign computer memory to be faster and more efficient. They'll need to design machines that won't crash when one operation runs into trouble or stalls. And along with these demands and many others, they'll need to design a machine that costs somewhere between $100 million and $200 million. The upshot, Harrod says: "We really need to change the design of the system itself."

    That change is complicated by the fact that academic researchers don't build supercomputers: Computer companies such as IBM, HP, and Fujitsu do. But those companies are driven by commercial markets for technology found in desktops, laptops, tablets, and smartphones. And according to Harrod, the gulf between commercial computer technology and the technology at the heart of supercomputers is widening. In 1996, for example, Intel built ASCI Red, the first supercomputer made with off-the-shelf CPUs. By contrast, the custom-built designs that integrate large numbers of CPUs and GPUs in today's high-end machines have no counterparts in lower end machines. What's more, because the commercial chip market dwarfs the HPC market, there is little incentive for chip makers to sink massive investments into a technology that will likely net them only a handful of sales.

    Exaflop bound?

    Despite drastic changes in computer architecture in recent decades, supercomputer speed has been on a steady rise.

    CREDIT: TOP500 PROJECT/WWW.TOP500.ORG

    To make matters worse, many computer giants are shifting the focus of their business to the emerging field of Big Data, where they help other industries mine vast amounts of data to better target and serve their customers. "To be honest, that market segment has better [profit] margins than HPC," says IBM's Ed Seminaro, the chief architect of the IBM POWER7 supercomputer technology. "We haven't given up on [exascale] technology," Seminaro says. However, he adds, the company has not yet committed to being a leader in the field. In fact, in 2011 IBM backed out of building Blue Waters, a 1 petaflop supercomputer being built at the University of Illinois, Urbana-Champaign, citing high costs (Science, 25 November 2011, p. 1044).

    Intel's Hengeveld agrees that it's up to government funding agencies to take the lead. "Unless they step up, it isn't going to happen," Hengeveld says. Harrod says he has no illusions otherwise: "Industry is not going to develop exascale systems for the technology alone. It's not going to happen without the federal government."

    Who and where?

    The question is, whose government? If mere talk is any indication, there could be plenty of competitors. The Russian and Indian governments have both said that they're interested, but neither has announced formal plans yet. The European Union has backed several modest scale research efforts, including PRACE, the Partnership for Advanced Computing in Europe, a $67 million effort of 25 member countries to advance supercomputing software and hardware in Europe. PRACE isn't explicitly an exascale research effort, and its funds are due to end in 2014. But it could be extended if it is included in Europe's 8th Framework Programme (FP8), which coordinates research funding across member countries. According to Dietmar Erwin, a computer scientist at the Jülich Supercomputing Centre in Germany, the PRACE countries will likely be asked to have PRACE funds increased by 50% for the 2014 to 2020 FP8 session. But other infrastructure programs could up that number considerably.

    Erwin notes that in Europe, "at the moment there is no plan in place to purchase an exascale computer." And others doubt that Europe will be the first out of the blocks. Not only are European governments grappling with their worst economic tumult in decades, but they also have few hardware vendors like Intel and other computer chip makers that they'd have to rely on to build the machine. "Europe cannot actually do it unless they want to create something new," Simon says.

    Top spot.

    To reach exascale, researchers need to design a supercomputer that's 57 times faster than today's best machine.

    CREDITS (LEFT TO RIGHT): OAK RIDGE LEADERSHIP COMPUTING FACILITY (OLCF)/OAK RIDGE NATIONAL LABORATORY; NCSA/UNIVERSITY OF ILLINOIS

    Japan is in a better position. The country recently spent nearly $1 billion to construct the K computer, a 10-petaflop machine that topped the TOP500 list in 2011. Fujitsu built that machine using its own internal technology. Toshiyuki Shimizu, who directs Fujitsu's System Development Division in Kawasaki, says that Japan's Ministry of Education, Culture, Sports, Science and Technology (MEXT) is currently conducting a feasibility study outlining possible technological paths to reach exascale. That study is expected to be completed in March 2014, at which time MEXT is likely to spell out its goals for its next-generation supercomputer, Shimizu says. Shimizu says he believes its "likely" that government officials will back a move toward exacale. However, he adds, "we don't know when."

    Thus far, China's plans are perhaps furthest along. The country has already committed 600 million yuan ($96 million) to building a 100-petaflop machine by 2015 as part of the nation's current 5-year plan. China has also developed its own domestic processing chip technology. But so far there's been no word on exascale. At the SC12 supercomputing conference, held last November in Salt Lake City, Depei Qian, a supercomputer expert at Beihang University in Beijing, said that despite its recent rapid progress in supercomputing technology, China remains 3 to 5 years behind the United States and other supercomputing powers. Qian estimates that China won't build its first exascale computer until between 2022 and 2025.

    Simon says he isn't sure China is that far behind. Tianhe-1, China's 2.5-petaflop machine that topped the TOP500 list in 2010, as well as the nation's commitment to a 100-petaflop machine, proves that China has caught up with international supercomputing standards. However, he adds: "I don't know if they are willing to make the investment to create the breakthroughs needed to go beyond that." David Kahaner, who closely follows supercomputing advances in Asia as director of the Asian Technology Information Program, which is headquartered in Albuquerque, New Mexico, agrees. "Everybody is looking to the U.S. for intellectual leadership," he says.

    Until recently, the United States seemed be on track to produce an exascale supercomputer by the end of this decade. Over the past 2 years, the U.S. Congress made an initial exascale investment by funding more than $200 million in advanced hardware and software research. In its 2012 budget, Congress also asked DOE officials to submit a report detailing an exascale program's components, funding needs, and research benchmarks. That report was due on 10 February 2012. But almost a year later, there's still no sign of it.

    On 12 October, senators Dianne Feinstein (D–CA) and Lamar Alexander (R–TN), who lead the Senate Appropriations subcommittee on energy and water development, wrote a letter to DOE Secretary Steven Chu and Jeffrey Zients, deputy director of the Office of Management and Budget, asking again for the report and calling it "critically important to help us evaluate funding needs in fiscal years 2013 and 2014." Harrod says the report is still in the works, but has been delayed by the complexity of the problem and the task of coming up with an acceptable budget. DOE leaders, Harrod says, "are trying to determine what level of funding to go for."

    Even though DOE's exascale program has yet to be officially released, at SC12 Harrod spelled out many of the likely key components if an exascale computing initiative is eventually approved. For starters, Harrod says, any exascale initiative would include both hardware and software research; construction of a prototype, probably between 2019 and 2022, followed by an exascale machine; and support for the scientific applications that would run on any such machine. As part of this effort, Harrod says it's critical that any U.S. effort support supercomputing companies to create a technology that is commercially viable, and not useful for merely building a one-off machine.

    But just how fast any DOE effort can produce that remains up in the air as Congress struggles with bitter negotiations over the nation's finances. Congress and DOE must also sort out how exascale computing fits among other high-ticket DOE priorities such as supporting ITER, the international fusion program, and the Facility for Rare Isotope Beams, a nuclear research lab being designed at Michigan State University. "The biggest problem is the budget," Harrod says. "Until I have the budget, I don't know what I'm doing."

    The best-case scenario, Harrod adds, is that exascale computing initiative funding would start in fiscal year 2014, which begins in October 2013. That gives any U.S. effort only 7 years to build an exascale machine by 2020. Given the financial hurdles and technical challenges of doing so, Simon's bet is looking better every day.

  4. Neuroscience

    The Promise and Perils of Oxytocin

    1. Greg Miller

    Is oxytocin the next revolution in psychiatric medicine—or an overhyped hormone that could make some patients worse?

    CREDIT: SAL BURCIAGA /THINKSTOCK

    Few substances produced by the human body have inspired as much hoopla as oxytocin. Recent newspaper articles have credited this hormone with promoting the kind of teamwork that wins World Cup soccer championships and suggested that supplements of the peptide could have prevented the dalliances and subsequent downfall of a certain high-ranking U.S intelligence official. Although the breathless media coverage often goes too far, it reflects a genuine and infectious excitement among many scientists about the hormone's role in social behavior. First studied by biologists for its role in childbirth and lactation, oxytocin has more recently captivated neuroscientists and psychologists who have found that it can promote trust and cooperation and make people more attuned to social cues.

    Now psychiatrists have caught oxytocin fever. Dozens of clinical trials are under way, or will be soon, to investigate the hormone's potential benefits for a wide range of psychiatric disorders. The interest isn't hard to understand. Many psychiatric conditions have social symptoms, such as the characteristic lack of empathy in autism, the attachment anxiety of borderline personality disorder, and the paranoia of schizophrenia. Yet no drugs currently approved for psychiatric use directly target social behavior.

    For autism in particular, hopes for oxytocin run high. A large trial of the hormone on 300 affected children is expected to begin this spring. Meanwhile, thousands of impatient parents of autistic children have persuaded physicians to prescribe oxytocin nasal spray, which can be obtained from compounding pharmacies.

    At first glance, oxytocin might seem like just what the doctor should be ordering. But as researchers have continued to explore the hormone's effect on human behavior, a darker side has emerged. Oxytocin seems to promote aggression or other antisocial behavior in some circumstances. Its effects also appear to vary depending on a person's genetic makeup and psychological status. And no one knows what long-term oxytocin treatment does to the developing human brain. Disconcertingly, one recent study found that male voles treated for several weeks with oxytocin nasal spray around the time of adolescence later exhibited impaired social bonding with females. "The more we know, the more complicated it's getting," says Sue Carter, a behavioral neuroendocrinologist and a pioneer of research on oxytocin's role in social behavior now based at RTI International in Research Triangle Park, North Carolina.

    Carter is particularly worried about giving oxytocin to children before more is known about the hormone's developmental effects. "I think there probably is a place for oxytocin in several aspects of medicine," she says. "But what worries me, and should worry others, is that so much of the basic background is missing."

    At the same time, those leading the trials say that the scientific rationale for using oxytocin is already strong enough, especially given the lack of better options. "This could be the first drug to address the core symptoms of autism," says Geraldine Dawson, a developmental and child clinical psychologist and chief science officer of Autism Speaks, which has funded some of the early pilot studies. At the heart of the debate is the tension between scientific caution and the desperation of patients and families living with disruptive disorders day in, day out.

    From bonding to bedside

    The hypothalamus, an evolutionarily ancient part of the mammalian brain, makes oxytocin. Released into the bloodstream by the nearby pituitary gland, it signals the uterus to contract during childbirth and stimulates the release of milk for nursing. The hormone was the first peptide to be synthesized in the laboratory, a feat that earned American biochemist Vincent du Vigneaud the 1955 Nobel Prize in chemistry.

    Given the hormone's known roles, researchers soon wondered whether it also played a role in reproductive behavior. In the late 1970s and early 1980s, work with rats and sheep found that oxytocin enhances mother-infant bonding. In the '90s, Carter and others established its role in fostering pair bonding in prairie voles. Unlike most rodents, these furry inhabitants of the North American plains form lifelong bonds and share the work of raising offspring (although trysts are not uncommon). In 2000, Larry Young and colleagues at Emory University in Atlanta reported that genetically engineered mice lacking oxytocin are unable to recognize other individuals, pointing to an even broader role for the hormone in nonreproductive social behavior.

    Although much of this work has been written into textbooks, the more recent oxytocin research in humans has frequently found its way into tabloids. In one of the first eye-catching studies, neuroeconomist Ernst Fehr of the University of Zurich in Switzerland and colleagues gave oxytocin nasal spray or a saline spray placebo to university students before a game in which they had to decide how much money to entrust to a stranger. (The more money a player entrusts, the larger the potential gains and potential losses.) Those who got oxytocin were more trusting, the researchers reported in Nature in 2005. A torrent of studies followed, suggesting that oxytocin not only increases trust and cooperation, but also boosts social perceptiveness, such as face recognition and the ability to read what's on someone's mind from the look in their eyes.

    These findings quickly led to speculation about clinical applications. The first published study in which oxytocin was given to autistic children appeared online in Biological Psychiatry in late 2009. In an experiment conducted by Adam Guastella, a clinical psychologist at the University of Sydney in Australia, and colleagues, 16 autistic boys between 12 and 19 years old received a single dose of oxytocin nasal spray or a placebo in one session, and the alternative in another. (Neither the boys nor the researchers evaluating them knew which time they'd gotten the hormone.) On oxytocin, the boys performed better on a common test of social cognition that involves looking at photographs of faces cropped to show just the eyes and reporting what emotion the person is most likely experiencing. The improvement was modest: from about 45% to 49% correct on average. People without autism typically get more than 70% correct.

    Studies in adults with autism have also demonstrated improvements on standard lab tests of social cognition. But the vast majority of published work on oxytocin to date has looked at the effects of a single dose over the course of an hour or so in the lab. The real question is whether the hormone can restore normal behavior in real life.

    To find out, Guastella and others are conducting trials in which people with autism take daily sniffs of oxytocin for several weeks or months. These pilot studies are in various stages and several researchers told Science that it's too soon to talk about the findings in detail. "Interesting things are coming out of these studies," Guastella says of his group's work. "At the same time, we're not seeing a ginormous result that makes us think this is a cure for autism."

    Caring family.

    Prairie vole parents share the work of raising offspring, but a recent study suggests long-term oxytocin treatment can disrupt bonding between partners.

    CREDIT: KAREN BALES/UNIVERSITY OF CALIFORNIA, DAVIS

    A far larger trial scheduled to get under way this spring should help clarify things. It will be led by psychiatrist Linmarie Sikich at the University of North Carolina (UNC), Chapel Hill, who received a $12.6 million Autism Centers of Excellence grant from the National Institutes of Health in September for this trial. Her team plans to enroll 300 autistic children between the ages of 3 and 17, half of whom will receive oxytocin nasal spray twice daily for 6 months in a placebo-controlled, double-blind trial, and all of whom will receive the hormone for 6 months in a subsequent open-label extension of the trial. Researchers will look for any adverse side effects and monitor the kids with various checklist measures of social behavior filled out by a clinician or parent.

    Autism is hardly the only disease being investigated. Out of 44 neuropsychiatric trials of oxytocin listed on clinicaltrials.gov, roughly three-quarters are for other disorders. Pilot studies in people with schizophrenia, who often suffer from paranoia and difficulty reading social cues, suggest that oxytocin can reduce psychotic symptoms and improve social cognition. The benefits are modest, but encouraging, says Cort Pedersen, a psychiatrist and behavioral neurobiologist at UNC Chapel Hill.

    Pedersen's work in the 1970s established the role of oxytocin in mother-infant bonding, but more recently his interest has turned to the hormone's clinical potential. "One of the real deficits in psychiatry research is a complete lack of appreciation of evolution," Pedersen says. "The human brain evolved to evaluate and maneuver in very complex social environments." Pedersen argues that the role of the brain's social circuitry in psychopathology is too often ignored. And that's what makes oxytocin so exciting in his view. "One of the really cool things about oxytocin is that it probably plays a central role in the social brain," he says.

    Cause for concern

    The explosion of clinical trials with oxytocin, particularly those in children, troubles Karen Bales, a behavioral neuroscientist at the University of California, Davis. "There's been this quick leap from looking at a single dose of oxytocin in healthy adults to trying to give it to children with autism whose brains are still developing," she says. Bales says that she looked and couldn't find a single published study on the long-term behavioral effects of multiple doses of oxytocin in developing animals. "It seemed to me that we were really skipping a step."

    From work she did as a postdoctoral fellow with Carter, Bales knew that even a single dose of oxytocin can have long-lasting effects. In a series of studies published in the 2000s, they found that prairie vole pups treated with oxytocin on the day of birth exhibited abnormal pair bonding and parental behavior as adults. The effects were messy—treated animals grew up to be more social or less social than normal, depending on their sex and the dose they received. "The clearest message was that any exposure to oxytocin can cause long-term behavioral and neuroendocrine effects," Bales says. In one study, Bales found that males given a single dose of oxytocin at birth had reproductive difficulties as adults: They deposited sperm in the female reproductive tract in only 50% of mating attempts, for example.

    More recently, Bales and colleagues tried to better mimic the type of oxytocin treatment now in clinical trials for autism, giving young prairie voles daily squirts of oxytocin in the nose for 3 weeks. In developmental terms, Bales says that the voles were roughly equivalent to 12- to 17-year-old children, the target group for several trials. In the short term, oxytocin made the voles more social, as expected: After a dose, they spent more time in close contact with a cage mate. As adults, however, treated males had abnormal relationships with their partners, the researchers reported online on 15 October 2012 in Biological Psychiatry.

    The standard test of pair bonding in voles, Bales explains, is to put a male in an empty chamber connected to two other chambers: one containing his mate, and another containing an unfamiliar female. "A normal male prairie vole will run around and check everything out and then go hang out with his partner," Bales says. But males that had gotten a daily dose of oxytocin comparable to that being given to autistic children—or an even lower dose—were more likely to spurn their partner in favor of the stranger. To Bales, the findings raise the troubling possibility that repeated use of oxytocin nasal spray may cause long-term changes in the brain that negate or even reverse the hormone's benefits, perhaps by tricking the brain into making less oxytocin of its own.

    Other signs that there's more to oxytocin than cuddles and hugs have emerged from human experiments. In 2010, psychologist Carsten De Dreu and colleagues at the University of Amsterdam gave oxytocin nasal spray to men before they played a computer game in which small teams competed for money. Compared with men who got a saline spray, those who sniffed oxytocin behaved more altruistically to members of their own team—but at the same time, they were more likely to preemptively punish competitors, the team reported in Science. In a 2011 study in the Proceedings of the National Academy of Sciences, De Dreu's team found that oxytocin increased favoritism toward subjects' own ethnic group (native Dutch men) on a series of tasks and thought experiments done on a computer, and in some situations the treated men exhibited more prejudice against other groups (Germans and Middle Easterners, in this case).

    To some researchers, this suggests that oxytocin is a double-edged sword: promoting bonds with familiar individuals, but promoting unfriendly behavior toward strangers. "In the beginning, everyone thought it would have very robust prosocial effects, but it seems to depend on how you interpret the term prosocial," says René Hurlemann, a psychiatrist at the University of Bonn in Germany. In a study published on 14 November 2012 in The Journal of Neuroscience, his team reported that when men who reported being in a stable heterosexual relationship took oxytocin, they put a bit more distance between themselves and an attractive female experimenter who entered the room. To Hurlemann, these findings, like De Dreu's, suggest that oxytocin promotes bonding within an established pair (or group) at the expense of outsiders. That makes sense from an evolutionary perspective, he says, but may not be ideal for a prosocial drug. Though optimistic that oxytocin can help some people with psychiatric disorders, Hurlemann cautions that it might not have the same benefits for all patients.

    An illustration of just that comes from work by Jennifer Bartz, a social psychologist at McGill University in Montreal, Canada. Encouraged by the reports that oxytocin increases trust, Bartz thought it might help people with borderline personality disorder (BPD), who are plagued by fears of abandonment and separation, and have profound difficulties with relationships as a result. But when she and colleagues gave a single dose of oxytocin nasal spray to people with BPD, they became less trusting and less likely to cooperate with a partner in a social dilemma game, the researchers reported in 2011 in Social Cognitive and Affective Neuroscience. This effect was strongest in those with BPD who scored highest on self-report measures of relationship anxiety and fear of rejection.

    Social studies.

    New clinical trials seek to determine if oxytocin can boost social behavior in children with autism.

    CREDIT: TONY GUTIERREZ/AP

    One possibility, Bartz says, is that oxytocin increases the desire to connect and heightens attention to social cues. That may backfire in people with BPD, who are already hyperattentive and anxious in social situations. "The picture that's now emerging is that it's not this global social panacea," Bartz says. "In many cases it depends on the situation in which it's given or the person to whom it's given."

    A risk worth taking?

    Going forward, the success or failure of oxytocin as a psychiatric drug may hinge on figuring out which disorders and which people respond positively to the hormone—there's evidence that people with variants of the oxytocin receptor gene respond differently—and in what context. "In my view, the best benefit from stimulating the oxytocin system is going to be to combine it with a controlled behavioral therapy," Emory's Young says. He believes that oxytocin's main effect is to make people more sensitive to social cues. In a therapist's office, children could be assured of receiving positive, reinforcing social cues while under the hormone's sway. Not so if they simply take the hormone and went about their day. "Say you give it to a kid and then he goes to school and gets bullied. That's not going to have a positive impact, and it may even make things worse," Young says.

    A better handle on the basic biology of intranasal oxytocin, such as how it enters the brain and which receptors it hits, might enable researchers to develop more effective drugs, Young adds. "If we want to move beyond this initial investigatory era and get more sophisticated and potent effects, we need to understand the mechanisms."

    Despite the unknowns, Sikich and others insist that the clinical trials are justified. "A lot of people in this country, probably a few thousand, are going to compounding pharmacies and having them put together preparations of oxytocin," Sikich says. "We feel like it's really important, for something that's being used in this unregulated way, to get some data on how safe it is … and figure out does it work or does it not work."

    For Dawson, the lack of better options is a powerful motivator. Only two drugs are currently approved for autism, she notes: Both are antipsychotic medications prescribed to cut down on tantrums, aggression, and self-injury. These drugs don't directly address the social deficits at the core of the disorder, and they have potentially dangerous side effects, not to mention unknown effects on brain development. Behavioral interventions such as the Early Start Denver Model, which Dawson co-developed, have proven successful in improving social behavior, but they require 25 hours or more a week of intensive one-on-one therapy and can cost $25,000 to $50,000 a year. In contrast, a year's supply of oxytocin, which is currently only available in a proprietary synthetic version, costs roughly $5000. And it could get much cheaper if a generic version becomes available.

    Among parents of autistic kids, there's long been a willingness to try experimental treatments, even before they're fully vetted by researchers, Guastella says. A driving factor, he says, is frustration that science has let them down by moving too slowly. At the same time, researchers such as Carter and Bales hope that science won't let these families down again by rushing too quickly into clinical trials with a hormone whose effects aren't adequately understood.

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