News this Week

Science  15 Feb 2013:
Vol. 339, Issue 6121, pp. 742
  1. Around the World

    1 - Tokyo
    High Cost of Scientific Whaling
    2 - Geneva, Switzerland
    LHC Intermezzo
    3 - Lompoc, California
    Landsat's Lucky Number Is Eight
    4 - Kano, Nigeria
    Health Clinics Attacked
    5 - Strasbourg, France
    Inching Toward E.U. Fisheries Reform


    High Cost of Scientific Whaling


    Japan's scientific whaling effort is in the red, costing taxpayers $378 million since 1987, even as demand for whale meat has shrunk and the research has proven of little value, according to a 5 February report by the International Fund for Animal Welfare. Under the International Whaling Commission convention, scientific whaling is allowed despite a moratorium on commercial whaling since 1986. The meat can be sold to cover the cost of research.

    Backers of the scientific whaling program insist that it has value, stating that the numbers of scientific whales taken actually fall far short of official targets, which limits the usefulness of the data for studying the size and health of stocks. But critics disagree. "It is well established in the scientific literature that there are many ways to study whale diet and condition without killing them," says Leah Gerber, a marine conservation biologist at Arizona State University, Tempe.

    Geneva, Switzerland

    LHC Intermezzo

    Physicists have shut down the world's biggest atom smasher, the Large Hadron Collider (LHC) at the European particle physics laboratory, CERN, for 2 years of repairs. The work should allow the LHC to run at full energy from 2015 onward. The collider had been cantering at about half energy since it broke down in September 2008—just 9 days after starting up—and sidelined itself for 14 months.

    It may be an anxious wait. The LHC triumphed last summer when physicists discovered a particle that appears to be the Higgs boson, the last piece of their standard model of the known particles. But if the LHC produces nothing else, it could be the last collider physics gets.

    "If the standard model Higgs is all that emerges from the LHC then, yes, justifying the expense of a major future facility is not obvious," says CERN spokesperson James Gillies. Still, he says, "we have every chance of making a discovery with this machine when it comes back on again or—who knows?—with the data we already have."

    Lompoc, California

    Landsat's Lucky Number Is Eight


    The world's oldest Earth-observing satellite system is still alive and off death row—at least for a while. Landsat 8, the latest in a line of U.S. orbiters first launched in 1972, was carried into space on 11 February by an Atlas V rocket launched from Vandenberg Air Force Base in California (pictured). The spacecraft is expected to reach its final orbit 705 kilometers above Earth by mid-April, and begin transmitting data by early summer. Researchers have long relied on Landsat data to monitor environmental and climate changes, but the program has faced several near-death budget crises. Landsat 8, which is expected to operate for at least 5 years, cost nearly $900 million. It will ultimately replace two existing orbiters: Landsat 5, which was launched in 1984 and decommissioned late last year after a record 28 years and 10 months of service, and Landsat 7, which was launched in 1999 but has struggled with technical glitches since 2003. It is uncertain whether Congress and the White House will be willing to find money for a Landsat 9.

    Kano, Nigeria

    Health Clinics Attacked

    Nine polio coworkers were killed on 8 February when gunmen stormed two health clinics in Kano state in northern Nigeria. Details remain murky, but the attacks occurred at the tail end of a polio immunization campaign. The shootings sparked fears that the assailants were targeting the polio eradication program in Nigeria, in an unsettling echo of recent events in Pakistan, where nine polio workers were shot and killed in December. As a precaution, the government of Kano halted polio vaccination activities, and U.N. agencies pulled their polio staff members from the field.

    No one has claimed responsibility for the attacks. In a statement, Nigerian Health Minister Muhammad Ali Pate promised an aggressive investigation, describing the "heinous" attacks as part of a "long standing cycle of violence that has engulfed [the northern states] in recent months."

    Nigeria is one of three countries, with Pakistan and Afghanistan, where polio remains endemic. Cases are concentrated in the north, which is largely Muslim. Efforts to wipe out the virus there have been hobbled by rumors that the vaccine is part of a Western plot to sterilize Muslim children.

    Strasbourg, France

    Inching Toward E.U. Fisheries Reform


    The European Parliament approved a plan on 6 February to reform the European Union's Common Fisheries Policy by a 502-to-137 vote. The plan aims to improve the much-criticized policy, last reviewed in 2002, by capping catches at sustainable levels, banning discards of unwanted species, and making better use of scientific data for long-term planning. According to the European Commission, 68% of the European Union's stocks are overfished.

    Under the revamped rules, starting in 2015 regulators would set catch limits using a data-driven standard known as maximum sustainable yield that is commonly used in fisheries regulation in the United States. If fully adopted, the rules will allow fish stocks to "recover by 2020, enabling us to take 15 million tons more fish and create 37,000 new jobs," predicted Ulrike Rodust, a German member of the Parliament who was responsible for revising and offering a legislative proposal originally developed by the European Commission in July 2011.

    The reform plan still has to be discussed with governments from the European Union's 27 member states. If they reach an agreement by the end of June, the plan could come into force next year.

  2. Newsmakers

    They Said It

    "Funds currently spent by the government on social science, including on politics, of all things, would be better spent helping find cures to diseases."

    —House of Representatives Majority Leader Eric Cantor (R–VA), renewing his attack on National Science Foundation funding of the social sciences in a speech on 5 February at the American Enterprise Institute in Washington, D.C.

    'Arab Nobels' Honor Genetics of Obesity, Superfast Physics

    Paul Corkum


    Score a "twoonie" for Canada. Paul Corkum, a Canadian physicist at the University of Ottawa, and Ferenc Krausz, a Hungarian-Austrian physicist of both the Max Planck Institute of Quantum Optics in Garching, Germany, and Ludwig Maximilians University in Munich, Germany, have won the 2013 King Faisal International Prize for Science for their independent work on ultrashort pulses of laser light. Such work has enabled scientists to track the motion of electrons within atoms and molecules. The two will share the roughly $200,000 prize, which is awarded annually and is sometimes called an "Arab Nobel Prize."

    Meanwhile, American Jeffrey Michael Friedman, a geneticist with Rockefeller University and the Howard Hughes Medical Institute in New York City, and Canadian-born Douglas Coleman, retired from Jackson Laboratory in Bar Harbor, Maine, share the 2013 King Faisal International Prize for Medicine for their pioneering work together on the hormone leptin and the genetics of obesity. Friedman and Coleman have racked up several prizes in recent years.

    David Evans to Lead U.S. Science Teachers Group

    David Evans


    David Evans has never taught science at the precollege level. Nor has he carried out research on how to improve science teaching and learning. But the new executive director of the National Science Teachers Association says he sees value in bringing a fresh eye to the rapidly changing field.

    "Information is much more accessible, and people can get it in a variety of new ways," says Evans, who last week took the helm at the 60,000-member society, based in Arlington, Virginia. He says two important changes for teachers—whom he calls "classroom teachers of science rather than science teachers, because not all of them have a background in the subject"—are the proliferation of free online courses and the arrival later this year of the Next Generation Science Standards, a national effort to get states to voluntarily adopt improvements in teaching science in elementary and secondary schools.

    Trained as a physical oceanographer, the 66-year-old Evans spent 2 decades with the federal government, including a stint as undersecretary for science at the Smithsonian Institution.

  3. Random Sample

    Ribbon 'Round The Solar System


    More than 3 years ago, stunned space physicists reported the discovery of a narrow band of sky lit up in the cameras of NASA's Interstellar Boundary Explorer (IBEX). The spacecraft's cameras, trained toward the outer edge of the heliosphere where the sun's wind of charged particles encounters the oncoming magnetic field that courses between the stars, were observing a mysterious ribbon of high-powered hydrogen atoms streaming inward from that boundary. A dozen theories later, a pair of IBEX researchers reports this week in The Astrophysical Journal that the interstellar magnetic field (thin gray lines wrapping around the region filled by solar wind in the image) may be temporarily trapping and concentrating outbound particles. The trapping would be most effective where the solar wind squarely crosses interstellar magnetic field lines (gray "life preserver"). IBEX "sees" those particles that escape the trap as the ribbon, here rendered in reds, yellows, and greens.

    Diamonds Are a Sperm's Best Friend

    It's hard out here for a sperm—even the petri dishes researchers use to store and culture the cells might actually harm their delicate cargo. Researchers in Germany suspect that exposing your standard polystyrene petri dish to water can cause its surface to soften into a layer of toxic goo made of chemicals called reactive oxygen species, or ROS. ROS have been wreaking havoc on sperm and egg cells during in vitro fertilization (IVF) procedures for decades, but until now, nobody thought to blame the petri dish.


    So the researchers, led by materials scientist Andrei Sommer of Ulm University in Germany, came up with a solution that could bring back the sparkle: Make a petri dish out of quartz, and then coat it with a nanolayer of diamond. About 20% more sperm survived for 42 hours in diamond-coated petri dishes than in the polystyrene containers usually used for IVF, the researchers report in the Online Proceedings Library of the Materials Research Society.

    "It's an interesting preliminary study," says Pravin Rao, a urologist at Johns Hopkins' James Buchanan Brady Urological Institute in Baltimore, Maryland, who was not involved in the study. "The most important thing to see is whether [the diamond-coated dishes] would improve IVF success rates"—particularly in cases complicated by low sperm counts, he says. "If you just have 10 sperm, it's great if even one extra sperm survives."


    This week, Science is reporting from the AAAS Annual Meeting in Boston. Visit for full coverage.

  4. The Many Ways of Making Academic Research Pay Off

    1. David Malakoff

    Universities are learning that commercialization means more than patents, licensing fees, and startups.

    Three years ago, Ahmed Ellaithy left a high-tech startup in Dubai to help his alma mater, the prestigious American University in Cairo, launch one of the first offices in Egypt dedicated to turning academic research into commercial products. "I faced some very existential questions," recalls the 31-year-old engineer. "What's the point of commercialization? What are we trying to accomplish? How will we know if it's working?"

    New start.

    Ahmed Ellaithy is helping the American University in Cairo pioneer one of Egypt's first academic commercialization programs.


    A lot of academic administrators around the world have similar questions about a suite of activities that goes by the name "technology transfer." Research universities are under growing pressure to play a more active, entrepreneurial role in commercial innovation. Intent on fueling economic growth—and dazzled by the ability of research-intensive campuses such as Stanford University in Palo Alto, California, to spawn multibillion-dollar businesses—governments are trying to encourage academic researchers to transform their discoveries into products. University leaders, in turn, increasingly regard tech transfer as a prerequisite for luring top faculty members and students, raising research funds, and potentially cashing in on lucrative inventions. "There's this growing sentiment that you can't be a strong university without having a serious plan for research commercialization," says Steven Price of Oklahoma State University (OSU), Stillwater, who helps mentor aspiring tech transfer administrators like Ellaithy.

    But efforts to turn universities into commercial hothouses often don't succeed: Tech transfer is a net money-loser at most universities, studies suggest, with legal and administrative costs often exceeding revenues. Indeed, a growing number of scholars warn that government and university officials too often create unrealistic expectations by overstating the potential benefits of commercialization and underestimating how hard it is to do and what it will cost. Many advise schools to focus instead on "knowledge transfer"—helping society benefit from the discoveries and skills of faculty members and students without focusing just on finances. That's the broader approach Ellaithy is taking at the American University in Cairo, at least initially.

    "You are seeing a lot of reassessing, a lot of experiments," says Phyl Speser, CEO of Foresight Science & Technology, a consulting firm in Providence, and a vice president of the U.S. Association of University Technology Managers (AUTM). "People are trying to figure out the best way to do this."

    Universities have a big stake in getting it right. A well-tailored tech transfer effort can bolster a school's bottom line, enhance its contribution to society, and please politicians. A flawed program, however, can become a financial drain, raise potential conflicts of interest, and interfere with an institution's mission to teach and carry out research.

    "Technology transfer has become a focus of innovation policy in many places, and there are some high expectations," says economic sociologist Martin Kenney of the University of California, Davis. The challenge, he says, is "to get the incentives aligned right, so that everyone benefits: the inventor, the university, society. And there are plenty of ways you can get them wrong."



    This is the fifth in a series of articles on global research universities. Previous stories have examined how mobility shapes an institution (7 September 2012, p. 1162), the growth of satellite laboratories (28 September, p. 1600), how France and Germany hope to strengthen a handful of elite universities (2 November, p. 596), and the problems facing the fledgling King Abdullah University of Science and Technology (7 December, p. 1276).

    Image credit:

    Singles and home runs

    Although the idea of commercialization seems straightforward, its implementation is not. Legal and institutional arrangements vary by nation, by university, and even by academic department and discipline, and so do strategies. "There's really no such thing as 'typical' tech transfer," says Foresight's Speser.

    Some schools try to commercialize as many discoveries as possible in hopes that a few will hit it big. Others are pickier, choosing quality over quantity. Some put their own money into spinoff companies; others don't want to run the financial risk, or are prohibited from doing so. Given the vastly different budgets, cultures, and goals of modern research universities, "there cannot be a single template for technology transfer," concluded a 2010 report from the National Research Council (NRC) of the U.S. National Academies entitled Managing University Intellectual Property in the Public Interest.

    In general, however, Egypt and most other nations are following a path blazed by the United States. In 1980, federal legislators responded to concerns that government red tape was trapping many inventions in the lab by passing the Bayh-Dole Act. The law gave U.S. universities an unambiguous right to claim ownership of promising discoveries, such as cancer-fighting molecules or better computer algorithms, even if the research was conducted with public funds. Since then, dozens of countries have adopted similar policies.

    Generating good ideas is just the first step. If an invention appears to have commercial value, a university can create intellectual property (IP) by applying for a patent, copyright, or some other form of ownership that it can legally enforce. The university can then sell or license the right to use the invention to one or more companies—or assume the risks of launching its own startup. Any payments or profits are typically divided equally among the inventor, the inventor's academic department, and the university's general fund.

    The Bayh-Dole system has opened the door to some eye-popping payouts. In 2005, for example, Stanford earned $336 million from selling its stake in Google, and New York University and its researchers have earned more than $650 million since the mid-2000s from the science underpinning Remicade, an arthritis drug. In 2011 alone, Northwestern University in Evanston, Illinois, earned $192 million from its tech transfer operation, topping the most recent annual chart assembled by AUTM. And a federal jury recently awarded a whopping $1.2 billion to Carnegie Mellon University in Pittsburgh, Pennsylvania, after it found that a semiconductor company had used the university's inventions without permission. (The company is appealing the verdict.)

    The problem facing would-be copycats is that such windfalls are the exceptions, not the rule. "The great majority of [university] inventions generate modest revenues and many generate none," the NRC report found. "A handful of universities and a small fraction of all inventions are responsible for a large fraction of the revenues received."

    In recent years, for example, analysts estimate that fewer than 15 of the roughly 100 major U.S. universities have reaped more than 50% of all commercialization revenues, which totaled $2.5 billion in 2011. And less than 1% of the thousands of academic licenses granted in the last few decades have generated more than $1 million in royalty income. (That low batting average is true even at Stanford.) Indeed, many U.S. schools earn much more from television contracts to broadcast athletic events than they do from tech transfer. Universities in Europe and Asia fare even worse, on average, using similar financial metrics.

    The bottom line, the NRC report says, is that tech transfer programs "should not be predicated on the goal of raising significant revenue for the institution. The likelihood of success is small and the probability of disappointed expectations high."


    A USTAR is born

    Those fiscal realities haven't prevented technology transfer from becoming a powerful tool for some research universities in attracting star scientists, obtaining more funding, and moving up in the academic rankings. In Utah, for example, the state's two major public universities—the University of Utah (UU) and Utah State University—have used a high-profile commitment to commercialization to help persuade state officials to spend nearly $100 million since 2007 on the Utah Science Technology and Research Initiative (USTAR).

    The program has helped the two universities build state-of-the-art laboratories, strengthen their tech transfer off ices, and offer hefty startup packages to new faculty members working in a handful of fields. Those areas, including biomedicine, nanotechnology, and energy, were deemed most promising by a USTAR governing board made up of business and education leaders. In return, the universities have promised to generate new patents, licenses, and spinoff companies that would create good jobs and plenty of tax revenue (and potentially revenue for the inventor and the school).

    The link between commercialization and academic quality makes sense, outsiders say. "A good commercialization record is an outcome of having a good university, not the other way around," says economist Jerry Thursby of the Georgia Institute of Technology (Georgia Tech) in Atlanta. It didn't hurt, however, that UU already had a solid record of commercializing research and ranks among the top 20 U.S. institutions in creating startup companies and earning commercialization revenue.

    So far, USTAR seems to be paying off for the two schools. The money has helped them hire about 50 scientists, who in turn have won more than $190 million in government research grants. That's definitely punching above their weight, university officials say: Although USTAR researchers represent just 1% of the total faculty at both schools, their presence has boosted extramural funding at the two schools by 5%. "USTAR was designed to allow us to aggressively recruit very productive scientists, and it is working," says USTAR chief Ted McAleer.


    A new research laboratory at the University of Utah is part of a state-funded effort to attract star scientists.


    UU chemist Shelley Minteer is one of those scientists. "I was intrigued and impressed by how well tech transfer was integrated into the effort—the process is really valued by the university," says Minteer, who was recruited last year from Saint Louis University in Missouri. She has two technologies, including one involved in producing solar power, under review for their commercial potential, and says that tech transfer officials "make it very easy to get help with developing your ideas."

    Overall, USTAR researchers have so far filed about 340 such invention disclosures that have generated more than 200 patents. Those numbers top the performance of the average faculty member, as well as USTAR's own projections.

    Turning USTAR into cash and jobs, however, has proven difficult. The patents have so far produced less licensing revenue than originally forecast, and although the program has spun off nine companies, many are struggling to thrive, McAleer says. However, he cautions that it often takes 7 years for ventures to start to pay off.

    The program has also experienced growing pains. The recession led to a cut in state funding, one of the new state-funded buildings has higher than expected operating costs, and officials are still tinkering with the best way to organize the USTAR teams.

    Still, university officials see many advantages from USTAR. The program has created a buzz in the business community and solidified the standings of both universities in world rankings of science departments. UU, for instance, has jumped 11 slots since 2007, to 82nd in 2012, in a world ranking of research universities developed by China's Shanghai Jiao Tong University.

    State politicians appear happy with the results. The governor has asked for $20 million to keep USTAR rolling in 2013, and $25 million for 2014. University administrators don't know how long that political support will hold up, however, if USTAR fails to generate long-term jobs or licensing revenue.

    Going with the flow

    Although many university and government officials point to USTAR as a promising commercialization model, some question the wisdom of using patenting and licensing metrics to prove its worth. Those statistics, although relatively easy to collect and present, can overshadow an array of factors that are harder to quantify, including other ways that knowledge flows from academia into the private sector. Too often, those pathways are overlooked because public discussion is "skewed by the abundance of data regarding licensing" and other financial metrics, the NRC report concluded.

    In recent years, scholars have identified at least eight major pathways for "knowledge transfer" from universities—of which licensing intellectual property is just one (see graphic). The others include informal contacts between researchers and industry, private consulting contracts between university scientists and firms, and research collaborations that allow students to take jobs in industry and government. The use of a broader array of metrics would bolster the rankings of some universities that are now seen as tech transfer weaklings, researchers argue, especially in Europe, where universities often lag behind comparable U.S. campuses in traditional commercialization measures.

    To capture a more complete picture, many academics and university groups are now trying to devise new metrics. The Association of Public and Land-grant Universities, a collection of 218 U.S. institutions, for example, is in the midst of a multiyear effort to quantify knowledge transfer with such metrics as the number of times local businesses seek advice from a professor or the number of student interns that a company hires.

    Such interactions were very much on the mind of engineer C. Daniel Mote Jr., incoming president of the U.S. National Academy of Engineering, during his 12 years as president of the University of Maryland (UMD), College Park. When he began his tenure, in 1998, he recalls, many universities were ramping up their tech transfer offices, with some making "pretty unrealistic claims about how much money they could make." Mote preferred a knowledge transfer approach that placed less emphasis on the bottom line.

    "I was much more inclined to build relationships [with industry] rather than build revenues," he says. "I wanted to create an entrepreneurial culture with lots of opportunities for interactions between faculty, students, and companies." Students, he adds, "are basically your principal tech transfer asset; they transfer skills and enterprise to the community."

    That philosophy has helped shape an array of institutional arrangements at UMD, including events intended to maximize interactions with potential industry partners. Along with a traditional patenting and licensing operation and "incubators" where entrepreneurial faculty members and students can nurture their startups, there's also a growing undergraduate entrepreneurship program and informal mixers with business leaders and local venture capitalists. The school's Maryland Technology Enterprise Institute (Mtech) also hosts regular entrepreneur hours where anyone can get advice from experts on commercializing their ideas regardless of their relationship to the university.

    Intellectual property.

    Academic discoveries related to biotechnology and new drugs have been the top sources of patents won by U.S. universities in recent years.


    At one gathering last year, for instance, two UMD geneticists wondered if they could sell information about equine DNA to racehorse breeders, while a local businessman described trying to commercialize a patented recipe for converting discarded crab shells into a valuable biochemical. "We're interested in creating connections in the broader community, not just on campus," says Dean Chang, a former computer science entrepreneur who now helps lead UMD's innovation programs. Those connections are in line with the university's mission to help develop the local and national economy, Chang and other college officials say.

    UMD's approach is consistent with research showing that "innovation requires an ecosystem and experience, not just an office," says Lesa Mitchell, a vice president of the Ewing Marion Kauffman Foundation in Kansas City, Missouri, which has funded extensive studies of commercialization. "You want a rich mixing bowl where people are running into each other in all kinds of settings." Large urban campuses with diverse, well-developed economies often have an edge, she adds, because cities can provide a critical mix of skilled talent, influential contacts, and investment capital.

    Many universities are also experimenting with ways to cut the red tape surrounding IP. One approach is to offer potential partners standardized online legal agreements executed with the click of a mouse. Other institutions are going further, allowing professors and students to found startups without a license from the university. Todd Sherer, the president of AUTM and head of the technology transfer office at Emory University in Atlanta, says schools taking that approach are essentially saying: "Don't worry too much about charging for this technology now; we'll get it back in donations later if the company succeeds."

    Economist Marie Thursby of Georgia Tech, who has spent decades studying tech transfer, likes those approaches. "Inventions shouldn't get tied up just so the university can get its cut," she asserts.

    Making an impact

    In Egypt, Ellaithy has tried to draw on such advice as he builds a tech transfer office at his nearly century-old university. Although relatively small, AUC is known as one of the country's best. Roughly one-third of its approximately 5500 undergraduates and 1500 graduate students study science and engineering, and the university recently launched its first doctoral programs, starting with technical fields.

    But research spending is sparse by U.S. and European standards, representing only 5% of the university's $180 million operating budget. And AUC professors often aren't eligible for government funding because of national policies favoring public institutions. "We're used to being creative and fending for ourselves," he says.

    That creativity got a new outlet in 2002 when the Egyptian government rewrote intellectual property laws to make it easier for universities to take ownership of ideas developed by their scholars. In 2009, AUC and three other Egyptian universities won a grant from the European Union to set up academic commercialization offices and hired Ellaithy to lead the effort. He says he spent much of his first year "looking for approaches that might work for us."

    In the end, AUC leaders opted for a version of what some call an "impact first, income later" strategy. They hope tech transfer will become a platform for building relationships with industry that might lead to collaborative research funding, jobs for graduates, and other, more personal forms of transferring technology. In the short run, new companies and licensing revenue would be icing on the cake, Ellaithy says.

    One of Ellaithy's first jobs was to persuade faculty members to reveal their discoveries so his office can vet them for possible IP protection. Faculty members around the world are often reluctant to make such "disclosures," and Ellaithy notes that entrepreneurial academics in Egypt have traditionally felt entitled to own and commercialize their work.

    At AUC, however, he has been pleasantly surprised by the faculty's response. Since the 2.5-person office formally opened in 2010, it has prepared a dozen patent applications and is in the process of standing up its first startup company, which is developing a quick diagnostic tool for hepatitis C invented by AUC chemist Hassan Azzazy. Ellaithy is also drafting new conflict of interest rules in a bid to head off problems. "We're sort of swamped," he admits.

    Despite these early achievements, Ellaithy knows that tech transfer is a marathon—and that success isn't measured solely by monetary gains. "We might shoot ourselves in the foot if we do really well with licensing one year," he says. "People could come to expect that's the way it is always going to be."

  5. Physiology

    Opsins: Not Just for Eyes

    1. Elizabeth Pennisi

    Studies in invertebrates are enriching our sense of how versatile and ancient these light-sensitive proteins are.

    Light sensors.

    Opsin-laden photoreceptor cells (green, red) provide juvenile sea urchins a means to detect light.


    When researchers got their first glimpse of the sea urchin genome in 2006, they were surprised to find genes for opsins, light-sensitive proteins without which vision as we know it today would be impossible. Living in the subtidal zones, sea urchins are not only eyeless, but also headless, and, ostensibly brainless. They seemed to lack the specialized photoreceptor cells that house opsins in the eyes of other animals. "Nobody knew what [the opsins] were for," recalls Maria Ina Arnone, a developmental biologist who has long studied sea urchins at the Stazione Zoologica Anton Dohrn in Naples, Italy, one of the world's oldest marine labs.

    Arnone's preliminary analyses suggested an opsin gene was active at the base of the tube feet, the tiny projections located in and around urchin spines. And in 2011, her group showed that these tube feet were loaded with photoreceptor cells that had been missed because they lack pigment typically associated with opsins.

    That work and other recent studies have driven home the fact that a wide variety of organisms don't need traditional eyes to make use of opsins, and that opsins can likely sense more than light. Last month, at the annual meeting of the Society for Integrative and Comparative Biology (SICB) in San Francisco, Arnone and other researchers revealed the rich history and unexpectedly broad utility of these proteins. In fruit flies, for example, they may be involved in hearing. "Opsins can be expressed in many more tissues than the simple eye," Arnone says.

    Beyond eyes

    Hints that opsins existed outside the eye started dribbling in almost 25 years ago, with suggestions that fish skin and dove brains contained the molecules. Among the first to pin down an extraocular opsin protein were Ignacio Provencio and Mark Rollag at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, and their colleagues. They knew that pigment cells in amphibian skin reacted to light and eventually isolated an opsin in frog skin that they named melanopsin in 1998. Until then, researchers thought there was one kind of opsin in vertebrates, called ciliary opsin, and another, more ancient kind, rhabdomeric opsin, in invertebrates. But though melanopsin was found in a frog, it looked more like the invertebrate opsin.

    Provencio and Rollag also found melanopsin in the frog eye and brain and over the next few years, a flurry of papers teased out which other vertebrates possess the protein and provided clues to melanopsin's function. Researchers have found it in mouse and human neural tissue, for example, and in some animals, it helps establish circadian rhythms (Science, 20 December 2002, p. 2297).

    Melanopsin hinted at an underappreciated complexity of opsins. And a 2003 survey of opsins throughout the animal kingdom by Detlev Arendt from the European Molecular Biology Laboratory in Heidelberg, Germany, drove home that both rhabdomeric and ciliary opsins are ancient and that the invertebrate/vertebrate divide for these types doesn't hold up. But the search for opsins in animals other than vertebrates and insects and in places other than eyes didn't really take off until recent advances in DNA sequencing made it possible to probe the genomes of a wide variety of organisms, such as the sea urchin.

    Arnone has slowly homed in on how opsins help this simple creature use light and "see." These spiny echinoderms tend to avoid direct sunshine. Some will cover themselves with debris; others move under rocks in search of shadow. Researchers have shown some that sea urchins can even distinguish different shaped objects. Last month at the SICB meeting, Arnone proposed that the opsin photoreceptor cells in the sea urchin are positioned at the base of the tube feet such that they lie partially in the shadow of its calcite skeleton, allowing the skeleton to serve the same purpose as pigment in typical eyes—most opsins co-occur with pigment, which shields part of a photoreceptor cell so it can register the direction of incoming light. She has also shown that the photoreceptor cells connect to the five radial nerves in the brainless urchin, which may enable the input from the different photoreceptor cells to be compiled, much like an insect's compound eye does.

    In echinoderms, the opsin story is complex. The opsin at the base of the tube feet is the rhabdomeric type, and Arnone has also found this version in microscopic light-sensitive "eyes" located at the tips of starfish arms. At the meeting, she described a second, ciliary opsin in the tips of urchin tube feet, in urchin skin, and possibly in its muscles. It's also present in their larvae, she said. Arnone is not sure what this ciliary opsin does. But because echinoderms, which include starfish and sea urchins, sit at the base of the deuterostomes, the animal group that includes vertebrates, both types of opsins were likely already present in the earliest deuterostomes. How the different opsins later became specialized for use in vision remains a mystery, she notes.

    Opsins everywhere

    Opsins galore.

    Opsins have been discovered in eyeless chitons, comb jellies and hydra, and in the skin of octopus (clockwise from top).


    After opsins were found in sea urchins, evolutionary biologist Todd Oakley from the University of California (UC), Santa Barbara, wondered where else they might be. He and his colleagues started looking even closer to the base of the animal tree of life for these proteins. In 2007, Oakley recalls, "that led us to Cnidaria," the group of animals, including hydra and jellyfish, characterized by specialized cells that fire venom-equipped barbs that sting prey or deter predators. His group found opsins in cells associated with cnidarian stinging cells, and in the 5 March 2012 issue of BMC Biology they reported that stinging cells were less likely to fire in bright light. "Even though [stinging cells] had been studied for decades, there were very few hints that light was involved in firing," Oakley says. The prevailing wisdom was that chemicals in the water influenced firing. But here was a light-sensing role for opsins that did not involve image generation or true vision.

    His team has now found that opsins have a similar sway over the firing of stinging cells in several distant cnidarian relatives—two anemone species and moon jelly polyps—suggesting that this nonvisual role for opsins is ancient. "It may be that [a] role in vision came later," suggests Craig Montell, a neurobiologist who recently moved to UC Santa Barbara.

    At the San Francisco meeting, David Plachetzki from UC Davis reported that the hydra's opsin-laden cells near the stinging cells also contain taste receptors. That leads Plachetzki to propose that the ancestor to specialized photoreceptor cells was a cell that responded to several types of stimuli.

    Supporting evidence for that scenario comes from other work. Desmond Ramirez in Oakley's lab reported finding opsins in the cilia of octopus skin, which are already known to be sensitive to mechanical stimuli. "So it's potentially another case where there is multimodal sensation," Oakley says. And his postdoc Daniel Speiser found opsins in small sensory tentacles extending from the shell plates of mollusks called chitons. Whether these proteins are involved in mechanosensing or light-sensing is still to be determined.

    Probing even deeper down the animal tree of life, Christine Schnitzler from the National Human Genome Research Institute in Bethesda has found three strange-looking opsin genes in the recently completed genome of the comb jelly Mnemiopsis leidyi. Comb jellies are considered by many to be among the first multicellular animals to arise. Two comb jelly opsins loosely resemble the rhabdomeric and ciliary opsins, while a third looks like neither, Schnitzler reported at SICB. The proteins show up in two parts of the animal's gelatinous body—in a sensory organ opposite the comb jelly's mouth that helps the creature stay oriented in the water and in the cells that generate bioluminescence. Because the opsins in those cells are sensitive to the same wavelength as the light given off, they may be used by the animal to sense and control how much it's glowing, Schnitzler proposed at the meeting.

    Other roles

    Even in animals with eyes, researchers are finding they have more to learn about opsins. These proteins have been long studied in eyes of the fruit fly Drosophila melanogaster, but Martin Göpfert from the University of Göttingen in Germany has now come across them in the insect's antennal ear. His team had been screening for insect ear genes to try to find genes that might be involved in human hearing loss. They looked for genes that were more active in normal fruit flies than in mutant fruit flies lacking the antennal ear. Among the 275 upregulated genes identified were four genes for opsins previously found expressed only in the fly's eyes.

    These four genes are also expressed in the mechanosensory cells of the ear and are required for hearing, the Göpfert team reported in the 31 August 2012 issue of Cell. "Finding that these cells use opsins for mechanosensation suggests that these proteins may have already served sensory roles before photoreceptors have evolved," Göpfert says. "In the ear, opsin function seems light-independent."

    Montell's group has identified what may be another nonvisual role for opsins: temperature sensation. Drosophila larvae prefer 18°C, seeking it out over subtly different temperatures, such as 19° to 24°C. In trying to find the temperature sensor, "we weren't expecting opsin to be important," Montell recalls. But in 2011, Montell and his colleagues discovered that mutant flies lacking the visual opsin ninaE no longer showed this preference. When the researchers put a mouse melanopsin gene into the mutant fruit flies, the larvae oriented to 18°C (Science, 11 March 2011, p. 1333). Fruit flies have seven opsins, and Montell says that still unpublished work from his lab establishes nonlight-sensing roles for five of them.

    Montell predicts that researchers are just beginning to appreciate all that opsins can do. Arnone agrees. When she first looked at opsins 6 years ago, the project was very much a sideline effort. But, aided by a new grant to study the proteins, she expects that opsin research will grow to take up half her lab. In the next year, Montell says, "there will be a lot more to talk about."

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