News this Week

Science  10 Feb 2012:
Vol. 335, Issue 6069, pp. 640
  1. Around the World

    1 - Washington, D.C.
    Whistleblowers' Lawsuit Puts Focus on FDA
    2 - Indianapolis
    Creationism School Bill Unlikely to Advance
    3 - Moscow
    New Fobos-Grunt Mars Mission?
    4 - Leipzig, Germany
    Extinct Human Genome Goes Online
    5 - Tokyo
    Kavli's First Endowment in Japan, For Physics of the Universe
    6 - St. Paul, Minnesota
    Minnesota Discards Newborn Blood Records
    7 - Amsterdam, the Netherlands
    Scientists Boycott Elsevier to Protest Pricing
    8 - Washington, D.C.
    Report Outlines Steps to More U.S. Science Degrees

    Washington, D.C.

    Whistleblowers' Lawsuit Puts Focus on FDA

    A senior U.S. Senator wants to know why officials at the U.S. Food and Drug Administration (FDA) monitored the personal e-mail of six technical staffers who complained to the White House, Congress, and the press about the agency's approval process for cancer-screening devices. The 31 January letter to FDA from Senator Charles Grassley (R-IA), the top Republican on the Senate Committee on the Judiciary, came shortly after the six whistleblowers filed a lawsuit against FDA, alleging officials improperly monitored their computers and retaliated against them for publicizing their complaints.

    Grassley

    CREDIT: U.S. SENATE

    The lawsuit was filed by two doctors, one M.D./Ph.D., a scientist, an engineer, and a statistician. All served on scientific review committees for FDA's Center for Devices and Radiological Health. In 2008, they were among nine FDA reviewers who told Congress that agency officials had approved devices despite negative reviews. Freedom of Information Act requests revealed that FDA began monitoring government computers used by the “FDA nine,” even capturing personal photos. Some of the staffers have since left FDA or been fired. Among other things, Grassley wants to know if FDA is still monitoring those who remain.

    Indianapolis

    Creationism School Bill Unlikely to Advance

    The Indiana state Senate last week approved a bill specifying that any classroom discussion of creationist views must include origin-of-life stories from “multiple religions.” But the Indiana House of Representatives seems unlikely to go along after the House speaker described the legislation as “someplace where we don't need to go.”

    The original bill cited creation science as a topic that teachers could include in any discussion of “various theories on the origins of life.” An amendment broadened the bill's scope to include “Christianity, Judaism, Islam, Hinduism, Buddhism, and Scientology.” Opponents said the legislation, if enacted, would violate a 1987 Supreme Court ruling against the teaching of religion in public schools.

    One veteran Indiana science teacher says the controversy is a reminder that some students might regard any lesson on evolution as a threat to their beliefs and that educators should be prepared to handle any questions in a sensitive manner. Says Bruce Kendall of Mt. Vernon High School in Fortville, Indiana, “I tell my teachers, ‘Please don't kill God just to make your point.’”

    http://scim.ag/Indiana_bill

    Moscow

    New Fobos-Grunt Mars Mission?

    Russian space scientists this week floated the idea of building a new version of the Fobos-Grunt sample return spacecraft after the first model failed to escape Earth orbit and crashed in the Pacific on 15 January. Fobos-Grunt was launched on 9 November with the aim of bringing back samples from Mars's moon Phobos. But once in orbit it failed to respond to commands from the ground and did not ignite rockets which would set it on course for Phobos. Its orbit eventually degraded.

    Phobos

    CREDIT: NASA/JPL-CALTECH/UNIVERSITY OF ARIZONA

    Lev Zelenyi, director of Moscow's Space Research Institute, said at a 1 February press conference that the team behind the mission wanted to try again. Fobos-Grunt-2 would be “improved and simplified,” he says, and would save money by using much of the original craft's infrastructure. But Russian Space Agency chief Vladimir Popovkin told the press that this all depends on ExoMars. This ESA/NASA project will send an orbiter to Mars in 2016 followed by a large lander in 2018. Last year the agencies asked Russia to join too and discussions are expected to be concluded this month.

    Leipzig, Germany

    Extinct Human Genome Goes Online

    Nice view.

    Denisova Cave attracted three kinds of humans.

    CREDIT: ANN GIBBONS

    Researchers in Germany posted the first high-resolution version of an extinct human's genome this week on the Web site for the Max Planck Institute for Evolutionary Anthropology (www.eva.mpg.de/denisova/). A year after extracting ancient DNA from the finger of a girl who lived in Denisova Cave, Siberia, at least 30,000 years ago, paleogeneticist Svante Pääbo's team has now sequenced every position in her genome at least 30 times. They can compare even small differences in copies of genes that this ancient girl inherited from her mother and father—and differences in her DNA and that of living humans and Neandertals.

    Tokyo

    Kavli's First Endowment in Japan, For Physics of the Universe

    The Kavli Foundation, known for supporting basic research in targeted fields, is endowing its first institute in Japan, giving $7.5 million to University of Tokyo's Institute for the Physics and Mathematics of the Universe (IPMU). “They are doing excellent science” in theoretical physics, astrophysics, and cosmology, says Kavli Foundation President Robert Conn. In addition, the foundation wants to support the institute's example of “a new way for science to be done in Japan,” he says. IPMU is among the most international of Japan's research institutes. English is the official language, and more than half of its 200 researchers are non-Japanese.

    This is also the first time a Japanese research institution's endowment has received such a large international contribution, says IPMU Director Hitoshi Murayama. “It's a new model of support for science in Japan,” he says. IPMU was established in 2007 as one of Japan's World Premier International Research Center Initiatives, which are receiving about $17 million per year for 10 years (Science, 14 September 2007, p. 1493). The Kavli grant will ensure permanent funding and hopefully lead to more contributions, says Murayama.

    St. Paul, Minnesota

    Minnesota Discards Newborn Blood Records

    Minnesota bowed to the state's supreme court ruling last week and began destroying blood samples collected in its newborn-screening program. Minnesota and Texas are among the latest states to yield to families who sued, arguing that retaining and studying such samples—even anonymously—is a violation of privacy if consent isn't obtained first (Science, 10 April 2009, p. 166). Minnesota Health Commissioner Edward Ehlinger issued a statement saying, “We're going to begin destroying a valuable public health resource, the residual blood spots from about 200 babies born in Minnesota each day.”

    Screened.

    A newborn is tested for phenylketonuria.

    CREDIT: ERIC T. SHELER/WIKIPEDIA

    For nearly 2 decades, the state health department has taken a few drops of blood from every newborn to check for rare congenital and heritable disorders that can be treated, such as phenylketonuria. The state lab also retained samples for test validation and disease research. But last week Minnesota put into effect its new policy of holding samples only 71 days for screening, then destroying them. Some positive test results may be retained for medical use, and some older records are being held until the court says what should be done with them.

    Amsterdam, the Netherlands

    Scientists Boycott Elsevier to Protest Pricing

    More than 4000 researchers and students have signed an internet petition pledging to boycott scientific publishing giant Elsevier because of its journal pricing. At thecostofknowledge.com, the signers vow not to publish papers in Elsevier's journals, referee other researchers' studies, or do other types of editorial work for the company.

    The petition was initiated on 23 January by Fields medalist and blogger Timothy Gowers, a mathematician at the University of Cambridge in the United Kingdom. It highlights a number of gripes including the “exorbitantly high prices” of Elsevier's journals and the publisher's support of legislative proposals in the U.S. Congress that would roll back “open access” policies at the U.S. National Institutes of Health.

    Elsevier, however, said in a written statement that its prices “have been among the industry's lowest for the past ten years,” and that it has taken steps to make more of its material freely available. “We respect the freedom of authors to make their own decisions,” the publisher wrote. “We hope the ones who sign the boycott reconsider their position, however, and we are keen to engage to discuss their concerns.” http://scim.ag/_Elsevier

    Washington, D.C.

    Report Outlines Steps to More U.S. Science Degrees

    Making sure that college students interested in earning science and engineering degrees don't switch fields or drop out is the fastest and least expensive way to meet the future needs of the U.S. workforce, says a new report from the President's Council of Advisors on Science and Technology (PCAST).

    To retain them, the PCAST report says that faculty in STEM (science, technology, engineering, and mathematics) fields need to be trained to become better teachers. The report calls for a national program to improve the math skills of all entering students, noting that inadequate preparation in math is preventing many of them from pursuing STEM degrees. It also suggests that students be given more ways to earn a STEM degree than the traditional route of attending one school full time for 4 or 5 years.

    The report got a shout-out this week at a White House science fair, the second event President Obama has hosted to demonstrate the administration's commitment to STEM education. The PCAST report follows a 2010 study on how to improve precollege instruction. http://scim.ag/sci-degree

  2. Random Sample

    Microscopy on Broadway

    CREDIT: © 2012 GENERAL ELECTRIC COMPANY

    Geoffrey V. Grandjean's elegant, colorful image of human ovarian cancer cells could become a tourist attraction this spring: From 20 to 22 April, Grandjean's image, along with two other regional winners of GE's 2011 IN Cell Analyzer Image Competition, will appear on NBC Universal's high-definition screen at Times Square in New York City.

    The company announced its three regional winners 2 February. Grandjean, a research assistant at MD Anderson Cancer Center at the University of Texas, Houston, won the regional prize for the Americas for his image of cancer cells stained to show DNA (in red) and microtubules (in green). Marie Neguembor from the San Raffaele Scientific Institute in Italy took the European prize for her image of a myoblast, a precursor to a muscle cell. And research scientist Leslie Caron at Genea in Australia won for the Asia/Pacific region, for her image of vascular smooth muscle cells derived from human embryonic stem cells.

    Giant Eye on the Sky

    CREDIT: ESO/F. KAMPHUES

    On 2 February, scientists at the European Southern Observatory's Paranal Observatory in Chile for the first time successfully linked together all four telescopes of the observatory's Very Large Telescope (VLT) array. In a technique called interferometry, light beams collected by each telescope are routed through tunnels and combined in a central laboratory. Researchers at Paranal tried such a linkup in March 2011 but failed. Together, the telescopes of the VLT array form the largest ground-based optical telescope in the world, with a diameter of 130 meters and high spatial resolution high enough to see details up to 25 times finer than the individual telescopes can.

    They Said It

    “Contrary to circulating online reports, Komen has not ‘defunded’ any grantee based on human embryonic stem cell research conducted at their institution.”

    —A statement from Susan G. Komen for the Cure, a charity embroiled in a firestorm over abortion politics last week. Komen's cancer research grants total about $300 million, but it has never specifically funded work on human embryonic stem cells.

    By the Numbers

    $294,000 — Amount per year that a new cystic fibrosis drug approved by the U.S. Food and Drug Administration will cost (see p. 645).

    $32.26 million — Amount raised by a disco dance party on 4 February for pediatric cancer research at Texas Children's Cancer and Hematology Centers.

    Pluto's Second Shot At Post Office Fame

    CREDIT: © DAN DURDA

    Will Pluto rise again? Yes, if Alan Stern and Dan Durda get their way. Stern, the principal investigator of NASA's New Horizons mission to the dwarf planet, and Durda, an astronomer and space artist, have posted a petition on the website change.org urging the U.S. Postal Service (USPS) to issue an official stamp in 2015 honoring the mission's arrival at Pluto.

    It's been a long time coming. In the 1990s, when USPS issued a series of stamps commemorating the first missions to visit the planets in the solar system, “Poor old Pluto didn't have anything,” Durda says. All Pluto got was a sad little stamp featuring a nondescript white ball floating in darkness above the slogan, “Not yet explored.”

    Now, with New Horizons (which launched in 2006) on its way, Stern and Durda, both of the Southwest Research Institute's Department of Space Studies in Boulder, Colorado, want Pluto to get another taste of postal glory.

    In designing a stamp for the petition (pictured), Durda says, he steered clear of a standard “looking back toward the sun” shot. “I said, nope, not this time. It's not just some boring iceball; we know it has an atmosphere, a lot of potential for interesting atmospheric phenomena, a lot of albedo contrast. So let's try to indicate that it's going to be an interesting world.”

    The petition went online 1 February and closes 15 March. Success won't guarantee that Durda's design makes the final post office cut, but he says “it would be a great honor to have the artwork.”

    Meanwhile, the original 1991 stamp is on its way to Pluto itself, one of nine mementos in New Horizons's payload. So “not yet explored” will fly past Pluto, even as the message becomes obsolete.

  3. Indoor Ecosystems

    1. Courtney Humphries*

    The microbial ecology of buildings gets a boost from a foundation and researchers trying to better understand the invisible communities in our homes, hospitals, and workspaces.

    What's inside?

    Buildings are ecosystems in their own right and are now being studied as such.

    CREDIT: JESSICA GREEN

    Until 3 years ago, Noah Fierer was your typical microbial ecologist. At the University of Colorado, Boulder, he focused on the outdoors, studying the microbes inhabiting soils and leaf litter. Then he tackled ecological questions closer to home—first in the microbes living in humans and next in mundane places like computer keyboards. After realizing how much time he spends indoors, he began thinking bigger. While many scientists have counted the germs on indoor surfaces, few had systematically tried to assess the biodiversity of interior spaces. He and Rob Dunn, an ecologist at North Carolina State University in Raleigh, have just mounted a large citizen-science survey to do just that.

    Volunteering to be its first participant, I rubbed 10 cotton-tipped swabs along surfaces of my apartment—including my door sills, toilet, pillowcase, and counters—and sent them back to Fierer for DNA sequencing. His analysis showed that my home hosts a wide variety of microbes.

    Hardy Acinetobacter are burrowed into the crevices of my cutting boards. Counter-tops are biodiversity hot spots of bacteria and fungi, including sphingomonads that may have settled out of the tap water used to wipe the counter. The toilet seat is coated with bacteria associated with human skin, and doorsills are crawling with fungi and grass pollen. The front doorknob and TV screen harbor unusual bacteria not typically found in water, soil, or the human body—perhaps representing entirely new communities unique to those surfaces.

    Fierer and Dunn plan to compile similar microbial survey data from the homes of thousands of volunteers like myself from different parts of the world. The pair wants to explore whether the microbial makeup of homes differs depending on location, the density of the surrounding population, or whether a home is freestanding or an apartment. It will be the first comparison of houses from a wide geographic range.

    This “basic Lewis and Clark exploration” will offer new information. But the real goal, Dunn says, “is to understand not just what is there but why, and to see the extent to which these species are associated with our lifestyles, geography, and climate.”

    While some scientists worry that such efforts may simply lead to meaningless lists of microbes, new information is pouring in about the microbial denizens of other kinds of buildings as well. In work that blends microbial ecology, indoor air science, and building engineering, researchers have begun scouring classrooms, offices, and hospitals for microbial life and analyzing the factors that affect human exposure to it.

    So far, most of this work on indoor microbial ecology has been funded by the Alfred P. Sloan Foundation, not by the U.S. or other governments. Since 2004, the foundation has spent more than $23 million on dozens of such research projects. While novel molecular techniques have made it possible to study microbes in many environments, the interiors of buildings rarely drew the attention of microbial ecologists, says Sloan Program Director Paula Olsiewski. At the same time, building scientists were assessing chemicals and particles in indoor air but ignoring its biology. “We thought it was important to study where people live,” Olsiewski says.

    A needed field

    The 2001 National Human Activity Pattern Survey estimated that people in the developed world spend nearly 90% of their time indoors; yet “so much funding and effort goes into thinking about ecosystems in which we spend 10% of our time,” complains Jessica Green, a microbiologist at the University of Oregon, Eugene. She heads the Biology and the Built Environment (BioBE) Center, which was created in 2010 with a $1.8 million grant from the Sloan Foundation.

    There are certainly health reasons to pay more attention to the microbes inside our buildings. The air circulated by heaters and air conditioners can spread infectious diseases, for example, and some cases of so-called sick building syndrome can stem from unchecked mold. Fungi in buildings are also associated with allergies, asthma, and other pulmonary conditions.

    And then there's the impact on the edifices themselves. Microbes contribute to the deterioration of buildings by breaking down wood, stone, concrete, and other materials.

    Yet little is known about what microbes live in buildings and why they reside in certain places but not others. As a result, homeowners and building managers who invest time, money, and energy cleaning surfaces and filtering air do not really know the effects of these activities. Choices in construction materials, ventilation systems, building design, and maintenance also influence an interior's microbial complement, but how? “In order to understand what shapes the diversity and function of microbes indoors, you must understand the indoor environment from an abiotic context—its chemistry, structure, and dynamics,” Green says.

    Green's background provides her with a strong appreciation of the need to blend abiotic and biotic factors. She began her studies in civil engineering and earned a Ph.D. in nuclear engineering, but eventually switched to microbial ecology because of a passion for biodiversity. Before coming to Oregon, she had focused on microbial diversity in soils and oceans. But attracted to the university's program in sustainable building design and inspired by the potential of Sloan support, she joined forces with two university colleagues, microbiologist Brendan Bohannan and architect G. Z. “Charlie” Brown, to launch BioBE.

    Systematic study.

    Researchers collected microbes from air (left, middle) and surfaces (right) in a campus building to understand its microbial ecology.

    CREDIT: ANGIE PONSO; JESSICA GREEN (2)

    Because indoor ecology is an emerging field, Green and other researchers must struggle with developing effective protocols for assessing these ecosystems and finding practical applications for their insights. For example, Fierer and Dunn are taking steps to standardize their citizen-science microbial survey; they'll place extra weight on samples from a core set of participants—including other scientists—who will provide more indepth data by sampling the same spots several times. Fierer and Dunn hope to identify reproducible patterns in their results that will yield real insights into what factors determine the microbial residents, rather than just a census.

    “That's my criticism of the field, that you're just getting a list,” says Jordan Peccia, an environmental engineer at Yale University who studies how moving air affects microbes in buildings. But, Fierer counters, “without that basic knowledge, it's hard to take the next step.”

    Anybody home?

    To help them take that next step, Fierer and others in the field turn to software programs that help match the microbial DNA sequences from their surveys with known bacteria and the other environments in which those microbes have been found. As genome sequencing costs have come down, the databases of microbial DNA have exploded. These resources help researchers track whether microbes that live indoors come from soil, outside air, humans, other animal occupants, or some other source.

    Using these databases, Fierer's group recently identified the probable sources of microbes from several surfaces in 12 public bathrooms. The results, published on 23 November 2011 in PLoS ONE, were not surprising: Bacteria associated with human skin abound on surfaces people touch; bacteria from the gut occupy toilet seats; and a higher level of vaginal microbes was found in women's bathrooms than men's. But Fierer says the study shows it's possible to see spatial patterns in the origins of microbes, and his team is now working on a project to create a detailed atlas of the typical spatial patterns of microbes found in kitchens.

    For Green's latest project, she and her colleagues conducted a classical ecological study on the microbial diversity in one University of Oregon building. Similar to how Green and others have examined microbes in natural environments, the researchers repeatedly took samples from the building, hoping to provide enough data to make inferences about the causes and consequences of microbial diversity indoors. For example, they collected air from six rooms at different times of the day to understand the dynamics of microbes over time and their response to human presence. They also gathered dust from each of the building's more than 300 rooms to understand how microbial populations vary across an entire building. To study the microbial variability within individual rooms, Green's team chose different “habitats”—floors, walls, desktops, and seats—and used square sample plots set up the same way as those historically used to study plant biodiversity.

    Microbe collector.

    Jessica Green is applying ecological methods and theory to indoor spaces.

    CREDIT: ANGIE PONSO

    The analysis by the Oregon group is ongoing, but part of the goal is to model relationships between building use and design and microbial diversity. The team is also trying to discover whether ecological theories developed from studying plant and animal diversity on islands, a well-researched topic, can help them make sense of the ecology of microbes indoors.

    “You can think of a building as a collection of islands,” Bohannan says. Although individual rooms are somewhat self-contained environments, like islands are, they are linked through ventilation and the movement of occupants. If this island model turns out to be true, Bohannan says, it would mean that the movement of microbes between rooms affects their ecology as much as the conditions of the room, and building design and management could be manipulated to control this dispersal.

    Moving air moves microbes

    Green and Bohannan have already begun to look at how ventilation affects indoor microbes. Over the past few decades, the push to reduce energy use has created buildings that are highly sealed to outside air, and the Oregon researchers are trying to understand the consequences of this reduced air exchange. To do that, Green's team recently turned to an Oregon hospital, because hospitals typically have ventilation that is tightly controlled. They initially surveyed the microorganisms in mechanically ventilated rooms with windows closed and repeated the census after opening the rooms' windows for 2 hours. In just that short time, the microbes had begun to take on a “signature” of outside air (more types from plants and soil), and 2 hours after the windows were shut again, the proportion of microbes from the human body increased back to previous levels.

    Bathroom biogeography.

    By swabbing different surfaces in public restrooms, researchers determined that microbes vary in where they come from depending on the surface (chart).

    CREDIT: (PHOTO) COURTESY GILBERTO FLORES; (CHART) G. E. FLORES ET AL., PLOS ONE 6, 11 (2011)

    The study, which appeared online 26 January in The ISME Journal, found that mechanically ventilated rooms had lower microbial diversity than ones with open windows. The availability of fresh air translated into lower proportions of microbes associated with the human body, and consequently, fewer potential pathogens. Although this result suggests that having natural airflow may be healthier, Green says answering that question requires clinical data; she's hoping to convince a hospital to participate in a study to see if the incidence of hospital-acquired infections is associated with a room's microbial community.

    For his part, Peccia, who is also a Sloan grantee, is merging microbiology and the physics of aerosols to look more closely at how the movement of air affects microbes. Peccia says his group is building on work by air-quality engineers and scientists, but “we want to add biology to the equation.”

    Outside influence.

    Students prepare to sample air outside a classroom in China as part of an indoor ecology study.

    CREDIT: PHOTO BY SISIRA GORTHALA

    Bacteria in air behave like other particles; their size dictates how they disperse or settle. Humans in a room not only shed microbes from their skin and mouths, but they also drum up microbial material from the floor as they move around. But to quantify those contributions, Peccia's team has had to develop new methods to collect airborne bacteria and extract their DNA, as the microbes are much less abundant in air than on surfaces.

    In one recent study, they used air filters to sample airborne particles and microbes in a classroom during 4 days during which students were present and 4 days during which the room was vacant. They measured the abundance and type of fungal and bacterial genomes present and estimated the microbes' concentrations in the entire room. By accounting for bacteria entering and leaving the room through ventilation, they calculated that people shed or resuspended about 35 million bacterial cells per person per hour. That number is much higher than the several-hundred-thousand maximum previously estimated to be present in indoor air, Peccia reported last fall at the American Association for Aerosol Research Conference in Orlando, Florida.

    His group's data also suggest that rooms have “memories” of past human inhabitants. By kicking into the air settled microbes from the floor, occupants expose themselves not just to the microbes of a person coughing next to them, but also possibly to those from a person who coughed in the room a few hours or even days ago.

    Peccia hopes to come up with ways to describe the distribution of bacteria indoors that can be used in conjunction with existing knowledge about particulate matter and chemicals in designing healthier buildings. “My hope is that we can bring this enough to the forefront that people who do aerosol science will find it as important to know biology as to know physics and chemistry,” he says.

    Still, even though he's a willing participant in indoor microbial ecology research, Peccia thinks that the field has yet to gel. And the Sloan Foundation's Olsiewski shares some of his concern. “Everybody's generating vast amounts of data,” she says, but looking across data sets can be difficult because groups choose different analytical tools. With Sloan support, though, a data archive and integrated analytical tools are in the works.

    To foster collaborations between microbiologists, architects, and building scientists, the foundation also sponsored a symposium on the microbiome of the built environment at the 2011 Indoor Air conference in Austin, Texas, and launched a Web site, MicroBE.net, that's a clearinghouse of information on the field. Although Olsiewski won't say how long the foundation will fund its indoor microbial ecology program, she says Sloan is committed to supporting all of the current projects for the next few years. The program's ultimate goal, she says, is to create a new field of scientific inquiry that eventually will be funded by traditional government funding agencies focused on basic biology and environmental policy.

    Matthew Kane, a microbial ecologist and program director at the U.S. National Science Foundation (NSF), says that although there was interest in these questions prior to the Sloan program, the Sloan Foundation has taken a directed approach to funding the research, and “I have no doubt that their investment is going to reap great returns.” So far, though, NSF has funded only one study on indoor microbes: a study of Pseudomonas bacteria in human households.

    As studies like Green's building ecology analysis progress, they should shed light on how indoor environments differ from those traditionally studied by microbial ecologists. “It's important to have a quantitative understanding of how building design impacts microbial communities indoors, and how these communities impact human health,” Green says. But it remains to be seen whether we'll someday design and maintain our buildings with microbes in mind.

    • * Courtney Humphries is a freelance writer in Boston and author of Superdove.

  4. Profile : Stephen Friend

    The Visionary

    1. Jocelyn Kaiser

    Seeking to spur drug development, Stephen Friend has launched a daring series of initiatives to make biomedical research more open and effective.

    CREDIT: JOHN LOK

    It's late afternoon and everyone's heading home after an open-access conference in suburban Maryland where Stephen Friend has just delivered yet another of his signature stump speeches. In the past 10 days, his dizzying schedule included stops in Norway, New York City, Boston, and the nearby National Institutes of Health (NIH) in Bethesda, Maryland. But he's more than willing to hop on his soapbox again when a reporter asks. Most biomedical researchers are hunter-gatherers, holding their data close until they've published their findings, Friend says. But that won't lead to the development of new drugs or therapies, he insists: Untangling the biology of diseases such as cancer and diabetes requires finding patterns in enormous amounts of data, such as the torrent of information now pouring out of big genomics projects. Identifying the needles in such haystacks—culprit proteins or genes causing disease—demands a new kind of science. “The scale of and scope of the problem will need to be solved by sharing the data and networking.”

    Friend should know something about what's needed for biomedical science: He's treated children with cancer, helped discover a new class of cancer genes while an academic at Harvard University, and co-founded a biotech company that Merck bought for more than $600 million and, as part of the deal, hired him to head its cancer research. Now he's trying to do nothing less than change the competitive culture of science.

    Three years ago, frustrated by the constraints of working in a big company, Friend negotiated a friendly separation from Merck and co-launched a nonprofit called Sage Bionetworks, based at the Fred Hutchinson Cancer Research Center in Seattle, Washington. Among its goals, Sage wants to persuade drug companies, academics, clinicians, and patients to share genomic and other biomedical information freely in a huge database. Other researchers would download and work on it together, mapping out the intracellular pathways that contribute to human diseases and building computational models of those conditions that would be better than the animal models now used in preclinical drug development. In short, Friend wants to bring to biomedical science the same open-source ethos embraced by the computer programmers who wrote the Linux operating system and by the people who contribute information to Wikipedia.

    “What I realized was that drug discovery would continue to be consistently hampered by the lack of good models of disease. And to build those models was going to take massive amounts of data being shared over many iterations, over decades,” says Friend, 58, who enlivens his usual semicasual attire—sport coat, button-down shirt, no tie—with green metal-rimmed glasses.

    Friend isn't the only researcher who wants colleagues to take a more open approach to biomedical problems, but he is one of the most driven and persuasive. Thanks to his legendary persistence, dozens of big names in biomedical research have signed on to various Sage projects. “He's able to galvanize people to do things,” says cancer biologist Robert Weinberg of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, who once trained Friend and has followed his career. In his new position, Friend has also forged ties beyond the scientific community: He works with open-access activists on data-sharing rules, gets free cloud-computing space from Amazon, and collaborates with major patient advocacy groups.

    Even some of the scientists who have signed on, however, are skeptical. Several point out that systems biology, the disease-modeling approach that Sage promotes, is still a young and evolving field. Others are confused by Sage itself, which Friend admits is “big, ill-defined,” and has yet to hit a home run that might clarify its purpose.

    But many believe Friend is on to something—or at least trust his track record enough to give him the benefit of the doubt. “He's an incredible innovator. He's always at the forefront of new things,” says William Chin, executive dean for research at Harvard Medical School in Boston and a former senior vice president at Eli Lilly. Friend is a “machine on ideas,” adds Eric Schadt, a longtime scientific collaborator. “Stephen has a very idealistic vision of how we as scientists in the bioarena should be working together and why that hasn't happened.”

    A change in philosophy

    Friend didn't expect to become a scientist; he majored in philosophy in college, veered toward medical ethics, and wound up in medical school and graduate school as part of an M.D.-Ph.D. program. As a pediatric oncologist, Friend was moved by the patients he saw, including a boy and his father who had both lost an eye to a rare inherited cancer called retinoblastoma. Frustrated by how little was known about the disease, he accepted a postdoc position in Weinberg's lab with the goal of finding the gene behind retinoblastoma.

    One small problem: “He had no idea how to do it,” Weinberg says—Friend's doctorate was in biophysics. “I taught him, basically,” says René Bernards of the Netherlands Cancer Institute, a fellow postdoc in the Weinberg lab. Yet within 2 years, Friend was first author of a Nature paper on the cloning of RB1, the first tumor suppressor gene—a major milestone in cancer research.

    At the time, Bernards was struck by Friend's sense of direction. “He said he would divide his life into three parts: basic science, drug development, and art collecting,” Bernards recalls. “I thought he was bullshitting.” (Friend now collects art and creates it himself, working on a new project each year with artists in the Seattle area.)

    After starting his own lab at the Harvard-affiliated Massachusetts General Hospital, Friend later moved to Seattle to work with geneticist Leland Hartwell of the Hutchinson Center, who later shared the Nobel Prize for work on the cell cycle. They eventually teamed up with University of Washington, Seattle, immunologist Leroy Hood, one of the early pioneers of systems biology, to make inexpensive gene expression arrays—chiplike devices that were becoming increasingly popular for measuring gene activity—and look for differences in gene expression in healthy and diseased tissue. That led the three to found the biotech company Rosetta Inpharmatics and, in collaboration with Bernards, to develop the first commercial gene expression test, MammaPrint, which was approved by U.S. regulators in 2007 for predicting whether breast cancer will recur.

    In 1999, Friend hired Schadt, a young, maverick mathematician, to expand Rosetta's bioinformatics efforts. Schadt worked on combining DNA mutation data with gene expression levels in particular tissues from healthy animals or people and those with a disease. Massive computations using a supercomputer revealed networks of genetic interactions that pointed to genes that play a key role in the disease. These could then become potential targets for drugs or indicate which patients would not benefit from a treatment. In an influential 2005 Nature Genetics paper, for example, the Schadt team used their approach to find a network of genes active in obese mice.

    Hoping to use Rosetta's gene expression analysis for drug development, Merck bought the company in 2001 for $620 million, netting Friend over $10 million. The company also made Friend its director of oncology drug development. The network analysis yielded a string of papers in top journals and new drug candidates for diseases such as diabetes and heart disease.

    Friend and Schadt saw the next step as taking their network analyses from animals—the source of much of their data—into humans. But because people are much more genetically diverse than strains of mice, and diseases such as depression come in many subtypes, Friend realized they would need a wide variety of data from tens or hundreds of thousands of patients to reach the needed statistical strength for human studies. “It became apparent that you would need these megascale analyses,” he says. So Friend began several Merck collaborations with academic cancer centers to build massive databases, eventually to be open to all, that could be used to identify which subsets of cancer patients might benefit from a treatment.

    Friend says he and Schadt realized, however, that “no one company” could do what was needed. So 3 years ago, when Merck decided to close down much of Rosetta as part of a companywide downsizing, Friend, according to Hartwell, now at Arizona State University in Tempe, “talked Merck into letting him” take Rosetta's bioinformatics division and an estimated $150 million in computers, software, data, and intellectual property and create Sage Bionetworks.

    An uncommon approach

    Sage, which has grown from 15 to 35 staff members and has a modest $5 million budget, has some characteristics of a conventional nonprofit research organization. Its team of computational biologists have NIH and foundation funding and collaborate with academics and companies on network modeling studies. Schadt, now at Pacific Biosciences in Menlo Park, California, and Mount Sinai Medical Center in New York City, is one such partner. And Sage has inked a deal with Pfizer to use its modeling approach to develop cancer drugs.

    But Sage is also part think tank, one with a grand vision of creating what Friend calls a “commons” where researchers come together to share and analyze vast amounts of biomedical data. At Sage's invitation-only annual meetings, participants refine their ideas for breaking down cultural barriers. For example, Sage and outside experts are working on data-sharing rules that Friend calls “a set of principles about what is good behavior, what is bad behavior.”

    Indeed, those who collaborate with Sage, including companies, agree to share data and models online within a year of the end of a project. The mandatory policy is reminiscent of the so-called Bermuda rules developed to compel DNA sequencing centers to release their data within a reasonable period, says Robert Cook-Deegan of the Duke Institute for Genome Sciences & Policy in Durham, North Carolina, who collaborates with Sage. “I think the way they're doing it is really smart.”

    As scaffolding for the commons, Sage is building an online repository for data sets. It differs from existing databases such as NIH's GenBank because the data sets are more extensively curated, Friend says, and the repository will also host the software underlying their computer models of diseases. That is important and “much more complicated than genomic data,” says David Haussler of the University of California (UC), Santa Cruz, who led the way in developing tools for sharing human genome data. “I applaud Sage for taking on this task.”

    But building the repository has gone slowly. When Sage staffers set out to gather 100 or so data sets that they had their eye on, such as gene expression and proteomics data from cancer patients, more than half were not available or were missing key underlying data such as annotations describing how and when clinical measurements were collected. Often the consent forms signed by patients did not allow even data stripped of personal identifiers to be shared publicly. “I've been disappointed in how difficult sharing data is,” says Sage staffer Lara Mangravite. Sage is now working on a tiered access system to its gathered data sets that would comply with privacy rules.

    Muscular model.

    Sage wants to spur modeling of cell networks, such as this one showing how in muscle cells, circadian clock genes modulate expression of other genes, such as those involved in the cell cycle and extracellular matrix (red indicates genes with increased activity, green decreased).

    CREDIT: JONATHAN DERRY/SAGE BIONETWORKS

    Data-sharing frustrations have driven another project that Sage supports: an online consent form that allows people to control which scientific studies use their genomic and health data. “It's a shift from giving data to institutions where they really can't share it to shifting control to the patient,” Friend says.

    The project's leader is Sage board member John Wilbanks, formerly with Creative Commons, the nonprofit group that works to eliminate copyright issues and other factors limiting the exchange of information. Friend is convinced that only “patient-oriented, citizen-oriented projects” will generate enough data to build disease models complete enough to help suggest or test treatments. Volunteers are now testing a draft version of the form, and several patient groups will begin using it this spring.

    Sage is also experimenting with a version of “networked” science. Friend recruited five research teams to work together on “superhard problems” in aging, cancer, and diabetes, such as finding genes driving the Warburg effect, a metabolic process used by tumor cells. “It was a pilot to see whether science got done faster and whether people felt as though their ideas were benefiting by sharing them or whether they felt robbed,” Friend says. After more than a year of work, the so-called Federation has submitted two papers to journals—one, for example, found patterns in methyl groups attached to DNA that correlate with a person's age. Friend says the result “would have taken much longer and may never have come about” without the Federation.

    But Stanford University bioinformatics researcher Atul Butte, a Federation member, says that although members “learned to trust each other,” the lack of specific funding for the collaboration slowed progress. “The jury is out on whether we did more than we could have as individual labs collaborating” with an NIH grant, he says.

    A successor project will use a new software platform under development at Sage to make it easier to build disease models together in real time the way software engineers now do, Friend says. Other efforts at Sage aim to coax data out of drug companies. One that is furthest along invites companies to contribute genetic and clinical data on people with a disease who were enrolled in the control arms of drug clinical trials. The companies have little incentive to keep these data proprietary, yet they could be a gold mine as a shared resource for studying mechanisms of disease, Friend says. Seven companies initially agreed to submit data sets, and two, GlaxoSmithKline and Johnson & Johnson, have begun to do so, but the rest realized that the consent forms signed by the patients wouldn't allow the companies to share the data. That experience, too, has underscored the need for a new kind of consent, Friend says.

    Climbing a big hill

    Friend's most ambitious project attempts to speed drug development and reduce its financial risk to companies by bringing companies and academics together for the initial testing of potential drugs. Dubbed Arch2POCM and led by Friend, Aled Edwards of the University of Toronto, and Chas Bountra of the University of Oxford, participants will freely share compounds and data until a potential drug has shown safety and efficacy in a phase II clinical trial. (The unwieldy acronym stands for Archipelago to Proof of Clinical Mechanism, with the initial word symbolizing groups collaborating.) The reasoning is that companies don't need intellectual property protection up to that point because they will want to modify and improve any compounds that work in this initial efficacy trial, says Harvard's Chin, who is not directly involved. But compared with other public-private partnerships, Arch2POCM would reach much further into the drug-development pipeline. “It's a very good idea” but “risky,” Chin says.

    Arch2POCM's leaders are talking to five companies and hope to have commitments by midsummer for projects involving drug candidates for cancer, autism, and schizophrenia. “Stephen has a big hill to climb,” says molecular biologist Keith Yamamoto of UC San Francisco, who is helping run Arch2POCM. “But I think we're at a stage where we need to be trying new experiments.”

    Some researchers who aren't disease modelers themselves but would contribute data to Sage caution that its systems biology approach is still experimental. Cardiologist Eric Topol, director of the Scripps Translational Science Institute in San Diego, California, says that until one of the drugs Merck found using network analysis reaches the market, the approach “isn't validated yet.” Still, Topol calls systems biology “increasingly important” in human genomics. And although the diagrams in a disease-modeling paper can be bewildering to a clinician, he expects “that the juice we'll get out of it will be useful.”

    If that happens, Friend may have already moved on to something else equally ambitious. Sage's mission is deliberately fuzzy so that it can “evolve,” he says. “We are not under the illusion that our solution has to be what happens.” And claiming success for specific projects is not the objective but rather being a “catalyst for others doing it,” Friend says. Once projects are set up, “our hope is that Sage drops out of the picture, and in 5 to 10 years no one knows what Sage is.”

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