News this Week

Science  04 Apr 2014:
Vol. 344, Issue 6179, pp. 14
  1. Around the World

    1 - Woods Hole, Massachusetts
    Iconic Sub Returns to the Deep
    2 - Swindon, U.K.
    Funding Fears Dominate Physics Report
    3 - Madrid
    Scientists Warn Against Vulture-Killing Drug

    Woods Hole, Massachusetts

    Iconic Sub Returns to the Deep

    Upgrade.

    Divers recover Alvin after a test mission.

    CREDIT: CHRIS LINDER/WOODS HOLE OCEANOGRAPHIC INSTITUTION

    After a 3-year rebuild, the Alvin deep-sea submersible is returning to scientific service. The $42 million overhaul by the Woods Hole Oceanographic Institution in Massachusetts involved forging a titanium "personnel sphere," changing the imaging, lighting, and data systems, and upgrading its manipulator arms. In January, the Navy cleared Alvin for use at a diving depth of 3800 meters, and scientific trials of the revamped sub were completed 26 March. A second stage of upgrades includes developing new batteries that will allow the sub to descend to 6500 meters.

    First launched in 1964, the craft is the world's longest operating deep ocean submersible, responsible for many iconic discoveries—including the first hydrothermal vents, in 1977, and its explorations of the sunken Titanic—in its 50-year life. The improvements are meant to allow Alvin to explore the deep ocean for another 5 decades.

    Swindon, U.K.

    Funding Fears Dominate Physics Report

    Physics research in the United Kingdom faces irreversible damage if it doesn't get a funding boost, an expert panel warns in a report to the United Kingdom's Science & Technology Facilities Council (STFC). In its Programmatic Review 2013, released 26 March, STFC argues that failure to increase physics funding would have catastrophic consequences: "The UK would lose leadership and credibility as an international partner on the world's scientific stage."

    As the United Kingdom's main funding body for nuclear physics, particle physics, and astronomy, the council is struggling under the constraints of the 2015 to 2016 budget, unveiled in February. The government didn't cut STFC funding, but it froze it at the current levels through March 2016. That amounts to a cut after considering inflation, says Jonathan Butterworth, a physics professor at University College London and one of the authors of the report. "If it continues, the number of Ph.D. students, the amount of science, and the economic benefits, will all decrease," he says.

    Madrid

    Scientists Warn Against Vulture-Killing Drug

    CREDIT: MAURICE KOOP/FLICKR

    Researchers are urging the Spanish government to rescind approval of a drug that could threaten Europe's wild vulture populations. In a letter published online on 27 March in Conservation Biology, five scientists from Spanish and Swiss universities point to the devastating effects of diclofenac, an anti-inflammatory commonly used to treat pain in livestock, on vultures in India.

    In 2003, researchers discovered that the drug was causing kidney failure in birds who ingested it while feeding on carcasses. It was banned for veterinary use in India, Nepal, Pakistan, and Bangladesh, but not before it wiped out most of India's vultures and left an ecological hole filled by feral dogs that help spread rabies.

    Diclofenac is currently approved for human and veterinary use in many countries and is the active ingredient in more than 100 trade-named medications. Since the Spanish Agency for Medicines and Health Products approved it in March 2013, advocates have petitioned the government to reverse the move. So far, there has been no government response. http://scim.ag/_vulture

  2. Newsmakers

    March of Dimes Prize Honors Neuroscientist's Genetic Quest

    Zoghbi CREDIT: BAYLOR COLLEGE OF MEDICINE

    The nonprofit foundation March of Dimes has bestowed its annual developmental biology prize on neuroscientist Huda Zoghbi of Baylor College of Medicine in Houston, Texas, for helping demystify Rett syndrome and other neurological disorders through more than a decade of genetic sleuthing. Zoghbi calls her career "a winding road," leading from medical school in Lebanon, which she fled in 1976 amid civil war, to becoming an authority in the genetics of neuropsychiatric disease.

    Zoghbi's fascination with Rett syndrome began during a residency at Baylor, where she saw two young girls with previously normal development gradually stripped of motor coordination and cognitive abilities. It would take more than a decade to identify the responsible mutation, but the 1999 discovery and subsequent research linking the gene methyl CpG-binding protein 2 (MECP2) to functions from feeding behavior to social skills "influences the entire field of autism and other neuropsychiatric disorders," said Joe Leigh Simpson of March of Dimes' Research and Global Programs in a statement announcing the winner of the $250,000 prize this week.

    Dynamical Systems Dynamo Nabs Abel Prize

    Sinai CREDIT: JOHN JAMESON/PRINCETON UNIVERSITY OFFICE OF COMMUNICATIONS

    Mathematician Yakov Sinai of Princeton University has won the Norwegian Academy of Science and Letters' million-dollar Abel Prize in mathematics for his work on dynamical systems—mathematical descriptions of the way physical systems change over time, from the rhythmic swings of a pendulum to turbulence in the oceans and atmosphere. The 78-year-old mathematician, also a senior researcher at the Landau Institute for Theoretical Physics of the Russian Academy of Sciences, focused on ergodic theory, an aspect of dynamical systems that averages a system's behavior over space or time. Such averages are often provably simple, even when the underlying dynamics are chaotic.

    Sinai is famous for one such system, the "Sinai billiard," which mimics the behavior of electrons in metals. (See http://www.dynamical-systems.org/sinai/ for a headache-inducing demonstration.) His work "has changed our understanding of change," said David Vogan, president of the American Mathematical Society, in a statement. Sinai will receive the award, given annually since 2003, at a ceremony in May.

    Livermore Veteran Ascends to Director

    Goldstein CREDIT: LAWRENCE LIVERMORE NATIONAL LABORATORY

    William Goldstein, a theoretical physicist, is the new director of Lawrence Livermore National Laboratory in California, one of three national labs run by the Department of Energy's National Nuclear Security Administration. A 29-year Livermore veteran, Goldstein most recently served as the lab's deputy director for science and technology.

    With more than 6300 employees and an annual budget of more than $1.5 billion, Livermore works primarily to ensure the reliability and safety of the United States' nuclear arsenal. It's also home to the National Ignition Facility, a gigantic battery of lasers that is used to test nuclear materials but has also been used to try to achieve nuclear fusion as a potential energy source. Goldstein himself helped develop the lab's smaller Jupiter Laser Facility. He trained as a particle theorist at Columbia University. Goldstein started on 31 March, replacing Parney Albright, who stepped down in November, and Bret Knapp, who led the lab in the interim.

  3. Random Sample

    Noted

    The University of Konstanz in Germany has broken off negotiations with scientific publisher Elsevier over the price of a new site licensing agreement. In a statement last week, university Rector Ulrich Rüdiger condemned the Dutch publishing giant, which puts out more than 2500 titles, for its "aggressive pricing policy." To view 2014 articles, University of Konstanz researchers will now rely on interlibrary loans and Elsevier's pay-per-view arrangement. http://scim.ag/Elsev

    NASA's Virtual Fashion Show

    CREDIT: NASA (3)

    NASA engineers are adding a touch of flair to the next generation of space suits. In collaboration with the Philadelphia University Kanbar College of Design, Engineering and Commerce, the engineers dreamed up outlandish designs for the new Z-2 suits and are holding an online poll to decide which will become a prototype, set to be built by November.

    The Z-2 offers handy new features such as 3D-printed hardware tailored for better mobility and a hard upper torso that can attach to the hull of a spacecraft or rover for exit and reentry. But the style of the prototype will depend on which of three designs—on display at http://jscfeatures.jsc.nasa.gov/z2/—gets the most votes by 15 April. The ocean-inspired "Biomimicry" model sports a squiggle-coated torso that glows in low light. Even more vibrant are the glowing teal patches on "Technology"—a retro-chic "homage to spacesuit achievements of the past," notes NASA's Z-2 website. And "Trends in Society" evokes future street clothing in the apparently to-be-trendy colors purple and neon green.

    Alas, these styles will never leave Earth. They are just "cover layers" designed to protect the nuts and bolts of the suits while NASA tests them in vacuum chambers and its giant indoor pool. The final version will be plain white, NASA advanced suit team lead Amy Ross told an online commenter in a 26 March Reddit Q&A. In other words, space walks after Labor Day will continue to be déclassé.

    They Said It

    "We have been in a really quiet time. It can't stay that way."

    —U.S. Geological Survey seismologist Lucy Jones to the Associated Press after a magnitude-5.1 earthquake shook Los Angeles last week.

  4. Chasing the Money

    1. Jennifer Couzin-Frankel

    As constraints take hold in biomedicine, scientists are forced to adapt.

    CREDIT: MARKSMITHILLUSTRATION.COM

    Money. It is what fuels research, and these days, it's almost all biomedical scientists in the United States can talk about.

    They've been buffeted by funding swings at the National Institutes of Health (NIH), their field's primary benefactor. And now they're anxious about the future, as Congress tries to rein in debt by slowing government spending.

    One result: Morale is as low and uncertainty as high as she's ever seen it, says molecular biologist Shirley Tilghman, president emerita of Princeton University. "The image that comes into my head is a seesaw," she says. "The highs are higher and the lows are lower."

    Not everyone is teetering. Some researchers and universities are raking in record-setting sums, in part by aggressively diversifying their funding sources (Science, 21 June 2013, p. 1394). But the triumphs only underscore a dominant theme: The U.S. funding landscape is shifting. And with change comes adaptation.

    For this special package, Science explored how biomedical research at U.S. universities—a $32 billion enterprise that involves hundreds of thousands of people—is reshaping itself. We found a complex mosaic, captured in the profiles that follow. To put them in context, it helps to examine what the hard data can—and can't—tell us about what's really happening on the ground.

    What we know

    Over the past 20 years, federal investment in R&D as a share of the gross domestic product has fluctuated above and below 1%, and now stands a bit under it. Biology has long been a favored child of funders, its allure growing with time. Today, roughly two-thirds of federal R&D money at universities goes to the life sciences, about 10% more than in the early 1970s. Industry spending also increased in the 1980s and 1990s, and now provides about 7% of the R&D dollars that flow to universities.

    At the same time, NIH's budget has sustained wild swings that many economists say make for an inefficient research enterprise. Between 1998 and 2003, the agency's budget doubled, from less than $14 billion to more than $27 billion. For the next 5 years it stayed largely flat. Then came an infusion of $10.4 billion in 2009, part of the federal stimulus plan to fight the recession—followed by a sizable bump downward in 2013, a 5% across-the-board cut from the sequester.

    Universities responded predictably to the budget doubling: They expanded, adding new buildings and filling them with staff members and trainees, who needed money of their own to thrive. In 2002, a commentary in Science suggested that biomedical researchers had become dependent on annual budget increases of at least 6% (24 May, p. 1401). But that didn't happen. "[T]he fundamental problems are structural in nature," concluded Michael Teitelbaum of the Alfred P. Sloan Foundation in New York City 6 years later (Science, 1 August 2008, p. 644). "[B]iomedical research funding is both erratic and subject to positive-feedback loops that together drive the system ineluctably toward damaging instability."

    CREDITS: (DATA) NIH;(ILLUSTRATIONS) G. GRULLÓN/SCIENCE

    That instability is now on vivid display. On the one hand, the future looks a tad brighter: NIH's 2014 budget increased 3.5%, to $30 billion. But that will likely not be enough to sustain the community as it hopes. NIH's grant approval rate dropped below 17% last year, compared with about 30% in the late 1990s, and the average size of standard research grants fell for the first time in recent memory.

    What it all means

    Some say the endless complaints about money are a bit much: After all, NIH is still the biggest funder of biomedical research in the world. Universities and other institutions kick in another $7 billion from various sources to support their biology researchers.

    But inflation is taking a bite. In 2013, the NIH budget of $29.15 billion was, when adjusted for inflation, almost $5 billion less than the $27.17 billion available in 2003. And some economists argue the losses are even greater, because the cost of gene sequencers, supercomputers, and even mice usually rise faster than the general rate of inflation.

    The funding swings have also exposed a mismatch between how the government supports biomedical research—one fiscal year at a time—and how science is practiced—incrementally, with progress measured in years or even decades. Because NIH now approves less than one in five grant applications, scientists say they are spending more of their time submitting proposals—leaving less for the research needed to win grants in the first place.

    What we don't know

    It's "appalling how little is known" about how the community is adjusting to these pressures, says Julia Lane, an economist at the American Institutes for Research in Washington, D.C. Are young investigators suffering more than established ones? Are smaller labs contracting more than larger ones? Which fields of research are most affected? "You have these major adjustments, and it's shocking that there is no method of understanding what the impacts are," Lane adds. "The science agencies are charged with building, identifying, and funding the best science. They don't have as their mandate to answer these questions." Dark rumors abound, fueling the sense of unease.

    For NIH, the knowledge gap can hamper its decision-making. The agency makes it easier for new investigators to get funding, for example, but it doesn't know how they fare 5 years out, when their first big grant is up for renewal. "We want to make sure we're not setting them up for failure," says Sally Rockey, NIH's deputy director for extramural research. The agency plans to start tracking these people, to gauge whether they're headed for dire straits.

    Also hotly debated is whether NIH should scale back support for the 1600 or so "millionaires," the principal investigators who boast more than $1.5 million a year in grant money. NIH gives their proposals extra review, but in most cases offers additional support with peer reviewers' blessings, "because," Rockey says, "we're a meritocracy." Jeremy Berg, a former NIH institute director who's now at the University of Pittsburgh, recently found that more than 80% of those who already receive about $650,000 a year in direct support from the Howard Hughes Medical Institute also get money from NIH—an average of two grants each, or roughly another $400,000 a year. (This funding does not include so-called indirect costs, which allows the institution to cover overhead.) "Should we be supporting a smaller number of investigators but at a very rich rate," Tilghman wonders, "or should we be letting 100 flowers bloom?"

    Economists are trying to answer some of these questions (see Policy Forum, p. 41). At the University of North Carolina, Chapel Hill, Maryann Feldman is poring over records from nine universities to understand how the support that labs receive influences publications, patents, and researcher characteristics. Feldman is also studying "venture philanthropy," which applies businesslike goals to charity work, to see how academics are relying on it and whether it redirects their research. At Ohio State University, Columbus, economist Bruce Weinberg is exploring how the structure of a lab and its funding shape the training of graduate students and postdocs and their professional future. "Hopefully the data will be built" to show how the community is adjusting, Weinberg says. "But it's not there yet."

    Some suggest a rethinking of the entire enterprise. "I think for a long time people in biomedical science bought into what you hear in industry, which is, 'If you don't grow, you die,' " Tilghman says. "And it's not true, it's absolutely not true." Maybe, she suggests, scientists and their institutions should question whether they are well served by ever-expanding labs, flanked by construction cranes building still more facilities.

    The end result for some senior scientists right now is caution: Play it safe, tighten your belt. That could have a trickle-down effect to the mouths they help feed. "I cannot take a grad student and make a 5- to 6-year commitment," says Arturo Casadevall, a microbiologist and immunologist at Albert Einstein College of Medicine in the Bronx, New York. "I don't know where we're going to be in 5 or 6 years."

  5. The Vulnerable: Talene Yacoubian

    1. Jocelyn Kaiser

    A young Parkinson's researcher struggles to establish herself, a task made much harder by the challenge of landing her first big grant.

    CREDIT: UAB NEWS

    Talene Yacoubian is exactly the kind of researcher the federal government says we need more of: a Duke- and Harvard-trained physician-scientist, a neurologist who balances her care for Parkinson's patients with a hunt for treatments that slow the disease. But at 43, Yacoubian's career has been one long slog, and she sometimes wonders if she should just give up on academic research.

    Once upon a time, scientists her age would be well on their way—with their own blossoming lab, their own stable funding. Instead, Yacoubian, an assistant professor at the University of Alabama, Birmingham, has spent the past 3 years churning out grant proposals and struggling to win her first R01, the basic research grant from the National Institutes of Health (NIH) that is the ticket to an independent research career. Around her, scientists she admires are shuttering their labs.

    "This is what I've spent all these years wanting to do," she says. "But it just may not be feasible with everything changing in science." Her dilemma illustrates one of the biomedical research community's biggest worries: that it is losing a generation of young scientists.

    Yacoubian grew up in Chattanooga, Tennessee; though her first language was her parents' Armenian, she now speaks with a trace of a Southern accent. As a freshman at Harvard University, she took a neurobiology course and was hooked. After an M.D.-Ph.D. program at Duke University, she moved back to Boston and to a neurology residency through a joint program of the Harvard-affiliated Massachusetts General and Brigham and Women's hospitals—where she fell in love with the idea of combining bench research with patient care.

    In the summer of 2007, Yacoubian settled into her own lab space at the University of Alabama. She had a career development award from NIH, and a fellowship from the American Parkinson Disease Association to study proteins that protect against cell death. The tenure clock was ticking: She had 10 years before it was up and would need an R01 to be considered.

    But that clock was competing with another, the age at which the average Ph.D. receives his or her first R01—36 in 1980 and 42 today. (It is 44 for M.D.-Ph.D.s like Yacoubian.) To support this vulnerable group, many NIH institutes have a more lenient cutoff for grant applications from those who finished graduate school or medical residency within the last 10 years. It's not clear that the policy is working, however; so far, the average age for a first R01 has not budged, according to the agency.

    In fall 2011, Yacoubian sent off her first R01 application. She didn't make the cut, so she revised and resubmitted the proposal for a second and last shot. A year earlier, her score would likely have meant success. But NIH was bracing for a 5% funding cut from the automatic reductions in federal spending known as the sequester. In March 2013, after the White House and Congress failed to reach a compromise, the sequester hit. Yacoubian became a casualty, and her proposal was turned down.

    What followed was a flurry of grant applications and mounting stress. A new R01 proposal failed, too: NIH's Center for Scientific Review deemed it too similar to her previous application, making it ineligible. "I spent the summer really frustrated and trying to figure out what direction I needed to go," Yacoubian says.

    CREDIT: (DATA) NIH;(ILLUSTRATIONS) G. GRULLÓN/SCIENCE

    To wow reviewers with a brand-new topic, she generated data for yet another R01, on how a misfolded protein spreads through the brain in Parkinson's. She opted not to replace a departing postdoc, graduate student, and technician, so her staff dropped from six to three. Small foundation grants and bridge funding from her department kept her afloat, barely. In February, after ice storms closed her 4- and 7-year-olds' schools for 6 days, Yacoubian hit a low point. "I've seen folks I've known who've been very successful in science just finally say, 'It's just not worth it,' " she says.

    Last month, as winter thawed into spring, Yacoubian finally got some good news. Nearly 7 years after she finished her training, she learned that her latest R01 submission scored well within the funding window for early stage investigators. Just one step remains—approval by an NIH council in May. "A weight is off my shoulders," she says. But she won't relax until she has the award letter in her hand. After so much time struggling to make it, she's still not sure she has.

  6. The Veteran: Russ Hille

    1. Eliot Marshall

    After a long and successful career, a biochemist is shocked when his grants aren't renewed—and he seeks alternatives to stay in the game.

    CREDIT: PETER PHUN FOR UC RIVERSIDE

    Russ Hille was smitten with science back in high school. But it wasn't until he took a biochemistry course in college in the 1970s that, he says, "the angels started singing." The infatuation led to an illustrious career—a Ph.D. in biochemistry in 1979, research awards from the Alexander von Humboldt Foundation in 2003 and 2011, honors from two universities for his work in enzymology, and international recognition from his peers. But in 2012 at the University of California (UC), Riverside, he hit a wall. His longtime patron—the National Institutes of Health (NIH)—told him it was cutting him off.

    CREDIT: (DATA) NIH;(ILLUSTRATION) G. GRULLÓN/SCIENCE

    The news came as a shock, Hille says—as astonishing as the act of generosity that launched his lab more than 3 decades ago. Back in the 1980s, he was a postdoc with renowned biochemist Vincent Massey at the University of Michigan, Ann Arbor. The science was about as basic as it gets: They studied an essential enzyme called xanthine oxidase that, among many roles, helps make uric acid that is excreted in urine. As he dug into the project, Hille became fascinated by an active site in xanthine oxidase that contains the trace metal molybdenum. He decided to focus on the class of molybdenum-containing enzymes. Massey agreed. More than that, he let Hille keep half of the National Science Foundation (NSF) grant on which they were co-investigators; Hille later took it to a new job at Ohio State University, Columbus.

    Now 62, bearded, and congenial, Hille, like many older scientists, says he has no plans to retire anytime soon. He speaks with irony about his money problem—not his first. In the mid-1980s, after NSF declined to continue its support, he turned to NIH and won two grants worth a total of $1 million per year.

    At regular intervals, NIH readily renewed his grants, sustaining his group of about 10 researchers. In 2007, he moved from Ohio to sunny UC Riverside to head its biochemistry department. His colleague and friend at Riverside, Thomas Baldwin, the former dean of the university's College of Natural and Agricultural Sciences, recalls that Hille's NIH portfolio seemed like a "phenomenal amount of money."

    No more. In 2011 and 2012, for the first time in nearly a quarter-century, Hille's grants from two NIH institutes were not renewed. Stunned, he appealed. His merit scores remained below the fundable level, and he was out.

    A shrinking NIH budget likely forced Hille's research to the sidelines. For more than 20 years, his proposals had won merit rankings near the top 10% of grants considered. He says that such rankings are no longer a guarantee of success: "It's clear that for the foreseeable future a score in the teens will not get you funded. You've got to be in single digits."

    One reviewer's evaluation, Hille says, "dinged" his grant for not being "innovative." Hille disagrees. Furthermore, he argues, "innovativeness" is a subjective measure, one that he thinks NIH favors more now than in the past.

    Even after decades of devotion, Hille concedes that molybdenum enzyme research is "an unsexy area." But, he insists, it is important. The enzymes modulate oxidation and reduction reactions that are critical to life. "Very bad things happen to humans when they are not able to utilize molybdenum properly," Hille says. Mutations in the four known human molybdenum enzymes can lead to toxicity and death. A 1988 Nobel Prize celebrated work in which molybdenum enzymes were critical, including the discovery that the anticancer drug 6-mercaptopurine can stop leukemia if given with a molybdenum enzyme inhibitor. But Hille doesn't focus on medicines, just the biology.

    Richard Holm, former chair of Harvard University's chemistry department and now a professor emeritus there, calls Hille "one of the most important if not the most important molybdenum biochemist of the last 40 years." But he also intimates that the field has lost its fizz. Holm was fascinated by these enzymes 2 decades ago, but now he says, "from my point of view, the most interesting questions have been answered."

    Without NIH's support, Hille's lab has shrunk. Now it's just him, an associate to manage the research, and three grad students. This slimmed-down team found a new patron last summer. The Department of Energy awarded Hille a $480,000, 3-year grant, backing his plan to study an exotic enzyme with a unique active center that contains both molybdenum and copper. It's found in bacteria that consume carbon monoxide; Hille argued it might prove useful in bioenergy production.

    "I'm still in the saddle," Hille insists. Before long, he aims to take another run at NIH.

  7. The Adapter: Rachel Brewster

    1. Jennifer Couzin-Frankel

    Her funding tight, a biologist adapts her work on early brain development as she strives to keep training young scientists.

    CREDIT: TIM FORD FOR UMBC

    Rachel Brewster is 46, an explorer of brain development with a dogged determination. "Maybe you talk to me 5 years from now, and I tell you I fought the battle and I caved in," she says. For now, "I refuse to accept that."

    Brewster is tenured at the University of Maryland, Baltimore County (UMBC), and she's scrambling to remake her lab and her science as her first major research grant expires this month. She is letting her postdoctoral fellows go; a frantic search to secure them alternate employment has met with partial success. She's on the cusp of winning a small grant from the National Institutes of Health (NIH) and is preparing to manage her lab on $50,000 a year, down from about $200,000. In 2 years, that shoestring budget itself will run dry.

    Brewster landed at UMBC in 2003, after marrying a biologist she met at New York University (NYU) who accepted a job at Johns Hopkins University in Baltimore. Since securing tenure, she aspired to create a different culture from the one she experienced during her postdoc, in a prestigious lab at NYU's Skirball Institute of Biomolecular Medicine. "I do not want to have the kind of cutthroat lab where people feel the pressure to work Saturday, Sunday, 16 hours a day," she says. "But then there's of course a price to pay," she admits. "The price to pay is in productivity."

    Her lab uses zebrafish to disentangle how the early brain is shaped, and Brewster has also made it a priority to support women and students from minority groups. In part that reflects her own background—she grew up in Switzerland, the child of a Jamaican mother and a British Guyanese father who worked for the United Nations. She's fiercely proud of UMBC, a state school that graduates a remarkable 40% or so of its students, many of them minorities, from science-based majors, well above the national average of 25%. "A lot of our students are daughters and sons of recent immigrants, people who still believe in the American dream and who are investing every penny and dime they have to get their kids an education," she says.

    Brewster's funding fortunes have tracked biomedicine's budget gyrations. In early 2009, just as she was up for tenure—and just as her training grant from the National Science Foundation was about to run out—she received a congratulatory phone call from NIH. Her application for an R01, the individual research grant that's manna to many scientists, had been funded on the first try.

    CREDIT: (DATA) NIH;(ILLUSTRATIONS) G. GRULLÓN/SCIENCE

    Relief mingled with surprise. Brewster had received strong but not stellar reviews, scoring in the 23rd percentile, below the official cutoff for funding. But timing was on her side: President Barack Obama's stimulus package to combat the national recession had begun a $10.4 billion, one-time infusion into NIH. Brewster became a beneficiary. For the next 5 years, she was safe.

    Taking nothing for granted, she immediately began thinking ahead. Within a year, Brewster had submitted a new proposal to the nonprofit March of Dimes, to study a protein that unexpectedly guides neural tube development. It was rejected. She turned to NIH, and there received a review score in the 14th percentile—her highest ever—but it wasn't enough. Back to the March of Dimes, which turned her down again. Then finally last fall, Brewster logged on to her computer, shaking, to learn how she'd fared in a second and final attempt at NIH. The news was exceptionally good: She'd hit the 2nd percentile and was nearly guaranteed to receive $100,000 over 2 years.

    Still, things were looking grim for her lab. Productivity lagged, in part because she and her postdocs had been busy churning out more than a dozen grant applications. Brewster hadn't published since 2011 and decided not to even bother trying to renew her R01 yet, certain her lack of papers all but assured rejection.

    As this spring closed in, Brewster knew her postdocs had to go. She was paying for them out of the expiring grant. Unlike fellows at top research schools who often secure their own funding, those at UMBC are less likely to do so. Brewster describes one as "totally brilliant" but unlikely to progress on an academic track. The other, a Johns Hopkins Ph.D., had a strong desire to teach and had joined Brewster's lab to keep her options open.

    Meanwhile, Brewster constantly considers how to stretch the dollars she has. One challenge is finding cheap labor. A dozen undergraduates now rotate through her lab. She recruited a woman she knows, who never completed her Ph.D. and is home with her three children, to spend 2 months training lab members to perform cell transplants on zebrafish. Brewster shares a technician with a colleague. Her four graduate students are supported by teaching assistantships. And Brewster herself, who receives a 9-month stipend from UMBC but relies on grants to cover the summer months, is taking no money to cover the 3-month gap, a substantial salary cut.

    Brewster sees her future in sharp relief: To survive, she believes, she must remake her science and her funding strategy. It may be years, if ever, before she applies again for an R01 as a solo scientist, and she is in discussion with a colleague in Washington, D.C., about a joint application. She's weighing a high-risk, high-payoff NIH grant, for a study with colleagues on the effects of low oxygen in the zebrafish brain, and considering seeking money from the Department of Defense or the American Heart Association.

    Brewster recognizes that her small lab, with students and trainees who may need extra nurturing, isn't a powerhouse on par with the Harvards and Stanfords of the world. "But if the measure is what am I contributing by training the next generation of scientists, I am doing more" than colleagues at far more prestigious universities, she contends. Furthermore, "creativity can come from anywhere, good critical thinking, innovative thinking, can come from anywhere," she says. She points to the movie business, which includes big-budget films along with tiny independent ones. Both have a contribution to make. In science, she asks, "do you want to have a world with nothing but blockbusters?"

  8. The Administrator: Jay Walsh

    1. Jocelyn Kaiser

    A vice president for research enjoys a healthy budget and strategizes to pull more dollars in.

    Jay Walsh's spacious second-floor office suite may be tucked away in a drab, concrete building in Evanston, Illinois, but it sits at the heart of Northwestern University's vibrant research enterprise. Walsh is all about the big picture. At 54, after 2 decades at Northwestern as a faculty member, he has risen to be vice president for research. There, he sees the disconnect between the upbeat view from 10,000 feet and the strain playing out in individual labs.

    CREDIT: © 2013 EARL RICHARDSON
    CREDIT: (DATA) NIH; NORTHWESTERN UNIVERSITY;(ILLUSTRATIONS) G. GRULLÓN/SCIENCE

    Walsh's days focus on money: helping his staff navigate the rules required to bring in state dollars, traveling to meetings with funding agencies and local and state officials, and courting donors whose checkbooks he's keen to crack open. In many ways, life these days is good for Walsh—and Northwestern. The university celebrated an 8% rise in overall research funding in 2013, to $550 million dollars. Its support from the National Institutes of Health (NIH) has soared 90% in the last 13 years, far faster than NIH's budget. Like other institutions, Northwestern suffered under the sequester that knocked 5% off NIH's 2013 budget. But while its own NIH funding dipped 4%, it was able to compensate with money from other government agencies, nonprofits, and industry.

    Walsh, who worked on developing laser ablation and optics as medical tools before stepping into his current post in 2007, credits several factors for the university's financial success. There are medical school alliances with local hospitals and research partnerships with the Department of Energy's nearby Argonne and Fermi national laboratories, on whose boards he serves. Northwestern is drawing on the annual payout from its roughly $8 billion endowment to help it fund startup packages for new faculty in renewable energy, biomedical sciences, nanoscience, and other areas. With Northwestern Medicine, the university's medical school in Chicago is embarking on a $1 billion expansion. A new building is slated to break ground next year.

    The school's growth backs a common perception among biomedical scientists: that the rich are getting richer, while universities with more modest resources are shrinking. But on a big scale, that perception is simply incorrect, says Sally Rockey, NIH's deputy director for extramural research. "Over a 25-year period we've hardly seen a difference in which are our top 100 institutions," says Rockey, who notes she likes to "blow up urban myths." She adds, "we don't see growth, we don't see decline" in how institutions are faring relative to one another.

    Northwestern, however, is an exception: Its ranking among NIH-funded institutions has climbed from 36th to 22nd from 2002 to 2012. But while Walsh savors the numbers, his scientists struggle to maintain them. One center director told Walsh that he now submits nine proposals to win a couple of grants, rather than the five he used to. Even if the money still flows into the center director's bank account in the end—which so far it has—securing the dollars remains fraught with uncertainty.

    One way the university has tried to ease this burden is by embedding staff within departments to handle the administrative portions of grants, such as budgets and faculty biosketches. Last year, a donor chipped in to create a dedicated bridge fund, available to faculty whose applications score within striking distance of the funding cutoff. But only eight, including seven of about 540 principal investigators in the medical school, are relying on formal bridge money now.

    Others are making do in different ways—for example, by tapping unused grant funds they'd previously stashed away. This cohort is largely invisible, and Walsh doesn't know how many apparently secure scientists belong to it.

  9. The Well-Heeled: Donald Bowden

    1. Kelly Servick

    A geneticist with nearly $3 million in grants considers what's behind his financial success.

    Donald Bowden likes to say that his field favors "the most adaptable, or the best adapted." And in the Darwinian environment of biomedical research, the 63-year-old geneticist is undeniably well adapted. Last year, his lab at Wake Forest University in Winston-Salem, North Carolina, received more than $2.8 million from the National Institutes of Health (NIH), all of it research project grants known as R01s. In 2010, he ranked in the top 2% of about 26,000 project grant recipients. Bowden's success reflects a mix of factors—a hot area of research, good timing, strong collaborations. And, most likely, a healthy dose of luck.

    "It isn't like my career was this can't-miss, success-is-obvious kind of career," Bowden maintains. But his research focus—the genetic underpinnings of type 2 diabetes and its complications in African-Americans—is attracting more and more attention and concern. Using funding that first trickled in from foundations, then gushed from NIH when the agency was at its most generous, Bowden drew on nearby neighborhoods to build a large genetic database. It continues to fuel new research questions and attract new grants.

    CREDIT: WFBMC PHOTOGRAPHY

    Meanwhile, he found collaborators in other Wake Forest investigators, who offered both a scientific sounding board and a financial safety net. When one lab's funding runs thin, a colleague's money keeps projects chugging forward. The research network, with Bowden's 16-person genomics lab at its core, is prospering and extending support to more vulnerable young scientists.

    "The threads all go back quite a long way," Bowden says. As a young Ph.D. student in molecular biology at the University of California, Berkeley, he was drawn to clinical questions while many around him championed basic research. After finishing a postdoc in 1981, he spent 9 years at a now-defunct Massachusetts biotechnology company, exploring the genetic underpinnings of endocrine diseases. In 1989, he made the jump to Wake Forest, bringing with him a modest NIH grant for diabetes genetics.

    In Winston-Salem, Bowden found himself at the heart of a large African-American community deeply affected by the disease and its complications. He soon teamed up with a young Wake Forest nephrologist named Barry Freedman, and the two began recruiting volunteers to examine the genetic basis of kidney disease. Bowden was most interested in the disease as a complication of diabetes, but remained open to other questions, too. "He didn't have tunnel vision," Freedman says. "He very early on recognized the value of what a genome center could do."

    CREDIT: (DATA) NIH;(ILLUSTRATION) G. GRULLÓN/SCIENCE

    Still, Bowden says the early '90s were "anxious times" financially. When NIH didn't come through, an aging center at Wake Forest offered him a small pilot grant to collect heart CT scans on diabetic patients. The preliminary data convinced the American Diabetes Association to kick in more cash.

    As the database of scans and DNA samples grew, NIH took notice. In 2001, in the midst of the agency's celebrated budget doubling, its National Heart, Lung, and Blood Institute offered Bowden and his collaborators roughly $1 million a year for 3 years.

    Bowden's database now contains more than 15,000 DNA samples, 2000 CT scans, and MRIs and cognitive testing outcomes on hundreds of volunteers. His network includes dozens of clinicians, geneticists, statisticians, and epidemiologists. He has created a resource that continues to entice those with deep pockets.

    One reason for that, Bowden believes, is his work's obvious clinical implications. He suspects tighter budgetary times are "driving things to be more translatable, which I actually don't think is bad." His current projects—he has seven active R01s, plus modest support from individual donors—aim to pinpoint genetic loci for diabetes risk and diabetic kidney disease in African-Americans, and find rare gene variants that contribute to risk of cardiovascular disease in both African-Americans and Hispanics.

    Bowden's advice to fledgling researchers: Seek shelter with a well-funded lab and join an existing study, then steer toward independence—one step at a time. His career, Bowden acknowledges, hasn't been marked by dramatic breakthroughs. "Everybody hopes to have a really big hit, which I don't think I've really gotten yet," he says. But after a "slow and painful" climb, he's enjoying the payoff.

  10. The Crowd-Funder: Heidi Moretti

    1. David Malakoff

    Looking for new dollars, a nutritionist turns to crowd funding, and hopes she can raise what she needs by the deadline.

    CREDIT: MARK BRYANT/BRYANT PHOTOGRAPHICS

    27 January 2014: 35 days remaining, $0 raised—Heidi Moretti's plea for $4350 has gone live. The nutritionist was halfway through a 40-patient clinical trial examining whether vitamin D can help people with heart problems when some of her small grants and institutional support ran out. "With your help," Moretti writes on the website Experiment.com, "we can complete our study, publish our findings and influence the care of chronic heart failure for the better."

    A clinician at St. Patrick Hospital in Missoula, Montana, Moretti, 40, had discovered the website a few months earlier as she pondered how to raise some extra cash. Like many other biomedical researchers, Moretti is hunting for money beyond traditional sources such as the National Institutes of Health. Some have tapped private foundations, wealthy individuals, and businesses. "Crowd funding" has opened yet another avenue, demonstrating that small donors can pile up millions of dollars for projects such as movies, smarter phones, and even a better backyard telescope. Now, a few science-focused groups, including the websites Experiment, SciFund Challenge, and Petridish, want to replicate that success.

    Acting on a tip from a staffer at the Vitamin D Council, a California-based nonprofit, Moretti was soon polishing punchy graphics and prose for her 35-day campaign. But she wondered: "Could it really work?"

    33 days remaining, $1000 raised—The first donations roll in, including some from friends and family in Moretti's hometown of Valier, Montana, population 509. To spread the word, she spends evenings on e-mails, Facebook updates, and testing her wings on Twitter. "Vitamin D research for heart failure patients in progress," she tweets. "Please help or retweet!"

    CREDIT: (DATA) NSF;(ILLUSTRATION) G. GRULLÓN/SCIENCE

    Thinking about how to attract $10 or $100 at a time was a "very creative and exciting process," Moretti says. It took about 10 days to prepare her plea—relatively painless compared with the grind of assembling a formal proposal to a big government funder or foundation. But the yield is almost certain to be much lower, too.

    7 days remaining, $2100 raised—"The deadline was getting closer, and I was stuck at about 50%," Moretti says. "But they warn you to expect most donations at the beginning and the end. So I just kept reaching out." Each week, she got a small surge after the Vitamin D Council featured her project in its e-mail newsletter.

    Moretti knew it was all or nothing. Like many crowd funding sites, Experiment takes a cut of successful campaigns—5% in this case. But if the goal isn't met, neither the site nor the researcher get anything, and donors aren't charged. Active social networking can tip the scales, says Experiment.com staffer Oscar Jasklowski, a former bioengineering doctoral student. It was especially critical for Moretti, whose hope of $4350, as modest as it sounds, placed her in a danger zone. About 70% of those who ask for less than $3000 have met their goal, but the success rate dips for bigger asks. Overall, as of the end of March, about 39% of the site's 298 completed projects had raised what they'd sought. The 117 successful projects raised some $732,000; the two largest about $25,000 each.

    5 days remaining, $4300 raised—The Internet's global reach is suddenly on vivid display. "Out of nowhere, from someone I didn't know" comes a gift of $2000, Moretti says. The donor, who lives in Turkey, finds her through a mention in the Vitamin D Council newsletter.

    Although generous, $2000 is a drop in the bucket for most biomedical researchers. Private dollars aren't about to replace government funding: In 2012, for instance, 7.25% of the estimated $37.2 billion spent on life sciences research at U.S. universities came from philanthropic sources, according to the National Science Foundation. Still, for scientists like Moretti operating on shoestrings, this money-raising tactic offers a chance to stay in the game.

    0 days remaining, $4510 raised—Elated and relieved to have surpassed her goal, Moretti says she "wouldn't hesitate" to crowd fund again. The final tally: 37 gifts, an average of $122 each. "With grants, there is waiting and waiting," she says. "This way, you get a pretty immediate response from people you know care about the research."

  11. Anatomy of a Grant: Michael Imperiale

    1. Yudhijit Bhattacharjee

    A microbiologist opens his books to share his expenses and where his grant money goes.

    CREDITS: STEVE KUZMA FOR THE UNIVERSITY OF MICHIGAN HEALTH SYSTEM

    Every year, about $16 billion flow from the coffers of the National Institutes of Health (NIH) to labs lucky enough to have won an individual research grant. From there, the money buys microscopes and gene sequencers, pays for graduate student stipends, supports travel, keeps the lab lights lit and the bathrooms stocked with toilet paper, and serves a myriad of other purposes. Science wanted to track this spending, following where exactly grant money goes.

    So we asked some researchers if they would open their books for us. The answer was usually no: Scientists told us they worried about inviting an audit from their funding agency. One who agreed was Michael Imperiale, a microbiologist at the University of Michigan, Ann Arbor. He shared details for a 5-year R01 grant, the individual research award from NIH on which many scientists rely. Imperiale won his R01 in 2010, to study the molecular biology of BK polyomavirus, which causes urinary tract infections in childhood and can cause life-threatening illness in recipients of kidney and bone marrow transplants. Like many scientists, he balances essentials like salaries with supplies—all the while paying a heavy overhead charge to his university.

    GRANT TOTAL

    $1,150,979

    So far, this is how much NIH has paid out. And here is where the money went, from the time Imperiale was awarded funding in 2010 until January 2014.

    SALARIES + BENEFITS

    $504,184 / 43.8%

    Paying for the people doing the research takes a huge bite. For Imperiale, that includes support for a postdoc, a research technician, and two part-time undergrads. Unlike some researchers in this era of "soft money," Imperiale isn't relying on the grant to pay most of his salary. His R01 provides for a quarter of the roughly $220,000 a year that supports him and his family. In addition, Imperiale gives a cut to the university for tuition for one graduate student; so far, that's amounted to $46,640.

    "Until about 3 years ago, I had a second grant," Imperiale says. "When it didn't get renewed, I had to shut that project down and cut back on personnel." Fortunately, the affected lab members were already transitioning elsewhere.

    SUPPLIES

    $225,971 / 19.6%

    The antibodies Imperiale uses to determine whether the virus is replicating "cost a ton of money," Imperiale says: between $300 and $500 dollars for 200 micrograms, which typically covers a batch of 1000 slides. "We also use primary cells, which are expensive to buy and culture."

    It doesn't help that the cost of supplies Imperiale buys keeps going up. And he is not alone. The Biomedical Research and Development Price Index, which goes by the catchy acronym BRDPI (pronounced "bird pie"), has for decades tracked biomedical inflation and how it compares with inflation in the general economy. Since 1980, BRDPI has outpaced economic inflation in every year but one.

    When funding is tight, the lab tries to cut costs in every way possible: by rationing supplies, for example.

    TRAVEL

    $10,024 / 0.87%

    Airplane tickets and hotels are expensive, but Imperiale and two to three lab members attend two conferences every year: the American Society for Virology's annual gathering and the smaller DNA Tumour Virus Meeting. There, they catch up with colleagues from around the world, swap ideas for experiments, and showcase their work.

    Imperiale's grant doesn't cover all the meeting costs—just registering for the virology meeting costs $500 for a member of the society and $400 for each graduate student. He draws on discretionary funds from the university to close the gap. Even in the age of Skype and other video-conferencing technologies, meetings remain immensely popular and a huge moneymaker for dozens of scientific societies.

    INDIRECT COSTS

    $410,800 / 35.7%

    The University of Michigan—like all institutions—charges the federal government a fee for providing the infrastructure needed to carry out federally funded research projects. So far, it has collected $410,800 from NIH to host Imperiale's grant, a fairly typical rate. This amount works out to a little more than a third of the total funding that NIH is shelling out for his R01.

    Where does this money go? It pays for maintenance of the 120-square-meter space that Imperiale's lab occupies—everything from electricity and heating to janitorial services. Accountants and other employees on campus who manage the grant take a cut. The university must maintain biosafety and chemical safety, and keep Imperiale's lab in compliance with an ever increasing list of federal regulations. The upshot is that this portion of the overall grant never reaches Imperiale.

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