Scientists Must Share Data > As Condition for Funding

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To Speed Discovery Process,> Scientists Must Share Data> As Condition for Funding> An Ex-CEO Tackles His Illness> By SHARON BEGLEY> Staff Reporter of THE WALL STREET JOURNAL> September 29, 2004; Page A1>> Trent Watkins had just made an extraordinary discovery. The young graduate> student had identified a rogue enzyme that could be a key to treating> multiple sclerosis, the neurological disease that can leave victims blind> and unable to walk.>> If Mr. Watkins had been conducting science-as-usual, no outsider wouldhave> learned of his "eureka" for years, as it wended its way through scientific> review to publication in a top journal. Instead, within days of thefinding,> his lab shared the data with four research groups at other universities.Two> of them quickly set to work on blocking the enzyme in mice and human brain> tissue to see if that would protect the nervous system.>> "My heart almost stopped, it's so against how we usually do things," says> Ben Barres, a Stanford University neurobiologist and head of the lab where> Mr. Watkins is pursuing his doctorate. "Normally, the kind of work we do> would go for seven or eight years before moving to an animal model, which> would take several more years before moving to human tissue.">> The Stanford group reached out to other scientists for one reason: It wasa> condition of a grant from a new research foundation that is supporting the> lab's work. Without assurance that Prof. Barres and his colleagues would> quickly share important findings with other scientists, the foundation> wouldn't have written the check.>> The requirement reflects a growing movement among patient-advocacy andother> private funding organizations -- ranging from the powerhouse Juvenile> Diabetes Research Foundation to newcomers like the J. FoxFoundation> for Parkinson's Research -- to shake up the structure and culture of> biomedical research. Fed up with the glacial pace at which new discoveries> become medical treatments, the groups are insisting that the scientiststhey> fund swear off secrecy in favor of collaboration.>>> Traditionally, academic biomedical researchers get federal grants andtenure> by working largely alone toward basic discoveries, usually collaborating> only with colleagues in their own labs. Now some are calling that model> flawed. Despite the flood of new knowledge in the biosciences, there has> been "a slowdown instead of an expected acceleration in innovative medical> therapies reaching patients," says Janet Woodcock, an acting deputy> commissioner at the Food and Drug Administration.>> What's needed, many agree, is more "translational" research to turn> fundamental discoveries into practical treatments. And fundingorganizations> are realizing that translational research is by its nature collaborative.A> lone genius might find a disease-causing gene, for example, but turningthat> into a cure requires biologists to figure out what the gene does and> chemists to work with them designing drugs to block that action.>> Even the National Institutes of Health, the primary funder of basic> biomedical research in the U.S., is beginning to put more weight on> translational research as part of a "road map" unveiled in September 2003.> In addition to funding projects scientists dream up on their own, the NIHis> setting more of its own big goals and directing scientists to work toward> them.>> There isn't any assurance that the new strategy will work. It may not> shorten the time required for clinical trials of new drugs or devices, for> instance, which typically take a decade or more. Many scientists say the> traditional system is working fine. Siphoning money -- public orprivate -- > away from basic research and setting direction from above could choke off> discoveries that underpin every treatment and drug now in use, they say.It> could also stifle the independent spirit that leads talented people to> academia in the first place.>> But funders say they're tired of writing checks for research that doesn't> lead anywhere. Five years after the juvenile-diabetes foundation raisedand> distributed millions of dollars for basic-science research in a 1990s> campaign called "The Only Remedy Is a Cure," it had no real clinical> progress to show for the money. In one instance, a foundation-supported> scientist discovered a gene that increases the risk of developing juvenile> diabetes. All well and good, says Insel, the foundation'sexecutive> vice president for research, "but then the scientist, being a geneticist,> went and looked for another risk gene." The first discovery just sat there> in a scientific paper.>> "We used to leave it to chance that someone would pick up on the discovery> and advance it," says Dr. Insel. That has seldom happened. The foundation> distributes more than $100 million a year in research grants but the> scientists it funds haven't found a cure for an illness that afflicts at> least 1.3 million adults and children in the U.S. and 5.3 million> world-wide.>> An Active Role>> This spring, the foundation began taking a much more active role in someof> the research it supports. It listed steps deemed crucial to treating or> curing juvenile diabetes, such as coaxing the body's insulin-making cells,> which are destroyed in the disease, to regenerate. Then it invited> scientists to propose experiments toward achieving those steps. It also> began requiring that scientists seeking its money either hook up with> researchers from other disciplines or let the foundation playmatchmaker -- > or look for funding elsewhere.>> Left on their own, says Dr. Insel, "academics aren't skilled attranslating> discoveries into cures. It's incumbent on us to figure out how to do that,> and it's only going to work if we take a hands-on approach.">> The Fox Foundation for Parkinson's disease, only four years old, also> started out the old-fashioned way, inviting scientists to propose studies> that promised a better understanding of Parkinson's. "But then we looked> around and asked how we could have the biggest impact," says Hood,> director of the group's research programs. Its answer: Identify specific> advances that will likely help patients and ask scientists to propose ways> of making them happen. "We've become more a partner than just a funder,"> says Ms. Hood.>>> , a longtime Silicon Valley executive who started the Myelin> Repair Foundation, decided to go even further. In 1976, when he was 20, he> was diagnosed with multiple sclerosis. In this disease, the immune system> attacks the fatty sheath that coats axons, the long cables that carry> electrical transmissions from one neuron to the next. Without this sheath,> called myelin coating, electrical current leaks and the neuronal signal> peters out before it reaches its target. As a result, patients can suffer> extreme fatigue, blindness, loss of balance, slurred speech and problems> with cognition.>> After years of consulting and running start-ups, among them a company that> developed technology to destroy air pollutants, Mr. found it more> and more difficult to function with his MS. Today, his right hand is> virtually useless and he walks with a cane. Three years ago, he decided to> pursue a cure full-time.>> A Handful of Scientists>> In February 2002 he attended a research conference in Ventura, Calif., on> myelin. While Mr. found the studies presented in formal sessions> interesting, he hit paydirt chatting up the scientists in hallways and at> the bar of the Ventura Beach Hotel. If you had to choose just a handful of> scientists to receive funding for research on MS, he asked about 30 ofthem,> whom would you pick? The names of the same five scientists came up againand> again.>> Mr. invited the quintet to a meeting over Memorial Day weekend2002.> In the boardroom of Silicon Valley Bank in Santa Clara, Calif., hepresented> his vision. Repairing myelin, he said, is a "finite and definable" goalfor> MS therapy. He was prepared to raise significant sums for such research,but> there was one condition.>> Mr. had come to realize that scientists typically keep their> discoveries secret for years, the time it takes to methodically repeat an> experiment to make sure the results are sound, write up a description ofthe> methods and results, submit the manuscript to a scientific journal, waitfor> it to be critiqued, make the requested revisions, resubmit it, and waitsome> more until the journal publishes it. In the kind of research he wasprepared> to bankroll, the scientists had to agree to work as a team to develop and> execute a coordinated research plan. Anyone who made a discovery had to> share it with the other four labs right away.>> That flew in the face of the culture of academic biomedicine and itsreward> system. Scientists earn prestige, tenure and more grants by making basic> discoveries, and by doing it first. Being part of a collaboration candilute> prestige. As a result, scientists typically do not share their hunches or> plans with people outside their own research group. Although studies may> list a dozen authors from several institutions, in many cases thescientists> did not actually work together. They just supplied materials (anythingfrom> lab mice to biochemicals), for instance, or did a statistical analysis of> the data.>> " 'Can you send me your reagent and I'll put your name on the paper?' -- > that's what counts as collaboration in the usual model," saysneurobiologist> of Case Western, one of the five scientists invited to Santa> Clara by Mr. . "It was very hard to get used to this way of doing> things.">> Laying Out a Plan>> Despite some qualms, all five scientists Mr. recruited decided to> take the plunge. They agreed on what should be accomplished by the end of> the first year, "and from that we laid out a business plan," says Mr.> , who holds a masters in business administration from theUniversity> of California, Berkeley. He and the scientists spent the next six months> refining that plan, scheduling monthly teleconferences and four-month> reviews where the researchers would share results. Starting with a $1> million donation in March from Cook, co-founder of softwarepublisher> Intuit Inc., Mr. established the Myelin Repair Foundation. It has> raised about $2 million toward its five-year goal of $25 million.>> The five universities employing the scientists in the collaboration haveall> signed intellectual property agreements under which any royalties from> discoveries funded by MRF will be shared 50-50 with the foundation, which> would plow the earnings back into more research grants.>> Last November, when the five foundation scientists met in Chicago,> Stanford's Prof. Barres shared his lab's latest discovery. He explainedhow> Mr. Watkins, the graduate student, was examining rodent brain cellsgrowing> in lab dishes when he saw something striking. Usually, special cells inthe> nervous system called oligodendrocytes slather myelin on axons, which is> exactly what MS patients would love to happen in their own bodies. Butwhen> a certain enzyme is present, Mr. Watkins noticed, these special cells fail> to do their job. They sit right next to axons that need myelin but don'tdo> anything about it. The Stanford group figured that blocking the enzymemight> unleash myelination and maybe heal MS patients.>> If he had held back the discovery until it could be published in a> scientific journal, says Prof. Barres, "it would have been years and years> before anyone got around to the next logical step" -- seeing what happensin> lab mice in which the myelination-blocking enzyme is knocked out -- "and> only years after that would anyone get to doing this with human tissue.">> Instead, revealing the unpublished discovery was like shooting off a> starter's pistol. A molecular geneticist at the University of Chicago said> he had mice with an MS-like disease and would see what happened when he> blocked the rogue enzyme. Case Western's Prof. said he had human> brain tissue from MS patients that he would test. "You wouldn't hear this> stuff anywhere else," says Prof. . "We're thinking about it> immediately, which has probably saved us two years.">> Since then, the Stanford scientists have gone on to identify a moleculethat> knocks out the myelination-blocking enzyme and are preparing to file forat> least one patent on it, in the hope that it might be the basis for a new> myelin-repair drug.>> On the Trail>> At the most recent meeting of the five teams of Myelin Repair Foundation> scientists, ideas flew through the air. Neuroscientist Popko of the> University of Chicago described another molecule that seems to knock outthe> myelin-making oligodendrocytes. Now the foundation's team is on the trailof> ways to sideline that molecule.>> Prof. unveiled unpublished discoveries about ways to manipulate> precursor cells in ways that make them develop into oligodendrocytes. "The> brain and spinal cord contain these precursor cells, so why don't theyturn> into oligodendrocytes?" he asked. Whenever a precursor cell interacts witha> certain molecule, it seems to develop into a kind of cell that is no goodat> myelination. By tying up the molecule, precursor cells might take the path> to becoming oligos.>> The scientists' goal is to identify a drug target and find a promising> compound by 2009 -- 10 years to 15 years faster, they say, than the> traditional approach. Even then it would take a decade or more to test the> new drug. And only 8% of compounds that enter human trials become approved> drugs.>> Mr. is convinced that the hard-driving style he used at his> start-ups is the way to cure the disease that is crippling him. "To make> progress against this disease," he says, "you have to do things> differently.">> _________________________________________________________________> Is your PC infected? Get a FREE online computer virus scan from McAfee®> Security. http://clinic.mcafee.com/clinic/ibuy/campaign.asp?cid=3963>>>>>>