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    Research Push Anxious for Cures, Grant Givers Turn More Demanding http://webreprints.djreprints.com/1078341336760.html To Speed Discovery Process, Scientists
    Message 1 of 1 , Oct 2, 2004
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      Research Push
      Anxious for Cures, Grant Givers Turn
      More Demanding
      To Speed Discovery Process, Scientists Must Share Data
      As Condition for Funding An Ex-CEO Tackles His Illness

      Staff Reporter of THE WALL STREET JOURNAL

      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
      have learned of his
      "eureka" for years, as it wended its way through scientific review to
      publication in a top
      journal. Instead, within days of the finding, 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

      The Stanford group reached out to other scientists for one reason: It
      was a 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
      other private
      funding organizations—ranging from the powerhouse Juvenile
      Diabetes Research
      Foundation to newcomers like the Michael J. Fox Foundation for
      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 scientists they fund swear off secrecy in favor of

      Traditionally, academic biomedical researchers get federal grants and
      tenure 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 funding organizations are realizing that
      translational research is by its nature collaborative. A lone genius
      might find a disease-causing gene, for example, but turning that 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
      dream up on their own,
      the NIH is 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 or
      private—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

      But funders say they're tired of writing checks for research that
      doesn't lead anywhere. Five
      years after the juvenile-diabetes foundation raised and 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 Richard Insel, the foundation's executive vice president for
      research, "but then the
      scientist, being a geneticist, went and looked for another risk
      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
      some of 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
      other disciplines or let
      the foundation play matchmaker—or look for funding elsewhere.

      Left on their own, says Dr. Insel, "academics aren't skilled at
      translating 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
      the biggest
      impact," says Katie Hood, director of the group's research programs.
      Its answer: Identify
      specific advances that will likely help patients and ask scientists
      propose ways of making
      them happen. "We've become more a partner than just a funder," says
      Ms. Hood.

      Scott Johnson, a longtime Silicon Valley executive who started the
      Myelin Repair Foundation, decided to go even further. In 1976, when
      was 20, he was diagnosed with multiple sclerosis. In this disease,
      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
      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. Johnson
      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,
      on myelin. While Mr.
      Johnson found the studies presented in formal sessions interesting,
      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 of them,
      whom would you pick? The names of the same five scientists came up
      again and again.

      Mr. Johnson invited the quintet to a meeting over Memorial Day
      2002. In the
      boardroom of Silicon Valley Bank in Santa Clara, Calif., he presented
      his vision. Repairing
      myelin, he said, is a "finite and definable" goal for MS therapy. He
      was prepared to raise
      significant sums for such research, but there was one condition.

      Mr. Johnson 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 of the methods and results, submit the
      manuscript to a scientific
      journal, wait for it to be critiqued, make the requested revisions,
      resubmit it, and wait some
      more until the journal publishes it. In the kind of research he was
      prepared 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 its
      reward system. Scientists
      earn prestige, tenure and more grants by making basic discoveries,
      by doing it first. Being
      part of a collaboration can dilute 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 the scientists
      did not actually work
      together. They just supplied materials (anything from 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," says neurobiologist
      Robert Miller of Case
      Western, one of the five scientists invited to Santa Clara by Mr.
      Johnson. "It was very hard to
      get used to this way of doing things."

      Laying Out a Plan

      Despite some qualms, all five scientists Mr. Johnson recruited
      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. Johnson, who holds a masters in
      business administration
      from the University 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 Scott
      Cook, co-founder of software publisher Intuit Inc., Mr. Johnson
      established the Myelin
      Repair Foundation. It has raised about $2 million toward its
      goal of $25 million.

      The five universities employing the scientists in the collaboration
      have all 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

      Last November, when the five foundation scientists met in Chicago,
      Stanford's Prof. Barres
      shared his lab's latest discovery. He explained how Mr. Watkins, the
      graduate student, was
      examining rodent brain cells growing in lab dishes when he saw
      something striking. Usually,
      special cells in the nervous system called oligodendrocytes slather
      myelin on axons, which is
      exactly what MS patients would love to happen in their own bodies.
      when a certain
      enzyme is present, Mr. Watkins noticed, these special cells fail to
      their job. They sit right
      next to axons that need myelin but don't do anything about it. The
      Stanford group figured that
      blocking the enzyme might unleash myelination and maybe heal MS

      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 happens in lab mice in which the
      myelination-blocking enzyme is
      knocked out—"and only years after that would anyone get to
      this with human

      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.
      Miller said he had human brain tissue from MS patients that he would
      test. "You wouldn't
      hear this stuff anywhere else," says Prof. Miller. "We're thinking
      about it immediately, which
      has probably saved us two years."

      Since then, the Stanford scientists have gone on to identify a
      molecule that knocks out the
      myelination-blocking enzyme and are preparing to file for at least
      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 Brian Popko of the University of
      Chicago described
      another molecule that seems to knock out the myelin-making
      oligodendrocytes. Now the
      foundation's team is on the trail of ways to sideline that molecule.

      Prof. Miller unveiled unpublished discoveries about ways to
      precursor cells in
      ways that make them develop into oligodendrocytes. "The brain and
      spinal cord contain these
      precursor cells, so why don't they turn into oligodendrocytes?" he
      asked. Whenever a
      precursor cell interacts with a certain molecule, it seems to develop
      into a kind of cell that is
      no good at 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
      compound by
      2009—10 years to 15 years faster, they say, than the
      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. Johnson 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 differe
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