Anxious for Cures, Grant Givers Turn
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
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
funding organizations—ranging from the powerhouse Juvenile
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
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
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
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
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
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
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
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
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
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
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
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
The scientists' goal is to identify a drug target and find a
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