[Ip-health] Collaborative models in science

[Kevin Outterson]

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>From Wednesday's Wall Street Journal, page one, a good (long) article
supporting collaborative R&D models in biomedical science.  The article
does not develop a critique of patent blocking, laying most of the blame
on the 'culture' of research scientists, ignoring how Bayh-Dole has
driven patents into the culture.  Nevertheless, interesting:
                                              The Wall Street Journal
                                     Wednesday, September 29, 2004
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 By Sharon Begley
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 would 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
tissue."

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 and
other private funding organizations -- ranging from the powerhouse
Juvenile Diabetes Research Foundation to newcomers like the Michael J.
Fox Foundation 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 scientists they fund swear off secrecy in favor of collaboration.

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 scientists 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 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
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 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.

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 from 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 have 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 to 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 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. Johnson 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.

In February 2002 he attended a research conference in Ventura, Calif.,
on myelin. While Mr. Johnson 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 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 weekend
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, and 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."

Despite some qualms, all five scientists Mr. Johnson 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. 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 five-year
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
grants.

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. But when 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't do anything about it. The Stanford group
figured that blocking the enzyme might 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
happens in 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. 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 one patent on it, in the hope that it might be the
basis for a new myelin-repair drug.

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 manipulate
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 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. 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
differently."   Associate Professor of Law
West Virginia University
304 293 8282
kevin.outterson@mail.wvu.edu
LL.M. (Cantab.)
J.D. (Northwestern)
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