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ne entered the gleaming new headquarters of Cogent Neuroscience
by climbing a broad, burnished stainless-steel spiral staircase,
ascending each step as a scientist might trace the individual units
of a gene along the spiraling DNA double helix. Cogent's metaphorical
staircase was apt. The company's ambitious aim was to understand
the genetics underlying malfunctioning neural machinery and to
develop drugs for a stunning array of neurological disorders, including
stroke, traumatic brain injury, and Huntington's, Parkinson's,
and Alzheimer's diseases.
But today, Cogent's spacious state-of-the-art laboratories are
empty, its sophisticated robot manipulators for genetic experiments
sit inert. In developments that exemplify both the pitfalls and
the continuing promise of applying Duke discoveries, Cogent closed
its doors last October when its funding consortium collapsed.
The company's failure is not one of science but of changing priorities
in the venture-capital markets in a weak economy. Founded five
years ago, Cogent was based on a startling achievement of Duke
neurobiologists Lawrence Katz and Donald Lo. They discovered a
way to insert genes efficiently into living slices of rat brain
tissue and to persuade the genes actually to switch on. The technique
suddenly made possible a drug-screening system that the scientists
believe is nothing short of amazing, says Lo. "By putting
compounds into the brain cells that would interact with the genes
you had introduced, you could make the equivalent of hundreds of
thousands of transgenic animals per day, because you are looking
at intact brain tissue. So, you retain all the normal physiology
and, importantly, you could examine the pathophysiology of neurons
in specific disease states, but with all the power of molecular
biology and biotechnology behind it."
The catch was that when Katz and Lo invented their technique, they
realized that a university was not an appropriate place to make
use of it. "About a split-second after we understood the importance
of the technique, we also realized that there was no academic funding
structure or even laboratory structure to exploit it, because so
much had to do with scale and production," says Lo. "Thus,
it was not compatible with the educational and mentorship mission
of the university. You couldn't in clear conscience try to have
fifty people in your laboratory working on a project whose intellectual
content is relatively low--different than the mentorship you want
to provide a graduate student or a postdoctoral fellow."
Katz and Lo enlisted veteran biotech entrepreneur Max Wallace '74
as president and chief executive officer, and together they launched
Cogent. Cogent joined an alphabet-soup of other Duke-spawned startups
with names like Merix, Norak, StemCo, and Trimeris. In fact, according
to Lo, Cogent may soon rise out of its financial ashes, transformed,
at least in part, into a nonprofit research institute aimed at
continuing its efforts to develop new drugs for neurological disorders.
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Such high-energy, high-promise companies represent a new era of
possibilities for Duke research, say administrators. These startups,
and the other burgeoning corporate collaborations with faculty
scientists and engineers, constitute the only way that the university
can ensure that its basic discoveries and knowledge benefit society.
In fact, despite the perils facing such startups as Cogent, Duke
leaders see this growing entrepreneurial spirit as critical for
the continued vitality of the university's research and teaching.
Yet they also caution that the boom in partnerships between corporations
and Duke academics could present problems that, if not wisely managed,
could compromise the quality and integrity of the university's
research mission and programs.
Among the nation's research universities, Duke is a relative latecomer
to the arena of high-tech startups; in fact, it has only recently
begun to make a concerted effort to commercialize its discoveries. "One
reason we haven't had a lot of spectacular commercial successes
is that venture capital is relatively new to our geographical area," says
Robert Taber, director of Duke's Office of Science and Technology,
which was established in 1993. According to Taber, the local venture-capital
scene has changed drastically over the past five years, with funds
under management growing from about $50 million to more than $400
million today. "Such venture capital leads to companies," he
says, "and you need a home-grown source, since people are
not going to come here from California to start a company."
"
The second reason for our relatively few commercial successes to
date is that Duke's research mandate has been largely biomedical,
and developing a product from basic biomedical research takes longer," says
Taber. "A decade between discovery and product is not unusual,
given the lengthy approval process required by the Food and Drug
Administration for drugs and medical devices."
However, Duke has become an entrepreneurial player, as evidenced
by both licensing income and startup companies. Licensing revenue
from Duke patents has climbed from $1.5 million in 1999 to $4.1
million in 2000 to $5.7 million in 2001. Duke discoveries, mainly
biomedical, have spawned some twenty-two companies, and eleven
others are now in development. Duke holds an equity position in
all of them.
Amidst this explosive growth of startups, collaborations, and corporate
consulting, Duke's leaders remain acutely aware of the potential
for problems. Chief among them is conflict of interest, as evidenced
by recent developments at other institutions. In 1999, for example,
a University of Pennsylvania trial of gene therapy for a rare metabolic
disorder went tragically awry when teenager Jesse Gelisinger died
after the experimental treatment. The government ruled that federal
research guidelines were not followed. Critics of the study worry
that the trial might have been influenced by the fact that the
lead investigator was a co-founder and major stockholder in the
company that supported his laboratory. Also, Penn held an equity
stake in the company.
And in 2002, it was reported that M.D. Anderson Center in Houston
failed to inform patients enrolled in trials of an experimental
cancer drug that the institution's president held a major financial
interest in the product. While there was no evidence that the trials
were affected, the center acknowledged that it should have informed
patients. It has adopted strict new policies to avoid such problems
in the future.
Multiple surveys of clinical trial results over the last few years
have found that those sponsored by companies producing the drug
being tested tend to show more favorable results than independently
funded studies. Reviewing these surveys, Thomas Bodenheimer, a
clinical professor at the University of California at San Francisco,
said, "The evidence I have...makes a reasonable case that
scientific misconduct does take place in clinical drug trials,
that conflict of interest is a risk factor for scientific misconduct,
and that something must be done about it."
Quoted in The Washington Post, Bodenheimer told an August 2000
National Institutes of Health conference on academic-corporate
ties, "Pharmaceutical companies--with a little help from their
friends in academia and the NIH--have created products of great
benefit to the world. This activity must continue. But to reduce
the risk of scientific misconduct, investigators and authors need
greater independence from their funders."
Bodenheimer cites as an example a 1999 study in the Journal of
the American Medical Association analyzing forty-four articles
that explored the economics of cancer drugs. According to the analysis,
only 5 percent of the drug-company-funded studies offered conclusions
unfavorable to the companies' products; 38 percent of those with
no industry funding reached unfavorable conclusions.
And in a 1996 study, Mildred Cho and colleagues at the Stanford
Center for Biomedical Ethics found that 98 percent of company-sponsored
drug studies published in peer-reviewed journals or in symposium
proceedings between 1980 and 1989 reported that new therapies were
more effective than standard drugs. In comparison, only 79 percent
of studies without industry financing found that the new drug was
more effective.
"
Can you imagine an election in which someone gets 98 percent of
the vote?" Bodenheimer asked in an article he wrote on conflict
of interest. "I guess if you pay for the votes, it's possible.
It seems likely that some of these trials were designed to favor
the sponsor, or the data were analyzed to favor the sponsor, or
the trials were written to favor the sponsor, or the trials that
didn't favor the sponsor were not published."
Some policy experts would ban any financial involvement of researchers
with companies whose drugs they are testing. "I'm not comfortable
with scientists' owning substantial equity in small firms that
are sponsoring their clinical research," David Blumenthal,
director of the Institute for Health Policy at Massachusetts General
Hospital, told The New York Times. "I think it creates a conflict
of interest, and the conflict is particularly difficult to justify
in cases where patients' welfare may be affected."
To Sandy Williams M.D. '74, dean of Duke's medical school, the
key to avoiding conflict-of-interest problems is preparation. "My
view is that conflicts of interest are inevitable," he says. "Powerful
conflicts potentially exist even in a school that has no contact
with industry. Our academic reward system creates conflicts of
interest even when it has nothing to do with personal profit.
"
These conflicts need to be managed, and the first step is to require
complete disclosure," he continues. "I believe we do
have policies in place that protect us from the dark side of conflict-of-interest
problems."
Nevertheless, Williams and his colleagues are all too aware of
the professional pitfalls of corporate involvement. "I know
of sad circumstances where excellent scientists have wrecked their
careers by the failed pursuit of commercial interests that stemmed
from their discoveries," he says. "What's needed is knowledge
and good counseling, particularly at the early stages of their
lives, for faculty members who make discoveries they believe have
practical value.".
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