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Should Go Forward
But programs must meet the highest standards.
By Judith Rodin
The September 17, 1999, death of a young gene-therapy
volunteer named Jesse Gelsinger was a tragedy that we continue to mourn.
It has left us resolved to redouble our efforts to run biomedical research
programs that aim to save lives while upholding the highest possible standards
for safety, accountability, conduct and informed consent.
blizzard of sensational news stories has blurred fact with rumor, and
threatened to smother the nascent but promising field of human gene therapy.
As alumni and friends of Penn, you deserve to know
what happened and what Penn has done to uncover all the facts surrounding
this tragedy. As supporters of Penn, you should know the measures we are
taking to uphold the highest ethical standards and to strengthen all phases
of clinical research that relies on human volunteers. With the media frenzy
unlikely to cool down anytime soon, I am using this column to answer your
questions as well as I can.
Researchers at the Institute for Human Gene Therapy
(IHGT) were conducting a clinical trial to test the safety of delivering
a potentially corrective gene to the livers of adult volunteers afflicted
with ornithine transcarbamylase (OTC) deficiency, a rare genetic disorder
that usually kills babies within days of their birthalthough some do
survive and are kept alive by a strict regimen of diet and medication.
Jesse Gelsinger was one of 18 adult OTC patients who
volunteered for the trial. Like his fellow volunteers, Jesse displayed
a rare kind of selfless courage by agreeing to submit to a clinical trial
whose purpose he knew was not to treat or cure his disease, but to determine
whether the experimental gene transfer would prove harmful.
Unlike any other human subject in this or any other
clinical trial performed at the IHGT, Jesse suffered an extreme adverse
reaction and died of multiple organ failure four days after receiving
his initial intravenous infusion.
We may never be able to pinpoint, with medical precision,
the reason the gene transfer killed Jesse Gelsinger. However, we know
that the IHGT team screened all volunteers, including Jesse Gelsinger,
for eligibility before enrolling them in the OTC trial.
We know our researchers informed all participants
of the risks before obtaining their signed, written consent.
We also know now that the IHGT team was neither 100
percent meticulous in its record-keeping nor 100 percent compliant in
meeting each and every reporting requirement set forth by the federal
Food and Drug Administration and by our own Institutional Review Board.
But it is extremely important to recognize that none of these lapses appears
to have had any connection to the tragic event of Gelsingers death.
this University cannot condone any lapse that creates confusion or raises
doubts about Penns respect for the rights and welfare of others. We simply
must hold ourselves to the highest possible standards for the conduct
of research throughout Penn and render the highest possible level of cooperation
and compliance with federal regulators.
With this in mind, we had already begun taking a harder,
critical look more than a year ago at our work with animal and human subjects
across-the-board, in all schools, research centers and institutes
at Penn, and in all our practices and procedures.
In the aftermath of Jesse Gelsingers death, we have
done still more:
I asked an independent committee of eminent scientists who have no affiliation
with Penn to specifically investigate and assess the IHGTs monitoring
and oversight of all clinical trials, and offer their recommendations.
Already, the IHGT has taken aggressive measures to standardize its operating
procedures, ensure full compliance with all regulations and promote
precise, unambiguous and comprehensive communications with volunteers,
IRB members and federal regulators.
The institute has added senior, experienced staff in toxicology and clinical
trials, and it has established a high-level position for a chief operating
officer who will have broad oversight responsibilities.
The IHGT has also engaged an outside contract research organization to
monitor all clinical trials.
Restoring the FDAs confidence
in the IHGT is critically important to this Universitys mission to pursue
cutting-edge biomedical research that can save lives. We must also demonstrate
persuasively that private-industry sponsorship remains critical to clinical
research, and that Penn should not abandon the field of gene therapy.
Since the passage of the
Bayh-Dole Act 20 years ago, the federal government has encouraged universities
and industry to collaborate closely and productively to move the fruits
of federally-funded research from the laboratory bench to the bedside
and the marketplace. In the case of experimental gene therapy, to produce
and test the vectors that deliver the corrective gene to patients would
be prohibitively expensive without financial sponsorship from the private
sector. The fruits of successful university research simply cannot adequately
save lives without the support and business acumen that only private industry
Is the field of gene therapy
I believe it is. Gene
therapys potential to find treatments and cures for cystic fibrosis,
muscular dystrophy and other devastating genetic diseases is enormous.
Recent headlines in The New York Times (Hint of Success Indicated
in Gene Therapy, March 2) and the Wall Street Journal (A Harmless
Virus Shows Promise, May Revive Hopes for Gene Therapy, March 29) demonstrate
the great promise and fundamental scientific validity of gene therapy.
At the Childrens Hospital of Philadelphia, scientists reported that two
of the first three hemophilia patients treated with small quantities of
corrective genes delivered by an adeno-associated virus showed signs of
As all human gene-therapy
trials move forward, researchers must proceed cautiously and do everything
possible to minimize risk to volunteers. However, researchers in any cutting-edge
medical field cannot eliminate risk completely. Testing the risk is one
of the primary purposes of clinical trials. Had zero-risk been the threshold
for proceeding with clinical trials involving human volunteers, medical
science never would have produced vaccines for smallpox, diphtheria, polio
and influenza. We never would have improved the management of heart disease
or seen the introduction of increasingly effective treatments for AIDS
and a wide range of cancers.
As the proud home of the
nations first medical school, Penn shoulders a historic responsibility
to discover and develop the next generation of drugs, therapies and procedures
to extend the frontiers of life. That is why human gene therapy experiments
at Penn should go forward. But they will do so in a model program that
will meet the highest standards for safety and accountability.
Jesse Gelsinger was a pioneer
who gave his life to a field that is only a decade old. When human gene
therapy produces cures for genetic defects, the millions of saved lives
will be Jesses enduring legacy.
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