Four years later, Gelsinger case still has lasting implications

Julia Zhou

Daily Pennsylvanian 11/6/03

It has been over four years since 18-year-old Jesse Gelsinger died while participating in a gene therapy experiment at the University. And in those years, the incident has served as both a catalyst for changes in research practices and as a cautionary tale told even in Penn classrooms.

Gelsinger's Sept. 17, 1999 death was the first ever to be caused by gene therapy. He was being treated for ornithine transcarbamylase, or OTC deficiency, a disease that inhibits the liver's ability to process proteins. But four days after receiving an injection of a genetically modified cold virus, he died of organ failure.

In the aftermath of Gelsinger's death, his family filed a lawsuit against the University, alleging serious ethical breaches. Amidst national uproar, fingers were pointed both at the Food and Drug Administration for failing to properly monitor the experiment and at James Wilson, the Penn professor who led the experiment, for misconduct in research.

The FDA placed prohibitions on research involving human subjects, including a temporary ban on Penn's Institute for Human Gene Therapy and a permanent one on Wilson himself.

But "all the noise amounted to a lot of hand waving and handwringing," said Arthur Caplan, director of the Penn Center for Bioethics.

"Not a single regulatory change has happened post-Gelsinger" on a national level, he said.

Caplan blames the lack of change on opposing desires within the public about how closely to regulate medical research.

"The American people are very ambivalent about changing the regulatory system," Caplan said.

"They are obviously horrified when a death happens, but they want speed" in developing new treatments.

While major changes may not have taken place on a national level, Penn has been deeply affected by the controversy surrounding Gelsinger's death and has modified its research protocol as a result.

Caplan said that Penn has improved its research protection programs significantly. He cited "outside third parties," which now keep "an eye on how we're implanting research," a mandatory bioethics course for every student in the Medical School and an online certification course for researchers who are involved in human research of any kind.

Youhai Chen, an associate professor of Pathology and Laboratory Medicine, called the online certification course that he has taken, "helpful, to a degree." He added that it probably is not overly beneficial to those who already know the rules, but is helpful for younger researchers.

Chen also said that the post-Gelsinger protection measures make research "a little bit more tedious, but in the long run it protects the patients more."

"We have a very good system in place," Caplan said. "We're doing about as much as anybody anywhere is doing."

Structurally, Penn has also changed the way it approaches gene therapy studies.

Wilson stepped down from his position as director of the IHGT in 2002, although he remains on the faculty as a researcher in the Medical School's Division of Medical Genetics. The institute itself was disbanded later that year.

According to his office, Wilson is also currently chairman of the gene therapy program, a graduate group formed after the dissolution of the IHGT.

While Lenore Gelb, a spokeswoman for the FDA, refused to comment on the ban on research into human subjects, saying that they do not typically issue statements on such matters, Penn officials said that the University now can and does conduct such studies.

According to Rebecca Harmon, Health System spokeswoman, human gene therapy research is now done by Penn faculty under the oversight of the Office of Human Research -- formed in response to Gelsinger's death -- which is led by Gregg Fromell.

Caplan confirmed this, explaining that there are ongoing gene therapy projects involving human subjects.

Chen added that he doesn't think the gene therapy program at Penn has been slowed down.

But despite this, the University is still dealing with the repercussions of Gelsinger's death and its effect on Penn's reputation as a research institution.

Just last September, NBC's Dateline aired a piece about the incident. In addition, Gelsinger's father, Paul, has been a vocal advocate for improving research methods to enhance subjects' safety. Most recently, he spoke out against the corporate funding of some University research.

Still, Penn officials say they believe the University has recovered from any embarrassment and lack of credibility that ensued following the death.

"In terms of the school's reputation, we weathered the storm by acknowledging and addressing the problems head-on -- and taking aggressive steps to create and implement our Office of Human Research...," Harmon wrote in an e-mail statement. "We continue to make significant contributions to the field of academic medicine, and we continue to attract some of the best faculty and students in the nation."