Previous patients in the trial had experienced flu-like symptoms, but he had a much worse reaction. Within a day he became disoriented and showed signs of jaundice. He had an intense inflammatory response and developed a dangerous blood-clotting disorder, followed by kidney, liver, and lung failure. Four days after receiving the shot Jesse was declared brain dead and taken off life support. The team of doctors and nurses caring for him were stunned by his rapid decline and death.
The news that an experimental treatment had killed a basically healthy volunteer rocked the field of gene therapy and the broader world of biological research. News coverage portrayed the trial researchers as overeager and undercautious, taking shortcuts and disregarding rules meant to protect the people in their care. In a flash the field of gene therapy collapsed, taking its grandiose promises of miracle cures along with it.
Biochemist Jennifer Doudna , who later discovered the CRISPR-Cas9 gene-editing mechanism, remembers feeling the shock waves as a young researcher, even though her work had nothing to do with gene therapy or any kind of medical research.
Even the term gene therapy became kind of a black label. Of course, the field eventually rebounded. To date, these efforts have produced just a few marketable medicines—two therapies for lymphoma, a treatment that reverses a form of inherited blindness, and most recently, a therapy for spinal muscle atrophy. But innovation has accelerated in the past few years thanks to CRISPR, which has enabled highly targeted editing of genes that is vastly cheaper and quicker than earlier methods.
Treatments for hemophilia, muscular dystrophy, and other genetic diseases now seem almost within reach. Scientists say this new generation of gene-therapy research is safer. But how safe is safe enough? How much risk is acceptable, how can researchers assess the risks, and who should bear them? They focused on the possibility that the adenovirus had triggered a fatal immune response for reasons that were not yet clear. Meanwhile, journalists and federal health officials discovered several troubling lapses in the conduct of the study.
When two patients suffered serious side effects, the scientists did not immediately inform the agency or put the study on hold as required. But perhaps most damning were failures in the informed-consent process.
If he had been properly briefed about these previous issues, he might have dropped out of the study and still be alive today. Wilson was also accused of a conflict of interest: he had a stake in the company that owned the gene-transfer technology and stood to benefit if the trial succeeded. Wilson denied that financial considerations affected the study and said it was impossible to predict that Jesse would suffer such a bad reaction.
The FDA charged Wilson with several violations, and in he agreed to restrictions on his human research for five years. The investigations drew attention to wider problems in oversight of gene-therapy experiments and human research generally. The agencies tightened monitoring of trials, increased inspections, and created a new system for reporting serious side effects, among other steps. Penn responded to the crisis by strengthening the institutional review boards that oversee its trials, putting in new protections for patients, and prohibiting researchers from having financial stakes in their trials.
Yet as the pharmaceutical industry continued growing and its profits soared, demand for test subjects increased, and more research was undertaken by private companies rather than academic or government institutions. That raised new fears that patient safety could be compromised in the rush to get products to market. It was a striking reversal for a renowned scientific pioneer.
Although the IOM's view represents the dominant narrative about financial conflicts of interest, it is not the only one. One influential group urges that financial conflicts can never be removed from medical research and, indeed, should not be.
This Essay evaluates these polar positions by examining Jesse's participation in human research and his death. Drawing on new evidence from the documents collected in the Gelsingers' lawsuit, this Essay asks specifically whether new and better restrictions on financial conflicts of interest would have made a difference in Jesse's case and concludes that more robust restrictions would not have mattered. This Essay argues that rather than attempting to expunge financial interests from research, those interests should trigger significant, ongoing review of the affected clinical trials, much like the post-approval monitoring now used randomly by leading research institutions.
Indeed, had Wilson's outsized financial stake triggered mandatory monitoring, people inside Penn likely would have stumbled upon the string of questionable decisions in Jesse's trial, including departures from the research protocol, long before those mistakes cascaded, culminating in Jesse's death. This Essay describes the research trial Jesse participated in and the lawsuits spawned by his death, and recaps the cavalcade of errors that the FDA says plagued the trial long before and up to Jesse's death, errors now largely acknowledged by Wilson.
Next, this Essay reviews what the researchers told Jesse about the trial's risks, the results of prior animal studies, and the basic protections he would receive as a participant, and contrasts those disclosures with the frank disclosures approved by regulators at the trial's start.
This Essay then follows the money, showing the nature and extent of Wilson's financial conflict of interest, and demonstrates that a lot of good people inside Penn sounded alarm bells about Wilson's hefty stake, to no avail.
Throughout the reports to the NIH, scientists repeatedly acknowledge that their gene treatments caused various nonlethal symptoms, but they invariably conclude that any deaths likely resulted from underlying illnesses or other causes. But these scientists had a duty to report, and they failed in that duty. By trying to sweep their mistakes under the rug they were, at best, fooling themselves. The temptations are real; successful therapies can generate a lot of money, not to mention career advancement.
But deliberate concealment makes oversight impossible. His name is still regularly mentioned by NIH regulators and by activists calling for stricter oversight of developing technologies. Ironically, it is also cited by advocates of heritable human genetic modification such as George Church and Steven Pinker who of course want to avoid such an incident.
Strangest of all, perhaps, is that He Jiankui, the one person known to have brought genetically modified embryos to term, ended a lecture in with a call for caution and a picture of Jesse Gelsinger. Indeed, his work with monkeys and pigs, who had toxic reactions to gene therapy, has made him a voice of scientific caution.
The failure 20 years ago was institutional, not just individual. There were rules, and they were routinely flouted. As scientists push the boundaries of biology in ways that could establish a modern techno-eugenics , society as a whole has a responsibility to assess the risks and benefits, individual and social, of genetic technologies.
In the late s, self-regulation clearly failed, and so did passive oversight. Perhaps, in the long run, that knowledge will be the primary legacy of Jesse Gelsinger. These labs were deciphering the secrets of embryos and had a particular interest in how eggs are formed.
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