In an effort to find a gene-therapy cure for a metabolic disorder, which he was also a victim, Jesse Gelsinger consented to participate in a gene-therapy clinical trial that led to his death. Gelsinger consequently entered history books as the first ever person to perish from involvement in a clinical trial research. The resultant lawsuit against the gene-therapy research firm paved the way for enactment of regulatory framework to govern gene-therapy research in the United States.
Gelsinger gene-therapy tragedy began with his diagnosis with deficiency of ornithine transcarbamoylase (OTC), a metabolic dysfunction diagnosed in one of the forty thousand newborns through its impediment on ammonia elimination ( Steinbrook, 2008 ). The majority of infants with OTC deficiency go into comatose three days after delivery leading to serious brain damage. Consequently, half of OTC deficient infants dies in a month after delivery, and the rest dies before their fifth year birthday.
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Gelsinger’s condition was uniquely different from other OTC cases. His OTC deficiency was partial and therefore managed to hold on to life by taking drugs and a diet with low protein nutrients. Institute for Human Gene Therapy director James Wilson at University of Pennsylvania considered Gelsinger as an ideal candidate for gene-therapy clinical trial. Consequently, Wilson administered Gelsinger with an OTC gene corrective infusion on 13 th September 1999 ( Wilson, 2010) . The OTC administration involved infusion of encased OTC corrective gene in the attenuated dose of a recombinant cold adenoviral vector through injection into Gelsinger’s hepatic artery. Immediately after the injection, Gelsinger suffered a serious immune response to the vector meant to deliver the gene into his body. Gelsinger died four days following the injection ( Wilson, 2010) .
Subsequent lawsuits against the Institute for Human Gene Therapy revealed several ethical violations in conducting the gene-therapy trial that killed Gelsinger. Among the ethical violations filed by Gelsinger family lawyer included failure of the Institute to disclose to Gelsinger on past tragedies involving gene-therapy trials, including severe side effects suffered by past human participants ( Reardon, 2016 ). The Institute further failed to inform Gelsinger about the death of three monkeys from blood clotting and serious inflammation of the liver following injection with the gene-therapy recombinant adenoviral vector infusion. Researchers at the Institute for Human Gene Therapy also downplayed the risk posed by the recombinant adenoviral vector as only Gelsinger’s death was solely attributable to the vector from over 400 of gene-therapy clinical trials with a sample of over 4000 patients. Subsequent FDA investigation further faulted the Institute’s inclusion of Gelsinger in the trial as a replacement for another participants who discontinued with the trial. The Institute also disregarded Gelsinger’s high ammonia level, which made him unfit for the gene-therapy clinical trial ( Wilson, 2010) . University of Pennsylvania and the Institute’s director Wilson also held back information about their financial stakes at the human gene-therapy research, which drove them to violate all ethical precautions. Ultimately, the Institute and its Children’s National Medical Center partner agreed to an out of court settlement by paying half a million dollars to the government as compensation.
Gelsinger’s death and subsequent lawsuit triggered a flurry of reactionary policy directives by federal agencies. Among the decisions included suspension of gene-therapy trial at the Pennsylvania based Institute for Human Gene Therapy by United States Food and Drug Administration (FDA) in response to the Institute’s failure to adequately recruit its staff, get informed consent, and design standard operating procedures ( Steinbrook, 2008 ). The FDA ultimately banned entire clinical trials at the University of Pennsylvania in gene-therapy that involved human participants in January 2000 ( Reardon, 2016 ). FDA further launched an investigation on sixty nine more gene-therapy clinical trials in progress across the country. Ultimately, FDA reviewed twenty eight trials and ordered remedial action for thirteen trials.
FDA further partnered with the National Institutes of Health to develop programs for enhancement of patients’ protection. Among the groundbreaking patient protection program inaugurated by the partnership includes the Gene Transfer Safety Symposia and the Gene Therapy Clinical Trial Monitoring Plan. FDA monitoring requires sponsors’ to submit financial prospects that potentially revealed conflicts of interest as applicants for licensure or approval of their gene-therapy products ( Reardon, 2016 ). Nevertheless, the FDA monitoring requirement ineffectively regulated gene-therapy research by legislating for an end of process regulation that targeted gene-therapy products rather than the trial itself ( Wilson, 2010) . Nevertheless, FDA monitoring requirements helped in the unearthing Institute for Human Gene Therapy director, Wilson’s interest in Genovo, the institute’s sponsor as one of the company’s shareholder.
The latest Gene Therapy Clinical Trial Monitoring Plan stipulates for clinical oversight and disclosure prior to commencement of a gene-therapy clinical trial. It also clarifies mandatory reporting requirements for the trial. Lately, FDA further enacted a policy that forbid researchers and colleagues directly participating in patient sampling, the informed-consent procedure or a trial’s clinical administration from owning shares, holding equity or similar financial interests in companies that financed the trials. On the other hand, the Gene Transfer Safety Symposia requirement enables investigators to share clinical expertise and data especially in severe circumstances. Nevertheless, business interests impede the sharing of information among gene-therapy researchers due to fear of loss of a valuable gene-therapy patent.
References
Reardon, S. (2016). First CRISPR clinical trial gets green light from US panel. Nature News .
Steinbrook, R. (2008). The gelsinger case. The Oxford textbook of clinical research ethics , 110-120.
Wilson, R. F. (2010). The death of Jesse Gelsinger: new evidence of the influence of money and prestige in human research. American journal of law & medicine , 36 (2-3), 295-325.
