pants' consent, leading to congressional hearings and a subsequent change in VA policies (see below) (U.S. House of Representatives, Committee on Veterans Affairs, 1999).

The Death of Jesse Gelsinger

Attention was already focused on the protection of human research participants when 18-year-old Jesse Gelsinger died in a phase I gene transfer study at the University of Pennsylvania in September 1999. He was a relatively healthy (i.e., medically stable) young adult with a genetic condition—ornithine transcarbamylase deficiency—who had suffered intermittent health crises because of his condition throughout his life but who was doing relatively well on medications when he entered the gene transfer trial (Gelsinger, 2000; Lehrman, 2000a,b). The details of the case are complex and to some extent contested. Although Gelsinger was aware that he was in a gene transfer study, the FDA found that the consent form had been altered from that which had been approved and that data relevant to safety had not been reported. Questions were raised about whether some patients in the trial, including Gelsinger, fit the revised inclusion criteria and whether the IRB and relevant federal agencies were notified of adverse events that had occurred in studies with animals and in previous patients (Weiss and Nelson, 1999).

The Gelsinger case was heavily reported in the national media and drew the attention of clinical investigators and research administrators throughout the world. It also became the focus of a Senate hearing and commanded direct attention from the Secretary of HHS, who subsequently requested the Institute of Medicine (IOM) study presented in this report (see discussion below) (Shalala, 2000; U.S. Senate, Subcommittee on Public Health, Committee on Health, Education, Labor, and Pensions). Problems with the system of protections for those participating in research were already apparent in 1999, but the Gelsinger death brought a sharp escalation in attention because it resulted from the experimental intervention and failures in the system of protections more than his underlying condition.


The events of the 1990s that led to this report continuously highlighted the need for reform of the system of protections for humans involved in research. The rapid growth in the size of the research enterprise, the constant innovations in experimental tools and approaches, and growing demands on the review process from the public and research sponsors alike led PRIM&R and others to ask whether improvements could be gained by the establishment of standards for systems for the protection of humans, accompanied by a method for the measurement of compliance. Others argue that current ethical principles codified in

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