University of Pittsburgh Library System

The Starzl archive is a collection of the correspondence and life’s work of Dr. Thomas E Starzl, the father of modern organ transplantation; this archive provides unique insight into the medical ethics involved in developing experimental kidney and liver transplant protocols beginning in the late 1950s. In the beginning of Dr. Starzl’s transplant practice, ethical oversight committees were in their early stages, so physicians were primarily responsible for ensuring the proper treatment of human subjects in experimental trials. This is distinct from the process research follows today, in which researchers are required to receive direct written approval from the institutional review boards (IRB) before proceeding with their experimental trials. As Starzl developed his protocols for transplant and tested anti-rejection drugs to prevent graft rejection, the IRB developed concurrently. Suddenly in the late 1970s, Dr. Starzl found himself in contention with the IRB, as his notion of tolerable risk differed greatly from the IRB’s conception. In one set of correspondence with the FDA and IRB, Dr. Starzl reveals his propensity to follow his own judgement despite the accepted guidelines to treat patients with no alternative options - his breach in protocol prompted an FDA investigation of his clinical practice.

Specifically, the issue the FDA investigated involved his requests for compassionate use of the experimental anti-rejection drug OKT3 in organs of patients who failed conventional therapies, at high risk for rejection. Although OKT3 later became the first monoclonal antibody approved for human use in 1986, at the time of the correspondence 1984-1986 with IRB and subsequent FDA investigation in 1986, OKT3 was an experimental compound. This case study provides excellent context for a discussion into the degree of autonomy we grant physicians to make ethical decisions in compassionate use cases, and what amount of oversight is necessary to protect patients. Although this case is historical, we may be able to draw many modern parallels between Dr. Starzl’s compassionate use requests and patient groups suffering from diseases with poor prognoses and only experimental drugs options. I plan to write and publish a research paper on the medical ethics involved in compassionate use cases and the IRB oversight of physicians.