As the father of a child who succumbed to globoid cell leukodystrophy (Krabbe disease), Dr. Leon Martel was passionate about his research to find a cure for this autosomal recessive neurological disorder, for which there is no satisfactory treatment. Martel’s initial gene therapy research at Great Eastern University used mice for modeling the disease, and he found increased longevity, improvement of clinical signs, and no adverse side effects attributed to the therapy. He then progressed to treating affected dogs. Bone marrow transplantation, combined with or without gene replacement therapy, showed similar early indications of success, although some signs of mild liver and neural toxicity were found postmortem in two treated normal control animals.

Martel’s work was published and presented at meetings, which eventually led to a phone call from his U.S. senator, who served on the Health, Education, Labor and Pensions Committee. The senator urged Martel and the college dean to push ahead with testing on rhesus monkeys as these nonhuman primates were previously used for Krabbe disease research. The senator’s altruistic goal was to have Martel accumulate enough data for the school to apply for accelerated approval of the procedure from the Food and Drug Administration and then begin clinical trials with afflicted human children. Nevertheless, after initial talks between Martel, the dean, and the chair of the IACUC, it became obvious that Martel and the IACUC chair were hesitant to move forward with nonhuman primate studies until more work was done to elucidate the cause of the mild toxicity seen in the dog studies.The dean, under continuing pressure from the senator, argued that the mouse studies showed no toxicity at all and that the mild toxicity in dogs had no overt clinical impact and was found in only two of the twelve control animals. The discussion led to a key question: If affected and nonaffected monkeys were to be studied, what clinical signs would be used to determine if there was either improvement or toxicity to the animals? Clinical signs in affected monkeys were known1, but clinical signs in normal monkeys subjected to Martel’s gene therapy technique were unknown. Martel feared that given the infrequent and mild aberrant findings in dogs and the long life span of rhesus monkeys, there may no simple way for him to determine a clear and meaningful study endpoint.

If you were Martel, how would you deal with the pressure from the dean? Would you submit a protocol amendment to add monkeys to the study? Is there any federal regulation or policy that prohibits the senator from pressuring the dean, Martel, or the IACUC?