Jeffrey T. Holt was born and raised in Battle Creek, Michigan—the "Cereal City"—the middle child of three siblings. His father was an electrical engineer who worked for the Kellogg Company in packaging-type machines; his mother was a homemaker. Holt had what he considered a typical childhood, though he developed a great interest in playing piano and then the organ. He won a scholarship to attend the Interlochen Center for the Arts summer camp and was a finalist in the concerto competition; he also decided to play the organ for his church. Norman Rubell, a high school biology teacher who taught using the Socratic method, proved to be quite influential. He attended Kalamazoo College in Michigan, in part because it was close to his home, intending to pursue both music and premed majors, though he ultimately gave up music. Kalamazoo did not provide any opportunities for laboratory research. Following (somewhat) in his brother's footsteps, Holt went on to matriculate at the University of Michigan to pursue his medical doctorate. After completing medical school he went on to his residency in pathology at the Strong Memorial Hospital at the University of Rochester, before beginning postdoctoral work in the Arthur W. Nienhuis lab at the National Heart, Lung, and Blood Institute in Bethesda, Maryland, studying globin mRNA in thalassemia and investigating the effects of antisense fos. Some of the research in the Nienhuis lab was stymied due to leakage from the Xenopus oocyte nuclei which undermined transport experiments. From there he went on to a faculty position in the Departments of Cell Biology and of Pathology at the Vanderbilt University School of Medicine. Throughout the interview Holt talks about the ways in which the practice of medicine differs from research, applying insights in pathology to cancer research, and the difficulties in applying molecular biology cancer research in practice. He also discusses how the antisense field gained acceptance and his application for a patent on a topical antisense delivery system. The interview concludes with his thoughts on applying fos antisense research to human cancer; searching for transcriptional differences between c-fos and v-fos; Marilyn D. Resh's study of reticulocyte lysates and myrisylation; and Inder M. Verma's mapping of the fos phosphorylation site. Holt ends the interview with reflections on his decision not to patent his HL60 leukemia cell antisense; marketing basic science research to the public; and the need to try risky experiments.
Access this interview