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Oral history interview with Timothy J. McDonnell

  • 1996-Jun-17 – 1996-Jun-19

Timothy J. McDonnell spent his first six years in Indiana and Spain; then the family moved to San Diego, California. His father was a mechanical engineer in the Navy and then the Air Force. His mother had been a weather forecaster in the military during the war and then became a police officer. She gave up work to be a housewife when her children were born. McDonnell was always fascinated with the natural world, wanting first to be a veterinarian and later a herpetologist or an oceanographer; he even worked as a bat bander for a time. He attended public schools; his grade school was very good, but his junior high and high schools less so. In fact, he felt his performance worsened the longer he stayed in school, so after his sophomore year he left high school without having been graduated and entered the United States International University. There he majored in biology, which he continued when he transferred to University of California, San Diego, although his interest shifted from organismic to cellular biology, as exemplified particularly by an interest in the causes of cancer. McDonnell then attended graduate school at the University of North Dakota, where he taught anatomy in addition to doing his own research. He entered the John O. Oberpriller laboratory; there his research on cardiac muscle demonstrated that differentiated cells are not necessarily postmitotic. After receiving his PhD , McDonnell stayed at the University of North Dakota to study for an MD degree. Because he had already had most of the first two years' medical school classes he was able to be a research assistant, teaching anatomy and doing his own research. He decided to transfer to Washington University in St. Louis for his residency in diagnostic pathology. He wanted to specialize in pathology in order to combine research with practice, so he accepted a postdoc in the Stanley Korsmeyer lab, searching for cancer-causing genes in mice. Here McDonnell talks about how he learned molecular biology techniques; established that bcl-2 is an oncogene and discovered that bcl-2 functions not by enhancing cell growth but by preventing cell death. He discusses the concept of apoptosis, programmed cell death; the slow growth rate of most cancer cells; searching for factors which supplement bcl-2 in causing cancer; Korsmeyer's research background and lab management style; and the creation and patenting of transgenic mice. McDonnell continued to be interested in cardiac muscle biology. After his second year he married Sherry Wetsch, at that time a law student. Being newly married and moving to a new city and university was challenging during his third-year, but his fourth-year internship in pathology, diagnosing frozen tissue sections, went well and was well suited to his meticulous personality. Here he explains the technique of flow cytometry. Then it was time to apply for academic positions. McDonnell accepted an appointment at the University of Texas MD Anderson Cancer Center and began staffing his laboratory. He talks about his start-up package and lab space. He shifted his research focus to prostate cancer. He discusses areas of overlap between his own and Korsmeyer's research interests; he goes into his focus on the regulation of cell death and how the disruption of regulation contributes to cancer; he explains his interest in bcl-2's role in regulating transmembrane traffic. McDonnell gives a critique of traditional prostate cancer treatment and discusses the therapeutic potential of apoptosis research. He believes he has insights gained by being a combined MD/PhD He explains the degree to which cancer is associated with infectious diseases and the role of the environment in causing cancer, explaining the difference between cancer cells and normal cells. He tells why mice are models of human disease and of biological systems. Mostly he thinks experiments with animals are ethical, provided they are for health benefits—specifically cancer—but he is a vegetarian.

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