Jeffrey T. Holt

Born: May 24, 1954 | Battle Creek, MI, US

Jeffrey T. Holt was born and raised in Battle Creek, Michigan. He attended Kalamazoo College in Michigan, intending to pursue both music and premed majors, though he ultimately gave up music. After completing medical school he went on to his residency 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. He went on to a faculty position in the Departments of Cell Biology and of Pathology at the Vanderbilt University School of Medicine. Holt talks about the ways medical practice differs from research, applying insights in pathology to cancer research, and the difficulties in applying molecular biology cancer research in practice.

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Interview Details

Interview no.: Oral History 0509
No. of pages: 109
Minutes: 451

Interview Sessions

Neil D. Hathaway
3-5 January 1993
Vanderbilt University School of Medicine, Nashville, Tennessee

Abstract of Interview

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.

Education

Year Institution Degree Discipline
1976 Kalamazoo College BA Health Sciences
1979 University of Michigan School of Medicine MD

Professional Experience

University of Rochester

1979 to 1982
Strong Memorial Hospital, Resident, Pathology
1982 to 1983
Strong Memorial Hospital, Chief Resident, Clinical Pathology

National Heart, Lung, and Blood Institute, National Institutes of Health

1983 to 1986
Staff Fellow, Clinical Hematology Branch
1986 to 1987
Senior Staff Fellow, Clinical Hematology Branch

Vanderbilt University School of Medicine

1987 to 1991
Assistant professor, Department of Cell Biology and Department
1991
Associate professor, Department of Cell Biology and Department

Honors

Year(s) Award
1975

Phi Beta Cappa

1978

Alpha Omega Alpha, University of Michigan School of Medicine

1988 to 1992

Scholar, Pew Scholars Program in the Biomedical Sciences

1992 to 1994

Fogarty Fellowship

1992

National Cancer Institute Principal Investigator

1992

Vanderbilt Toxicology National Cancer Institute Cancer Grant

Table of Contents

Early Years
1

Childhood in Battle Creek, Michigan. Parents. Piano and organ lessons. Attends Interlochen music camp and is a finalist in the concerto competition. Plays the organ in church. Performing skills transfer over to public speaking. Siblings. Teaching children to excel. Discovers the world beyond Battle Creek. Meets future wife, Susan Sallee.

College and Medical School
22

Attends Kalamazoo College. The Vietnam War and the draft. Focus on health rather than political issues. Majors in premed. Role models in science. State of college biology in the early seventies. Absence of undergraduate laboratory research at Kalamazoo College. Learns laboratory research as a fellow in the National Heart, Lung, and Blood Institute. Rationale behind the National Institutes of Health physician-scientist training program. Increasing interest in pathology research. Attends the University of Michigan School of Medicine. Internship. Wife's work in music education. University hospitals and community hospitals. Funding cutbacks. The lengthy training required of MD/PhDs. Ranking scientific journals. Shifting research interests. How oncogenes react differently in mice and humans.

Research and Its Applications
46

How the practice of medicine differs from research. Applying pathology insights to cancer research. Concern that human cancer may be significantly different from cancers produced in mice. Applying gene expression methods to identify premalignant cells. Limits to epidemiological cancer research. Difficulty of applying molecular biology cancer research in practice. Extent to which cancer is not hereditary. Religious faith and its relation to his scientific training. Studies globin mRNA in thalassemia in the Arthur W. Nienhuis lab. Investigating the effects of antisense fos-Nienhuis's lab management.

Antisense Experimentation and Faculty Years
58

Leakage from the Xenopus oocyte nuclei undermines transport experiments in Nienhuis's lab. The frustration of working on dead-end experiments. Early work on antisense ignored. Technical constraints on antisense experiments. Difficulty of distinguishing true leads from false leads. How the antisense field gained acceptance. The future of antisense research. Applying for a patent on a topical antisense delivery system. 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 myristylation. Fos suppression experiments. Inder M. Verma's mapping of the fos phosphorylation site. Trying to translate animal-systems research into under-standing human systems. The possibility that cancer can be explained by a relatively simple model. Doubts about gene therapy for cancer.

Final Thoughts about Research and Scientific Practice
91

Decides not to patent his HL60 leukemia cell antisense. Application for a patent on topical antisense. Topical antisense's potential usefulness. Marketing basic science research to the public. Need to try risky experiments. Significance of fos genes. How redundancy may minimize the effect of a fos knockout in mice.

Index
106

About the Interviewer

Neil D. Hathaway