Oral History Center, The Bancroft Library, University of California Berkeley Oral History Center University of California The Bancroft Library Berkeley, California J. Michael Bishop Scientist, UCSF Chancellor, and Nobel Laureate Interviews conducted by Sally Smith Hughes in 2016 and 2017 Copyright © 2017 by The Regents of the University of California Oral History Center, The Bancroft Library, University of California Berkeley ii Since 1954 the Oral History Center of the Bancroft Library, formerly the Regional Oral History Office, has been interviewing leading participants in or well-placed witnesses to major events in the development of Northern California, the West, and the nation. Oral History is a method of collecting historical information through tape-recorded interviews between a narrator with firsthand knowledge of historically significant events and a well-informed interviewer, with the goal of preserving substantive additions to the historical record. The tape recording is transcribed, lightly edited for continuity and clarity, and reviewed by the interviewee. The corrected manuscript is bound with photographs and illustrative materials and placed in The Bancroft Library at the University of California, Berkeley, and in other research collections for scholarly use. Because it is primary material, oral history is not intended to present the final, verified, or complete narrative of events. It is a spoken account, offered by the interviewee in response to questioning, and as such it is reflective, partisan, deeply involved, and irreplaceable. ********************************* All uses of this manuscript are covered by a legal agreement between The Regents of the University of California and J. Michael Bishop dated June 22, 2017. The manuscript is thereby made available for research purposes. All literary rights in the manuscript, including the right to publish, are reserved to The Bancroft Library of the University of California, Berkeley. Excerpts up to 1000 words from this interview may be quoted for publication without seeking permission as long as the use is non-commercial and properly cited. Requests for permission to quote for publication should be addressed to The Bancroft Library, Head of Public Services, Mail Code 6000, University of California, Berkeley, 94720-6000, and should follow instructions available online at http://www.lib.berkeley.edu/libraries/bancroft-library/oral-history-center/rights It is recommended that this oral history be cited as follows: J. Michael Bishop, “Scientist, UCSF Chancellor, and Nobel Laureate,” conducted by Sally Smith Hughes in 2016 and 2017, Oral History Center, The Bancroft Library, University of California, Berkeley, 2017. Oral History Center, The Bancroft Library, University of California Berkeley iii J. Michael Bishop with a model of DNA Photograph courtesy of UCSF Archives and Special Collections. Oral History Center, The Bancroft Library, University of California Berkeley iv In Memoriam Kathryn Ione 1937-2016 Oral History Center, The Bancroft Library, University of California Berkeley v This oral history with J. Michael Bishop is one in a series documenting bioscience and biotechnology in Northern California. Selecting Rous sarcoma virus, a cancer-causing retrovirus, after arriving at UCSF in 1968, Bishop was soon joined by Harold E. Varmus with whom he established a partnership legendary for its length and productivity. In a seminal publication of 1976, they established the proto-oncogene as a normal cell component and precursor of oncogenes. In 1989, Bishop and Varmus were awarded the Nobel Prize in Physiology or Medicine for this research. With some reluctance, Bishop agreed to become UCSF Chancellor in 1998. His highly productive eleven years saw the creation and staffing of the Mission Bay campus and record-breaking fundraising success, among other important events he oversaw. The oral history consists of five interviews conducted in 2016 and 2017, with an introduction by colleagues Bruce Alberts and Harold Varmus. Oral History Center, The Bancroft Library, University of California Berkeley vi Table of Contents—J. Michael Bishop Interview History by Sally Smith Hughes xi Introduction by Harold Varmus and Bruce Alberts xiv Interview 1: September 29, 2016 Audio File 1 Hour 1 1 Childhood in Goldsboro, Pennsylvania — Father’s work as a Lutheran minister — Attending classes in a two-room schoolhouse — Influence of religion on adolescence — Church services “seeded an interest, really a passion, for good music, classical music” — Taking vocal, piano, and organ lessons — Mother’s inability to pursue higher education — Memories of grade school teacher as demanding, rigorous, and inspiring — Scholarship to Gettysburg College: “This small liberal arts college was the perfect place for me” — Convinced by aunt’s general practitioner to study medicine — High school courses in chemistry, physics, biology — Taught comparative anatomy from an evolutionary standpoint — Father’s view that no conflict necessarily exists between theology and evolution — Naturally taking to science as a student — Joining then leaving ROTC — Meeting wife Kathryn in college — Belief in the importance of a liberal arts education for scientists — Applying to and interviewing for medical school — Choosing Harvard — Initial challenges of Harvard: “I began to figure out what being an academician really was all about” — Post-sophomore fellowship; first forays into research — Class on animal viruses leads to work in instructor’s lab — Research on RNA virus — Decision to do research rather than clinical courses; believed to be professional suicide — Post-graduation internship at Massachusetts General Hospital — Plan of going into training program at National Institutes of Health (NIH) Hour 2 21 Massachusetts General Hospital fellowship — Learning how to purify viruses — Student group Bolyston Society and peers as source of stimulation — More on purifying viruses — Interest in the microbiology of poliovirus — Moving research in a more molecular direction — Research with Leon Levintow — State of animal virology at the time — Levintow’s move to UCSF, being recruited by him to join the microbiology department — More on time at NIH — Becoming a Public Health Service lieutenant instead of being drafted into service — On being considered a “yellow beret:” “I was doing what I wanted to do, and I wasn’t happy with what our military was doing” — Partnerships and work environment at NIH — Mentorship with Aaron Shatkin — Discoveries and talent of David Baltimore — Time in Gebhard Koch’s lab in Hamburg — Koch’s work on expressing nucleic acids inside cells — Publishing a paper with Koch — More on Oral History Center, The Bancroft Library, University of California Berkeley vii double-stranded poliovirus RNA research — Failure to grow cells in Hamburg — Publishing independent paper in The Journal of Molecular Biology — Beginning of work on Rous sarcoma virus Interview 2: December 09, 2016 Audio File 2 Hour 1 38 Recap of research at NIH, going from a “mere MD” to a research scientist — More on collaborations with Leon Levintow — Receiving job offer at NIH — More on work with Gebhard Koch — Visiting San Francisco to work with Levintow at UCSF: “I was in town about twelve hours before I decided I had to live in this place” — Pleased with smallness of UCSF microbiology department; no feeling of intense academic pressure — Accepting UCSF offer; differences in hiring process then and now — Levintow’s approach to scientific writing — Writing grant application at NIH for polio research — Unexpectedly asked by department chair to teach — Chair’s dedication to quality teaching — Teaching style: “I always worked historical narrative into my lectures” — Course with pharmacy students as first attempt at teaching — Research collaboration with Warren Levinson on Rous sarcoma virus — Using new form of molecular hybridization — Phasing out polio work to focus on Rous — Motivation for studying Rous, to understand cancer — Assay used in Rous research — Studying quantifiable neoplastic transformation of Rous — Reverse transcriptase discovery — Howard Temin’s early research on RNA virus replication — Challenging “central dogma” of molecular biology — “Scientists are guilty of this kind of preconception” — Teaching graduate course at UCSF on tumor viruses — Finding right assay to break the lipid envelope around Rous — Disappointment over failed thymidine assay — Beaten to discovery of reverse transcriptase by Temin and David Baltimore circa 1970 — Maintaining momentum of Rous research anyway — State of cancer theories Hour 2 59 Notion of a cancer gene — More on reverse transcriptase discovery — More on the “central dogma” and preconceptions of scientists — George Todaro and Robert Huebner’s oncogene hypothesis — Partnering with Harold Varmus and Peter Vogt — Making hybridization work from avians to mammals — Changing stringency (salt concentration and temperature) of assay — Discovering src in mouse DNA — Meeting Harold Varmus — Presenting data on reverse transcriptase — Relationship with post-doctoral students — Letting Varmus carve out his own space — Sharing mentorship of other postdocs — Publishing papers on RNA Rous hybridization in Nature — Proving the Heubner-Todaro theory wrong — Contributions of postdocs Dominique Stehelin and Deborah Spector — Bringing outside labs together to talk about unpublished data, evolves into West Coast Tumor Virus Cooperative Oral History Center, The Bancroft Library, University of California Berkeley viii